I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen &...
-
date post
21-Dec-2015 -
Category
Documents
-
view
222 -
download
0
Transcript of I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen &...
![Page 1: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/1.jpg)
![Page 2: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/2.jpg)
I. IntroductionII. Element of ImmunityIII. ImmunogeneticIV. Immune ResponseV. Antigen & Immunogen & VaccineVI. ImmunoglobulinVII. Complement SystemVIII. Cytokines
![Page 3: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/3.jpg)
IX. Antigen-Antibody Reaction X. Immunology in Infection
diseasesXI. ImmunoprophylaxisXII. Hypersensitivity ReactionXIII. Autoimmune DiseasesXIV. Immunodeficiency
![Page 4: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/4.jpg)
Immunology “Imunis”All of physiology mechanism => foreign agent => - neutralize with
or - eliminate => without
- metabolism tissue
damage
![Page 5: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/5.jpg)
X1st century => ChinaXV1st => variolasi1798 : E. Jenner : Cowpox => Smallpox1880 : Vaccine (L. Pasteur)1908 : => cellular (Metchnikof) => humeral (Ehrlich)>>> 1970 : molecular biology
![Page 6: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/6.jpg)
GeneticAgeMetabolismEnvironment & nutritionAnatomyMicrobePhysiology
![Page 7: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/7.jpg)
1. Defense2. Homeostasis3. Surveillance
![Page 8: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/8.jpg)
Innate (natural)Immunity Acquired (adaptive)
Natural : all of creature (+) Such as : 1. Physical hindered
2. Cellular hindered
3. Chemical hindered
![Page 9: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/9.jpg)
Adaptive
With functional characteristic :1. Specificity Heterogeneity
2. Differentiate : “SELF” & “NOT SELF”
3. Memory
![Page 10: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/10.jpg)
Operator of Immunity : Limphoreticular system
Phagocyte cells : MPS, Neutrophyl, EosinophylLymphoid cells : B cell & T cellMediator cells : Basophile, Mastocyt
Which come from : “Hematopoetic Stem Cell”
(0,001 % Bone marrow)
![Page 11: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/11.jpg)
NK cell
![Page 12: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/12.jpg)
Consists of : Lymphoid cells Lymphoid tissues
Lymphoid Cells
Lymphoid cell Immunocyt
Specific cellular product (Ig & CMI)
BM Primary Lymph glands Secondary Lymph
gland
Immunogen
(Prolif. & Dif)
![Page 13: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/13.jpg)
Thymus glandFunction : Maturity T cells
BM Thymus gland Circulation
Cortex Medulla
CD4+
CD4- CD8- CD4+CD8+ Circulation
CD 8+
![Page 14: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/14.jpg)
Only can be found in bird family B cell
BM Secondary lymphoid organ
Stem cell B cell
Secondary lymphoid organConsists of : lien, lymph node, Payer Patch, Tonsilas antigen filter
Bursa FabriciusBone Marrow
![Page 15: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/15.jpg)
Hematopoietic sterm cell
Myeloerythroid cells
SCF
Lymphoid stem cell
?Secondary lymphoid organs
IL-2SCF
IL-7SCF
B cell precursor
Virgin B lymphocyte
Bone Marrow
Thymus
IL-3SCF
T cellprecursor
VirginT lymphocyte
SCFThymicfactors
IL-2IL-7
![Page 16: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/16.jpg)
Blood Circulation
Tissues
Afferent lymph duct
Lymph node
Efferent Lymph duct
Ductus Thoracicus
Spleen
![Page 17: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/17.jpg)
PULMO SKIN GIT Resp. Tract. Circulation
Peribronchial Lymphoid Tissues
Tonsil
PP
Lymph node Regional Spleen
ANTIGEN
![Page 18: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/18.jpg)
Periarterioler sheet
Centralarteriole
Red pulp
Center germinal
Trabecular artery
Structure Immunology of Spleen
![Page 19: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/19.jpg)
Medulla
Cortex
Paracortex
Germinal Center
Artery
Vena
Efferent Lymph canal
Immunologist Structure of Lymph
node
![Page 20: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/20.jpg)
All of immune response processes with genetic basic. “All factors which regulate Immune Response to foreign agents => hereditary”
Very widely of scope : HLA & Blood GroupClinical aspects : Blood grouping, tissue/organ transplantation.Autoimmune disease, producing of vaccine,
etc.
![Page 21: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/21.jpg)
MHC = HLA (man)Genetic: position: short arm of
Chromosome 6 length: 3,5 x 106 bps
5’ C C A T T T A A C C - - - 3’3’ C C T A A A T T C C - - - 5’
![Page 22: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/22.jpg)
Class II
Figure 5-1. Organization of the HLA complex on the short arm of human chromosome 6. Regions encoding the 3 classes of MHC proteins are indicated by
braces. Endo denotes a cluster of genes within the class II region that encode protease components and peptide transport proteins required for processing endogenous antigens (see text). Class III proteins are unrelated to class I and II and are not
involved in antigen presentation. Among proteins encoded in the class III region are tumor necrosis factors and , and complement factors C2, C4, B and F.
Figure 5-1. Organization of the HLA complex on the short arm of human chromosome 6. Regions encoding the 3 classes of MHC proteins are indicated by
braces. Endo denotes a cluster of genes within the class II region that encode protease components and peptide transport proteins required for processing endogenous antigens (see text). Class III proteins are unrelated to class I and II and are not
involved in antigen presentation. Among proteins encoded in the class III region are tumor necrosis factors and , and complement factors C2, C4, B and F.
0 500 1000 1500 2000 2500 3000 3500kilobases
centromere
Class III Class I
21BC4B 21A
BFTNF BCDRDQ
EndoDP
TNFC4A C2
![Page 23: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/23.jpg)
CLASS I HLA
In all nucleus’s cells
Such: A, B, C=> L M A
Functions:- Immune aware- Tissue rejected
Figure 5-2. Schematic representation of a class I HLA protein. The molecule consists of an MW 44,000 polymorph transmembrane polypeptide ( chain) non covalently
associated with an MW 12,000 non polymorph polypeptide (2-microglobulin). The 3 extracellular domains of the chain are designated 1, 2, and 3. The binding site for immunogenic peptides (T cell determinants, is formed by the cleft between the 1
and 2 domains.
cytoplasm
membrane
COOH338PO4
306282
COOH259
3
21
2-microglobulin
Extracellularregion
203S
S
SS
SS
10186
CHO chain
164
NH2
NH2
Extracellularregion
![Page 24: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/24.jpg)
Figure 5.3. Diagrammatic structure of a class I HLA molecule (side view). In this ribbon diagram of the polypeptide backbone, the polypeptides are oriented as in Fig 3-2, but only the extracellular region is depicted. The peptide binding site as a cleft (or groove) formed by 8 strands of –pleated sheet and a pair of -helices from the 1 and 2
domains. The –sheet structure forms the floor and the type helices the walls of the cleft. –strands are depicted is broad arrows and –helices as narrow coils.
