BIOL412 W4-Antigen and Antibody

Antibodies & Antigens

Author: Asst. Prof. Dr. Deniz BalciContact: deniz.balci@emu.edu.tr

Outline

  • Antibody Structure (pg. 88-95)

  • Antigen Structure (pg. 99-101)

  • Structure-function Relationships In Antibody Molecules (pg. 102-105)Source: AK. Abbas, 10th edition, Chapter 5

Definition of Antigen

Antigen: Any substance provoking an adaptive immune response, including:

  • Immunogens: Induce specific immune responses.

  • Tolerogens: Induce non-responsiveness.

  • Haptens: Small molecules that become immunogenic when bound to carrier proteins.

  • Mitogens: Stimulate cell division.

Immunogens

Immunogen: Induces specific immune response; common ones include proteins, polysaccharides, and bacterial components. Non-microbial examples: pollen, egg white, transplanted proteins. Larger immunogens typically elicit stronger responses.

Features of a Good Immunogen

  • Chemical Complexity: Heteropolymers more immunogenic than homopolymers.

  • Size: Molecules >10,000 Daltons are more immunogenic.

  • Chemical Composition: Proteins are more immunogenic than carbohydrates and lipids.

  • Difference from Self-Antigens: Greater differences enhance immunogenicity.

  • Dosage and Administration Route: Routes influence response strength.

  • Adjuvants: Enhance response and prolonged immunity.

  • Genetic Composition: Genetic factors impact susceptibility to antigens.

Epitopes

Epitopes: Small groups on antigens that elicit immune responses; can be linear or conformational.

Immunogenicity Variance

Antigen complexity affects immunogenicity:

  • Small Simple Antigens: Less immunogenic.

  • Multivalent Antigens: Intermediate immunogenicity.

  • Univalent Antigens: Strongest immunogenic response.

  • Polyvalent Antigens: Stronger responses with multiple unique epitopes.

Characteristics of Antigens

  • Foreignness: Self molecules are non-immunogenic.

  • Molecular Size: Small foreign molecules are weakly immunogenic unless conjugated.

Tolerogens

Tolerogen: Induces immune system non-responsiveness; can become immunogenic with modifications. Associated with allergies and autoimmunity.

Allergens

Allergen: Specific tolerogen triggering allergic reactions via various exposure routes.

Autoantigens

Autoantigen: Normal proteins recognized by autoimmune immune systems, leading to self-tissue attacks due to loss of tolerance.

Antigen Recognizing Molecules

Features of Antigen Binding:

  • Antigen-binding Molecules: Includes Immunoglobulin (Ig), T cell receptors (TCR), and Major Histocompatibility Complex (MHC).

  • Binding Sites: Comprised of Complementarity Determining Regions (CDRs) facilitating specific binding.

Subtypes of Antigens

  • T Cell Dependent: Require T cell help for B cell activation, typically protein antigens.

  • T Cell Independent: Direct B cell activation without T cell help, usually involving polysaccharides and lipids.

Types of T-independent and T-dependent Antigens

T-independent: Polysaccharides and lipids that induce polyclonal B cell activation.T-dependent: Primarily proteins needing T cell help for effective responses.

Recognition by T Cell Receptor (TCR)

TCR: Recognizes peptides associated with MHC; distinguishes between helper T cells (MHC class II) and cytotoxic T cells (MHC class I).

Superantigens

Superantigens: Activate many T cells rapidly, potentially leading to pathogenic inflammation (e.g., cytokine storms).

Antigenic Determinants

T Cell Recognition: Processed protein fragments recognized by TCR bound to MHC; optimal size: 8-15 residues.B Cell Recognition: Epitopes include proteins, polysaccharides, and nucleic acids.

Functions of Antibodies

Antibodies mediate immune responses through:

  • Complement Activation

  • Pathogen Neutralization

  • Opsonization

  • Oxidative Burst

  • Agglutination

  • Antibody-dependent Cellular Cytotoxicity (ADCC)

Classes of Antibodies

  • IgM: First produced, pentameric form, short half-life (5 days).

  • IgG: Most common, long-lasting (23 days), crosses placenta.

  • IgA: Found in secretions, half-life around 6 days.

  • IgE: Involved in allergies, short half-life (2 days).

  • IgD: Naïve B cell receptor, half-life ~3 days.

Antibody Structure

Composed of light and heavy chains with:

  • Fab: Variable region binding to antigens.

  • Fc: Constant region mediating effector functions.

Complementarity Determining Regions (CDRs)

Concentrated variability in hypervariable regions essential for antigen binding, composed of CDR1, CDR2, and CDR3.

Levels of Variation in Immunoglobulins

  • Isotypes: Heavy chain variations.

  • Allotypes: Genetic polymorphisms among individuals.

  • Idiotypes: Unique determinants from hypervariable regions specific to B cell clones.

Antibodies Classes and Subclasses

Divided by heavy chain structure for specific antigen binding and functionality.

Membrane vs. Secreted Forms

  • Secreted: Hydrophilic for systemic responses.

  • Membrane: Hydrophobic for B cell activation.

Antigen Binding Sites

Different conformations influence binding strength and specificity.

Factors Affecting Ag/Ab Reactions

  • Affinity: Strength of antigen-antibody attachment.

  • Avidity: Overall interaction strength.

  • Ag:Ab Ratio: Affects binding dynamics.

Cross Reactivity

Ability of antibodies to react with multiple antigens due to similar epitopes, relevant in autoimmune conditions.

From B Cell to Plasma Cell

Involves increased immunoglobulin production and heavy chain isotype switching for tailored immune responses.

Features Related to Effector Functions

Changes in structure improve recognition, neutralization, and enable isotype switching during immune responses.

Conclusion

Acknowledgment of contributors and reference to AK. Abbas, 10th edition, Chapter 6.