U01.02.016 Antibody structure and function

Antibodies, or immunoglobulins (Ig), are specialized proteins that recognize and neutralize antigens. They consist of Fab (antigen-binding) and Fc (effector function) regions, which play distinct roles in immune defense. Understanding the structural and functional aspects of antibodies is crucial for USMLE Step 1 preparation.

Structure of Antibodies

Key Regions

Fab Region (Fragment, antigen-binding):
- Comprises light (L) and heavy (H) chains.
- Contains variable and hypervariable regions.
- Recognizes antigens via a unique antigen-binding pocket (idiotype).
- One antigenic specificity per B cell.
Fc Region (Fragment, crystallizable):
- Contains the constant region of heavy chains.
- Functions include:
  - Complement Binding: IgM and IgG activate the complement system.
  - Macrophage Binding: Promotes phagocytosis.
- Confers isotype (e.g., IgM, IgD, IgG).

Structural Components

Component	Details
Heavy Chain (H)	Contributes to both Fab and Fc regions.
Light Chain (L)	Contributes to Fab region only.
Disulfide Bonds (SS)	Stabilize antibody structure.
Variable (V) Region	Provides antigen-binding specificity.
Constant (C) Region	Determines antibody class and effector functions.

Detailed Diagram

Key structural features are illustrated below:

VH (Variable heavy)
VL (Variable light)
CH1, CH2, CH3 (Constant heavy)
CL (Constant light)
Hinge Region: Provides flexibility for antigen binding.

Region	Functions
Fab	Antigen binding; determines idiotype.
Fc	Effector functions: complement activation, macrophage interaction.

Generation of Antibody Diversity and Specificity

Antigen-Independent Diversity

Occurs during B cell development in the bone marrow.

Random Recombination:
- VJ (Light Chain): Random joining of variable (V) and joining (J) gene segments.
- V(D)J (Heavy Chain): Includes diversity (D) gene segments.
Random Nucleotide Addition:
- Mediated by terminal deoxynucleotidyl transferase (TdT).
Heavy-Light Chain Pairing:
- Random combinations of heavy and light chains form unique antibodies.

Antigen-Dependent Specificity

Occurs upon antigen exposure in secondary lymphoid organs.

Somatic Hypermutation:
- Mutations in the variable region increase antibody affinity.
Isotype Switching:
- Switching between Ig classes (e.g., IgM to IgG) via changes in the constant region.

Points to Remember

Fab Region: Responsible for antigen recognition and binding.
Fc Region: Mediates immune responses like complement activation and phagocytosis.
Antibody Diversity:
- Antigen-independent mechanisms generate a vast repertoire of antibodies.
- Antigen-dependent processes enhance affinity and functional specialization.
Key Enzymes:
- TdT: Adds diversity during recombination.
- Activation-induced cytidine deaminase (AID): Facilitates isotype switching and somatic hypermutation.

Mnemonic for Fc Region Functions (5 C’s)

Constant
Carboxy terminal
Complement binding
Carbohydrate side chains
Confers isotype

Bibliography

Abbas, A.K., Lichtman, A.H., & Pillai, S. (2021). Basic Immunology: Functions and Disorders of the Immune System.
Janeway, C.A., Travers, P., Walport, M., & Shlomchik, M.J. (2022). Immunobiology: The Immune System in Health and Disease.
Levinson, W. (2022). Review of Medical Microbiology and Immunology.

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