Specific (adaptive) immunity Immunology, 3rd year.
-
Upload
justina-baldwin -
Category
Documents
-
view
225 -
download
0
Transcript of Specific (adaptive) immunity Immunology, 3rd year.
![Page 1: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/1.jpg)
Specific (adaptive) immunitySpecific (adaptive) immunity
Immunology, 3rd year
![Page 2: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/2.jpg)
ContentsContentsSpecific immunity: Basics Immunoglobulins and T cell receptorB and T developmentT cell function Innate-like lymphocytesExamples: B and T cell function
![Page 3: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/3.jpg)
Characters and castCharacters and cast
T+
Non-specific, innate Specific, adaptive
![Page 4: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/4.jpg)
Components of immunityComponents of immunity
innate adaptive
cellular neutrophils T lymphocytes monocytes-
macrophages, DC, NK cells
humoral complement antibodies acute phase (B lymphocytes) proteins (CRP,MBL..)
![Page 5: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/5.jpg)
Differences between innate and Differences between innate and adaptive immunityadaptive immunity
innateinnate adaptiveadaptive
phylogeneticphylogenetic olderolder youngeryounger
reaction/speedreaction/speed minutesminutes hours-dayshours-days
immun. memoryimmun. memory nono yesyes
Ag receptorAg receptor shared structuresshared structuresindirect –opsonines; indirect –opsonines; all cells identically all cells identically equippedequipped
Ig, TCR,Ig, TCR,diverse diverse repertoire, clonesrepertoire, clones
![Page 6: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/6.jpg)
??• types of antibodies: why and when they types of antibodies: why and when they
are importantare important• molecular basis of immune memorymolecular basis of immune memory• what can I learn from serology in infantswhat can I learn from serology in infants• how do I find out which lymphocytes are how do I find out which lymphocytes are
(mono)clonal(mono)clonal• what are CD3 etc.? which other CDs do I what are CD3 etc.? which other CDs do I
need to memorizeneed to memorize• how do the antibodies improve in the how do the antibodies improve in the
nodesnodes• weapons of the immune killersweapons of the immune killers• what happens to T and B lymphocytes what happens to T and B lymphocytes
during EBV infectionduring EBV infection• why is why is Haemophilus influenzaeHaemophilus influenzae dangerous dangerous
to native American kids?to native American kids?• ……
![Page 7: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/7.jpg)
ContentsContentsSpecific immunity: Basics Immunoglobulins and T cell receptorB and T developmentT cell function Innate-like lymphocytesExamples: B and T cell function
![Page 8: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/8.jpg)
Antibody (immunoglobulin) Antibody (immunoglobulin) structurestructure
,,,,,,,,
variable part(Ag binding)
constant part(function)
![Page 9: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/9.jpg)
Antibody functionsAntibody functions•neutralizing
•opsonization
•complement activation
•sensitizing for NK cell killing (ADCC), or for granulocyte activation
•mast cell sensitizing
IgG, IgAIgG, IgA
IgGIgG
IgM, IgG3 >G1>G2,IgAIgM, IgG3 >G1>G2,IgA
IgGIgG
IgEIgE
![Page 10: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/10.jpg)
IsotypesIsotypes
![Page 11: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/11.jpg)
Ig isotypes, factsIg isotypes, facts
Iso type
Mol mass
Serum conc Localization T (1/2)biol Function
(kDa) (g/l) (days)
IgG 155 8-18serum, intersticialfluid 21
opsonization; neutralization; crosses placenta; secondaryí response
IgA 160-350
0.9-3.5serum, mucosae, tears, saliva
6mucosal defense, opsonization
IgM 900 0.9-2.5serum, B-cell surface
6complement activation; primaryresponse; Ag receptor
IgD 180 0.1 3Ag receptor
IgE 190 3x10-4 2anti-parasite defense
serum, B-cell surface
serum, intersticialfluid
![Page 12: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/12.jpg)
Ig after birth, physiological Ig after birth, physiological infantsinfants
% of adult values
maternal IgG (trans-placental)
gestation age (wks)
birthage (yrs)
![Page 13: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/13.jpg)
FcRn: neonatal FcRFcRn: neonatal FcR
transport across placentaextends T1/2
Beta-2-microglobulin
FcRn
