Immune system Study Guide

📖 Core Concepts Immune system – a network that distinguishes self from harmful agents (viruses, bacteria, parasites, cancer cells, foreign objects) and mounts protective responses. Innate immunity – rapid, non‑specific defense using pre‑set receptors (TLRs, NOD‑like, RIG‑like) and cells (neutrophils, macrophages, dendritic cells, NK cells, mast cells, eosinophils, basophils). Adaptive immunity – slower, specific response driven by B‑ and T‑lymphocytes that generate immunological memory through clonal selection and somatic hypermutation. Physical, chemical, biological barriers – first line of defense (skin, mucus, lysozyme, commensal flora). Antigen presentation – APCs process pathogens and display peptide fragments on MHC I (to CD8⁺ cytotoxic T cells) or MHC II (to CD4⁺ helper T cells). Hypersensitivity – immune reactions that damage host tissue; four types (I–IV) defined by mechanism and timing. Immunological memory – long‑lived memory B/T cells enable a faster, stronger response on re‑exposure. 📌 Must Remember Pattern‑recognition receptors (PRRs) detect PAMPs/DAMPs → trigger innate responses. Neutrophils = first responders; migrate by chemotaxis. Macrophages = phagocytosis, cytokine production, antigen presentation. Dendritic cells = bridge innate → adaptive by presenting antigen to naïve T cells. NK cells kill cells with ↓ MHC I; healthy cells inhibit NK activity via normal MHC I. Complement cascade → opsonization, inflammation, membrane attack complex (MAC). B‑cell receptor binds native antigen; each B cell has a unique specificity. T‑cell receptor recognizes peptide‑MHC complexes; CD8 = MHC I, CD4 = MHC II. Clonal selection → antigen‑specific lymphocyte proliferates into many identical effectors & memory cells. Hypersensitivity types: I – IgE‑mediated mast cell/basophil degranulation (allergy, anaphylaxis). II – Antibody‑dependent cytotoxicity (IgG/IgM + complement). III – Immune‑complex deposition (IgG/IgM + complement). IV – Delayed‑type, T‑cell mediated (24–72 h). Vaccination = active immunization → intentional antigen exposure + adjuvant → memory. Immunosuppressive drugs: glucocorticoids (broad anti‑inflammatory), cyclosporin (blocks T‑cell signaling). 🔄 Key Processes Phagocytosis Pathogen engulfed → phagosome → fuse with lysosome → phagolysosome → enzymes + ROS kill pathogen. Inflammatory cascade Tissue damage → release of eicosanoids (prostaglandins → fever/vasodilation; leukotrienes → chemotaxis) → cytokine release (ILs, chemokines, interferons) → vascular changes & leukocyte recruitment. Complement activation (classical pathway) Antibody bound to microbe → C1 complex → proteolytic cascade → C3 convertase → opsonization (C3b), chemotaxis (C5a), MAC formation (C5b‑C9). Antigen presentation APC processes protein → loads peptides onto MHC II (extracellular) or MHC I (intracellular) → migrates to lymph node → engages naïve T cell. Cytotoxic T‑cell killing Recognize peptide‑MHC I → release perforin → pores → granulysin enters → apoptosis of target cell. B‑cell activation Antigen binds BCR → internalize → present peptide on MHC II → helper T cell provides CD40L + cytokines → B cell differentiates into plasma cell (antibody secretion) & memory B cell. 🔍 Key Comparisons Innate vs. Adaptive Immunity – Rapid, non‑specific (innate) vs slower, antigen‑specific, memory (adaptive). Neutrophils vs. Macrophages – First‑line, short‑lived, abundant (neutrophils) vs tissue‑resident, long‑lived, antigen‑presenting (macrophages). IgE (Type I) vs. IgG/IgM (Type II/III) – IgE triggers mast cell degranulation; IgG/IgM mediate complement activation or opsonization. CD8⁺ Cytotoxic T cell vs. NK cell – CD8⁺ require peptide‑MHC I recognition; NK cells act on cells with ↓ MHC I without prior sensitization. Active vs. Passive Immunity – Active: host generates memory (vaccination, infection). Passive: short‑term antibodies transferred (maternal IgG, breast‑milk IgA). ⚠️ Common Misunderstandings “All antibodies kill pathogens directly.” Only certain isotypes (IgG, IgM) activate complement; IgE mainly recruits mast cells. “NK cells are part of adaptive immunity.” NK cells belong to innate immunity; they do not require prior sensitization. “Inflammation is always harmful.” Acute inflammation is protective; chronic inflammation can drive disease. “Vaccines contain live pathogens.” Most modern vaccines are acellular (protein, toxoid) plus adjuvant; they do not cause disease. 🧠 Mental Models / Intuition “Layers of a castle” – Physical barriers = moat; chemical = walls; innate cells = archers (rapid, generic); adaptive cells = elite knights (specific, trained). “Fire alarm system” – PRRs are smoke detectors; they trigger the alarm (inflammation) and call the fire brigade (phagocytes, complement). “Library catalog” – MHC molecules are catalog cards; they display “book titles” (peptide fragments) for T‑cells to scan. 🚩 Exceptions & Edge Cases Tumor immune evasion – Down‑regulation of MHC I (avoids cytotoxic T cells) or secretion of TGF‑β (suppresses immune activation). Chronic granulomatous disease – Phagocytes cannot generate reactive oxygen species → impaired killing despite normal phagocytosis. Severe combined immunodeficiency – Both B‑ and T‑cell development fail; patients lack adaptive immunity entirely. 📍 When to Use Which Identify a pathogen quickly → rely on innate mechanisms (PRRs, neutrophils, complement). Require long‑term protection or vaccine design → target adaptive arm (B‑cell epitopes + adjuvant to activate APCs). Treat autoimmune flare → immunosuppressive agents (glucocorticoids for broad suppression; cyclosporin for T‑cell specific inhibition). Manage Type I allergy → antihistamines (block histamine release) or anti‑IgE therapy; avoid mast‑cell degranulation triggers. Combat intracellular virus → boost NK activity and CD8⁺ cytotoxic response; consider interferon therapy. 👀 Patterns to Recognize “PAMP → PRR → cytokine storm” → look for Toll‑like receptor involvement in bacterial vs. viral infections. “MHC I down‑regulation → NK activation” – tumor or virally infected cells often lack MHC I, flagging NK cells. “IgE + antigen cross‑link → mast cell degranulation” – classic immediate hypersensitivity pattern. “Immune complex deposition + complement → tissue swelling” – hallmark of Type III hypersensitivity (e.g., serum sickness). 🗂️ Exam Traps Confusing CD4⁺ vs. CD8⁺ T‑cell functions – CD4⁺ = helper (MHC II), CD8⁺ = killer (MHC I). Assuming all inflammation is caused by pathogens – idiopathic inflammation can arise from sterile tissue damage. Choosing “antibody” as the sole effector for intracellular viruses – intracellular viruses are primarily controlled by cytotoxic T cells and NK cells, not antibodies. Mixing up hypersensitivity types – remember the key mediator: IgE (Type I), IgG/IgM + complement (Type II), immune complexes (Type III), T‑cells/macrophages (Type IV). Believing all vaccines are live‑attenuated – many modern vaccines are subunit/acytoplasmic with adjuvants; live vaccines are a specific subset. --- Use this guide for rapid review—focus on the bolded terms, the stepwise processes, and the comparison tables to cement high‑yield concepts before the exam.