🛡️Immunobiology Unit 3 – Antigens and Antibodies

What Are Antigens?

• Antigens are substances capable of eliciting an immune response and interacting with the products of that response (antibodies or T-cell receptors)
• Can be proteins, polysaccharides, lipids, or nucleic acids from various sources (bacteria, viruses, or even within the body)
• Antigens possess specific molecular structures called epitopes recognized by antibodies or T-cell receptors
• Epitopes are the specific regions on an antigen where antibodies or T-cell receptors bind
• Antigens can be classified as exogenous (originating from outside the body) or endogenous (originating from within the body)
• Exogenous antigens include pathogenic microorganisms (bacteria, viruses) and foreign substances (toxins, allergens)
• Endogenous antigens arise from within the body and include self-antigens (normal cellular components) and altered self-antigens (tumor cells, infected cells)

Types of Antigens

• T-dependent antigens require T-cell help to stimulate antibody production by B-cells (most proteins)
• T-independent antigens can directly stimulate B-cells without T-cell help (polysaccharides, lipids)
  • Type 1 T-independent antigens are mitogenic and polyclonally activate B-cells (lipopolysaccharide)
  • Type 2 T-independent antigens have repetitive epitopes that cross-link B-cell receptors (bacterial capsular polysaccharides)
• Immunogens are substances capable of eliciting an adaptive immune response
• Haptens are small molecules that can bind to antibodies but cannot elicit an immune response on their own
  • Haptens become immunogenic when conjugated to a larger carrier molecule (proteins)
• Superantigens are bacterial or viral proteins that non-specifically activate T-cells by binding to MHC class II molecules and T-cell receptors (toxic shock syndrome toxin)

Antibody Structure and Function

• Antibodies (immunoglobulins) are Y-shaped glycoproteins produced by B-cells in response to antigens
• Consist of two identical heavy chains and two identical light chains connected by disulfide bonds
• Heavy chains determine the class of antibody (IgG, IgM, IgA, IgE, or IgD)
• Light chains can be either kappa or lambda type
• Antibodies have a variable region (Fab) that binds to antigens and a constant region (Fc) that mediates effector functions
  • Variable regions contain hypervariable regions (complementarity-determining regions) that form the antigen-binding site
• Effector functions of antibodies include neutralization of toxins and viruses, opsonization of pathogens for phagocytosis, and activation of complement

Antibody Classes and Their Roles

• IgG is the most abundant antibody class in serum and provides long-term immunity
  • Crosses the placenta to provide passive immunity to the fetus
  • Activates complement and promotes opsonization and phagocytosis of pathogens
• IgM is the first antibody produced during an immune response and forms pentamers
  • Efficient at activating complement due to its pentameric structure
  • Important in the early defense against blood-borne pathogens
• IgA is the main antibody class in secretions (saliva, tears, breast milk) and protects mucosal surfaces
  • Exists as a dimer in secretions and neutralizes toxins and pathogens
  • Prevents the attachment of pathogens to mucosal surfaces
• IgE is involved in allergic reactions and defense against parasites
  • Binds to mast cells and basophils, triggering the release of inflammatory mediators (histamine)
  • Mediates hypersensitivity reactions (anaphylaxis) and provides protection against helminths
• IgD is expressed on the surface of naive B-cells and acts as a receptor for antigens
  • Role in B-cell activation and regulation is not fully understood

Antigen-Antibody Interactions

• Antigen-antibody interactions are highly specific and involve non-covalent bonds (hydrogen bonds, van der Waals forces, electrostatic interactions, hydrophobic interactions)
• Affinity refers to the strength of the interaction between a single antigen-binding site and an epitope
  • Determined by the complementarity of the antigen-binding site to the epitope
  • High-affinity antibodies bind strongly to their specific antigen
• Avidity refers to the overall strength of the interaction between an antibody and an antigen
  • Depends on the affinity of individual antigen-binding sites and the valency of the antibody (number of antigen-binding sites)
  • Multivalent antibodies (IgM) have higher avidity than monovalent antibodies (IgG)
• Cross-reactivity occurs when an antibody recognizes similar epitopes on different antigens
  • Can lead to false-positive results in diagnostic tests or autoimmune reactions

Immune Response to Antigens

• Innate immune response provides immediate, non-specific defense against pathogens
  • Includes physical barriers (skin, mucous membranes), chemical barriers (enzymes, pH), and cellular components (neutrophils, macrophages, natural killer cells)
  • Recognizes pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (toll-like receptors)
• Adaptive immune response is specific to the antigen and develops over time
  • Humoral immunity involves the production of antibodies by B-cells
  • Cell-mediated immunity involves the activation of T-cells (CD4+ helper T-cells and CD8+ cytotoxic T-cells)
• Antigen presentation is crucial for the activation of T-cells
  • Antigen-presenting cells (dendritic cells, macrophages, B-cells) process and present antigens on MHC molecules
  • MHC class I presents intracellular antigens to CD8+ T-cells, while MHC class II presents extracellular antigens to CD4+ T-cells
• Clonal selection and expansion of antigen-specific B-cells and T-cells occur in secondary lymphoid organs (lymph nodes, spleen)
  • Leads to the generation of memory B-cells and T-cells, providing long-lasting immunity

Clinical Applications

• Vaccines exploit the specificity of the adaptive immune response to generate protective immunity against pathogens
  • Attenuated vaccines contain weakened live pathogens (MMR vaccine)
  • Inactivated vaccines contain killed pathogens (polio vaccine)
  • Subunit vaccines contain specific antigens from the pathogen (hepatitis B vaccine)
• Monoclonal antibodies are produced by a single clone of B-cells and are specific to a single epitope
  • Used in the diagnosis and treatment of diseases (cancer, autoimmune disorders)
  • Examples include rituximab (anti-CD20) for B-cell lymphomas and infliximab (anti-TNF) for rheumatoid arthritis
• Serological tests detect the presence of specific antibodies in serum
  • Used to diagnose infections (HIV, hepatitis) or autoimmune diseases (systemic lupus erythematosus)
  • Examples include enzyme-linked immunosorbent assay (ELISA) and western blot
• Immunodeficiencies can result from genetic defects or acquired conditions (HIV/AIDS)
  • Characterized by increased susceptibility to infections and impaired immune responses
  • Treatment involves immunoglobulin replacement therapy or hematopoietic stem cell transplantation

Key Takeaways and Future Directions

• Antigens are substances that elicit an immune response and interact with antibodies or T-cell receptors
• Antibodies are glycoproteins produced by B-cells that recognize specific epitopes on antigens
• Antigen-antibody interactions are highly specific and involve non-covalent bonds
• The immune response to antigens involves both innate and adaptive components
  • Innate immunity provides immediate, non-specific defense
  • Adaptive immunity is specific to the antigen and generates memory B-cells and T-cells
• Clinical applications of antigen-antibody interactions include vaccines, monoclonal antibodies, serological tests, and the diagnosis and treatment of immunodeficiencies
• Future research directions include the development of more effective vaccines against emerging pathogens (COVID-19)
• Personalized immunotherapy approaches targeting specific antigens in cancer and autoimmune diseases
• Understanding the role of the microbiome in shaping the immune response to antigens
• Exploring the potential of mRNA vaccines and their ability to elicit robust immune responses