BIOL412 W4-Antigen and Antibody
Page 1: Title Page
Title: Antibodies & Antigens
Professor: Asst. Prof. Dr. Deniz Balci
Email: deniz.balci@emu.edu.tr
Page 2: Course Outline
Contents:
Antibody Structure (pg. 88-95)
Antigen Structure (pg. 99-101)
Structure-function Relationships In Antibody Molecules (pg. 102-105)
Reference: AK. Abbas, 10th edition, Chapter 5
Page 3: Definition of Antigens
Antigen: Any substance capable of provoking an adaptive immune response (e.g., antibody production or T cell response).
Immunogens
Tolerogens
Haptens
Mitogens
Page 4: Immunogen Characteristics
Immunogen: Induces a specific immune response; phenomenon known as immunogenicity.
Examples include:
Proteins, polysaccharides, bacterial components (coats, capsules, etc.)
Lipids and nucleic acids are antigenic only when combined with proteins or polysaccharides.
Non-microbial (exogenous) antigens, e.g., pollen, egg white, proteins from transplanted tissues.
Page 5: Features of a Good Immunogen
Key Factors Influencing Immunogenicity:
Chemical-Structural Complexity: Heteropolymers are more immunogenic than homopolymers.
Size: Large molecules > Small molecules
Chemical Composition: Proteins > Carbohydrates > Lipids
Similarity to Self-Antigens: Greater differences are more immunogenic.
Dosage and Route of Administration:
Subcutaneous > Oral
Use of Adjuvants: Increase titer and affinity.
Genetic Composition: Major Histocompatibility Complex (HLA) affects immunogenicity.
Page 6: Epitopes
Epitopes: Small chemical groups on antigen molecules that can elicit an immunological response.
Antigens can have multiple epitopes, each recognized by different antibodies.
Page 7: Variability of Antigens
Immunogenicity:
Small, simple antigens are less immunogenic.
**Types:
Multivalent:** Contain repeating epitopes; moderate immunogenicity.
Univalent: Few epitopes; the least immunogenic.
Polyvalent: Many different epitopes; most immunogenic.
Page 8: Characteristics of Antigens
Foreignness: Non-self molecules are immunogenic.
Molecular Size:
High molecular weight (>10,000 D) is usually required for immunogenicity.
Haptens are small molecules that must be linked to a carrier to be recognized by antibodies.
Examples of Haptens: Cortisol, Estradiol, Testosterone, Thyroid hormones, Penicillin.
Page 9: Tolerogens
Tolerogen: An antigen that induces specific immune non-responsiveness.
Changes in its molecular form can result in it becoming an immunogen.
Related to allergies, autoimmunity, and transplant rejections.
Page 10: Allergens
Allergen: A substance causing allergic reactions.
Reactions can occur via ingestion, inhalation, injection, or skin contact.
Page 11: Autoantigens
Autoantigen: Normal proteins (and sometimes nucleic acids) that trigger an immune response in autoimmune diseases.
These are usually ignored by the immune system but can trigger responses due to genetic and environmental factors.
Page 12: Antigen-Recognizing Molecules
Table 5-1: Features of Antigen Binding
Immunoglobulin (Ig) and T Cell Receptor (TCR):
Composed of CDRs (Complementarity Determining Regions).
MHC Molecules:
Peptide-binding clefts important for presenting antigens to T cells.
Nature of Antigens:
Macromolecules (proteins, lipids, carbohydrates) and small chemicals interact differently with immune receptors.
Page 13: Subtypes of Antigens
Types:
T Cell Dependent
T Cell Independent
Page 14: Types of T Cell Independent Antigens
Characteristics:
Include polysaccharides and lipids.
Examples: Pneumococcal polysaccharide, lipopolysaccharide.
Induce antibody production without T cell help.
Page 15: Types of T Cell Dependent Antigens
Characteristics:
Primarily proteins with numerous antigenic determinants.
Require T lymphocytes for antibody production.
Examples: Microbial proteins, non-self proteins.
Page 16: Recognition by T Cell Receptor
Recognition:
TCRs recognize only peptide fragments presented by MHC molecules.
Helper T Cells (Th): Recognize peptides associated with MHC class II.
