Study Notes on Antigens and Antibodies

Antigens

  • Definition of Antigen
      - An antigen is a part of a molecule that can induce the living body to form specific antibodies or elicit T cell responses that recognize their presence in the body.   - Antigens are made up of complex molecules including:
        - Proteins
        - Peptides
        - Polysaccharides
        - Occasionally, nucleic acids and lipids combined with carrier proteins or polysaccharides can evoke immune responses.
      - Other names:
        - Immunogens
        - Allergens

  • Properties and Roles of Antigens
      - Antigens can be found on the surface of various pathogens including viruses, fungi, bacteria, and other cells.
      - They form part of the coats, capsules, cell walls, flagella, fimbriae, and toxins of these pathogens.

Properties of Antigens influencing Immunogenicity

1. Foreignness

  • An antigen should differ significantly from the body's own molecules to induce an immune response.

  • Example: When a pathogen infects the human body, antibodies recognizing the antigen of that pathogen begin to increase in the blood.

  • The difference in the capacity of foreign molecules to stimulate an immune response is termed immunogenicity.

2. Molecular Size

  • Antigens must have a minimum molecular weight of 8-10 kDa to act effectively; optimal stimulators are in the range of 14 kDa to 600 kDa.

  • Molecules smaller than 8 kDa result in a weaker immune response.

  • Example: Serum albumin from mammals (69 kDa) is effective, while hormone angiotensin (1031 Da) is a poor antigen.

3. Chemical Nature and Composition

  • Molecules with complex structures are generally more immunogenic than simple molecules.

  • Types of immunogenic molecules include:     - Polymers made up of proteins, polysaccharides, lipids, and nucleotides.     - Molecules containing aromatic radicals are presumed to have greater immunogenicity.   - Example: Complex bacterial lipopolysaccharides (LPS) function as good antigens.

4. Physical Form

  • Soluble antigens exhibit decreased immunogenicity compared to particulate antigens.

  • Denatured molecules often become more immunogenic than their native forms.

5. Antigen Specificity

  • Unique sites on antigens provide their unique characteristics, known as Antigenic Determinants or Epitopes, which form bonds with antibodies.

  • Antigens can have one or multiple epitopes.

6. Species Specificity

  • Each species has specific antigens leading to unique immune responses when introduced to another species; human blood proteins can be differentiated from animal proteins through antigen-antibody reactions.

7. Organ Specificity

  • Some antigens are unique to a specific organ, and they can sometimes be found in similar organs of different species.

8. Auto Specificity

  • Typically, antigens from self-tissues do not provoke immune response; however, in disease, they may elicit response and result in auto-antibodies, called autoantigens.

9. Genetic Factors

  • Species exhibit varied responses to antigens due to genetic diversity affecting the capacity to mount an immune response against the molecule.

  • Individuals may possess absent or altered genes coding for receptors on B and T cells.

10. Age

  • The ability to generate immune responses is age-dependent; children and elders have lesser immunogenic power compared to younger adults.

11. Degradability

  • Antigens that are easily phagocytosed trigger better immune responses because the immune response requires that antigens be processed and presented to helper T cells by antigen-presenting cells (APCs).

  • Inert molecules, such as dust, can lead to allergic reactions rather than immunogenic responses.

12. Dose of the Antigen

  • The immune response varies depending on the dose of the antigen; either too low or too high doses fail to elicit optimal responses, only appropriately dosed antigens do so.

13. Route of Administration

  • Antigens can be administered via various routes (intravenous, subcutaneous, intradermal), with subcutaneous/intradermal routes eliciting better responses.

  • Intravenously administered antigens go to the spleen first, whereas subcutaneously administered antigens initially reach local lymph nodes.

14. Adjuvants

  • Molecules that are non-immunogenic on their own but enhance immune responses when combined with antigens are known as adjuvants.

  • Example: Aluminum hydroxide, commonly used to improve vaccine effectiveness.

Types of Antigens

  • Antigens can be classified based on specificity, origin, and functionality.

