Antigens. Bacterial Antigens. Bacterial antigens. Major antigens. Major

Histocompatibility Histocompatibility Complex.Complex.

Medical biology, microbiology, virology, immunology

department

The name antigens (Gk. anti against, genos genus) is given to organic substances of a colloid structure (proteins and different protein complexes in combination with lipids or polysaccharides) which upon injection into the body are capable of causing the production of antibodies and reacting specifically with them.

Antigenic substances must have certain properties: a colloid structure,

and solubility in the body fluids.

Antigenic properties are pertinent to

toxins of a plant origin (ricin, robin, abrin, cortin, etc.),

toxins of an animal origin (toxins of snakes, spiders, scorpions, phalangia, karakurts, bees),

enzymes, native foreign proteins, various cellular elements of tissues and

organs, bacteria and their toxins, rickettsiae and

viruses.

Antigens, consequently, are characterized by the following main properties:

1. the ability to cause the production of antibodies (antigenicity),

2. the ability to enter into an interaction with the corresponding antibodies (antigenic specificity).

The features of molecules that determine antigenicity and immunogenicity are as follows:

1.Foreignness. 2.Molecular Size. 3.Chemical-Structural

Complexity4.Antigenic Determinants (Epitopes)

Foreignness: In general, molecules recognized as "self” are not immunogenic; ie, we are tolerant to those self-molecules. To be immunogenic, molecules must be recognized as "nonself," ie, foreign.

Molecular Size: The most potent immunogens are proteins with high molecular weights, ie, above 100,000. Generally, molecules with molecujar weight below 10,000 are weakly immunogenic, and very small ones, eg, an amino acid, are nonimmunogenic. Certain small molecules, eg, haptens, become immunogenic only when linked to a carrier protein.

Chemical nature: Protein and polysaccharides are

most antigenic. Lipids and nucleic acids are less antigenic. Their antigenicity is enhanced by combination with proteins. A certain amount of chemical complexity is required, for example, amino acid homopolymers are less immunogenic than heteropolymers containing two or three different amino acids.

Antigenic Determinants (Epitopes): Epitopes are – small chemical groups on the antigen molecule that can elicit and react with antibody.

An antigen can have one or more determinants. Most antigens have many determinants; ie, they are multivalent.

Antigen epitopes

Antigen

epitopes

Hapten (incomplete antibody) is a molecule that cannot induce an immune response by itself but can react with specific antibody.

Nevertheless, haptens can induce a response if combined with larger molecules (normally proteins) which serve as carrier.

Haptens are usually small. Many drugs, eg, penicillins, are haptens, and the catechol in the plant oil that causes poison oak and poison ivy is a hapten.

hapten

No antibidiesproduced

Antibody againstepitope on antigen

protein

Immunogenic antigenepitope

epitopehapten

Immunogenic antigen as carier for hapten

Antibody againstepitope on antigen

Antibody againstepitope on hapten

A typical antigen:antibody reaction: gram-negative bacterial pathogen may have several antigens, or immunogens (flagella, pili and cell wall)

Antigenic structure of a bacterium

H

N

RNA

Protein М2

Protein М1

Lipid membrane

Antigenic structure of a virus

Antigenic properties of bacteria, toxins, rickettsiae and viruses, used in the practice of reproducing artificial immunity against infectious diseases, are of most practical importance.

When the antigenic structures of the host are similar to those of the causative agent, the macroorganism is incapable of producing immunity, as the result of which the disease follows a graver course. It is possible that in individual cases the carrier state and inefficacy of vaccination are due to the common character of the microbial antigens and the antigens of the person's cells.

It has been established that human erythrocytes have antigens in common with staphylococci, streptococci, the organisms of plague, E. coli. Salmonella paratyphi, Shigella organisms, smallpox and influenza viruses, and other causative agents of infectious diseases. Such a condition is called antigenic mimicry.

Isoantigens are those substances which have antigenic properties and are contained in some individuals of a given species. Isoantigens of leukocytes, blood platelets, lymphocytes, granulocytes, blood sera, liver, and kidneys and inter-organ (cell nuclei, mitochondria, ribosomes, etc.) and pathological (cancerous, bum, radiation) isoantigens have been revealed.

Isoantigens have been found in the erythrocytes of animals and man. At first it was established that in human erythrocytes there are two antigens (A and B), and in the sera — beta- and alpha-antibodies. Only heterogenic antigens and antibodies (agglutinins) can be found in human blood. On the basis of antigenic structure the erythrocytes of all people can be subdivided into 4 groups (A, B, AB and 0). These data are taken into account during blood transfusion.

