Innate + adaptive immunity: PRRs, complement, B/T cells, antibodies, V(D)J, MHC, clonal selection.
Immunology
Innate immunity
Germline-encoded, non-clonal, fast (<hours) first-line defence. Physical barriers, complement, phagocytes (macrophage, neutrophil,…
Adaptive immunity
Clonal, antigen-specific, memory-forming response (days-weeks). T cells (cellular) + B cells (humoral) with V(D)J-rearranged receptors.…
Pattern-recognition receptor (PRR)
Germline-encoded receptor detecting conserved pathogen features (PAMPs) or damage signals (DAMPs). Toll-like receptors (TLR1-10), NLRs,…
Complement system
Serum protease cascade of ~30 proteins. Three activation pathways (classical/lectin/alternative) converge on C3 convertase → C3b…
B cell
Bone-marrow-derived lymphocyte bearing surface immunoglobulin (BCR). Class-switches + somatically hypermutates in germinal centres.…
T cell
Thymus-matured lymphocyte bearing αβ-TCR (or γδ). Recognises antigen peptide + MHC. CD4+ helper, CD8+ cytotoxic, Treg, Th1/Th2/Th17, Tfh…
Antibody (immunoglobulin)
Y-shaped secreted BCR: two heavy + two light chains, variable antigen-binding (Fab) + constant (Fc) regions. Five classes: IgM (first), IgG…
V(D)J recombination
RAG1/2-mediated somatic rearrangement of V, D, J gene segments generating unique TCR and BCR per lymphocyte. Theoretical diversity ~10¹⁶.…
MHC (HLA)
Major histocompatibility complex: MHC-I (HLA-A/B/C) presents endogenous peptides to CD8+ T cells; MHC-II (HLA-DR/DP/DQ) presents exogenous…
Clonal selection theory
Burnet 1957: lymphocytes bear one receptor specificity before antigen encounter; antigen selects + expands cognate clones. Self-reactive…
Inflammation
Protective innate response to injury/infection: rubor (redness), calor (heat), tumor (swelling), dolor (pain), functio laesa. Mediated by…
Clonal-selection framework (Burnet 1957)
Burnet 1957 / Talmage 1957: the immune system contains a vast pre-existing repertoire of B and T lymphocytes each bearing one…
Clonal selection (Burnet 1957)
Burnet 1957 + Talmage 1957: each lymphocyte expresses single antigen-specificity; antigen-binding triggers clonal expansion; basis of…
V(D)J recombination (Tonegawa 1976)
Tonegawa 1976 (Nobel 1987) V(D)J: RAG1/RAG2 mediate site-specific recombination at RSS heptamer/nonamer; generates ~10^11 antibody-receptor…
MHC restriction (Zinkernagel-Doherty 1974)
Zinkernagel-Doherty 1974 (Nobel 1996): T-cell only recognizes antigen presented in self-MHC context; class-I (CD8) + class-II (CD4)…
Toll-like receptors (Beutler-Hoffmann)
Hoffmann 1996 Drosophila-Toll; Beutler 1998 LPS/TLR4; Akira-Medzhitov: 10 human TLRs recognize PAMPs; Nobel 2011; bridge between innate +…
Complement cascade
Bordet-Buchner 1898: serum-complement-system; classical (C1q-Ab), lectin (MBL), alternative (C3b-spontaneous) pathways converge on C3…
Cytokine signaling (JAK-STAT)
Darnell-Stark-Kerr 1990s JAK-STAT: cytokine-receptor dimerization recruits JAK1/2/3/TYK2 -> phospho-STAT1-6 -> nuclear-translocation ->…
Clonal selection (Burnet 1957)
M Burnet 1957 (Nobel 1960) clonal-selection theory; modern modern Tonegawa Nobel 1987 V(D)J + CAR-T + 2024 atlas T-/B-cell rep.
V(D)J (Tonegawa 1976)
S Tonegawa 1976 (Nobel 1987) V(D)J recombination; modern modern AID-mediated SHM/CSR + 10^11-diversity + 2024 DEEP-Seq fitting.
MHC restriction (Zinkernagel-Doherty 1974)
R Zinkernagel-P Doherty 1974 (Nobel 1996) MHC-restriction; modern modern HLA-typing + transplant + autoimmune-association GWAS.
Interferon (Isaacs 1957)
A Isaacs-J Lindenmann 1957 interferon-α/β/γ; modern modern type-I/II/III IFN + COVID-IFN-genetics 2024 + 2-5A OAS antiviral.
Checkpoint (Allison-Honjo 1996)
J Allison-T Honjo 1996/2002 (Nobel 2018) CTLA-4 + PD-1 inhibition; modern modern ipilimumab + nivolumab + 2024 LAG-3 + TIGIT.
CAR-T (Rosenberg 2010)
S Rosenberg-C June 2010-2011 CAR-T-CD19; modern Kymriah/Yescarta 2017 + bispecific BiTE + 2024 in-vivo CAR-T mRNA Pfizer.