KS

Introduction to Immunology – Key Terminology

Pathogens

  • Definition: Any biological agent that can cause disease by gaining access to and replicating inside (or on) a host organism.

  • Major Categories & Sub-types

    • Viruses

    • Enveloped (e.g. Influenza, HIV)

      • Lipid bilayer derived from host cell

      • Sensitive to detergents, desiccation, heat

      • Entry usually by membrane fusion (pH-dependent or receptor-mediated)

    • Non-enveloped (e.g. Adenovirus, Poliovirus)

      • Robust icosahedral or helical capsid

      • Environmentally stable; often transmitted via fecal–oral route

      • Entry via endocytosis & pore formation/lysis

    • Life-cycle summary

      • Attachment → Penetration → Uncoating → Replication → Assembly → Release (budding for enveloped, lysis for non-enveloped)

    • Bacteria

    • Gram-positive (thick \text{Peptidoglycan}, teichoic acids; e.g. Staphylococcus aureus)

    • Gram-negative (thin \text{Peptidoglycan} + outer membrane with LPS/endotoxin; e.g. E. coli)

    • Intracellular (can replicate within host cells; e.g. Mycobacterium tuberculosis, Listeria)

    • Extracellular (replicate in tissue fluids; e.g. Streptococcus pneumoniae)

    • Fungi

    • Yeasts (unicellular, budding; e.g. Candida albicans)

    • Hyphae/Molds (multicellular, filamentous)

    • Spores (dormant, environmentally resistant forms)

    • Parasites

    • Protozoa (unicellular; e.g. Plasmodium falciparum)

    • Helminths (multicellular worms; e.g. Schistosoma)

Organs of the Immune System

  • Bone Marrow

    • Structure: Highly vascularized soft tissue in medullary cavities of bones

    • Function: Hematopoiesis; B-cell maturation & negative selection

  • Thymus

    • Lobulated organ above heart; cortex & medulla compartments

    • Function: T-cell maturation, positive/negative selection, generation of central tolerance

  • Lymph Nodes

    • Cortex (B-cell follicles), paracortex (T-cell zones), medulla (plasma cells & macrophages)

    • Function: Antigen filtration from lymph; site of adaptive immune activation, germinal center formation

  • Spleen

    • White pulp (immune), red pulp (RBC filtration)

    • Function: Filters blood-borne Ag; removes aged erythrocytes; mounts responses to encapsulated bacteria

  • Mucosa-Associated Lymphoid Tissue (MALT)

    • Includes GALT (Peyer’s patches), BALT, NALT, tonsils, appendix

    • Function: First-line surveillance at mucosal surfaces; IgA production

Cells of the Immune System

  • Neutrophils (PMNs)

    • Innate, granulocyte

    • Origin: Bone marrow; circulate 6–8 h then migrate to tissues

    • Surface: \text{CD66b}, Fc\gammaR, CR1/3, \text{TLR2/4}

    • Function: Phagocytosis, respiratory burst, NETosis

  • Monocytes / Macrophages

    • Innate; monocytes circulate then differentiate in tissue

    • Surface: \text{CD14}, \text{TLR}s, MHC II, Fc/Complement receptors

    • Functions: Phagocytosis, cytokine secretion (IL-1, TNF), APC, tissue repair (M1 vs M2 polarization)

  • Dendritic Cells (DCs)

    • Link innate ↔ adaptive

    • Types: Conventional (cDC1/2), plasmacytoid (pDC)

    • Surface: High MHC II, B7 (CD80/86), \text{TLR7/9} (pDC)

    • Function: Sentinel APC; migrate to LN to prime naïve T cells

  • Eosinophils

    • Granules with MBP, ECP

    • Surface: IL-5R, \text{CCR3}, Fc\epsilonRI (low-affinity)

    • Function: Helminth defense, allergy, release ROS & enzymes

  • Basophils

    • Circulating counterpart of mast cells

    • Surface: High-affinity Fc\epsilonRI

    • Function: Histamine, IL-4 production; Th2 skewing

  • Mast Cells

    • Resident in connective tissue

    • Surface: Fc\epsilonRI, c-kit (CD117)

    • Function: Rapid degranulation (histamine, TNF); parasite defense, anaphylaxis

  • Natural Killer (NK) Cells

    • Innate lymphoid cell

    • Surface: CD56 (bright vs dim), absence of CD3

    • Receptors: \text{KIR}, \text{NKG2D}, \text{CD16} (Fc\gammaRIII)

    • Function: Cytotoxicity via perforin/granzyme; ADCC; early IFN-\gamma

  • B Lymphocytes

    • Adaptive humoral

    • Surface: \text{BCR (sIgM/IgD)}, CD19/20/21, MHC II, CD40

    • Function: Antibody production, memory, APC

  • T Lymphocytes

    • Subsets & Markers

    • \text{T}_H (CD4^+): orchestrate immunity

      • \text{T}_H1 → IFN-\gamma, IL-2; activate macrophages, CTL

      • \text{T}_H2 → IL-4/5/13; activate B cells, eosinophils

      • Other: \text{T}H17 (IL-17), T{FH} (help B in GC), Treg (CD25, FOXP3)

    • \text{T}_C (CD8^+): cytotoxic; perforin/granzyme, FasL

Molecules of the Immune System

  • Receptors / Membrane Molecules

    • Innate: Pattern-Recognition Receptors (PRR) (e.g. \text{TLR1–10}, NOD-like receptors, RIG-I-like receptors)

    • Fc Receptors: \text{Fc}\gamma R (I, IIa/b, III), \text{Fc}\epsilon RI

    • Complement Receptors: CR1 (CD35), CR2 (CD21), CR3 (CD11b/CD18)