Autoantigens are substances capable of immunizing the body from which they are obtained.

Self antigens are ordinarily non-antigenic, not normally found free in

circulation or tissue fluids, are not recognized as self

antigens.

Thus, they become modified and are capable of bearing an antigenic function.

Autoantigens

These substances include

the eye lens, spermatozoids, homogenates of the seminal

gland, skin, emulsions of kidneys, liver,

lungs and other tissues.

Autoantigens Under ordinary conditions they do

not come in contact with the immunizing systems of the body, therefore antibodies are not produced against such cells and tissues. However, if these tissues are injured, then autoantigens may be absorbed, and may cause the production of antibodies which have a toxic effect on the corresponding cells.

The origination of autoantigens is possible under the influence of

cooling, radiation, drugs (amidopyrine,

sulphonamides, preparations of gold, etc.),

virus infections "(virus pneumonias and mononucleosis),

acterial proteins and toxins of streptococci, staphylococci, tubercle bacilli, paraproteins,

aseptic autolysis of brain tissue, and other factors.

Histocompatibility antigens

There are the antigens present on the cells of each individual of species . These proteins are alloantigens; ie, they differ among members of the same species. These antigens are encoded by genes known as histocompatibility genes which collectively constitute major histocompatibility complex (MHC), These are located on the short arm of chromosome 6.

Major Histocompatibility Complex

MHC products present on the surface of leucocytes are known as human leukocyte antigens (HLA).

The success of tissue and organ transplants depends on the donor's and recipient's human leukocyte antigens (HLA). If the HLA proteins on the donor's cells differ from those on the recipient's cells, an immune response occurs in the recipient.

Major Histocompatibility Major Histocompatibility ComplexComplex

Three of these genes (HLA-A, HLA-B, and HLA-C) code for the class I MHC proteins. Several HLA-D loci determine the class II MHC proteins, ie, DP, DQ, and DR.

There are many alleles of the class I and class II genes. For example, there are at least 47 HLA-A genes, 88 HLA-B genes, 29 HLA-C genes, and more than 300 HLA-D genes, but any individual inherits only a single allele at each locus from each parent and thus can make no more than two class I and II proteins at each gene locus.

Expression of these genes is codominant, ie, the proteins encoded by both the paternal and maternal genes are produced. Each person can make as many as 12 HLA proteins: 3 at class I loci and 3 at class II loci, from both chromosomes. Between the class I and class II gene loci is a third locus, sometimes called class III. This locus contains several immunologically important genes, encoding two cytokines (tumor necrosis factor and lymphotoxin) and-two complement components (C2 and C4).

Class I MHC Proteins. These are glycoproteins found on the surface of virtually all nude ated cells. There are approximately 20 different proteins encoded by the allelic genes at the A locus, 40 at the B locus, and 8 at the C locus.

Class II MHC Proteins. These are glycoproteins found on the surface of certain cells, including macrophages, B cells, dendritic cells of the spleen, and Langerhans cells of the skin.

BIOLOGIC IMPORTANCE OF MHC The ability of T cells to recognize antigen is dependent on association of the antigen with either class I or class II proteins. For example, cytotoxic T cells respond to antigen in association with class I MHC proteins. Thus, a cytotoxic Tcell that kills a virus-infected cell will not kill a cell infected with the same virus if the cell does not also express the appropriate class I proteins.

BIOLOGIC IMPORTANCE OF MHCMHC genes and proteins are also important in two other medical contexts. One is that many autoimmune diseases occur in people who carry certain MHC genes, and the other is that the success of organ transplants is, in large part, determined by the compatibility of the MHC genes of the donor and recipient.

Disease HLA Frequency of an antigene at ill persons

of a presence at healthy persons

Antigene on which the

immune answer develops

Addison’s disease

DR5 70 20 Adrenal cortex

Behtyer’s disease

B27 89 9 Unknown

Hashimoto’s thyreoiditis

DR3, DR5

51 24 Thyroglobulin

Juvenile diabetes

DR3,

DR4 72 24 Insulin receptor

Rheumatoid arthritis

DR7,

DR21 59 21 Colagen, Fc

fragment of IgG

Narcolepsy DR2 100 34 Unknown

Goodpasture’s syndrom

DR2 88 29 Basement membrane of a kidney and lung