Immunology: Antigens and Immunogenicity

Antigens

• The immune system identifies foreign and self molecules as good or bad based on context.
• Antigens specifically interact with immunoglobulins (Ig) receptors on B-cells or T-cell receptors complexed with MHC.
• Immunogens are a subset of antigens that induce a specific immune response.

Immunogenicity

• Humoral immunogens stimulate B-cells and are mostly proteins.
• Cell-mediated immunogens stimulate T-cells and mainly consist of proteins, some lipids, and glycolipids.
• Four properties contribute to immunogenicity:
  • Foreignness: The greater the phylogenetic distance between the antigen and the host, the greater the immunogenicity.
  • Prolonged Exposure: Adjuvants like alum and Freund's adjuvant bind and precipitate antigens, prolonging exposure and enhancing immune response.
  • Co-stimulatory Signal: Adjuvants like LPS and Freund's adjuvant upregulate co-stimulatory signals, activating T-cells and amplifying the immune response.
  • Size and Complexity: Larger, more complex antigens are more likely to be immunogenic.

Epitopes

• Lymphocytes recognize specific sites on antigens called epitopes or antigenic determinants.
• B-cell epitopes must be accessible on the surface of native molecules, typically composed of 6-7 amino acids or sugars.
• T-cell epitopes are recognized only after antigen processing, presented within MHC molecules, and typically consist of peptides 7-20 amino acids long.

Antigen-Antibody Interactions

• Antigen-antibody interactions involve specific, reversible binding, driven by multiple non-covalent bonds.
• Affinity refers to the strength of interaction between a single antibody binding site and a single epitope.
• Avidity refers to the overall strength of multiple interactions between a multivalent antibody and antigen.

Antibody Isotypes

• Antibodies can undergo class switching, changing their isotype (e.g. IgM to IgG) without altering their variable regions.
• Class switching involves DNA rearrangement at the constant region of the antibody gene.
• The constant region determines the antibody's effector functions.

Vaccines

• Vaccines, derived from the Latin word for "cow" (vacca), were first used in the 12th century using smallpox pustules.
• Edward Jenner developed the first smallpox vaccine in 1798 using cowpox material.
• Louis Pasteur developed the first attenuated vaccines for cholera, anthrax, and rabies.
• Modern vaccines can be:
  • Inactivated (killed) vaccines: Contain killed pathogens or inactive toxins. Provide weaker and shorter-lived immunity than other types.
  • Subunit vaccines: Contain specific antigens or toxins. Can be produced through chemical extraction, recombinant DNA technology, or chemical synthesis.
  • Toxoid vaccines: Chemically modified bacterial toxins that are no longer toxic but still stimulate an immune response.
  • Engineered vaccines: "Trojan horse" approach using attenuated pathogens or other vectors (viruses/bacteria) to deliver antigens.
  • DNA/RNA vaccines: Introduce genetic material encoding antigens into the host.

Vaccine Development

• New vaccine development seeks to create safe and effective vaccines that trigger a robust immune response.
• Strategies include:
  • Designing vaccines that target conserved antigens.
  • Enhancing antigen presentation by incorporating adjuvant components.
  • Developing vaccines that elicit both antibody and T-cell responses.
• Vaccine development often focuses on addressing specific challenges like:
  • Antigenic diversity and variability of pathogens: Creating vaccines effective against multiple strains.
  • Safety concerns: Minimizing risks like allergic reactions or infection.

Explore the key concepts of antigens and immunogenicity in the immune system. This quiz covers the interaction between antigens and immune cells, the properties affecting immunogenicity, and how B-cells and T-cells respond to pathogens. Test your understanding of these fundamental principles in immunology.