Learning Objective:
Understand the structural features of antibodies, mechanisms of antigen recognition, effector functions, and generation of diversity for USMLE Step 1.
Antibody Structure
| Feature | Composition | Function |
|---|---|---|
| Fab fragment | Light (L) + Heavy (H) chains | Binds antigen; determines idiotype (unique antigen-binding pocket; one specificity per B cell) |
| Fc region | Heavy chain constant region | Mediates effector functions: complement fixation (IgM, IgG), macrophage binding, and determines isotype |
| Heavy chain | VH, D, JH, CH1-3 | Contributes to Fab (variable) and Fc (constant) regions |
| Light chain | VL, JL, CL | Contributes only to Fab |
| Hinge region | Flexible linker | Provides mobility for Fab arms |
| Hypervariable regions | Variable domain | Sites for antigen recognition |
Abbreviations:
- V = Variable, C = Constant, SS = Disulfide bonds
- CH = constant heavy, CL = constant light, VH = variable heavy, VL = variable light
Antibody Functions
| Function | Mechanism |
|---|---|
| Neutralization | Blocks bacterial/viral adherence to host cells |
| Opsonization | Mark’s pathogens for phagocytosis by macrophages |
| Complement activation | Fc region of IgM/IgG activates C1 → MAC → lysis |
| Isotype effector functions | Fc determines interaction with immune cells and complement |
Activity
Generation of Antibody Diversity
Antigen-Independent (Before Antigen Exposure)
- Random recombination of V(D)J (heavy chain) or VJ (light chain) genes → mediated by RAG1/2
- Nucleotide addition by TdT
- Random pairing of heavy and light chains
Antigen-Dependent (After Antigen Exposure)
- Somatic hypermutation & affinity maturation → improves antigen specificity in the variable region
- Isotype (class) switching → changes Fc region (IgM → IgG, IgA, IgE) without altering antigen specificity
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