![Page 14: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/14.jpg)
Antibody responseAntibody response
![Page 15: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/15.jpg)
Primary antigenic sinPrimary antigenic sin
ABCD A C EF A D E G
![Page 16: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/16.jpg)
B cell receptorB cell receptor
![Page 17: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/17.jpg)
T Cell ReceptorT Cell Receptor
![Page 18: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/18.jpg)
NK cells: no specific NK cells: no specific antigen receptorantigen receptor
![Page 19: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/19.jpg)
CD nomenclatureCD nomenclatureCD3 = T lineageCD4 = T helpers*CD8 = cytotoxic T*CD19 = B lineageCD10 = immature lymphoid cells*CD34 = progenitors*
*also other cells CD40/CD40L
![Page 20: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/20.jpg)
Adaptive immunity:Adaptive immunity:
B lymphoB lymphoT lymphoT lympho
Ag react with:Ag react with:
IgIgTCRTCR
IgM: first isotype after primary infectionIgM: first isotype after primary infection
MMDD GG AA
EE
[structure, function][structure, function]
IgG: IgG: main isotype of long-lasting defense, main isotype of long-lasting defense, crosses placentacrosses placenta
![Page 21: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/21.jpg)
ContentsContentsSpecific immunity: Basics Immunoglobulins and T cell receptorB and T developmentT cell function Innate-like lymphocytesExamples: B and T cell function
![Page 22: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/22.jpg)
Antigen specifity - clonal theoryAntigen specifity - clonal theory
![Page 23: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/23.jpg)
Immunoreceptor gene Immunoreceptor gene rearrangementrearrangement
V D J
![Page 24: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/24.jpg)
Genes for various chains..Genes for various chains..
Allelic exclusion
![Page 25: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/25.jpg)
B lymphocytes - developmentB lymphocytes - development
![Page 26: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/26.jpg)
Germinal center close-upGerminal center close-up
nemůžu najít obrázek
![Page 27: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/27.jpg)
![Page 28: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/28.jpg)
Somatic hypermutationSomatic hypermutationmutation in variable loci Ig genesin germinal centerstogether with isotype switch
AID (aktivation induced deaminase)
![Page 29: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/29.jpg)
Thymus-independent (TI) antigensThymus-independent (TI) antigens
Type 2:Type 2: - repetitive structures (often - repetitive structures (often polysaccharides)polysaccharides)
- no help: IgM only- no help: IgM only- mostly created by B1 cells or by marginal - mostly created by B1 cells or by marginal
zoneszones- children under 2 yrs: weak response- children under 2 yrs: weak response
Type 1:Type 1: mitogenic potential (e.g. mitogenic potential (e.g.: lipopolysacharide: lipopolysacharide))
![Page 30: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/30.jpg)
T cell developmentT cell development
![Page 31: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/31.jpg)
T lymphocyte subpopulationsT lymphocyte subpopulations
CD 8 - Tc, cytotoxic lymphocytes
CD4 - Th - helpers, Treg- regulatory [attacked by HIV]
Normal frequency in blood: CD4/CD8 cca 2
![Page 32: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/32.jpg)
ContentsContentsSpecific immunity: Basics Immunoglobulins and T cell receptorB and T developmentT cell function Innate-like lymphocytesExamples: B and T cell function
![Page 33: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/33.jpg)
Cytotoxic T lymphocyteCytotoxic T lymphocyte
![Page 34: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/34.jpg)
NK a Tc cells: granulesNK a Tc cells: granules
perforin granzymesgranulysin
![Page 35: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/35.jpg)
Cytotoxic T lymphocyte: other Cytotoxic T lymphocyte: other mechanismsmechanisms
Fas ligand
cytokines interferon γTNF αTNF β
![Page 36: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/36.jpg)
Th cells as effectorTh cells as effector
![Page 37: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/37.jpg)
If macrophages cannot eat it..If macrophages cannot eat it..
