Humoral Immunity Farmasi

7/31/2019 Humoral Immunity Farmasi

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MICROBIOLOGY LAB

HUMORAL IMMUNE RESPONSE


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Humoral immunity to combate microbe

Be divided into innateandadaptive immunity

Innate immunity is performed by complement,which have main role to lyse extracellularmicrobes

Adaptive humoral immunity is conducted byantibodies (Ab), which have physiologic functionin defense against extracellular microbes andmicrobial toxin


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ANTIBODIES

(Immunoglobulins/Ig)

are circulating protein that are produced in

vertebrate in responses to exposure toforeign structures known as antigens


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Antigens Most are proteins or large polysaccharides from a foreign

organism.

Microbes: Capsules, cell walls, toxins, viral capsids,

flagella, etc.

Nonmicrobes: Pollen, egg white , red blood cell

surface molecules, serum proteins, and surface

molecules from transplanted tissue.

Lipids and nucleic acids are only antigenic when

combined with proteins or polysaccharides.

Molecular weight of 10,000 or higher.

Hapten: Small foreign molecule that is not antigenic.Must be coupled to a carrier molecule to be antigenic.Once antibodies are formed they will recognize hapten.


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AntigensEpitope:

Small part of an antigen that interacts with anantibody.

Any given antigen may have several epitopes.

Each epitope is recognized by a different

antibody.


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Epitopes: Antigen Regions thatInteract with Antibodies


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Antibody

produced by B ly in the lymphoid organ and bonemarrow

their effector function at sites distant from theirproduction

derived from long-lived plasma cells (in secondaryimmune responses by the activation of memory Bcells)

the effector functions are mediated by the heavychain (Fc) constant regions of Ig molecules, e.g.

phagocytosis Ab activates effector function when they are neededeffector functions are triggered by binding of Ag tothe variable regions (Fab)


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Antibody structure

The simplest molecular structure is calledmonomer has four protein chains : Two identical light chains (L-chain)

Two identical heavy chains (H-chain)

The chains are joined by disulfide (S-S)bonds/links to form a Y shaped or T shaped

The two arms of Y shaped is called variable (V)regions as antigen (epitope) binding sites (Fabregions)

The stem of Y shaped is called Fc regions


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Fab

Fc Hingeregion

Light

chain

Heavy chain

Ag binding

siteEpitope

ANTIBODY


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Antibodies can exist in two forms:

1. As membrane-bound antibodies on the surface

of B lymphocytes function as receptors for Ag

2. As secreted antibodies in the circulation, tissues,

and mucosal site which will bind antigens,

neutralized toxins, and prevent the entry and

spread of pathogens


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EFFECTOR FUNCTIONS of Ab

1. Neutralization of microbes and toxins

2. Opsonization and phagocytosis of microbes

3. Mediate ADCC (Ab dependent cell-mediated cytotoxic)

4. Lysis of microbes and inflammation through

the activation of complement

5. Feedback mechanism


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ANTIBODYFUNCTIONS


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Functions of Ab isotypes

Ab isotypes Effector function

IgG Opsonization of Ag for phagocytosis by Mo and neutrophils

Activation of the classical pathway of complement

ADCC mediated by NK cells and Mo

Neonatal immunity: transfer of maternal antibosy across the

placental and gut Feedback inhibition of B cell activation

IgM Activation of the classical pathway of complement Ag receptor of naive B cells

IgA Mucosal immunity:secretion of IgA into the lumens of GIT and resp tract

IgE o ADCC involving eosinophilso Mast cells degranulation (immediate hypersensitivity)

IgD Antigen receptor of naive B cells


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Neutralization of microbes and

microbial toxin

requires only the Fab region

most neutralizing Ab in the blood are ofIgG,

in mucosal organs are of the IgA isotype


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Neutralization

of microbes and

toxins


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Opsonization and phagocytosis

IgG isotype coat (opsonize) microbes and

promote their phagocytosis by binding to Fc

receptors on phagocytes

Mononuclear and neutrophils express receptor forthe Fc portion of IgG (FcRI)

Microbes may also be opsonized by a product of

complement activation (C3b)

The IgG and C3b are called opsonin


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Opsonization and phagocytosis


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Antibody-Dependent Cellmediated Cytotoxic (ADCC)

NK cells and other leucocytes bind to Ab coatedcells by Fc receptors and destroy these cells

Eosinophils mediate ADCC against helminth

coated by IgE through FcRI Engagement FcRIII (Fc receptor on NK cells)

activates the NK cells to synthesize and

secrete cytokine such as IFN- as well as the

content of the granule

(killing functions of NK cells)


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Antibody-Dependent Cell mediatedCytotoxic (ADCC)


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Complement functions

opsonization to enhance phagocytosis

phagocyte attraction and activation

through inflammation process lysis of bacteria


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Complementfunctions


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Consequences of AntibodyBinding


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Immunological Memory

Antibody Titer: The amount of antibody in theserum.

Pattern of Antibody Levels During Infection

Primary Response:

After initialexposure to antigen, no antibodiesare found in serum for several days.

A gradual increase in titer, first of IgM and thenof IgG is observed.

Most B cells become plasma cells, but some Bcells become long living memory cells.

Gradual decline of antibodies follows.


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Immunological Memory (Continued)

Secondary Response: Subsequent exposure to the same antigen

displays a faster and more intense antibodyresponse.

Increased antibody response is due to theexistence of memory cells, which rapidlyproduce plasma cells upon antigen stimulation.


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Antibody Response After Exposure toAntigen


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