Chapter 19- Specific Immunity

8/14/2019 Chapter 19- Specific Immunity

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Ms. Pia Marie Albano, RMT, MSc



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




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)




Lymphatic vessels

- system of vessels that transports lymph constructedalong the lines of blood vessels

Lymphoid organs1. Primary organs

a) Thymus gland

one marrow













Clonal Selection TheoryMs. Pia Marie Albano, RMT, MSc



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



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







– 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




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




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







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




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







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






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




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







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




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




Cell-Mediated Immunity




Cell-Mediated Immunity




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



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







– 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







Pepsin

cuts here




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




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




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




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




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




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




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







Antibody-Mediated Immunity


B Cell Differentiation






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







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

Chapter 19- Specific Immunity

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