2m
-helixPeptidebindinggroove
28-strand-pleated
sheet1
3
C
C
N
N
![Page 25: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/25.jpg)
N
-helix
-pleated sheet forming floor of antigen-binding
groove
-helixN
Figure 5-4. Peptide-binding site of a class I HLA molecule, viewed along an axis
perpendicular to the cell surface. Eight strands of -pleated sheet contributed by the 1
and 2 domains forms the floor of the site, and 2 -helices, one from each of the 2 domains, form the walls. The groove accommodates peptides 8-9 amino acid residues
long, leaving them partially accessible for interaction with the T cell antigen receptors.
Figure 5-4. Peptide-binding site of a class I HLA molecule, viewed along an axis
perpendicular to the cell surface. Eight strands of -pleated sheet contributed by the 1
and 2 domains forms the floor of the site, and 2 -helices, one from each of the 2 domains, form the walls. The groove accommodates peptides 8-9 amino acid residues
long, leaving them partially accessible for interaction with the T cell antigen receptors.
![Page 26: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/26.jpg)
Class II HLA
At B cell => macrophage
Functions:- T cell aware- Tissue rejected
Extracellularregion
membrane
cytoplasm
COOH COOH
CHO
CHO
CHO
1
2
Extracellularregion
1
2
chain chain
NH2 NH2
229 237
214193
221200
173163
118107 117
7879
1519
SS
S
SSS
Figure 5-5. Schematic representation of a class II HLA molecule. The molecule consists of an MW 34.000 polypeptide ( chain) noncovalently associated with an MW
29.000 polypeptide ( chain).
![Page 27: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/27.jpg)
Figure 5-6. Structure of the peptide binding site of a class II HLA molecule. The binding site is similar to that of class I molecules, except that it is formed by the 1 and 1 domains of the class II molecule and is relatively open at both ends to
accommodate longer peptides.
-helix
COOH
COOH
-helix
-pleated sheet forming floor of antigen-binding
groove
1 NH2
NH2 1
![Page 28: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/28.jpg)
Figure 5.7. The pathway of assembly and transport for antigen-MHC complexescontaining class I (top) and class II (bottom) HLA molecules. MHC polypeptide of initially expressed in the rough endoplasmic reticculum (RER). Class I proteins sequentially bind endogenous peptides and 2-microglobulin (2m) in the RER lumen and are than transported to the cell surface. Class II proteins associate with invariant chain (li) in the RER and so are prevented from binding endogenous peptides, they are translocated instead to an endosomal compartment, where li dissociates and is replaced by exogenous peptides.
Figure 5.7. The pathway of assembly and transport for antigen-MHC complexescontaining class I (top) and class II (bottom) HLA molecules. MHC polypeptide of initially expressed in the rough endoplasmic reticculum (RER). Class I proteins sequentially bind endogenous peptides and 2-microglobulin (2m) in the RER lumen and are than transported to the cell surface. Class II proteins associate with invariant chain (li) in the RER and so are prevented from binding endogenous peptides, they are translocated instead to an endosomal compartment, where li dissociates and is replaced by exogenous peptides.
Endogenouspeptides
nucleus
Peptides Processing Exogenous antigen
Class IIMHC
RER
To cellsurfaces Surface Ag-
Class II MHCcomplex
To cellsurfaces
Surface Ag-Class I MHC
complexClass IMHC
2m
Peptide transporter
Cell surface
![Page 29: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/29.jpg)
![Page 30: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/30.jpg)
Erythrocyte antigen: A B O Rh
ABO GroupBefore 20th : transfusion ?1900 Landsteiner
![Page 31: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/31.jpg)
Sera Ery
1 2 3 4 5 6 Group
1 - + + + + - C
2 - - + + - - A
3 - + - - + - B
4 - + - - + - B
5 - - + + - - A
6 - + + + + - C
![Page 32: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/32.jpg)
ABO single gene ABO with 3 allele A,B,OA,B codominant KH binding + H substrate
Genotype
O/O
AO,AA
BO,BB
AB AB AB
Phenotype Er-Ag
A A
O O A,B anti
A anti B anti
A antiB anti
B B
- -
-+
- -
+ + -
Allo ab
![Page 33: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/33.jpg)
Levine & Stetson (1939) => Ag + Asera from post partum mother Ag + S.I rabbit by Rhesus of
erythrocyte => “Rh factor” => Rh. Ag.Natural antibody (-), except by
“immunization”
![Page 34: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/34.jpg)
Genetic of RhesusGenetic of Rhesus
> 30 Ag. Rhesus typeFisher & Race
3 gene with allele partner’s => 5 determinant antigen D, C, E, E, C.
Wiener 1 gene locus => “multiple complex allele”DA Rho, rh’, rh”, hr’, hr”.
![Page 35: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/35.jpg)
Definition:“Self” & “not self”“Virgin” lymphocyte (109/day), with IG & TCR => 108 antigen type“Clonal restriction”“Clonal selection”Each others cells communication.
![Page 36: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/36.jpg)
6
5
4
3
2
1
Imunogen
5
1
4
3
1
1
1
6
2
![Page 37: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/37.jpg)
![Page 38: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/38.jpg)
IMMUNOGEENendosome
lissome
MHC IITH cell
CD 4
MACROPHAGEAntigen-presenting
cell (AFC)
Figure 3-3. Capture, processing, and presentation of antigen by an APC. The immunogen is captured by phagocytosis, receptor-mediated endocytosis, or pinocytosis and is broken down into fragments. Some fragments (antigens) become associated with class II MHC proteins and are transported to the cell surface, where they can be recognized by CD4 T cells. TCR, T cell receptor.
Figure 3-3. Capture, processing, and presentation of antigen by an APC. The immunogen is captured by phagocytosis, receptor-mediated endocytosis, or pinocytosis and is broken down into fragments. Some fragments (antigens) become associated with class II MHC proteins and are transported to the cell surface, where they can be recognized by CD4 T cells. TCR, T cell receptor.
TCR
![Page 39: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/39.jpg)
MHC IImolecules
IL-1
Processedantigens
Costimulation
APCTH cell
CD4
Activation
IL-2R
Autoactivation
proliferation T cell
T cell
TH cell
IL-2
Release of cytokines and other growth and differentia-tion factors
Figure 3-4. The cell activation. The APC presents an antigen in the context of class II MHC to the TH cell and also provides a costimulatory signal. The 2 signals lead to
activation of the TH cell. The APC also releases IL-1, which acts on both the APC and the TH cell to promote activation. Activation leads to IL-2 receptor expression and IL-2
secretion by the TH cell, resulting in autocrine growth stimulation.
Figure 3-4. The cell activation. The APC presents an antigen in the context of class II MHC to the TH cell and also provides a costimulatory signal. The 2 signals lead to
activation of the TH cell. The APC also releases IL-1, which acts on both the APC and the TH cell to promote activation. Activation leads to IL-2 receptor expression and IL-2
secretion by the TH cell, resulting in autocrine growth stimulation.
