CD4+ = Helper T cells ("4 helps"). CD8+ = Cytotoxic T cells ("8 kills").
T Cell Subtypes
The two major T cell classes and their very different jobs
CD4+ Helper T cells: activate B cells and macrophages, coordinate immune response. Targeted by HIV β AIDS. CD8+ Cytotoxic T cells (CTLs): kill virus-infected cells and tumor cells via perforin/granzymes. Recognize antigen on MHC I (all nucleated cells). CD4 sees MHC II (antigen-presenting cells only).
Antibody Classes
IgG: most abundant, crosses placenta. IgM: first responder, pentamer. IgA: secretions. IgE: allergy. IgD: B-cell receptor.
Immunoglobulin Classes
Five antibody isotypes β each with a different role and location
IgG (most abundant): long-term protection, crosses placenta (passive immunity to newborn), opsonization. IgM: pentamer, first antibody in primary response, excellent complement activator. IgA: dimer in secretions (breast milk, saliva, gut) β mucosal immunity. IgE: binds mast cells β allergic response, antiparasitic. IgD: B cell surface receptor.
IgG
Most abundant, crosses placenta, secondary response
IgM
Pentamer, first responder, complement
IgA
Secretions β gut, saliva, breast milk
IgE
Allergy, mast cells, parasites
IgD
B cell surface receptor
MHC Classes
MHC I: on ALL nucleated cells, presents to CD8+. MHC II: on APCs only, presents to CD4+. "1Γ8=8, 2Γ4=8."
Major Histocompatibility Complex
How the immune system distinguishes self from infected or foreign cells
MHC I (HLA-A, B, C): displays intracellular peptides β viral proteins, tumor antigens. CD8+ T cells survey MHC I on all nucleated cells. MHC II (HLA-DR, DP, DQ): on dendritic cells, macrophages, B cells. Displays extracellular antigens after phagocytosis. CD4+ T cells read MHC II. Transplant rejection = mismatched MHC.
Complement System
Complement pathways: Classical (antibody), Lectin (sugar), Alternative (spontaneous) β all converge at C3.
Complement Activation
The cascade that punches holes in pathogens and flags them for destruction
Four categories of immune overreaction β each with different mediators
Type I (IgE, mast cells): anaphylaxis, asthma, allergic rhinitis β immediate. Type II (IgG/IgM + complement): autoimmune hemolytic anemia, Goodpasture's. Type III (immune complexes deposited): serum sickness, SLE, post-strep GN. Type IV (T cell, delayed): contact dermatitis, TB skin test (PPD), transplant rejection β 48β72 hrs.
Type I
IgE + mast cells β anaphylaxis, allergy
Type II
IgG/IgM vs cell surface β cytotoxic
Type III
Immune complexes deposited in tissues
Type IV
T cells β delayed, 48β72 hrs (PPD test)
B Cell Activation
B cells need 2 signals: antigen + CD4+ T cell help (CD40L-CD40 + cytokines) β antibody class switch
B Cell Activation and Class Switching
How B cells go from naΓ―ve to antibody-secreting plasma cells
Signal 1: antigen binds B cell receptor. Signal 2: CD4+ Th2 cell provides CD40L β CD40 interaction + cytokines. Without signal 2 β anergy (tolerance). Class switching: IgM β IgG/IgA/IgE based on cytokines from T cells. Affinity maturation in germinal centers. Memory B cells persist for rapid secondary response.
NK Cells
NK cells kill cells that LACK MHC I β "missing self." No prior sensitization needed.
Natural Killer Cells
The innate immune cells that hunt virus-infected and tumor cells
NK cells patrol for cells with reduced/absent MHC I (viruses downregulate MHC I to hide from CTLs β but this exposes them to NK cells). Activating receptors (NKG2D) see stress ligands. Inhibitory receptors (KIR) check for self-MHC I. Activated NK: releases perforin, granzymes β target cell apoptosis. Enhanced by IL-2, IL-12, interferons.
Autoimmune Disease Mechanism
Autoimmunity: loss of self-tolerance. Central (thymus/bone marrow) or peripheral tolerance failure.
Autoimmunity Mechanisms
Why the immune system sometimes attacks the body's own tissues
Central tolerance: autoreactive T cells deleted in thymus (negative selection). B cells deleted in bone marrow. Peripheral tolerance: regulatory T cells (Tregs) suppress autoreactive cells. Failure mechanisms: molecular mimicry (pathogen resembles self), bystander activation, Treg deficiency. Examples: type 1 diabetes (Ξ² cells), SLE (dsDNA), rheumatoid arthritis (joints), Graves' disease (TSH receptor).
Why the second infection (or second vaccine dose) produces stronger protection
First exposure: naΓ―ve B and T cells activated β lag 1β2 weeks. IgM predominates. Low antibody titer. Memory cells formed. Second exposure: memory B and T cells respond within hoursβdays. Predominantly IgG (high affinity, class-switched). Much higher titer. Longer duration. Basis of vaccination: prime + boost strategy exploits this.
Immunodeficiency Patterns
B cell defect β recurrent bacterial infections. T cell defect β viral/fungal infections. Combined β everything.
Immunodeficiency Patterns
What type of infections reveal which part of the immune system is deficient
B cell deficiency (X-linked agammaglobulinemia, CVID): encapsulated bacteria (S. pneumoniae, H. influenzae). T cell deficiency (DiGeorge β thymic aplasia): viral, fungal, intracellular pathogens. SCID (B+T): all pathogens + opportunistic. Complement deficiency: Neisseria. Phagocyte defect (CGD): catalase+ organisms (S. aureus, Aspergillus).
Cytokines Key Players
IL-2: T cell growth. IL-4/5/13: B cells/IgE/eosinophils. IL-10: anti-inflammatory. TNF-Ξ±: inflammation/fever. IFN-Ξ³: macrophage activation.
Key Cytokines and Functions
The signaling molecules that coordinate every immune response
IL-1, IL-6, TNF-Ξ±: acute phase response, fever (endogenous pyrogens). IL-2: T cell proliferation β target of tacrolimus/cyclosporine. IL-4/5/13: Th2 response, IgE class switch, eosinophil activation β allergies/parasites. IL-12: drives Th1 response, activates NK cells. IL-10: anti-inflammatory, suppresses macrophages. IFN-Ξ³: activates macrophages, key against intracellular pathogens.