Cytotoxic T Cells (Tc): Recognize peptides associated with MHC class I.
Page 17: Superantigens
Definition:
Proteins produced by pathogens that can activate a large number of T cells without processing.
Can lead to “cytokine storms” with pathological effects.
Examples: Staphylococcal enterotoxins, toxic shock toxin.
Page 18: Antigenic Determinants for T Cells
Composition: Primarily proteins; can also involve lipids.
Recognized epitopes must be processed (linear epitope) for MHC presentation.
Epitopes range from 8-15 residues in size.
Page 19: Antigenic Determinants for B Cells
Composition: Proteins, polysaccharides, nucleic acids, small chemicals.
Epitopes:
Sequence (linear) determinants
Conformational determinants must be accessible on the surface of antigens.
Epitopes are typically 4-8 residues in size.
Page 20: Functions of Antibodies
Antibodies Mechanisms:
Activation of complement and inflammation
Neutralization of pathogens
Opsonization for better phagocytosis
Killing through oxidation
Agglutination and antibody-dependent cellular cytotoxicity (ADCC).
Page 21: Classes of Antibodies
Five Classes: Based on differences in heavy chain structures.
IgM: First produced; half-life: 5 days
IgG: Most common; half-life: 23 days
IgA: Associated with secretions; half-life: 6 days
IgE: Involved in allergic responses; half-life: 2 days
IgD: Naive B cell receptor; half-life: 3 days
Page 22: Antibody Structure
Composition: Comprised of two identical light chains and two identical heavy chains.
Contains variable (V) regions for antigen recognition and constant (C) regions for effector functions.
Fab: Fragment for antigen binding
Fc: Fragment for crystallization and effector functions.
Page 23: Complementarity Determining Regions (CDRs)
Overview: Variability among antibodies is primarily found in the CDRs of the light and heavy chains.
CDRs facilitate the specific binding to antigens.
Types: CDR1, CDR2, and CDR3; the most variable regions.
Page 24: Conformational and Linear Antigenic Determinants
Details:
Antigenic determinants can be conformational (3D shape) or linear (sequential amino acids).
Denaturation of proteins can affect epitope recognition.
Page 25: Levels of Variation in Immunoglobulins (Igs)
Isotypes: Differences in the constant regions of heavy chains.
Allotype: Genetic differences in immunoglobulin chains among individuals.
Idiotype: Variation in specific amino acids in hypervariable regions of antibodies.
Page 26: Antibodies Classes and Hinge Region
Overview: Antibody classes are differentiated based on structure of heavy chain C regions.
Hinge Region: Provides flexibility, allowing antibodies to bind a variety of antigens effectively.
Page 27: Membrane and Secreted Forms of Ig
Characteristics:
Secreted form: Hydrophilic, found in blood and extracellular fluids.
Membrane-bound form: Hydrophobic, forms part of the B cell receptor.
Page 28: Antigen Binding Sites
Details: Antigens can bind to pockets, grooves, or extended surfaces within antibodies.
Epitope: The specific structure on the antigen recognized by the antibody.
Page 29: Factors Affecting Antigen-Antibody Reactions
Key Factors:
Affinity: Strength of attachment between epitope and antibody-binding site.
Avidity: Overall strength of attachment.
Ag:Ab Ratio: Influences reaction strength.
Interaction: Maintained by non-covalent binding.
Page 30: Valency and Avidity of Antibody Interactions
Valency: Number of binding sites on an antibody molecule.
Pentameric IgM has 10 identical antigen-binding sites, maximizing interaction.
Page 31: Cross Reactivity
Definition: Ability of an antibody to react with multiple antigens or epitopes.
Shared epitope: Recognized by multiple antibodies.
Page 32: Transition from B Cell to Plasma Cell
Processes:
Increased production of secreted Ig relative to membrane Ig.
Isotype switching of Ig heavy chains.
Page 33: Features Related to Effector Functions
Significance: Changes in antibody structure correlate with effector functions and antigen recognition.
Isotype determines specific effector functions within the immune response.
Page 34: Conclusion of Lecture
Next Topic: Antigen Processing
Reading Assignment: AK. Abbas, 10th edition, Chapter 6
Thank you messages in multiple languages.