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Ms. Pia Marie Albano, RMT, MSc
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Functions:
1. Provide an auxiliary route for the return of ECF to thecirculatory system
“ ”. -
3. Render surveillance, recognition, and protection against
foreign materials through a system of lymphocytes,
phagocytes, and antibodies
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Components
Lymphatic fluid
- formed when blood components (except RBCs) move
out of the blood vessels into the EC spaces and diffuse
- composition :
1. water
2. dissolved salts
3. 2-5% protein (especially proteins and antibodies)
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Lymphatic vessels
- system of vessels that transports lymph constructedalong the lines of blood vessels
Lymphoid organs1. Primary organs
a) Thymus gland
one marrow
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Clonal Selection TheoryMs. Pia Marie Albano, RMT, MSc
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B cells T cellsSite of maturation Bone marrow Thymus
Antigen surface markers Ig TCR
CD molecules
Circulation in blood Low numbers High numbers
Receptors for antigen Ig TCR
Distribution in lymphatic organs Cortex Paracortical sites
Require antigen presented with MHC Sometimes Yes
Product of antigenic stimulation Plasma cells and Ab Sensitized T cell types
Memory cells
General functions Ab production Regulate immune functions
Kill foreign cells
Hypersensitivity
Cytokine synthesisMs. Pia Marie Albano, RMT, MSc
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2. Secondary organs and tissues
a) Lymph nodes
» filter for lymph
» provide appropriate cells and niches for immune
reactions
b) Spleen» filter for blood
» remove worn-out RBCs from the circulation
»
c) SALT
d) GALT or MALT
» e.g. : Peyer’s patches
e) BALT
f) tonsils
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– inherent ability of a substance to induce an immune
response
– immune response:
B lymphocytes: immunoglobulins T lymphocytes: lymphokines
-
1. Foreignness
2. chemical complexicity
» proteins: most potent immunogens» conjugates of proteins: good immunogens
» most polysaccharides: weak antigens or even antigenic
» nucleic acids (pure form): nonimmunogenic
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3. antigen size
» the larger the molecule, the more immunogenic
4. degradability
» non-biodegradable: nonimmunogenic
5. route of immunization
» SC and IM: best routes
» IV: thwart or minimize immune response
6. nature of host
4. antigen dose
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EpitopeEpitopeEpitopeEpitope
- antigenic determinant
- size: 4 or 5 AA of a protein or an equal size area of apolysaccharide
- may be linear or conformational
- some are found on the antigen’s surface; whereas others are
- function: – determine the specificity of the antigen molecule
– stimulate immune response
- antigens are multivalent: carries a number of epitope
- haptens: small, nonimmunogenic molecules that can add a newepitope when combined with an existing antigen
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Two components:1. Primary immune response
Initial exposure to infectious agent
Precommitted lymphocytes proliferate and mature
Antibody-secreting plasma cells
HUMORAL IMMUNE RESPONSEHUMORAL IMMUNE RESPONSEHUMORAL IMMUNE RESPONSEHUMORAL IMMUNE RESPONSE
Specifically-reactive T cells
lymphokines
CELLCELLCELLCELL----MEDIATED IMMUNE RESPONSEMEDIATED IMMUNE RESPONSEMEDIATED IMMUNE RESPONSEMEDIATED IMMUNE RESPONSE
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2. Secondary (anamnestic) response
– increased resistance on further contact with the same antigen
abundant production of specific antibodies or sensitized lymphocytes
Characteristics
1. Ability to distinguish self from foreignness
2. Specificity
react onl with homolo ous anti ens
3. Immunologic memory
Mechanisms
1. Cell-mediated or cellular immunity Thymus-derived (T) lymphocytes
2. Antibody-mediated or humoral immunity Bone marrow-derived (B) lymphocytes
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A. Surface Markers A. Surface Markers A. Surface Markers A. Surface Markers
1. T-cell receptor (TCR )
2. Cluster of Differentiation (CD)
Major histocompatibility c omplex (MHC)- genes that produce human leukocyte antigens (HLA)
- 3 sets: class I, class II, and class III MHC molecules
- Class I & class II on macrophages: presentation of antigenicepitopes to T cells
Class I protein and epitope: CD8+ T cells
Class II protein and epitope: CD4+ T cells
- Class III: not involved in epitope presentationMs. Pia Marie Albano, RMT, MSc
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Ms. Pia Marie Albano, RMT, MSc
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Functions of MHCFunctions of MHCFunctions of MHCFunctions of MHC
Class I- markers that display unique characteristics of self
molecules & regulation of immune reactions
- required for T lymphocytes
Class II
- receptors that recognize & react with foreign antigens.- Located primarily on macrophages & B cells- involved in presenting antigen to T cells
Class III- secreted complement components, C2 and C4
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B. Functional Subsets of T cellsB. Functional Subsets of T cellsB. Functional Subsets of T cellsB. Functional Subsets of T cells
1. Cytotoxic T (Tc) lymphocytes also called CTLs (cytolytic T lymphocytes)
carry the CD8 surface marker
induced by and are active against:
i. tumors
ii. virus-infected cells
iii. transplanted allogeneic tissue
recognize foreign epitope in association with class I
MHC molecules
destroy their target cells by releasing:i. perforin
ii. granzymes
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2. Helper T (Th) lymphocytes