![Page 40: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/40.jpg)
CD4
IL-2RMHC II
Ig Ag receptors
B cell
TCRAg
Helper factorsB cell
B cell
Proliferation Progeny
differentiation Plasma cell
MemoryB cell
Antibody
Figure 3-5. B cell activation. Antigen binding to the surface immunoglobulins, coupled with soluble or contact-mediated helper factors from an activated TH cell, lead to
proliferation and differentiation. Cytokines involved in TH cell help include IL-2, IL-4 and IL-6.
Figure 3-5. B cell activation. Antigen binding to the surface immunoglobulins, coupled with soluble or contact-mediated helper factors from an activated TH cell, lead to
proliferation and differentiation. Cytokines involved in TH cell help include IL-2, IL-4 and IL-6.
![Page 41: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/41.jpg)
Figure 3-6. To cell activation requires contact with specific antigen in the context of a class I MHC molecule on the surface of a target cell. It also requires IL-2 from a nearby activated TH cell. The activated Tc cell kills the target cell either by secreting cytotoxins
(as shown) or by inducing it to commit suicide.
Figure 3-6. To cell activation requires contact with specific antigen in the context of a class I MHC molecule on the surface of a target cell. It also requires IL-2 from a nearby activated TH cell. The activated Tc cell kills the target cell either by secreting cytotoxins
(as shown) or by inducing it to commit suicide.
CD4
IL-2R
Auto-activation
IL-2
TCR(already
triggered)
TH cell Tc cell
TCR
Ag target cell(cell death)
MHC IToxins
MHC I
IL-2R
CD8
![Page 42: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/42.jpg)
Definition :
1. Immunogen2. Antigen3. Immunogenicity4. Antigenicity
Classification :1. Exogen antigen2. Endogen antigen : - Xenogeny Ag. (Heterolog) - Autolog Ag. - Alogenic Ag.
![Page 43: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/43.jpg)
Commonly is a macromolecule protein.1. Molecule antigenisity2. Molecule size3. Complexity of Chemistry structure4. Genetic constitution5. Method of entry 6. Dosage7. Digestibility
![Page 44: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/44.jpg)
Determinant Antigenic
![Page 45: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/45.jpg)
Hapten
HaptenHapten carriercarrier ImmunogenImmunogen
I KI K
I.K agentI.K agent HaptenHapten
![Page 46: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/46.jpg)
Thymus dependent Ag andThymus independent Ag
Thymus dependent Ag andThymus independent Ag
T
B
B
Macrophage cell
Plasma cell
B
Imunogenik
HLA DR
Receptor
![Page 47: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/47.jpg)
Cross Reaction
![Page 48: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/48.jpg)
>>> Immunogenicity antigen pathway
>>> Retention>>> Molecule size
Local stimulation
>>> Immunogenicity antigen pathway
>>> Retention>>> Molecule size
Local stimulation
![Page 49: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/49.jpg)
Definition : Protein as humoral immunity effectors
molecule
The function of Ig : Binding Ag Biological activity Thus as complex molecule
![Page 50: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/50.jpg)
Example Antibody to Viral It has particular part which
could :Binding virusBe able to enter respiratory tractNot be broken by enzymeBe able to joint with leukocyte
![Page 51: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/51.jpg)
1940 : Tiselius & Kabat Globulin - AB
1950 : Porter gave papain 3 fragments
1960 : Edelman : Multiple chains Porter : 4 chains
1969 : Edelman, AA chain.from BJ Prot> 1970 : Leder genetic
![Page 52: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/52.jpg)
Three-dimensional structure of an immunoglobulin moleculeThree-dimensional structure of an immunoglobulin molecule
![Page 53: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/53.jpg)
H3N+
H3N+
Vk Fab
CkVH
CH1
LchainH chain
Hinge region
Fc
CH2 CH3
COO-
COO-
H chain
PepsinPapain Cleavage sites
Fab
Hchain
LchainH3N+
H3N+
Figure 6-1. Schematic model of an IgG1 (x) human antibody Molecule showing the basic 4-chain structure and domains. Sites of enzymatic cleavage by pepsin and papain are shown
![Page 54: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/54.jpg)
c
Constant domain
Variable domain
NCDR I
CDR 3
CDR 2
Figure 6-5. Three dimensional structure of a light chain, in this ribbon
diagram tracing the polypeptide backbone, -strands are shown as wide ribbons, other region as
narrow string. Each of the 2 globular domains consists of a barrel-shaped assembly of
7-9 antiparallel -strands. The three hypervariable regions
(CDR1, CDR2, & CDR3) are flexible loop that project outward from the amino-terminal end of the VL
domain.
![Page 55: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/55.jpg)
![Page 56: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/56.jpg)
Side Chain Theory Abundant receptors as antibody
Instructive Theory
Selective Theory
Ag DA
DNA globulin
DNA
spontaneous
DA
![Page 57: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/57.jpg)
Clonal selectionAg
![Page 58: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/58.jpg)
Immunization
HPRT+Ig+
Spleen cells(10)8
Myeloma cell culture
HPRT -Ig-
Myeloma cells(2x107)
Selection of hybridcellsIn HAT medium
Assay for antibodyClone antibody-production (positive) hybrids
TumorInduction
Monoclonal AntibodyMonoclonal antibody
Mass culture growthFreeze hybridomafor future use
![Page 59: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/59.jpg)
Figure 12-40. Formation of hybridomas between mouse cells and myeloma cells. Mouse myeloma cells that do not produce their own immunoglobulins and lack hypoxanthine and phosphoribosyl transferase (HPRT) are fused to splenocytesFrom an immunized mouse with polyethylene glycol.The hybrid cells are selected in hypoxanthine-aminopterin-Thymidine (HAT) medium. Unfused myeloma cells are killedBy HAT, and unfused splenocytes die out.The hybridomas are cloned, and antibody is produced in tissueCulture or by ascites formation. (Reproduced, with permission,From Diamond BA, Yelton DE, Scharff MD: Monoclonal Antibodies: A new technique for producing serologic reagents. N Engl J Med 1981; 304: 1344
![Page 60: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/60.jpg)
C
N
I
46 + cell Lysis
health
V.ch
V.ch
V.ch
S1 Lysis (+)V.ch
S1
560C 30’Lysis (-)
S1/SN V.chLysis
![Page 61: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/61.jpg)
Complement Form & Shape
>>> ß Globulin : > 20 type 11 type : C1Q,R,S, C2 C9
Widely : C1C2C3 (5,6,7,8,9) comp. Biologic
function
C4Complement : CoE
![Page 62: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/62.jpg)
Classic Pathway
The Complement CascadeThe Complement Cascade
Alternative Pathway
Ag:Ab complex
C1 C1C4
C4a
C14bC2
C14b(2b)2a
C3
C3a
C3bBbP
C3b
C14b(2b)2a3b (C3b)BbPor
C5
C5a
C5bC6
C7
C5b67 C8
C9
C5b678(9)n
Factor D ProperdinFactor B
C3
H2O
C3(H2O)
Terminal Components
![Page 63: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/63.jpg)
Diagram of the complement cascade. A: The classic complement pathway. A doublet of IgG antibody molecules on a surface can bind and activate C1, a 3-part molecule composed of C1q, C1r & C1s. C1q has a core & 6 radiating arms, each of which ends in a pod. The pod recognizes & binds to the Fc fragment of the IgG. On activation the C1 binds & cleaves C4. The small fragment, C4a, is release. The large fragment, C4b, binds to the target to continue the cascade. In the presence of magnesium ion, C2 recognizes and binds to C4b. B: Once C2 is bound to C4b, it can be cleaved by C1. A small fragment C2b, is release, and the large fragment, C2a, remains bound to the C4b. This newly formed complex of 2 protein fragment can now bind and cleave C3. This molecule is, in turn, cleaved into 2 fragments, C3a & C3b. The small fragment, C3a, is release, & the large fragment, C3b, can bind covalently to a suitable acceptor, C3b molecules that bind directly to the C4b continue the cascade. C: The complex formed of C2a, C4b & C3b can bind and cleave C5. A small fragment of C5, C5a is released. The large fragment, C5b, does not bind covalently. It is stabilized by binding to C6. When C7 binds, the complex of C5b, C6 & C7 becomes hydro phonic. It is partially lipid-soluble and can insert into the lipid of the cell membrane bilayer.
