Antigens and Antigen Receptors

What is antigen and antiggen receptor and how its work?

Antigens and Antigen Receptors

Antigens have two important characteristics: immunogenicity

and reactivity. Immunogenicity is the ability to provoke an immune response by stimulating the production of specific antibodies, the proliferation of

specific T cells, or both. The term antigen derives from its func-

tion as an antibody generator. Reactivity is the ability of the antigen to react specifically with the antibodies or cells it provoked.

Strictly speaking, immunologists define antigens as substances

that have reactivity; substances with both immunogenicity and

reactivity are considered complete antigens. Commonly, however, the term antigen implies both immunogenicity and reactivity, and we use the word in this way.

 Entire microbes or parts of microbes may act as antigens.

Chemical components of bacterial structures such as flagella, capsules, and cell walls are antigenic, as are bacterial toxins. Nonmicrobial examples of antigens include chemical components of pollen, egg white, incompatible blood cells, and transplanted tissues and organs. The huge variety of antigens in the environment

provides myriad opportunities for provoking immune responses.

Typically, just certain small parts of a large antigen molecule act as

the triggers for immune responses. These small parts are called

epitopes (EP-i-toˉps), or antigenic determinants .

Most antigens have many epitopes, each of which induces production of a specific antibody or activates a specific T cell.

 Antigens that get past the innate defenses generally follow one of three routes into lymphatic tissue: 

(1) Most antigens that enter

the bloodstream (for example, through an injured blood vessel)

are trapped as they flow through the spleen. 

(2) Antigens that penetrate the skin enter lymphatic vessels and lodge in lymph nodes.

(3) Antigens that penetrate mucous membranes are entrapped by

mucosa-associated lymphatic tissue (MALT).

Chemical Nature of Antigens

Antigens are large, complex molecules. Most often, they are proteins. However, nucleic acids, lipoproteins, glycoproteins, and certain large polysaccharides may also act as antigens. Complete antigens usually have large molecular weights of 10,000 daltons or more, but large molecules that have simple, repeating sub-

units—for example, cellulose and most plastics—are not usually

antigenic. This is why plastic materials can be used in artificial heart valves or joints.

 A smaller substance that has reactivity but lacks immunogenicity is called a hapten (HAP-ten - to grasp). A hapten can stimulate an immune response only if it is attached to a larger

carrier molecule. An example is the small lipid toxin in poison

ivy, which triggers an immune response after combining with a body protein. Likewise, some drugs, such as penicillin, may

combine with proteins in the body to form immunogenic complexes. Such hapten-stimulated immune responses are responsible for some allergic reactions to drugs and other substances in

the environment (see Disorders: Homeostatic Imbalances at the

end of the chapter).

 As a rule, antigens are foreign substances; they are not usually

part of body tissues. However, sometimes the immune system

fails to distinguish “friend” (self) from “foe” (nonself). The result

is an autoimmune disease (see Disorders: Homeostatic Imbalances at the end of the chapter) in which self-molecules or cells

are attacked as though they were foreign.

Diversity of Antigen Receptors

An amazing feature of the human immune system is its ability to

recognize and bind to at least a billion (109) different epitopes.

Before a particular antigen ever enters the body, T cells and B cells that can recognize and respond to that intruder are ready and waiting. Cells of the immune system can even recognize artificially

made molecules that do not exist in nature. The basis for the ability

to recognize so many epitopes is an equally large diversity of antigen receptors. Given that human cells contain only about 35,000

genes, how could a billion or more different antigen receptors possibly be generated?

 The answer to this puzzle turned out to be simple in concept.

The diversity of antigen receptors in both B cells and T cells is

the result of shuffling and rearranging a few hundred versions of

several small gene segments. This process is called genetic recombination. The gene segments are put together in different combinations as the lymphocytes are developing from stem cells in red bone marrow and the thymus. The situation is similar to

shuffling a deck of 52 cards and then dealing out three cards. If you did this over and over, you could generate many more than 52 different sets of three cards. Because of genetic recombination, each B cell or T cell has a unique set of gene segments that

codes for its unique antigen receptor. After transcription and

translation, the receptor molecules are inserted into the plasma membrane.

Major Histocompatibility Complex Antigens

Located in the plasma membrane of body cells are “self-antigens,”

the major histocompatibility complex (MHC) antigens (his-toˉ-kom-pat-i-BIL-i-te¯). These transmembrane glycoproteins are also

called human leukocyte antigens (HLA) because they were first

identified on white blood cells. Unless you have an identical twin,

your MHC antigens are unique. Thousands to several hundred

thousand MHC molecules mark the surface of each of your body

cells except red blood cells. Although MHC antigens are the reason that tissues may be rejected when they are transplanted from one person to another, their normal function is to help T cells recognize that an antigen is foreign, not self. Such recognition is

an important first step in any adaptive immune response.

 The two types of major histocompatibility complex antigens

are class I and class II. Class I MHC (MHC-I) molecules are built

into the plasma membranes of all body cells except red blood

cells. Class II MHC (MHC-II) molecules appear on the surface of

antigen-presenting cells .

Pathways of Antigen Processing

For an immune response to occur, B cells and T cells must recognize that a foreign antigen is present. B cells can recognize and bind to antigens in lymph, interstitial fluid, or blood plasma. T cells only

recognize fragments of antigenic proteins that are processed and

presented in a certain way. In antigen processing, antigenic pro-teins are broken down into peptide fragments that then associate with MHC molecules. Next the antigen–MHC complex is inserted

into the plasma membrane of a body cell. The insertion of the complex into the plasma membrane is called antigen presentation.

When a peptide fragment comes from a self-protein, T cells ignore

the antigen–MHC complex. However, if the peptide fragment

comes from a foreign protein, T cells recognize the antigen–MHC

complex as an intruder, and an immune response takes place. Antigen processing and presentation occur in two ways, depending on

whether the antigen is located outside or inside body cells.