Classification based on Origin

Exogenous Antigens

  • Antigens entering the body from external sources via ingestion, inhalation, or injection.

  • Non-self antigens, present with MHC Class II molecules.

  • Examples: Bacteria, viruses, allergens (e.g., pollen).

Endogenous Antigens

  • Antigens originating from within the cell through normal metabolism or products of cellular metabolism.

  • Self or non-self, presented with MHC class I molecules.

  • Examples: By-products of normal metabolism, blood group antigens.

Alloantigens

  • Found only in some members of a species; can trigger immune responses in others.

  • Examples: Blood group antigens (A, B) and histocompatibility antigens.

Autoantigens

  • Recognized as self by the immune system under normal conditions but provoke responses in autoimmune disorders.

  • Examples: Nucleic acids, nucleoproteins.

Super Antigens

  • Can evoke nonspecific T cell responses bypassing normal antigen processing.

  • Often produced by viruses and bacteria, leading to potent immune responses.

  • Examples: Staphylococcal enterotoxins, streptococcal pyrogenic exotoxins.

Classification based on Function

  • Complete Antigens: Can elicit an immune response independently (immunogens).

  • Incomplete Antigens (Haptens): Require binding to carrier proteins to elicit immune responses.

Antibodies

Structure of Antibodies (Immunoglobulins)

  • Composed of four polypeptide chains: two identical heavy chains and two identical light chains linked by disulfide bonds, resulting in a Y-shaped structure.

  • Variable Region: Composed of 100-110 amino acids showing variability among immunoglobulins (Fab fragment).

  • Constant Region: Defines the class of antibody; composed of light chain constant region (CL) and heavy chain constant region (CH) with variation in amino acid composition.

  • Hinge Region: Present between heavy chain segments CH1 and CH2, providing flexibility to the Fab arm.

Types of Immunoglobulins

  • Classified into five major categories based on properties:  

  •  1. IgG
         - Largest group (80%); γ-type heavy chain; half-life 20-21 days; binding valency of 2.   

  • 2. IgM
         - γ-type heavy chain; highest binding valency (5-10); half-life ~5 days; comprises 5-10% of total antibodies.

  •   3. IgA
          - Second largest group (10-15%); found in secretions; half-life ~6 days; binding valency of 2.   

  • 4. IgE
          - Rarest group (0.002%); half-life of 2-3 days; involved in allergic reactions and antiparasitic defense.

  •   5. IgD
          - Very low concentration (0.2%); half-life of 3 days; involved in activating basophils and mast cells.

Functions of Antibodies

  • Facilitates humoral immune response, protects against extracellular pathogens, and toxins. Can be transferred for passive immunity.

  • Functions include:
        1. Neutralization: Prevents pathogen from entering host cells.     2. Opsonization: Antibodies enhance phagocytosis by binding to pathogens and phagocytic cells.     3. Complement Fixation: Antibodies fix complement proteins, forming membrane attack complexes and initiating inflammation.     4. ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity): Antibodies recruit cytotoxic cells like NK cells.

Affinity, Avidity, and Cross Reactivity

Affinity

  • Refers to the strength of a single antigen-antibody interaction—high specificity for the target.

Avidity

  • Describes the total strength of binding interactions (cumulative effect) demonstrating the overall stability of the complex.

Cross Reactivity

  • Measures similarity between different antigens relating to immune reactions; important for understanding antigenic variation.

Monoclonal and Polyclonal Antibodies

Monoclonal Antibodies

  • Generated from a single B cell clone targeting a specific epitope of an antigen.

  • Advantages: High specificity and affinity; widely used in therapy and diagnostics.

Polyclonal Antibodies

  • Consist of mixtures of antibodies targeting various epitopes; common in naturally occurring immune responses or vaccination.

Summary of Key Points

  • Antigens are critical components that stimulate immune responses and can vary widely in properties and specificity.

  • The structure and function of antibodies play integral roles in mediating immune responses and formulating therapeutic interventions.

  • Understanding the mechanisms involved with antibodies, including affinity and avidity, enhances insights into immune system dynamics and antibody efficacy in applications.