Diagram of the complement cascade. A: The classic complement pathway. A doublet of IgG antibody molecules on a surface can bind and activate C1, a 3-part molecule composed of C1q, C1r & C1s. C1q has a core & 6 radiating arms, each of which ends in a pod. The pod recognizes & binds to the Fc fragment of the IgG. On activation the C1 binds & cleaves C4. The small fragment, C4a, is release. The large fragment, C4b, binds to the target to continue the cascade. In the presence of magnesium ion, C2 recognizes and binds to C4b. B: Once C2 is bound to C4b, it can be cleaved by C1. A small fragment C2b, is release, and the large fragment, C2a, remains bound to the C4b. This newly formed complex of 2 protein fragment can now bind and cleave C3. This molecule is, in turn, cleaved into 2 fragments, C3a & C3b. The small fragment, C3a, is release, & the large fragment, C3b, can bind covalently to a suitable acceptor, C3b molecules that bind directly to the C4b continue the cascade. C: The complex formed of C2a, C4b & C3b can bind and cleave C5. A small fragment of C5, C5a is released. The large fragment, C5b, does not bind covalently. It is stabilized by binding to C6. When C7 binds, the complex of C5b, C6 & C7 becomes hydro phonic. It is partially lipid-soluble and can insert into the lipid of the cell membrane bilayer.
C4a C4a
C4b
C4b C4bC4b
C2C2
C2aC2b
C4b
C2b
C2a
C4b
C3a
C2a
C4b
C3
C4b
C2aC3b
C5C5a
C2a C3b
C4C4b
C5 C7
C5b C5bC6 C7
![Page 64: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/64.jpg)
D: When the C5b67 binds C8, a small channel is formed in the cell membrane. Multiple molecules of C9 can bind and markedly enlarge the channel. The channel has a hydrophobic outer surface and hydrophilic central channel that allows passage of water and ions. E: The alternative complement pathway. In the presence of magnesium ions, C3b on a surface can bind factor B, just as C4b can bind C3, factor D, a fluid-phase factor, can cleave bound factor B into 2 fragments, Ba & Bb. Ba is released. The C3bBb complex can now bind an additional molecule of C3 and cleave it, just as C4b2a can bind & cleave C3. C3a is release, & the new complex of C3bBbC3b, usually written (C3b)2Bb, can bind C5 to continue the cascade
D: When the C5b67 binds C8, a small channel is formed in the cell membrane. Multiple molecules of C9 can bind and markedly enlarge the channel. The channel has a hydrophobic outer surface and hydrophilic central channel that allows passage of water and ions. E: The alternative complement pathway. In the presence of magnesium ions, C3b on a surface can bind factor B, just as C4b can bind C3, factor D, a fluid-phase factor, can cleave bound factor B into 2 fragments, Ba & Bb. Ba is released. The C3bBb complex can now bind an additional molecule of C3 and cleave it, just as C4b2a can bind & cleave C3. C3a is release, & the new complex of C3bBbC3b, usually written (C3b)2Bb, can bind C5 to continue the cascade
C8
C5bC6
C7 C8
C5b
C6C7
C9C9
C9
C9 C9
C9
B
B
Ba
Bb Bb
C3
C3a
C3a
C3
C3bC3bC3b C3b
C3bBb
C5
![Page 65: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/65.jpg)
Mechanism of complement regulation
1. Spontaneous destruction2. Enzymatic inactivation3. Specific bind with certain proteins
1. Spontaneous destruction2. Enzymatic inactivation3. Specific bind with certain proteins
![Page 66: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/66.jpg)
Complement Biologic Activity
Substance Biologic activityC3a Smooth muscle control,
capillary permeability, mastocyt degranulation
C3b Ossification
C3c PMN mobilization
C4a Smooth muscle control, capillary permeability
C52 = C3a
C5a-des-arg Chemotaxis, release En Hidrol from neutrophyl
BB Migration & induction inhibition, monocyt & macrophage spread
![Page 67: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/67.jpg)
Definition:protein (peptide/glycoprotein) as product of a cell group => mediator/communicator between cells for immune system regulation.
