unit 3 review
Antigens and antibodies are key players in our immune system's defense against pathogens. Antigens, which can be proteins, polysaccharides, or other molecules, trigger immune responses. Antibodies, produced by B-cells, specifically recognize and bind to antigens, neutralizing threats.
The immune system's response to antigens involves both innate and adaptive components. Innate immunity provides quick, non-specific defense, while adaptive immunity develops targeted responses. This interplay leads to the production of memory cells, enabling long-lasting protection against future infections.
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