- carry the CD4 surface marker- recognize foreign epitope in association with class II MHC
molecules
- collaborate with:a. B cells and macrophages Ig response
b. other T cells facilitate production of Tccells
- subsets:a. Th1 cells : produce IFN- γ, IL-2, IL-3 and TNF
b. Th2 cells: produce IL-3, 4, 5, 6, and 10
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3. Memory T (Tm) lymphocytes
- induced during the primary immune response
- recognize the specific antigen and participate in the
anamnestic response
- most have Th functions;- with CD4 surface marker
- subject to class II MHC restriction
4. Delayed-type hypersensitivity effector cells (Tdth or TD)
lymphocytes
5. Inducer T lymphocytes
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Cell-Mediated Immunity
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Cell-Mediated Immunity
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A. Surface Markers1. Pro-B cell
» CD45, CD19, and CD10
2. Pre-B cell» begins to synthesize mu CH
3. Immature B cell» expresses IgM
4. Fully mature B cell» expresses IgM and synthesizes IgD
» IgD predominates
B. Secreted products1. Immunoglobulin» major secretory product
2. lymphokines
» e.g. : IL-1 and I-6Ms. Pia Marie Albano, RMT, MSc
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C. Functions of B-cell Markers:
1. CD proteins
CD19 and CD35
» receptors for C3b of the complement system
CD25» an IL-2 receptor (produced by the Tc cells)
2. I M and I D
» receptors for antigen
3. B7 proteins
» function as adhesins
» enables the antigen-presenting B cells to bind to T cellsand stimulate T-cell production
4. MHC class II
» antigen-presenting molecule to CD4+ T cells
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– produced by B cells or plasma cells in response to
exposure to an immunogen
– react with the corresponding epitope of the antigen that
induced their production
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Pepsin
cuts here
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A. Heavy (H) and Light (L) Chains
H chain
• 50-75 kDa Mw; 400 AA
• AA differences in carboxy terminal portion
- identifies the distinct H chain isotype (γ, α, μ, δ, ε)
L chains
• 200 AA
• 2 types: κ and λ
• per Ig molecule: either 2 identical κ or 2 identical λ chainsbut never a κ and a λ combined
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B. Disulfide Bonds
hold together the 4 polypeptide chains
types: interchain and intrachain
C. Constant (C) and Variable (V) Regions
V region: wide variation in AA compostion
C region: much more uniform AA sequence
H chain domains: VH & CH1, CH2, CH3, and (CH4)
L chain domains: VL and CL
D. Hinge Region
between CH1 and CH2
highly flexible: allows movement of the Fab arms in relation to eachother
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E. Fragments
Papain1) 2 Fab fragments
– f ragment antigen-binding
– entire L chain and amino terminal half of the H chain
– monovalent
2) 1 Fc fragment
– f ragment crystallizable
– car oxy erm na por on o e c a n
– it binds the C1q complement component and activates thecomplement cascade
Pepsin
– digests most of the Fc fragment below the interchain
disulfide bond in the hinge region
– result: F(ab’)2 which has 2 Ag-binding sites
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Immunoglobulin Isotypes (Classes)
1. IgG – structure: monomer
– major Ig in human serum
– major Ab produced in 2° immune response
– only Ig that crosses the placenta
–
– activates complement via the classical pathway
– provides long-term
resistance to disease
as a product of the
memory cells
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2. IgA
– two forms: serum IgA and secretory IgA – structure: dimer + J chain + secretory component
• J component
» polypeptide synthesized by exocrine epithelial cells
» enables the IgA to pass through the mucosal tissues into secretions
– provides resistance in the respiratory and GIT
– present in tears, saliva, and colostrum
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3. IgM
– structure: pentameric + J chain + disulfide bonds in the Fcfragment
– 1st Ab produced by committed B cells
– predominant Ab in the 1° immune response
– predominant Ab produced by the fetus
an elevated IgM level in cord blood of NB: fetus could have been
infected before birth
– the most efficient Ig in activating complement
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4. IgD
- represents less than 1% of the total Ig pool
- occurs in large quantities
on B cell membrane
- may be involved as an Ag
receptor in B cell activation
5. IgE- present in trace amounts
in normal serum
- associated with atopicdiseases (asthma & anaphylaxis)
- may also be important in immunity
to certain helminthic parasites
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Antibody-Mediated Immunity
Ms. Pia Marie Albano, RMT, MSc
B Cell Differentiation
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1. Primary immune response – occurs during the 1st exposure to the Ag
– produces a relatively small amount of Ab
– Ab level decreases over time in the absence of re-exposure to Ag
2. Anamnestic response – evoked by a subsequent exposure to even a small amount of the
same Ag – also called booster response, memory response, or secondary
immune response
– consists of rapid proliferation of plasma cells production of
large amounts of Ab – large population of memory B and T cells are recruited into the
humoral immune system
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Antibody interactions mediate the disposal of antigens (pathogens) Formation of antigen-antibody complexes result in the antigen:
1. death2. inactivation
3. increased susceptibility Ms. Pia Marie Albano, RMT, MSc