MHC I: ALL nucleated cells β CD8+. MHC II: APCs only β CD4+. Memory: "1Γ8=8, 2Γ4=8."
MHC (HLA) β MHC I (HLA-A,B,C) on all nucleated cells presents to CD8+ Β· MHC II (HLA-DR,DP,DQ) on APCs presents to CD4+
How the immune system reads what is inside every cell in the body
MHC I: displays intracellular peptides (viral proteins, tumor antigens) to CD8+ CTLs. All nucleated cells express MHC I β this is how we identify infected/cancerous cells. MHC II: on dendritic cells, macrophages, B cells only. Displays extracellular antigens after phagocytosis β CD4+ T cell activation. Transplant rejection = MHC mismatch.
B cell activation: Signal 1 (antigen) + Signal 2 (CD40L-CD40 + cytokines) β class switch IgMβIgG/IgA/IgE
B Cell Activation and Class Switching β two signals required; Signal 1=antigen binds BCR Β· Signal 2=CD4+ Th2 provides CD40LβCD40 + cytokines
How B cells become antibody-secreting plasma cells β and why two signals are required
Signal 1: antigen binds B cell receptor (BCR). Signal 2: CD4+ Th2 cell provides CD40L β CD40 contact + cytokines (IL-4, IL-5, IL-13). Without signal 2 β anergy (tolerance). Class switching: IgM β IgG/IgA/IgE driven by cytokines. Affinity maturation in germinal centers. Memory B cells persist for rapid secondary response.
NK cells kill cells that LACK MHC I β "missing self." No prior sensitization needed.
Natural Killer Cells β innate lymphocytes that detect "missing self" (absent MHC I) and kill by releasing perforin and granzymes
The innate immune cells that hunt virus-infected and tumor cells
NK cells have activating receptors (NKG2D β detect stress ligands) and inhibitory receptors (KIR β check for MHC I). Viruses downregulate MHC I to hide from CTLs β this exposes them to NK cells. Activated NK: perforin creates pores + granzymes induce apoptosis. Enhanced by IL-2, IL-12, interferons.
Immunological Memory β primary exposure creates memory B and T cells; secondary exposure produces faster, stronger IgG-dominated response
Why the second infection produces stronger protection β the basis of vaccination
First exposure: naΓ―ve cells activated β 1β2 week lag. IgM predominates. Low antibody titer. Memory B and T cells formed. Second exposure: memory cells respond within hours-days. Predominantly IgG (high affinity, class-switched). Much higher titer, longer duration. Vaccines use prime + boost strategy to exploit this mechanism.
Q: What are the five immunoglobulin classes and the unique clinical significance of each?
A: IgG: most abundant (75% of serum Ig); only antibody that crosses placenta via FcRn β neonatal passive immunity for first 6 months; isotypes 1-4 with different effector functions; opsonization, complement activation, ADCC. IgM: pentamer (10 antigen-binding sites) β first antibody in PRIMARY response; most efficient complement activator; found on naΓ―ve B cell surface as monomer. IgA: secretory dimer with J chain and secretory component in mucosal surfaces (GI, respiratory, genitourinary, breast milk) β first line at mucosal barriers; protease-resistant form; selective IgA deficiency is the most common primary immunodeficiency. IgE: lowest serum concentration; bound to Fc receptors on mast cells and basophils; crosslinking by antigen β immediate hypersensitivity; elevated in atopy and parasitic infections. IgD: expressed on naΓ―ve mature B cells (with IgM) as antigen receptor; function in serum unclear.
Q: Explain MHC I vs MHC II β which cells express each, which T cell reads each, and what clinical situations involve each?
A: MHC I (HLA-A, B, C): expressed on ALL nucleated cells (not RBCs β no nucleus, no MHC I). Presents INTRACELLULAR peptides (viral proteins, tumor antigens, cytosolic proteins) via the endogenous pathway. Read by CD8+ CTLs β "8 reads 1 (MHC I)." Clinical: virally infected cells are killed by CTLs recognizing viral peptides on MHC I; tumor cells upregulate stress ligands. MHC II (HLA-DR, DP, DQ): expressed only on professional APCs β dendritic cells, macrophages, B cells. Presents EXTRACELLULAR antigens (phagocytosed bacteria, etc.) via the exogenous/endosomal pathway. Read by CD4+ helper T cells β "4 reads 2 (MHC II)." Clinical: transplant rejection occurs due to MHC mismatch (both Class I and II); HLA-B27 associated with ankylosing spondylitis; HLA-DR3/4 associated with T1DM.
Q: What complement deficiencies cause what clinical syndromes?
A: C1q deficiency: impaired immune complex clearance β SLE-like disease (most common presentation of C1q deficiency). C3 deficiency: most severe complement deficiency β recurrent severe bacterial infections (S. pneumoniae, H. influenzae, Staphylococcus) because C3b is required for opsonization; also susceptibility to encapsulated bacteria and immune complex diseases. C5-C9 (MAC) deficiency: specifically predisposes to NEISSERIA infections (N. meningitidis, N. gonorrhoeae) β these Gramβ organisms rely on MAC for killing; recurrent or disseminated gonococcal/meningococcal infections should prompt complement evaluation. DAF (Decay Accelerating Factor) deficiency: paroxysmal nocturnal hemoglobinuria (PNH) β uncontrolled complement lysis of RBCs. C1 esterase inhibitor deficiency: hereditary angioedema β recurrent attacks of edema without urticaria.
Q: What infection patterns suggest B cell vs T cell vs combined immunodeficiency?
A: B cell/antibody deficiency (XLA β Bruton's, CVID, selective IgA deficiency): recurrent sinopulmonary infections with encapsulated bacteria (S. pneumoniae, H. influenzae β need antibody for opsonization); Giardia (IgA deficiency); enteroviral encephalitis; PNH GI infections. T cell deficiency (DiGeorge/thymic aplasia, HIV/AIDS): opportunistic infections β viral (CMV, EBV, HSV, VZV), fungal (PCP, Candida, Cryptococcus), intracellular pathogens (Toxoplasma, Mycobacteria, Histoplasma); also viral live vaccines can cause disease. Combined immunodeficiency (SCID, Wiskott-Aldrich): all of the above β the most severe presentation. Complement C5-C9: specifically Neisseria bacteremia/meningitis. Neutrophil defects (CGD): catalase-positive organisms (S. aureus, Aspergillus, Nocardia, Serratia).