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Chapter 4: Innate vs. Adaptive Immunity

1. Main Differences between Innate and Adaptive Immunity

  • Innate Immunity: Provides initial defense against pathogens; responds to molecular patterns.

  • Adaptive Immunity: Recognizes a wide variety of specific antigens.

2. Antigen Definition

  • An antigen: Molecule or part of a molecule recognized by lymphocyte recognition proteins.

B-Cell Receptors and Antibodies

3. Antigen Recognition Proteins on B Cells

  • Called Immunoglobulins (Igs): Function as B-cell receptors (BCRs) when membrane-bound, and as antibodies when secreted.

4. Main Effector Function of B Cells

  • Secretion of antibodies binding to pathogens in extracellular spaces.

5. Functions of Antibodies

  1. Specific binding to pathogens or their products.

  2. Recruiting other immune cells and molecules to eliminate pathogens.

6. Structural Regions of Antibodies

  • Variable Region (V region): Binds antigens.

  • Constant Region (C region): Engages immune effector functions.

7. Antibody Isotypes

  • Different forms of antibodies defined by their constant region structure, specialized in activating distinct immune responses.

T-Cell Receptors (TCRs) and MHC Molecules

8. Differences between TCRs and BCRs

  • TCRs: Always membrane-bound; recognize antigen fragments presented by MHC molecules.

  • BCRs: Can recognize whole antigens and can be secreted as antibodies.

9. MHC Molecules

  • Major Histocompatibility Complex (MHC): Transmembrane glycoproteins presenting short peptide fragments of antigens to T cells.

10. MHC Polymorphism

  • Existence of multiple versions (alleles) of MHC molecules within a population, enhancing antigen presentation.

11. Heterozygosity for MHC Molecules

  • Most individuals are heterozygous, inheriting different MHC alleles from each parent, increasing peptide presentation range.

12. MHC Restriction

  • T-cell receptor requires recognition of both antigenic peptide and specific MHC molecule presenting it.

General Structure and Function of Immune Receptors

13. Shared Structural Features

  • Immunoglobulins and T-cell receptors both have variable (V) and constant (C) regions, facilitating antigen recognition and immune activation.

14. Determinants of Antigen Specificity

  • Determined by the variable region (V region), which exhibits significant diversity.

15. Importance of Antibodies as Drugs

  • Antibodies target and neutralize pathogens or harmful substances with high specificity.

Basic Antibody Structure

1. Relationship between Antibodies and BCRs

  • Antibodies are the secreted form of B-cell receptors.

2. Shape of Antibody Molecules

  • Generally Y-shaped.

3. Main Structural Regions and Functions of Antibodies

  • V Regions: Bind antigens.

  • C Region: Interacts with effector molecules and cells.

4. Antibody Classification into Isotypes

  • Classified by differences in heavy-chain constant (C) region structure.

Antibody Isotypes Overview

5. Major Classes of Immunoglobulins

  • IgM, IgD, IgG, IgA, IgE.

6. Most Abundant Immunoglobulin in Serum

  • IgG is the most abundant.

7. Greek Letter Designations of Heavy Chains

  • IgM (μ), IgD (δ), IgG (γ), IgA (α), IgE (ε).

Antibody Chains and Structure

8. Polypeptide Chains in Antibody Molecules

  • Comprised of Heavy (H) chains and Light (L) chains.

9. Types of Light Chains in Antibodies

  • Lambda (λ) and Kappa (κ).

10. Mix of Light Chains in an Antibody

  • An antibody may contain either κ or λ chains but never a mix.

11. Affinity vs. Avidity

  • Affinity: Strength of a single antigen-binding site interaction.

  • Avidity: Combined strength of all binding interactions in an antibody.

12. Antibody Molecule Structure

  • Each antibody has two identical antigen-binding sites due to the pairing of heavy and light chains.

13. Differences between BCRs and Antibodies

  • BCRs have a hydrophobic carboxy-terminal region for membrane anchorage.

  • Antibodies have a hydrophilic sequence, allowing them to be secreted.

Clinical Relevance of Antibodies

14. Kappa to Lambda Light Chain Ratio

  • An abnormal κ/λ ratio may indicate a B-cell tumor.

Immunoglobulin Domains and Structure

1. Features of Immunoglobulin Chains

  • Chains consist of repeating Ig domains and vary significantly in amino-terminal sequences across antibodies.

2. Imunoglobulin Domains (Ig Domains)

  • Compactly folded protein regions, approximately 110 amino acids long.

3. Ig Domains in Light and Heavy Chains of IgG

  • Light chains possess two Ig domains; heavy chains have four.

4. Variability in Ig Domains

  • Variability in amino-terminal Ig domains determines antigen-binding specificity.

5. Components Responsible for Antigen Binding

  • V Region: Comprised of variable domains from heavy (VH) and light (VL) chains.

6. Function of Constant Ig Domains

  • Form C region, determining antibody isotype and effector functions.

7. Numbering of Heavy-Chain Constant Domains

  • Numbered from amino-terminal to carboxy-terminal (e.g., CH1, CH2, etc.).

β Sheets and Immunoglobulin Fold

8. β Sheet Structure

  • Arrangement of β strands, stabilized by hydrogen bonds.

9. Formation of Immunoglobulin Fold

  • Two β sheets fold onto each other, connected by disulfide bonds.

10. Differences between V and C Domains

  • V domain is larger, containing extra β strands (C′ and C′′).

11. Role of Flexible Loops in V Domain

  • Contributes to the antigen-binding site, enhancing specificity.

12. Ig-Like Domains

  • Found in other immune system proteins, analogous to Ig domains.

13. Immune System Proteins with Ig-Like Domains

  • Includes KIRs on NK cells, T-cell receptors, and adhesion molecules.

14. Immunoglobulin Superfamily

  • Group of proteins, including antibodies, T-cell receptors, and adhesion molecules sharing similar structure.