ANTIGENS

ByDEVI PRIYA SUGATHANMSC BIOCHEMISTRY AND

MOLECULR BIOLOGY

ANTIGENS Substances that are capable of

inducing specific immune response.

They can be recognized by the surface antibody(B cells) or by the T cell receptors when associated with MHC molecule.

They can bind specifically with the antibody or T- cell receptor.

CLASSIFICATION OF ANTIGENS

EXOGENOUS ANTIGENS Exogenous antigens are

those antigens which enter into the host body from their surroundings or external environments. These are basically of pollutants, microorganisms, pollens, drugs etc.

ENDOGENOUS ANTIGENS They are again classified onto –

Xeno-genic or Heterogenic antigens Allogenic or Idiotypic antigens Autologous antigens.

XENOGENIC ANTIGENS - Foreign items which are related with tissue transplantation and serology.

ALLOGENIC ANTIGENS - Foreign items which enter when an individual receives a blood transfusion or undergoes transplantation operation.

AUTOLOGOUS ANTIGENS - This group of antigens is very rare and unnatural. In normal condition, self-components are non-immunogenic in nature, but in an abnor mal condition self-body components are started to be considered as non-self or antigenic component.

IMMUNOGENICITY V/S ANTIGENECITY

Immunogenicity – Ability to induce a humoral or cell mediated immune response.

Antigenicity – Ability to combine specifically with the final products of humoral or cell mediated immune response.

All molecules possessing the property of immunogenicity also possess the property of antigenicity.

Some molecules that possess the property of antigenicity but lack immunogenicity is known as haptens.

FACTORS THAT INFLUENCE IMMUNOGENICITY.

Contribution of the Immunogen Foreignness Molecular size Chemical Composition Physical Form Degradability

Contribution of the biological system Genetic factors Age

Method of administration Dose Route Adjuvants

Contribution of the Immunogen

1. Foreignness The immune system normally discriminates between self and non-self such that only foreign molecules are immunogenic. When an antigen is introduced into an organism, the

degree of its immunogenicity depends on the degree of its

foreignness.

2. Molecular Size There is not absolute size above which a substance will be immunogenic. However, in general the larger the

molecule the more immunogenic it is likely to be. The best immunogens tend to have a molecular mass approaching 100,000 Da .The poor immunogens generally have a molecular size b/w 5000 – 10000 Da.

3.Chemical Composition In general, the more complex the

substance is chemically, the more immunogenic it will

be. The addition of aromatic amino acids like tyrosine or phenyalanine

to synthetic polymers can have a profound effect on immunogenicity. All four levels of protein can

contribute to the antigenic determininant and hence affect the immunogenicity.

4.Physical form In general particulate antigens are more immunogenic than soluble ones and denatured antigens more immunogenic than the native form.

5. Degradability Antigens that are easily

phagocytosed are generally more

immunogenic. This is because for most antigens the

development of an immune response requires that the

antigen be phagocytosed, processed and

presented to helper T cells by an antigen presenting cell

(APC).

Contribution of the biological system

1. Genetic Factors

Some substances are immunogenic in one species but not in another.

Similarly, some substances are immunogenic in one individual but not in others.

The species or individuals may lack or have altered genes that code for the receptors for antigen on B cells and T cells or they may not have the appropriate genes needed for the APC to present antigen to the helper cell.

2. Age Age can also influence immunogenicity. Usually the very young and the very old have

a diminished ability to mount and immune response to an immunogen.

Method of administration1. Dose

The dose of administration of an immunogen can influence its immunogenicity.

There is a dose of antigen above or below which the immune response will not be optimal.

An insufficient dose will not stimulate an immune response either because it fails to activate enough lymphocytes or because it induces a nonresponsive state.

An excessively high dose also can fail to induce a response because it causes lymphocytes to enter a non responsive state.

2. Route Intravenous : into a vein Intradermal : into the skin Subcutaneous : beneath the skin Intramuscular : into a muscle Intraperitoneal : into the peritoneal cavity

The administration route determines which immune organs and cell populations will be involved in the response.

Antigen administrated intravenously is carried first to the spleen, whereas antigen administrated subcutaneously moves first to local lymph nodes.

