Adaptive Immunity

Hallmarks & Cells - Elite Squad Assemble

• Core Principles (Hallmarks):
  • Specificity: Tailored response to distinct antigens.
  • Memory: Enhanced, rapid recall upon re-exposure. 📌 "Never forget a face."
  • Diversity: Vast repertoire to recognize millions of antigens.
  • Self/Non-self Discrimination: Crucial tolerance to host tissues.
  • Clonal Expansion: Proliferation of antigen-selected lymphocytes.
• The Elite Squad (Lymphocytes):
  • T Lymphocytes (Cell-Mediated Immunity):
    • Helper T (CD4+): Orchestrate; activate B cells, macrophages, other T cells.
    • Cytotoxic T (CD8+): Directly kill virus-infected cells & tumor cells.
    • Regulatory T (Tregs): Modulate/suppress to maintain homeostasis.
  • B Lymphocytes (Humoral Immunity):
    • Differentiate into Plasma Cells: Antibody-secreting factories.
    • Produce Antibodies (Immunoglobulins): Neutralize/eliminate extracellular pathogens.
    • Memory B Cells: Provide long-term immunity.

⭐ T-cell receptors (TCRs) recognize processed antigen fragments presented by MHC molecules on APCs, whereas B-cell receptors (BCRs) can recognize intact, native antigens.

Antigen Presentation & MHC - The MHC Handshake

• MHC (Major Histocompatibility Complex): Cell surface glycoproteins presenting processed antigens to T lymphocytes.
  • MHC Class I: Presents endogenous antigens (e.g., viral, tumor proteins from within the cell) to CD8+ cytotoxic T cells. Expressed on all nucleated cells.
    • Processing: Cytosolic antigen → Proteasome → TAP transporter → ER → MHC I loading.
  • MHC Class II: Presents exogenous antigens (e.g., phagocytosed bacteria) to CD4+ helper T cells. Expressed only on Antigen Presenting Cells (APCs: e.g., macrophages, dendritic cells, B cells).
    • Processing: Endocytosed antigen → Lysosome → Invariant chain displaced → Peptide loading in MIIC compartment (HLA-DM facilitates).
• 📌 Rule of 8: Product of MHC class and CD molecule number is 8 (MHC I x CD8 = 8; MHC II x CD4 = 8).

⭐ MHC molecules are encoded by highly polymorphic Human Leukocyte Antigen (HLA) genes on chromosome 6. This diversity is critical for immune response range and transplant compatibility.

Humoral Immunity (B cells) - Antibody Arsenal

• B Cell Activation:

• Antibody (Ab) Structure: Y-shaped; 2 Heavy, 2 Light chains. Fab (binds antigen), Fc (effector).
• Ab Classes (Isotypes): 📌 GAMDE (serum abundance: IgG > IgA > IgM > IgD > IgE)
  • IgG: Main Ab in secondary response; crosses placenta; opsonizes.
  • IgM: Pentamer; first Ab in primary response; potent complement activator.
  • IgA: Dimer (secretory IgA); mucosal immunity (GIT, respiratory secretions).
  • IgD: Monomer; B-cell surface receptor; role in B cell activation.
  • IgE: Monomer; defense against helminths; allergic reactions (mast cell degranulation).
• Immune Responses:
  • Primary: Slow onset; mainly IgM, then IgG; lower affinity Abs.
  • Secondary: Rapid, robust (anamnestic); mainly IgG; higher affinity Abs due to memory B cells.

⭐ IgM is the largest antibody (a pentamer) and the first to appear during an initial exposure to an antigen, making it a key indicator of acute infection.

Cell-Mediated Immunity (T cells) - Cellular Commandos

• Core Function: T lymphocytes combat intracellular pathogens (viruses, some bacteria) & cancer cells.
• Activation (2 Signals):
  • Signal 1: TCR binds Ag-MHC complex on Antigen Presenting Cell (APC).
  • Signal 2: Co-stimulation (e.g., CD28 on T cell with B7 on APC).
• Major T Cell Subsets:
  • CD4+ Helper T cells (MHC-II restricted): Orchestrate immune response.
    • Th1: IFN-γ (macrophage activation, defense against intracellular pathogens).
    • Th2: IL-4, IL-5, IL-13 (B cell help, allergy, anti-helminth).
    • Th17: IL-17, IL-22 (inflammation, neutrophil recruitment, defense against extracellular bacteria/fungi).
    • Tfh (Follicular helper): IL-21, ICOS (B cell help in germinal centers).
  • CD8+ Cytotoxic T cells (CTLs) (MHC-I restricted): Directly kill infected or tumor cells (perforins, granzymes, FasL-Fas).
  • Regulatory T cells (Tregs) (CD4+, CD25+, FOXP3+): Suppress immune response (e.g., via IL-10, TGF-β), maintain tolerance.
• Memory T Cells: Provide rapid, robust secondary immune response upon re-exposure to antigen.

⭐ Th1 cells, by secreting IFN-γ, are crucial for activating macrophages to kill intracellular pathogens like Mycobacterium tuberculosis and play a key role in Type IV hypersensitivity (delayed-type hypersensitivity).

High‑Yield Points - ⚡ Biggest Takeaways

• T-cell development occurs in the thymus; B-cell development in bone marrow.
• MHC I presents endogenous antigens (e.g., viral, tumor) to CD8+ T cells (cytotoxic).
• MHC II presents exogenous antigens (e.g., bacterial) to CD4+ T cells (helper).
• B cells differentiate into plasma cells (antibody secretion) and memory B cells.
• Class switching and affinity maturation of antibodies require T-cell help (CD40-CD40L).
• Somatic hypermutation leads to ↑ antibody affinity during immune response.
• Central tolerance (thymus/bone marrow) and peripheral tolerance prevent autoimmunity anergy or deletion of self-reactive lymphocytes.