![Page 38: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/38.jpg)
Regulatory role of CD4+ cellsRegulatory role of CD4+ cells
Th0
Th3Th1 Th2
Treg
IFN-LFIL-2
IL-4, -5, -6IL-10TGF-IL-13
IFN- IL-12
IL-4
cellular immunity humoral immunity
Th-helpersTh-helpers Regulatory TRegulatory T
![Page 39: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/39.jpg)
Allergy:Allergy:possible role of possible role of
T[reg] cellsT[reg] cells
![Page 40: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/40.jpg)
ContentsContentsSpecific immunity: Basics Immunoglobulins and T cell receptorB and T developmentT cell function Innate-like lymphocytesExamples: B and T cell function
![Page 41: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/41.jpg)
Innate-like lymphocytesInnate-like lymphocytes
limited repertoirspecific function and localizationmostly autonomous
TγδB1NKT
![Page 42: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/42.jpg)
•Diversity stems from Diversity stems from rearrangements of genesrearrangements of genes•All lymphocytes arise from All lymphocytes arise from bone marrow precursorsbone marrow precursors•Autoreactive lymphocytes dieAutoreactive lymphocytes die•Non-productive and areactive Non-productive and areactive lymphocytes dielymphocytes die
•Somatic hypermutation of B lymphocytes leads to the Somatic hypermutation of B lymphocytes leads to the selection of the best Igselection of the best Ig•Main T lymphocyte subsets are Th (CD4+) and Tc (CD8+)Main T lymphocyte subsets are Th (CD4+) and Tc (CD8+)•Th comprise of Th1 and Th2, related are Th3 and Tr1 with Th comprise of Th1 and Th2, related are Th3 and Tr1 with regulatory functionregulatory function
![Page 43: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/43.jpg)
ContentsContentsSpecific immunity: Basics Immunoglobulins and T cell receptorB and T developmentT cell function Innate-like lymphocytesExamples: B and T cell function
![Page 44: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/44.jpg)
B and T lymphocyte disordersB and T lymphocyte disorders
decreased productioninborn errors (T, B, T and B)malnutritionTB and other infections
increased destruction steroids, radiation, chemotherapy
AIDS (T)
losses (gut, chylothorax,..) (T and B)
- lymphopenia:
![Page 45: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/45.jpg)
B and T lymphocyte disordersB and T lymphocyte disorders
normal absolute counts vary throughout agevirus infectionsother infections (mycoplasma, syphilis, ..)dif. dg.: clonal proliferations (incl. leukemias)
- lymphocytosis:
![Page 46: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/46.jpg)
B and T lymphocyte disordersB and T lymphocyte disorders
antibody deficiencyIgA
hereditary mutation CD40/CD40L
polymorphism of V(D)J in some ethnic groups
- functional defects:
![Page 47: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/47.jpg)
EBV, Epstein-Barr virusEBV, Epstein-Barr virus
•infants, preschool kids: mostly asymptomatic or infants, preschool kids: mostly asymptomatic or indistinguishable from other infectionsindistinguishable from other infections•adolescence (rarely at different age): inf. mononucleosis adolescence (rarely at different age): inf. mononucleosis
•Primoinfection:Primoinfection:
•95% world population95% world population
![Page 48: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/48.jpg)
Life cycle, EBVLife cycle, EBV
![Page 49: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/49.jpg)
+fever
Infectious mononucleosis: clinicsInfectious mononucleosis: clinics
splenomegaly up to 50% patientshepatomegaly (10%)elevated transaminases, LDHpetechiae na patřeeye-lid oedemasexanthemas (up to 15%)(typically no stomachache)
![Page 50: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/50.jpg)
Severe EBV complicationsSevere EBV complications
virus-associated hemophagocytic syndrome
X-linked lymphoproliferationfamiliar hemofagocytic lymfohistiocytosis
malignities: nasofaryngeal carcinomaendemic Burkitt lymphomaother malignancies (Hodgkin, ...)
Severe lymphoproliferations
![Page 51: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/51.jpg)
Burkitt lymphomaBurkitt lymphoma
![Page 52: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/52.jpg)
perforin deficiencyperforin deficiency
![Page 53: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/53.jpg)
T+
Imunodeficiencies: not just lossesImunodeficiencies: not just lossesAutoimmune lymphoproliferative syndromeAutoimmune lymphoproliferative syndrome
hyper-Ighyper-Igsplenomegalysplenomegalylymphadenopathylymphadenopathyautoimmunityautoimmunityincreased CD3+TCRαβ+CD4-CD8- cellsincreased CD3+TCRαβ+CD4-CD8- cellsrisk of lymphomasrisk of lymphomas
![Page 54: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/54.jpg)
Genetic causes of ALPSGenetic causes of ALPS
![Page 55: Specific (adaptive) immunity Immunology, 3rd year.](https://reader036.fdocuments.in/reader036/viewer/2022062423/56649ee65503460f94bf6b15/html5/thumbnails/55.jpg)
ALPS3: the clue ALPS3: the clue