Today >>> 100 types, contain of: - lymphokine - monokine>>> local effect & very closeMechanism of action: autocrine & paracrineThe most important: IL-1,-2,-3,-6,-7 TNF, IFNSynthetic cytokine: Recombinant DNA
![Page 68: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/68.jpg)
Actions of IL-1 and TNF on hematopoietic & lymphoid tissue (A) and nonlymphoid cells & tissue (B). Activities of the two individual cytokines differ in some respects
![Page 69: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/69.jpg)
Major properties of human interleukins and other immunoregulatory cytokines
Earlier Terms
Principal Cell
Source
Principal Effects
Interleukins
IL-1 and Lymphocyte-activating factor, B cell activating factor, hematopoietin
Macrophages, other APCs, other somatic cells
•Costimulation of APCs and T cells•B cell proliferation & Ig production•Acute-phase response of liver•Phagocyte activation•Inflammation & fever•hematopoiesis
![Page 70: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/70.jpg)
Earlier Terms
Principal Cell Source
Principal Effects
IL-2 T cell growth factor
Activated TH1
cells, TC cells,
NK cells
•Proliferation of activated T cells•Nk and TC cell functions•B cell proliferation & Ig G2 expression
IL-3 Multi-colony-stimulating factor
T lymphocyte Growth of early hematopoietic progenitors
IL-4 B cell growth factor I, B cell stimulatory factor I
TH2 cells, mast cells
•B cell proliferation, Ig E expression & class II MCH expression•TH2 & Tc- cell proliferation & function•Eosinophil & mast cell growth & function•Inhibition of monokine production
![Page 71: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/71.jpg)
Earlier Terms
Principal Cell Source
Principal Effects
IL-5 TH2 cells, mast
cell
Eosinophil growth & function
IL-6 IFN-2, hepatocyte-stimulating factor, hybridoma growt factor
Activated TH2 cells, APCs, other somatic cells
•Synergistic effects with IL-1 or TNF to costimulator T cell•Acute-phase response of liver•B-cell proliferation & Ig production•Thrombopoiesis
IL-7 Thymic & marrow stromal cells
•T & B lymphopoiesis•Tc cell function
IL-8 Macrophages, other somatic cells
Chemoattractant for neutrophils & T cells
![Page 72: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/72.jpg)
Earlier Terms
Principal Cell Source
Principal Effects
IL-9 Cultured T cell Some hematopoietic & thymopoietic effects
IL-10 Cytokine synthesis inhibitory factor
Activated TH2, CD8 T, & B lymphocytes, macrophages
•Inhibition of cytokine production by TH1 cells, NK cells & APCs•Promotion of B cell proliferation & antibody responses•Suppression of cellular immunity•Mast cell growth
IL-11 Stromal cells •Synergistic effects on hematopoiesis & thrombopoiesis
![Page 73: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/73.jpg)
Earlier Terms
Principal Cell Source
Principal Effects
IL-12 Cytotoxic lymphocyte maturation factor, NK cell stimulatiory factor
B cells,
macrophages
•Proliferation & function of activated Tc & NK cells•IFN production•TH1 cell induction, supresses TH2 cell functions•Promotion of cell-mediated immune responses
IL-13
IL-15
TH2 cells
Epithelial cells &Monocyte, non lymphocytic cell
IL-4 like effects
Mimics IL-2 T-cell effectsMast cell NK activation
![Page 74: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/74.jpg)
Earlier Terms
Principal Cell Source
Principal Effects
TNF Lymphotoxin
Activated
macrophages,
other somatic
cells
•IL-1 like effect•Vascular thrombosis & tumor necrosis
INF dan
Leukocyte interferons, type I interferons
Macrophages ; neutrophils, other somatic cells
•Antiviral effect•Induction of class I MHC on all somatic cells•Activation of macrophages & NK cells
![Page 75: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/75.jpg)
Earlier Terms
Principal Cell
Source
Principal Effects
INF Immune interferon, type II interferon
Activated TH1 & NK cells
•Induction of class I MHC on all somatic cells•Induction of class II MHC on APCs & somatic cells•Activation of macrophages, neutrophils & NK cells•Promotion of cell-mediated immunity•Induction of high endothelial venules•Antiviral effect
![Page 76: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/76.jpg)
Earlier Terms
Principal Cell
Source
Principal Effects
TGF Activated T lymphocytes, platelets, macrophages, other somatic cells
•Anti-inflammatory (supression of cytokine production & class II MHC expression•Anti-proliferative for macrophages & lymphocyte•Promotion of B-cell expression of Ig A•Promotion of fibroblast proliferation & wound healing
![Page 77: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/77.jpg)
Noncovalent binding:1. Electrostatic force: - NH+ - -OOC -2. Hydrogen binding force: - OH –
H2N
3. Hydrophobic force: 4. Van der Waals force
![Page 78: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/78.jpg)
Antibody affinityAntibody affinity
AG + AB AGAB
K1 > K2 Affinity
K1
K1
![Page 79: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/79.jpg)
AG – AB ReactionAG – AB Reaction
Primary ReactionSecondary ReactionTertiary Reaction
Primary ReactionTo look labeling:
FARRImmunofluorocentRIA ELISA
![Page 80: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/80.jpg)
Secondary reactionPrecipitate reaction Agglutinating reactionFloccules reactionNeutralisms reactionR I C
Tertiary reaction
Such AG – AB reaction in vivo
Can be: - advantages
- diseases
![Page 81: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/81.jpg)
Antigen Antibody
Schematic figure of antigen-antibody frame work performed
![Page 82: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/82.jpg)
Schematic figure of quantitative precipitation curve
Ab-remainder Equivalent Ag-remainder
Antigen Antibody
Precipitated antibody
Supernatant
Precipitate
Free Ab
No free Ab & Ag
Free Ag
Antigen increase
![Page 83: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/83.jpg)
Single radial diffusion in agar
(radial immunodiffusion)Petri dished is filled with semisolid agar solution containing antibody to antigen S. After agar hardens, the center well is filled with a precisely measured amount of material containing antigen S
Antigen S is allowed to diffuse radially from the center well for 24-48 hours
![Page 84: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/84.jpg)
Standard curve for single radial diffusion. Relationship between ring diameter and
antigen concentration is described by the line constructed from known amounts of antigen. Equation and curve for timed interval (Fahey)
method
Log C = D-Do KC = Antigen concentrationDo = Intercept with ordinateD = ring diameterK = Slope of lineA
nti
gen
con
cen
trat
ion
(n.
g/m
L)
9
![Page 85: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/85.jpg)
Identity reactionIdentity reaction
Nonidentity reaction
Nonidentity reaction
Partial identity reaction
Partial identity reaction
A = A antigen a-A = A antiB = B antigen a-B = B antiA1 = A antigen plus a-A1 = A1 anti more determinant
A = A antigen a-A = A antiB = B antigen a-B = B antiA1 = A antigen plus a-A1 = A1 anti more determinant
Schematic figure of 3 type Ouchterlony double diffuse reaction. B, Ouchterlony double diffusion bowl shows identity reaction between 1 & 2 fraction, partially identity reaction between all of Rabbit gammaglobuline (RGG) and 2 & 3 fraction and nonidentity reaction between 1 & 3 fraction.
Schematic figure of 3 type Ouchterlony double diffuse reaction. B, Ouchterlony double diffusion bowl shows identity reaction between 1 & 2 fraction, partially identity reaction between all of Rabbit gammaglobuline (RGG) and 2 & 3 fraction and nonidentity reaction between 1 & 3 fraction.