    • MHC I (HLA-A/B/C) – on all nucleated cells; present \text{endo}-derived \mathit{Ag} to CD8^+

    • MHC II (HLA-DP/DQ/DR) – on professional APC; present \text{exo}-derived \mathit{Ag} to CD4^+

    • Adaptive: BCR, TCR (\alpha/\beta or \gamma/\delta)

    • Co-receptors: CD4, CD8

  • Secreted / Soluble Molecules

    • Cytokines: IL-1 family, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, TNF, IFN-\alpha/\beta/\gamma

    • Chemokines: CCL2 (MCP-1), CXCL8 (IL-8), CXCL10 (IP-10)

    • Complement proteins: C1–C9; fragments C3a/C5a (anaphylatoxins), C3b (opsonin), MAC (C5b–9)

    • Antibodies: IgM, IgG (1–4), IgA (1–2), IgE, IgD

Key Immunological Processes

  • Cytotoxicity (Apoptosis) – NK & T_C Cells

    • Mechanisms

    • Perforin forms pores → Granzyme B enters → Caspase cascade → DNA fragmentation

    • FasL (on effector) binds Fas (CD95) → DISC → Caspase-8

    • Result: Target cell apoptosis; limits viral replication & tumor spread

  • Antibody-Dependent Cell-Cytotoxicity (ADCC)

    • IgG-coated target → Fc\gammaRIII on NK binds Fc → NK degranulation

  • Phagocytosis

    • Steps: Recognition (PRR, opsonins) → Engulfment → Phagosome-lysosome fusion → Killing via ROS/RNS, enzymes

  • Opsonisation

    • Coating with C3b/IgG enhances phagocyte binding via CR1/Fc\gammaR

  • Neutralisation

    • Antibody blocks pathogen attachment or toxin action

  • Inflammation

    • Vascular changes (vasodilation, permeability) driven by histamine, prostaglandins, C3a/C5a, IL-1/TNF

  • Complement Activation Pathways

    • Classical: Ag\text{-}Ab → C1qrs → C4b2a (C3 convertase)

    • Lectin: MBL/ficolin binds mannose → MASP-2 → same C3 convertase

    • Alternative: C3b binds surface → C3bBb stabilized by properdin

    • Outcomes: Opsonization (C3b), inflammation (C3a/C5a), lysis (MAC)

  • Antigen Presentation

    • MHC I: Cytosolic proteins processed by proteasome → TAP → ER loading

    • MHC II: Extracellular proteins endocytosed → MIIC → CLIP exchange via HLA-DM

  • T & B Cell Activation

    • Signal 1: TCR/BCR binding specific Ag

    • Signal 2: Co-stimulation (CD28–B7, CD40–CD40L)

    • Signal 3: Cytokine milieu → differentiation (e.g. IL-12 → T_H1)

  • Diversity Generation

    • V(D)J recombination: V + D + J gene segments (RAG1/2)

    • Junctional diversity: TdT adds N-nucleotides

    • Somatic hypermutation & class switch (in B cells) via AID

Immune Responses to Infections

Viral Infections

  • Extracellular recognition: Pre-existing IgG/IgA & complement neutralize virions

  • Intracellular PRR: RIG-I, MDA-5 detect dsRNA → Type I IFN (IFN-\alpha/\beta) → antiviral state (upregulate PKR, OAS)

  • Infected-cell elimination: ↓MHC I triggers NK; normal MHC I presenting viral peptides triggers T_C

  • Key effector roles

    • Antibodies: Neutralization, opsonization, classical complement

    • Complement: C3b opsonization, C5b–9 lysis of enveloped virions

    • Cytokines/chemokines: Recruit leukocytes; IFN-\gamma activates macrophages

    • Phagocytes: Clear debris, present Ag

Bacterial Infections

  • Determinants: Gram status, toxins, localization

  • Extracellular Bacteria

    • Innate: Neutrophils (phagocytosis, NETosis), macrophages, complement (MAC for Gram-−); inflammation

    • Adaptive: IgM \to IgG opsonization, neutralization of toxins; Th17 recruit neutrophils

  • Intracellular Bacteria (e.g. M.\ tuberculosis)

    • Innate: PRR detect PAMPs; IL-12 → T_H1 bias

    • Adaptive: TH1 → IFN-\gamma activates macrophages to form granulomas; TC lysis of infected cells

Fungal Infections

  • Recognition: \beta\text{-glucan} via Dectin-1; TLR2/4

  • Innate Rxs: Neutrophils (ROS, NETs), macrophages, complement (lectin & alternative)

  • Adaptive: T_H1 cytokines enhance macrophage fungicidal activity; antibodies opsonize spores

Parasitic Infections

  • Protozoa (intracellular): IFN-\gamma from T_H1, macrophage activation; IgG opsonization

  • Helminths (extracellular, large): T_H2 dominance → IL-4/5/13

    • IgE binds parasite → Fc\epsilonRI on eosinophils/mast cells → degranulation, ADCC

    • Complement (classical) & IgG/IgA also participate

Ethical, Philosophical & Practical Notes

  • Vaccination leverages adaptive memory: controlled antigen exposure triggers B/T memory without disease

  • Overactivation (e.g. cytokine storm) vs underactivation (immunodeficiency) demonstrates need for balanced responses

  • Antimicrobial resistance & emerging pathogens highlight importance of understanding immune mechanisms for new therapeutics

  • Autoimmunity arises when central/peripheral tolerance fails (e.g. defective AIRE in thymus)