3. Adjuvants

Substances that are mixed with an antigen and injected with it, serve to enhance the immunogenicity of the antigen.

They are often used to boost the immune response when an antigen has low immunogenicity or when only small amounts of an antigen are available, limiting the immunizing dosage.

Aluminum potassium sulfate acts to increase antigen persistence.

When an antigen is mixed with alum, the salt precipitates the antigen. Injection of this alum precipitate results in a slower release of antigen from the injection site, so that the effective time of exposure to the antigen increases from a few days without adjuvant to several weeks with the adjuvant.

The alum precipitate also increases the size of the antigen, thus increasing the likelihood of phagocytosis.

Freund’s water-in-oil adjuvants also function to prolong antigen persistence.

FREUND’S INCOMPLETE ADJUVANT Contains antigen in aqueous solution; mineral oil, and an emulsifing

agent such as mannide monooleate, which disperses the oil into small droplets surrounding the antigen; the antigen is then released very slowly from the site of injection.

FREUNDS COMPLETE ADJUVANT Contains heat killed Mycobacteria in the water-in-oil emulsion. In

addition, a muramyl dipeptide component of the myobacterial cell wall activates macrophages. Activated macrophages are more phagocytic.

• Alum and both Freund’s adjuvants stimulate a local, chronic inflammatory response with an increase in phagocytic cells as well as lymphocytes.

• This cellular inflammatory at the site of the adjuvant injection often results in formation of a dense, macrophage rich mass of cells called a granuloma.

• Because the macrophages in a granuloma are activated, this mechanism also enhance TH – cell activation.

• Other adjuvants such as synthetic polyribonucleotides and bacterial lipopolysaccharides stimulate nonspecific lymphocyte proliferation and thus increase the likelihood of antigen-induced clonal selection of lymphocytes.

EPITOPES

• An antigen is the part of an antigen that is recognized by the immune system specifically by antibodies, B cells or T cells.

• They are also known as epitopes or antigenic determinants.

• B and T cell recognize different epitopes on the same antigenic molecule.

• In the case of protein antigens, an epitope may involve elements of the primary, secondary, tertiary and even quartenary structure of the protein.

• In the case of polysaccharide antigens, excessive side chain branching via glycosidic bonds affects the overall three dimensional conformation of individual epitopes.

• T and B cell exhibit fundamental difference in antigen recognition.

• B cells bind antigen that is free in solution, the epitopes they recognize tend to be highly accessible sites on the exposed surface of the immunogen.

• T cells only recognize processed peptides associated with MHC molecule on the surface of antigen presenting cell and altered self cells.

MITOGENS

• Mitogens are agents capable of inducing cell division in a high percentage of T or B cells.

• A mitogen can activate many clones of T or B cells irrespective of their antigen specificity. Hence they are also known as polyclonal activators.

• Several common mitogens are sugar binding proteins called lecithins which bind specifically to different glycoproteins on the surface of various cells including lymphocytes.

• Binding of lectin molecules to membrane glycoproteins often leads to agglutination, or clustering of the cells which may trigger cellular activation and proliferation.

• Some mitogens preferentially activate B cells, some preferentially activate T cells and some activate both populations.

• Three common lectins with mitogenic activity are concanavalin A, phytohemagglutinin(PHA), and pokeweed mitogen (PMW).

• The lipopolysaccharide component of the gram negative bacterial cell wall functions as a B cell mitogen.

• The mitogenic activity of LPS is due to its lipid moiety, which is thought to interact with the plasma membrane, resulting in a cellular activation signal.

Superantigens They are the most potent T-cell mitogens

known. Superantigens bind to residues in the

V(variable) domain of the T-cell receptor and to residues in Class II MHC molecule outside of the antigen-binding cleft.

In this way a superantigen can cross-link a T cell to a Class II MHC molecule even when the TCR does not recognize the bound antigenic peptide, leading to activation of the T cell.

Thus a superantigen can activate all T cells expressing the V domain to which that superantigen binds.

Common superantigens include the staphylococcal enterotoxins(Ses) and toxic shock syndrome toxin(TSS1), which is produced by the gram positive bacterium Staphylococcal aureus.