![Page 86: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/86.jpg)
Single radial diffusion in agar
(radial immunodiffusion)
Where antigen S meet corresponding antibody to S in the agar, precipitation results. After reaction proceeds to completion or at a timed interval, a sharp border or a ring is formed
By serial dilution of a known standard quantity of antigen S-S/1,S/2, S/4,S/8- rings of progressively decreasing size are formed. The amount of antigenS is unknown specimens can be calculated and compared with standard in the timed interval (Fahey method)
![Page 87: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/87.jpg)
Reaction of identity Reaction of nonidentity
Reaction of partial identity
R
R
R
RS
R S
R
R R1
Reaction patterns in angular double imunodiffusion (Ouchterlony). R = antigen R, S = antigen S, R1 = antigen R1, R = antibody to R , S = antibody to S. reaction of identity: Precisely similar precipitin lines have formed in the reaction of R with R . Note that the lines intersect at a point. Reaction of nonidentity: precipitin lines completely cross owing to separate interaction of R with R and S with S when R and S are non cross reacting antigens. Reaction of partial identity: R reacts with both R and R1 but forms lines that do not form a complete cross. Antigenic determinants are partially shared between R and R1
Reaction patterns in angular double imunodiffusion (Ouchterlony). R = antigen R, S = antigen S, R1 = antigen R1, R = antibody to R , S = antibody to S. reaction of identity: Precisely similar precipitin lines have formed in the reaction of R with R . Note that the lines intersect at a point. Reaction of nonidentity: precipitin lines completely cross owing to separate interaction of R with R and S with S when R and S are non cross reacting antigens. Reaction of partial identity: R reacts with both R and R1 but forms lines that do not form a complete cross. Antigenic determinants are partially shared between R and R1
![Page 88: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/88.jpg)
X
AgX
X/8
X/16
X/32 X/2
Antibodyx
AgX
AgX/2
AgX/4
AgX/8
AgX/16
AgX/32
X/4
Semiquantitative analysis of antigen and antibody by double immunodiffussion. Antigen X (Ag X) is serially diluted and placed circumferentially in wells surrounding the central well containing antibody against antigen X. Precipitin lines form with decreasing thickness until no longer visible at dilution of 1:32 of antigen X. on the right, a similar pattern is generated but with serial 2-fold dilutions of antibody X (X). Formation of a single precipitin line indicates that a single antigen-antibody reaction has occurred.
Semiquantitative analysis of antigen and antibody by double immunodiffussion. Antigen X (Ag X) is serially diluted and placed circumferentially in wells surrounding the central well containing antibody against antigen X. Precipitin lines form with decreasing thickness until no longer visible at dilution of 1:32 of antigen X. on the right, a similar pattern is generated but with serial 2-fold dilutions of antibody X (X). Formation of a single precipitin line indicates that a single antigen-antibody reaction has occurred.
ANTIGEN X QUANTITATION
ANTIGEN X QUANTITATION
ANTIBODY X QUANTITATION
ANTIBODY X QUANTITATION
![Page 89: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/89.jpg)
Technique of immunoelectrophoresis
Semisolid agar poured onto glass slide and antigen well andantiserum trough cut out of agar
Antigen well filled with humanserum
Serum separated by electrophoresis
![Page 90: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/90.jpg)
Technique of immunoelectrophoresis
Antiserum trough filled with antiserum to whole human serum
Serum and antiserum diffuseinto agar
Precipitin lines form for individual serum proteins
![Page 91: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/91.jpg)
Comparison of patterns of zone electrophoresis and
immunoelectrophoresis of normal human serum
albumin
![Page 92: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/92.jpg)
![Page 93: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/93.jpg)
Complement Fixation Test
Indicator system
Positive testComplement Sheep red cell coated with
anti sheep red cell antibodyComplement reacts with anti sheep
red cell antibody and lyses cell
Antigen Antibody to antigen Complement
Antibody reacts with antigen and complement combines
No lysis of antibody coated red cells as
complement used up
+
++ +
Complement-fixation test. The indicator system (sheep red cells coated with antibody to sheep red cells) is normally lysed in the presence of complement (fresh guinea-pig serum) -top. If another antibody-antigen system is first mixed with the complement it will no longer
be available to lyse the indicator system –bottom.
Complement-fixation test. The indicator system (sheep red cells coated with antibody to sheep red cells) is normally lysed in the presence of complement (fresh guinea-pig serum) -top. If another antibody-antigen system is first mixed with the complement it will no longer
be available to lyse the indicator system –bottom.
![Page 94: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/94.jpg)
DIRECT METHOD
++ +
INDIRECT METHOD
+ +
+ +
Specificity Test
![Page 95: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/95.jpg)
Direct method Indirect method
+
+
Legend
+ +
+ +
Substrate AntigenFluorescent antibody
Fluorescent antiglobulin
Immune complex
Unlabeled antibody
Unlabeled antiglobulin
Fluorescent heterologous
antibody
Mechanism of immunofluorescence techniques. Direct method (top): Antigen in substrate detected by direct labeling with fluorescent antibody. (bottom): Antigen-antibody (immune) complex in substrate labeled with fluorescent antiglobulin reagent. Indirect method (top): incubation of antigen in
substrate with unlabeled antibody forms immune complex. Labeling performed with fluorescent antiglobulin reagent. (bottom): Immune complex in substrate reacted with unlabeled antiglobulin reagent and then stained with fluorescent antiglobulin reagent directed at unlabeled antiglobulin.
Mechanism of immunofluorescence techniques. Direct method (top): Antigen in substrate detected by direct labeling with fluorescent antibody. (bottom): Antigen-antibody (immune) complex in substrate labeled with fluorescent antiglobulin reagent. Indirect method (top): incubation of antigen in
substrate with unlabeled antibody forms immune complex. Labeling performed with fluorescent antiglobulin reagent. (bottom): Immune complex in substrate reacted with unlabeled antiglobulin reagent and then stained with fluorescent antiglobulin reagent directed at unlabeled antiglobulin.
![Page 96: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/96.jpg)
BLOCKING METHOD (Indirect method)BLOCKING METHOD (Indirect method)
NEUTRALIZING METHODNEUTRALIZING METHOD
+ +
+ +
Specificity test. Direct method (Left): Substrate antigen fails to react with fluorescent antiglobulin reagent. No fluorescence results. (Right): Immune complex –substrate fails to react with fluorescent
antibody directed again unrelated antigen. No fluorescence results. Indirect method (Top): Unlabeled specific antiglobulin is replaced by unrelated antibody. In second step, fluorescent antiglobulin can not
react directly with antigen in substrate that has not bound specific antiglobulin. No fluorescence results. (Bottom): First step performed by reacting specific antibody with substrate antigen. In second
stage, the specific conjugate is replaced by unrelated fluorescent heterologous antibody. No fluorescence results. Blocking method Substrate antigen is incubated with unlabeled specific antibody prior to addition of specific fluorescent antibody . Decreased fluorescence results. Neutralizing method
Substrate antigen is incubated with specific fluorescent antibody after it is absorbed with specific antigen substrate. No fluorescence results.
![Page 97: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/97.jpg)
Infection and Infection diseaseInfection = microorganism invasion local / systemic alteration.
Pathogenic M.O. has evasive mechanism with its photogenic factors.
Balance disturbance defense <<< iatrogenic disease.
Defense mechanism <<< Immune
Compromised Host.
Infection and Infection diseaseInfection = microorganism invasion local / systemic alteration.
Pathogenic M.O. has evasive mechanism with its photogenic factors.
Balance disturbance defense <<< iatrogenic disease.
Defense mechanism <<< Immune
Compromised Host.
![Page 98: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/98.jpg)
Predisposing factors Immune system effects Infection typesImmunosupression: X ray, cancer th/,
alograft res.Viral Infection: Rubella, EBV Herpes, HIV HepatitisTumor
Malnutrition
Smoking, Dust inhalation
Chronic endocrine diseases.
Primary I.D
CMI & humoral immunity decrease.
Viral replication in limfoid cell which cause immune function disturbance.
