Also known as an immunoglobulin ANTIBODY is a specific type of protein that is produced by an organism in response to the presence of a specific ANTIGEN

N One virus or microbe may have several antigenic determinant sites, to which different antibodies may bind. Present on the surface of B cells, or secreted by plasma cells Valence of an antibody: Number of antigen binding sites. Most are bivalent.

Fab Variable region

Heavy chain

Lightchain

Fc

Constant region

 Bifunctional

properties Target organism that are outside the cell Cross reactivity

 Antigen

binding domain/site Fab (fragment antigen binding)

activity domain/site Fc (fragment crystallizable)

Biological

Antigen binding site The site that bind to the antigen Consist of combined variable regions of the light and heavy chains Each monomeric Ab has 2 identical antigen binding site This site determine the specificity of the Ab Specificity = Ab can only recognize a precise segment of one antigen

Biological activity domain/site Immunologycal fate of the microbe depends on the constant region of the Ab heavy chain (Ab isotype) Determines biological activity

 Antibodies

are important for host defence against microbes (eg. Bacteria) that enter the body, but do not infect cell Antibodies can only target organism that are outside the cell

 Ab

against Virus? although viruses infected cell window of opportunity = prior to cell entry, or when they bud from cell When binds to virus, Ab can blocks the site that the virus uses to gain entry to cells neutralization

 Ab

secreted by one plasma cell have a specificity that is different from the specificity of Ab secreted by another plasma cell Some Ab secreted by 1 plasma cell can bind a similar, but not identical epitope, a phenomenon termed cross-reactivity Different binding strength (avidity)

 Affinity

: the binding strength between an epitope and its corresponding complementary site in the Fab regions of the antibody Avidity : overall binding strength; sum of affinities for all the antigen binding site in one antibody molecule

Idiotype

V, D, & J segments V&J segments

or

5 isotype: IgM IgA IgE IgG IgD

Structur of IgM

Structur of IgD

Structur of IgE

Structur of IgA1

Structur of sIgA

IgA

IgD

IgG

IgE

IgM

Constant heavy chain

Serum (mg/dL) t

~100

negligible

~1200

negligible

~150

~5.5 days

N/A

IgG1,2,4 ~21 days IgG3 ~7 days mopnomer

~2 days

~5 days

General form MW (kD)

Monomer, dimer ~160 (monomer) J chain secretory piece on mucosal IgA

monomer

monomer

pentamer

~180

~150

~200

~900

Protein attachments

J Chain

IgA
Distribution Vascular(in tra)+Mucos a Subclasses 2

IgD
Membrane (nave B cells) -

IgG
Vascular (intra & extra) 4

IgE
FcR on Mast cells, Basophils -

IgM
Vascular (intra) -

Breast Milk

+++

Placental transfer Compleme nt activation (Classical pathway)

++

+ (not IgG4)

+++

IgG1
concentrat ~840 ion % total serum IgG t (days) Compleme nt binding Placental transfer Binding to FcR 70 23 ++ +++ +++

IgG2
~240 20 23 + + +/~70 6 7 +++ +++ +++

IgG3
~50 4 23 _ +++ +

IgG4

 Activation

of the classical pathway of complement Targeting of mo for phagocytosis (neutrophils & macrophages) by acting as opsonin Targeting virally infected cells for destruction by ADCC (antibody-dependent cell mediated cytotoxicity) Neutralization of virus

 Complement

activation by IgM Natural isohemaggutinins

 Immune

response to some parasites Reagenic antibody (responsible for allergies and anaphylactic shock

 Present

on the surface of nave B cells Not secreted IgD found in serum likely represent IgD that has been released from dying B cells Function elusive

 Small

amount in serum Mucosal secretion (mucus, tears, saliva, colostrum) from MALT (Mucosa-associated lymphoid tissues) Secretory IgA neutralizing Ab Activate alternative pathway of complement (in aggregated form)

Isotype Switching
B

cells mature in bone marrow express both IgM and IgD. They then join the blood and recirculate in the periphery. In the periphery, B cells can potentially switch isotypes by producing sequentially IgMIgG IgA IgE. Therefore, the same specificity can be expressed as distinct isotypes starting always with IgM. Class switching is largely regulated by cytokines (IFN- for IgG2 class, and IL-4 for IgG1 and IgE) produced upon Ag stimulation.

Pattern of Antibody Levels During Infection

Primary Response: After initial exposure to antigen, no antibodies are found in serum for several days. A gradual increase in titer, first of IgM and then of IgG is observed. Most B cells become plasma cells, but some B cells become long living memory cells. Gradual decline of antibodies follows.

Secondary Response: Subsequent exposure to the same antigen displays a faster and more intense antibody response. Increased antibody response is due to the existence of memory cells, which rapidly produce plasma cells upon antigen stimulation.