Antigens, Epitopes, and Haptens

• Antigens are foreign substances that stimulate a specific immune response by B and/or T cells, also known as immunogens.

Epitopes

• The immune system reacts to smaller parts of the antigen molecule, known as epitopes or antigenic determinants, rather than the whole molecule.
• Epitopes are limited parts of the whole antigen and are very small, consisting of 4-5 amino acids or monosaccharides.
• They determine the specificity of the antigen, and one antigen may have many different epitopes.
• Antigen binding to the antibody binding site is like a "lock and key" situation.

Hapten

• A hapten is a low molecular weight substance that cannot stimulate an immune response alone.
• When coupled with a carrier molecule (protein), it can act as an antigen, for example, penicillin.

Factors influencing antigenicity

• Foreignness: Immunogen must be foreign because of auto-tolerance to its own components.
• Molecular size: Antigenicity is directly proportional to molecular size.
• Small molecules are usually not immunogenic, e.g., amino acids.
• Chemical nature: Proteins are the most potent antigens. Polysaccharides, lipoproteins, and lipopolysaccharides are antigenic of high molecular weight. Nucleic acids and lipids are non-antigenic.
• Method of administration of antigen: Repeated booster doses lead to a strong immune response.
• Parenteral routes (S.C, I.M) are better than oral routes as they induce a stronger immune response.
• Adjuvant: A non-antigenic substance (stimulator) mixed with an antigen before administration to increase the immune response.
• Host genetic factors: Individuals within a species will not show the same response to an antigen, where some are strong responders and others are weak.

Types of antigens

• According to cell type: Bacterial antigens, viral antigens, parasitic antigens, and human tissue antigens (isoantigens).
• According to the mechanism of stimulation: Classic antigen and superantigen.
• According to the specificity of the antigen: Specific antigen and heterophile antigen.
• Autoantigens and thymus-independent antigens.

Bacterial Antigens

• Soluble antigens are products excreted into the environment, e.g. exotoxins, enzymes.
• Cellular antigens such as capsular antigens (C or K), flagellar antigens (H), and somatic or "O" antigens.

Viral Antigens

• Viral capsid and VAP (viral attachment proteins) antigens

Human Tissue Antigens

• Blood group antigens: A and B + Rh on red cells
• Histocompatibility antigens: Molecules are present on the membrane of tissue cells.
• Human leukocyte antigens (HLA) or major histocompatibility complex (MHC) antigens.
• Types of histocompatibility antigens: Class I, Class II, and Class III.

Types of Histocompatibility Antigens

• Class I: Present on all nucleated cells
• Class II: Present on antigen-presenting cells (APCs), e.g., B cells, macrophages, dendritic cells, and activated T cells.
• Class III: Involved in the production of complement components.

MHC significance

• Organ transplantation and graft rejection.
• Paternity testing and forensic investigations.
• Disease association, e.g., HLA-DR4 with rheumatoid arthritis.
• MHC restriction.

Classic Antigens

• Classic antigens must bind to T cell receptors.

Superantigens (SAgs)

• These antigens are capable of activating large numbers of T cells non-specifically.
• Superantigens bind to class II MHC molecules on APCs and the TCR Vβ chain on Th cells outside the peptide binding groove (Clamp).
• They activate a large percent of T cells expressing a particular Vβ chain, resulting in a large amount of cytokines.
• Superantigens can cause systemic toxicity and suppression of the immune response.
• Staphylococcal enterotoxins, staphylococcal toxic shock syndrome toxins, streptococcal pyrogenic exotoxin, and some viral proteins are examples of superantigens.

Differences Between Classic Antigens and Superantigens

• Classic antigens are processed in APCs, whereas Superantigens are not processed.
• Classic antigens bind to variable regions of both α and β chains of TCR, while Superantigens bind to the variable region of the β chain only of TCR.
• Classic antigens cause specific activation of T cells, whereas Superantigens cause non-specific activation of T cells.
• Classic antigens release the required level of cytokines, while Superantigens release very high harmful levels.

Cross-Reactive (Heterophil) Antigens

• Antigens that share one or more similar epitopes.

Heterophil Antigen

• Heterophil antibodies and heterophil antigens are known as cross-reactivity.
• In acute rheumatic fever, antibodies produced against Streptococcus pyogenes M protein cross-react with cardiac muscle proteins, leading to rheumatic carditis and valve destruction.

Auto-Antigens

• The immune system can normally discriminate self from non-self antigens.
• Antibodies directed against the individual's own proteins (auto-antigens) are called autoantibodies, which cause many autoimmune diseases.

Thymus Independent Antigens

• Thymus-independent antigen is an immunogen that can stimulate B cells to produce antibodies without T cell help.