Immune cells replaced by tumor cells.Lymphoid hypolasia Lymphocyte << Phagocytes <<“Inflam. lung change”Immune Compl. to spore
Fag. Activ. <<
CMI & Hum. <<
Pulmonal inf., bacterium, fungal inf., UTI.
Secondary bacterial inf.
Bacterium, pneumonia, UTIMeasles, TB, Respiratory Tract Inf., GIT inf.
COPDAllergic response.
Staph. Inf., TB, Respiratory Tract Inf., bacterium.
![Page 99: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/99.jpg)
Evasi mechanism pattern:S. aureus : A
proteine,coagulaseStreptococcus : polisach. caps.,
streptolysin. Gonococcus & : protease to IG AMeningococcusIntracellular org. : intracellular defenseHerves Vi. & EBV : complement inhibit.
factor.
Evasi mechanism pattern:S. aureus : A
proteine,coagulaseStreptococcus : polisach. caps.,
streptolysin. Gonococcus & : protease to IG AMeningococcusIntracellular org. : intracellular defenseHerves Vi. & EBV : complement inhibit.
factor.
![Page 100: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/100.jpg)
Multiple defenses
Characteristic : Natural immunity Adaptive immunity
![Page 101: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/101.jpg)
Schematic form of phagocytes by poly morphonuclear leukocyte (PMN) and tissue macrophage after penetrating skin and the
pathogen bacteria entry to the deeper part of the tissue. PMN are more efficient in
phagocyting than macrophage. Attention to PMN which are mobilized to the tissue and vascular in
inflammatory response
Skin as first line defense
Tissue macrophage
Pathogenbacteria
PMN come from blood vascular
![Page 102: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/102.jpg)
Natural Immunity Preventing of entry
Intact skin Mucous membrane normal flora
Defense for attackingHumoral mechanismCellular mechanism as phagocytes, killing microorganism with :
Oxidize intra cellularADCCCytokine
![Page 103: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/103.jpg)
The last mechanism is very various depend on the etiology
Consist of :Immunity to bacterial infection :
toxin extra cell intracellular
Immunity to viral infectionImmunity to fungal infectionImmunity to bacterial toxin
ec : C. tetani, V. Cholera, C. Diphtheria
The most responsible is IgG
![Page 104: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/104.jpg)
Schematic form of immunology mechanism in neutralizing toxin by antibody. Toxin-antitoxin complex, which is neutralized, is showed being
ingested and destroyed in two type of phagocyte cells
Organism Toxin
Activating lymphocyte
Plasma cell
Antitoxin
Ab-Ag complex
PMN
Toxin degradation
Macrophage
![Page 105: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/105.jpg)
Immunity to Extra cellular Infection
Through specific immunoglobulin :IgG & IgM : OpsonisasiIgA for bacterial inside the lumenIgM and Ig (1,2,4) through C lysesIgG & IgM : agglutination phagocytesInhibit Fe uptake by bacteriaIgE at mastocyt cell histamineBacterial motility <<<
![Page 106: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/106.jpg)
Immunity to Intracellular
infection
Phagocytes & humoral immunity is not effective CMI with APC pathway CD4 Cytokine Activation of CD8 & CD4 as cytolysis cellAnother cytolytic cell is NK cell
![Page 107: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/107.jpg)
Immunity to Viral Infection
Vi is non cellular-organism, always intrasel with way :
Immune system Infection Various of membrane AntigenMoving antigen
![Page 108: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/108.jpg)
InterferonAMICMI
![Page 109: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/109.jpg)
Function :Delayed viral replication (type I = & )Activation immunity system(Type II = )
![Page 110: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/110.jpg)
Working Mechanism of Interferon
IFN SYNTHESIS
Gene activation
mRNA
dsRNA
IFNIFN IFN
mRNA
Protein synthesis
2,5 A Synthesize
2,5 A
Activated endonuclease
Protein kinase
PhosfhorylatedeiF2
Inhibit protein synthesis
dsRNA
Interferonreceptor
Virus
NK activation, macrophage activation, increase expression of MHC molecules
Host Cell
(A)
(B)
FIGURE
![Page 111: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/111.jpg)
Figure :Proposed mechanisms of induction of interferon synthesis and production of resistance to virus infection.Cell (A) is induced to produce interferon
(IFN) by the presence of double stranded RNA (dsRNA).The interferon ( or ß depending on the type of cell) is released and binds to receptors on other cells.
FIGURE
![Page 112: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/112.jpg)
The interferon ( or ß depending on the type of cell) is released and binds to receptors on other cells.This interaction can cause activation of host effectors functions and induce an intiviral state in neighboring cells (B). mRNA = messenger RNA; 2, 5-A = 2’, 5’ –oligoadenylate.
![Page 113: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/113.jpg)
Working Mechanism :(2’ – 5’ oligoadenylate synthetase-inactive) + ds RNA
2’ – 5’ oligoadenylate synthetase – Active
(endonuclease–inactive) endonuclease Active
RNA degradation
![Page 114: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/114.jpg)
Protein Kinase + ds RNA
elF 2 active (elF 2 INACTIVE)
Impaired protein synthesis
Mx protein(and its analogues in other
species)
Specific influenza virus inhibition in mice
![Page 115: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/115.jpg)
Specific Antibody :Delayed mix with receptorMaking immune complexStimulating viral coagulation
![Page 116: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/116.jpg)
AB was not effective for intracellular viral
Could changed membrane cell Antigen Example :
Oncogenic vi., Vaccinia vi., Influenza vi.Paramyxo vi., Toga virus, Papova, Rubella, Rabies.
Form main defense on viral infection.The effectors is Tc (CD 8 & cd 4).
![Page 117: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/117.jpg)
Immunity for Fungal Infection
Manifestation of Fungal Infection :
Superficial mycosis /cutaneusSubcutaneous mycosisSystemic mycosis
Defense Mechanism ?AMI or CMI ?
Cutaneus as DTH Subcutaneous and systemic depend on
activity from neutrophyl, macrophage, lymphocyte, NK cell ?
![Page 118: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/118.jpg)
Although we have immunity to fungal
infection :Patient with neutropenia easy to get infection as:Candidiasis, Aspergilosis, Zigomycosis.Patient with CMI disturbance easy to get infection as : Cryptococcosis, Histoplasmosis, Coccidiomycosis
![Page 119: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/119.jpg)
Basic of ImmunoprophylacticKnowledge of the immune system
Immune Response
Defense mechanism like AMI & CMIR.I have response of memory.Process : Immunization
Active immunization Passive immunization
![Page 120: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/120.jpg)
Active Immunization
Immunity gets actively.
Requirement :Immune System must be normal.Booster
The immunogen : vaccine consist of :Conventional vaccine : Toxoid
“Killed Vaccine” Subunit Vaccine “Attenuated Living
Vac.”
