Antibody-Mediated Immunity

 

Introduction :

The body contains not only millions of different T cells but also

millions of different B cells, each capable of responding to a specific antigen. Cytotoxic T cells leave lymphatic tissues to seek out

and destroy a foreign antigen, but B cells stay put. In the presence

of a foreign antigen, a specific B cell in a lymph node, the spleen,

or mucosa-associated lymphatic tissue becomes activated. Then it

undergoes clonal selection, forming a clone of plasma cells and

memory cells. Plasma cells are the effector cells of a B cell clone;

they secrete specific antibodies, which in turn circulate in the

lymph and blood to reach the site of invasion.

What does activate clonal Selection?

Activation and Clonal Selection of B Cells

During activation of a B cell, an antigen binds to B-cell receptors(BCRs). These integral transmembrane proteins are chemically similar to the antibodies that eventually are secreted by

plasma cells. Although B cells can respond to an unprocessed antigen present in lymph or interstitial fluid, their response is much

more intense when they process the antigen. Antigen processing in

a B cell occurs in the following way: The antigen is taken into the

B cell, broken down into peptide fragments and combined with

MHC-II self-antigens, and moved to the B cell plasma membrane.

Helper T cells recognize the antigenMHC-II complex and deliver the costimulation needed for B cell proliferation and differentia-

tion. The helper T cell produces interleukin-2 and other cytokines

that function as costimulators to activate B cells.

Once activated, a B cell undergoes clonal selection.The result is the formation of a clone of B cells that consists of plasma 

cells and memory B cells. Plasma cells secrete antibodies. A few

days after exposure to an antigen, a plasma cell secretes hundreds of

millions of antibodies each day for about 4 or 5 days, until the plasma

cell dies. Most antibodies travel in lymph and blood to the invasion

site. Interleukin-4 and interleukin-6, also produced by helper T cells,

enhance B cell proliferation, B cell differentiation into plasma cells,

and secretion of antibodies by plasma cells. Memory B cells do not

secrete antibodies. Instead, they can quickly proliferate and differen-

tiate into more plasma cells and more memory B cells should the

same antigen reappear at a future time.

 Different antigens stimulate different B cells to develop into plasma

cells and their accompanying memory B cells. All of the B cells of a

particular clone are capable of secreting only one type of antibody,

which is identical to the antigen receptor displayed by the B cell that

first responded. Each specific antigen activates only those B cells that

are predestined (by the combination of gene segments they carry) to

secrete antibody specific to that antigen. Antibodies produced by a

clone of plasma cells enter the circulation and form antigen–antibody

complexes with the antigen that initiated their production.

What is Antibodies and its work?

Antibodies

An antibody (Ab) can combine specifically with the epitope on

the antigen that triggered its production. The antibody’s structure

matches its antigen much as a lock accepts a specific key. In theory, plasma cells could secrete as many different antibodies as

there are different B-cell receptors because the same recombined

gene segments code for both the BCR and the antibodies eventually secreted by plasma cells.

Antibody Structure

Antibodies belong to a group of glycoproteins called globulins, and

for this reason they are also known as immunoglobulins (Igs).

Most antibodies contain four polypeptide chains Two of the chains are identical to each other and are called heavy

(H) chains; each consists of about 450 amino acids. Short carbohy-

drate chains are attached to each heavy polypeptide chain. The two

other polypeptide chains, also identical to each other, are called

light (L) chains, and each consists of about 220 amino acids. A

disulfide bond (S—S) holds each light chain to a heavy chain. Two

disulfide bonds also link the midregion of the two heavy chains;

this part of the antibody displays considerable flexibility and is

called the hinge region. Because the antibody “arms” can move

somewhat as the hinge region bends, an antibody can assume either

a T shape or a Y shape. Beyond the hinge region,

parts of the two heavy chains form the stem region.

 Within each H and L chain are two distinct regions. The tips of

the H and L chains, called the variable (V) regions, constitute the

antigen-binding site. The variable region, which is different for

each kind of antibody, is the part of the antibody that recognizes

and attaches specifically to a particular antigen. Because most anti-

bodies have two antigen-binding sites, they are said to be biva-

lent. Flexibility at the hinge allows the antibody to simultaneously

bind to two epitopes that are some distance apart—for example,

on the surface of a microbe.

 The remainder of each H and L chain, called the constant (C)

region, is nearly the same in all antibodies of the same class and is

responsible for the type of antigen–antibody reaction that occurs.

However, the constant region of the H chain differs from one class

of antibody to another, and its structure serves as a basis for distinguishing five different classes, designated IgG, IgA, IgM, IgD, and

IgE. Each class has a distinct chemical structure and a specific biological role. Because they appear first and are relatively short-lived,

IgM antibodies indicate a recent invasion. In a sick patient, the responsible pathogen may be suggested by the presence of high levels of IgM specific to a particular organism. Resistance of the fetus

and newborn baby to infection stems mainly from maternal IgG

antibodies that cross the placenta before birth and IgA antibodies in breast milk after birth.  summarizes the structures and functions of the five classes of antibodies.

Antibody Actions

The actions of the five classes of immunoglobulins differ some-

what, but all of them act to disable antigens in some way. Actions

of antibodies include the following:

• Neutralizing antigen. The reaction of antibody with antigen

blocks or neutralizes some bacterial toxins and prevents at-

tachment of some viruses to body cells.

• Immobilizing bacteria. If antibodies form against antigens on

the cilia or flagella of motile bacteria, the antigen–antibody

reaction may cause the bacteria to lose their motility, which

limits their spread into nearby tissues.

• Agglutinating and precipitating antigen. Because antibodies

have two or more sites for binding to antigen, the antigen–

antibody reaction may cross-link pathogens to one another,

causing agglutination (clumping together). Phagocytic cells

ingest agglutinated microbes more readily. Likewise, soluble

antigens may come out of solution and form a more easily

phagocytized precipitate when cross-linked by antibodies.

• Activating complement. Antigen–antibody complexes initiate the

classical pathway of the complement system (discussed shortly).

• Enhancing phagocytosis. The stem region of an antibody acts as a flag that attracts phagocytes once antigens have bound to the antibody’s variable region. Antibodies enhance the activity

of phagocytes by causing agglutination and precipitation, by activating complement, and by coating microbes so that they are more susceptible to phagocytosis.