![Page 121: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/121.jpg)
Genetic device vaccineEx. : Hepatitis B
Vaccine Preparation :Bacteria cell : Pertusis, Typhoid, BCGToxoid : Tetanus, DifteriVirus : Poliomyelitis, Morbilli, Rubella,MumpsPolysaccharide capsule :
Pneumococcus, Meningococcus, H. Influenza type B
![Page 122: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/122.jpg)
The successful of immunization depend on :Kind of VaccineBoosterInfection beforeHow to give
Immunization target in Indonesia :Neonatal until child with school age
![Page 123: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/123.jpg)
Kind of Immunization :Obliged :
Diphtheria, Pertusis, Tetanus (DPT)Tuberculosis (BCG)Polio (Sabin)Measles
![Page 124: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/124.jpg)
Immunization Procedure
Each country is different.
Conditions to give immunization :
Less protectionThe disperse specific antigen rate
is highest.
The biggest risk.
![Page 125: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/125.jpg)
Variety of vaccine
Immunization Count
Time Interval(Weeks)
Age(months)
Basic immunization
BCG 1 x - 0 – 11
DPT 3 x 4 – 8 2 – 11
Polio 4 x 6 – 8 2 – 11
Measles 1 x - 9 – 15
Immunization Program
in Indonesia
Table
![Page 126: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/126.jpg)
Variety of vaccine
Immunization Count
Time Interval(Weeks)
Age(months)
Booster :DPT 1 x - 1,5 – 2
Polio 1 x - 1,5 – 2
DT 1 x - 4 – 6
Td 1 x - 12 – 14(every 10 yrs)
Suggestion ImmunizationMMR 1 x >1 years
Hepatitis B 3 x Anytime(every 5 yrs)
![Page 127: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/127.jpg)
Immunization Program at Posyandu/ Puskesmas
Variety of Immunization
Age
BCG, DPT I, Polio I 2 months
HB I, DPT II, Polio II 3 months
HB II, DPT III, Polio III 4 months
HB III, Measles, Polio IV 9 months
![Page 128: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/128.jpg)
Direct giving AB which needed :
Homolog ABHeterolog ABAutolog AB
Specific AntibodyMaternalGamma GlobulinHeterolog Antibody
![Page 129: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/129.jpg)
Ag
Allergen Allergy
Immunity
Tolerance
Hypersensitive
N
![Page 130: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/130.jpg)
Coombs & Gell :I, II, III : A.M. HypersensitivityIV : DTH + C.M.HypersensitivityV : Stimulatory
![Page 131: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/131.jpg)
Type I = AnaphylacticAg
IgE
Ag
Vasoactive amin
Capiler activation
Bronchus autonomy muscleDegranulation
![Page 132: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/132.jpg)
Amine vasoactive substances :histaminesslow-reacting substance of anaphylaxis (SRS-A)ECF-Aserotonine
![Page 133: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/133.jpg)
Substances effects to arachidonic acid metabolism :
leukotriens (LTC4 & LTD4)prostaglandintramboxan
People with possibility to hypersensitive reaction : Atopi
![Page 134: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/134.jpg)
Binding between Ig G & Ig M (FAB) with cell antigen :phagocytescytotoxiclysise.c. : isoimmune reactionautoimmune reactiondrugs reaction
Type II reaction : cytotoxic
![Page 135: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/135.jpg)
Antigen-antibody complex abundant elimination not perfect precipitate in tissue and vascular blood
Antigen can produce from ;Pathogen persistent infectionInhalant antigenAutoimmune disease
Anomaly because immune complex depends
on :Absolute rate antigen-antibody complex
Antigen-antibody proportion
Antibody >>> localAntigen >>> systemic
Type III reaction : Immune Complex
![Page 136: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/136.jpg)
Type IV reaction : CMI : DTH
cell
Tissue damagee.c. : • Contact dermatitis• Tuberculin test• Tissue rejected
![Page 137: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/137.jpg)
Antibody CTC induce self tissue, e.c. thyroid tissue
Secretion
Type V reaction
![Page 138: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/138.jpg)
XIII.Autoimmunity and autoimmune disease
Immune system
“Self”
“Not Self” Antibody
(Autoantibody)
Autoimmunity
Autoimmune disease
Body complement
![Page 139: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/139.jpg)
Pathogenesis1. Forbidden-clone theory2. Sequestered-antigen theory3. Immunodeficiency4. Go away from T cell tolerance5. <<< T suppressor cell function
![Page 140: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/140.jpg)
Forbidden-Clone theory
Normal lymphocyte
Positive mutant as antigen
Destroyed by normallymphocyte
![Page 141: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/141.jpg)
Normal lymphocyte
Negative mutant as antigenic(Forbidden-Clone)
Survive, become sensitive and attack target tissue
![Page 142: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/142.jpg)
Immune Deficiency Theory
Positive mutant as antigenic
Immunoglobulin deficiency lymphocyte
Positive mutant as antigenic
Position & negative mutant attack tissue target
![Page 143: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/143.jpg)
Microbe pathogen survive
Antigen changeOr unknown antigen release
Cellular injury(Type IV)OrInjury mediated by antigen
+ Antibody
+ Complement
Injury immune complex (Type III)
![Page 144: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/144.jpg)
THYROID EMBRYONIC
Antigen surfaces
Unknown antigen
EMBRYONIC LYMPHOID
CELL
![Page 145: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/145.jpg)
ADULT THYROID
Unknown antigen that affected by
before
Sensitized lymphocyte
![Page 146: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/146.jpg)
Activated autoimmune process
![Page 147: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/147.jpg)
Spectrum of Autoimmune Disease
Variety ofDiseases
Antigen HLA Link Relative Risk
Hashimoto’s Thyroid
Tyro globulin
DR 5 3,2
PrimaryMiksedema
Surface cell DR 3 5,7
Grave’s disease
TSHreceptor
DR 5 3,7
Diabetic autoimmune
Islet cells DR 5, DR 4, DR 3/4
5,0 - 6,0 - 14,3
![Page 148: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/148.jpg)
Variety ofDiseases
Antigen HLA Link Relative Risk
Goodpasture Syndrome
GlomerulusBasal
membrane of lung
DR 2 13,1
Primary Cirrhosis Billiary
Mitochondria - -
Colitis ulcerative
Colon lypopolisachari
da
- -
Rheumatoid arthritis
Ig G DR 4 4,2
S.L.E. nucleoprotein DR 3 5,8
![Page 149: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/149.jpg)
Pioneer :Bruton found the 8 yrs child who hashypogamaglobulinemia.As clinical squelae S.I. Disturbance.
![Page 150: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/150.jpg)
GeneticMetabolic & Biochemistry deficiencyVitamins & mineral deficiencyDisturbance Embryogenesis Autoimmune diseasesAcquired immunodeficiency.
![Page 151: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/151.jpg)
B Cell ImmunodeficiencyT Cell ImmunodeficiencyB Cell & T Cell Immunodeficiency
(combined)Phagocytic Dysfunction
![Page 152: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/152.jpg)
![Page 153: I. Introduction II. Element of Immunity III. Immunogenetic IV. Immune Response V. Antigen & Immunogen & Vaccine VI. Immunoglobulin VII. Complement System.](https://reader035.fdocuments.in/reader035/viewer/2022062221/56649d625503460f94a44519/html5/thumbnails/153.jpg)