Immune response

Related Subjects: |Major Histocompatibility complex |Immune response |Complement |Opsonisation |Toll-like Receptors (TLRs) |Immunoglobulins |Immunology |Antigen presenting cells |T lymphocytes |Beta-2 Microglobulin

🛡️ Overview of the Immune Response

• The immune system is a network of cells, tissues, and organs that protects against bacteria, viruses, fungi, and parasites.
• Two arms work together: innate immunity (fast, non-specific) and adaptive immunity (slower, highly specific with memory).
• Goal: detect → contain → clear → remember pathogens for immediate defence and long-term protection.

⚡ Innate Immune Response

First line of defence, acting within minutes–hours. Recognises conserved patterns (not specific antigens) and buys time for adaptive immunity.

• Physical/Chemical barriers: Skin, tight junctions, mucous, low gastric pH, defensins, lysozyme in tears/saliva.
• Sentinel cells: Macrophages, dendritic cells, neutrophils; recognise PAMPs via PRRs (e.g., TLRs, NOD) → phagocytosis + cytokines.
• Cytokines: IL-1, IL-6, TNF-α (fever, acute-phase response), Type I interferons (IFN-α/β) induce antiviral state.
• NK cells: Kill “missing-self” (↓MHC I) virally infected/tumour cells via perforin/granzymes.
• Complement (3 pathways): Classical (antibody-C1q), Lectin (MBL), Alternative (C3 tick-over). Effects: opsonisation (C3b), inflammation (C3a/C5a), MAC lysis (C5b-9).
• Inflammation: Vasodilation and ↑permeability recruit neutrophils/monocytes (rubor, calor, tumor, dolor).

🎯 Adaptive Immune Response

Highly specific; generates memory. Requires antigen presentation and clonal selection.

• Antigen presentation: Dendritic cells present peptides on MHC II→CD4⁺ T cells; infected cells present on MHC I→CD8⁺ T cells.
• CD4⁺ T helper subsets:
  • Th1 (IFN-γ): intracellular microbes; activates macrophages, supports CD8⁺.
  • Th2 (IL-4/5/13): helminths; class switch to IgE, eosinophils, allergy.
  • Th17 (IL-17/22): extracellular bacteria/fungi; neutrophil recruitment.
  • Treg (IL-10, TGF-β): immune tolerance, dampens inflammation.
• CD8⁺ cytotoxic T cells: Kill infected/tumour cells via perforin/granzyme or Fas–FasL.
• B cells (Humoral): With T-cell help (CD40–CD40L + cytokines) undergo germinal-centre class switching and affinity maturation.
  • IgM (first response), IgG (opsonisation, placenta), IgA (mucosa, milk), IgE (allergy/parasites), IgD (naïve B-cell receptor).
• Immunological memory: Memory B/T cells drive faster, stronger secondary responses (basis of vaccination).

🧩 Types of Immunity

• Active: Infection or vaccination → own antibodies + memory (durable).
• Passive: Transferred antibodies (placenta IgG, breast milk IgA, immunoglobulin therapy) → immediate, short-lived.

🦠 Examples

• Viral infection: IFN-α/β induced; NK early killing; APC→Th1; CD8⁺ clears infected cells; neutralising IgA/IgG prevent reinfection; memory persists.
• Bacterial infection: Neutrophils + macrophages; complement C3b opsonisation; Th17 recruitment; antibodies (IgG/IgM) neutralise toxins and opsonise.

🧪 Clinical Pearls

• 📈 Inflammatory biomarkers: CRP/ESR (inflammation), procalcitonin (bacterial sepsis guide).
• 🧫 Asplenia: Risk of encapsulated organisms (Strep pneumoniae, H. influenzae b, Neisseria) → vaccinate + prompt antibiotics for fever.
• 🧬 Complement deficiencies: C5–C9 → recurrent Neisseria; C1 esterase inhibitor deficiency → hereditary angioedema (avoid ACEi).
• 🧪 Primary immunodeficiencies: CGD (defective NADPH oxidase → catalase-positive infections); SCID (severe recurrent infections; urgent HSCT).
• 🔥 Hypersensitivity: I (IgE, anaphylaxis), II (cytotoxic), III (immune complex), IV (T-cell mediated, e.g., contact dermatitis).

💉 Vaccination & Adjuvants

• Vaccines simulate infection to generate memory (live-attenuated, inactivated, subunit, mRNA, conjugate).
• Adjuvants (e.g., aluminium salts) boost innate sensing → better T- and B-cell responses.

📌 Summary

Innate immunity provides rapid, pattern-based defence; adaptive immunity offers precision and memory. Effective protection requires antigen presentation, T-helper coordination, antibodies, cytotoxic T-cell killing, and a safe return to homeostasis. Disruption at any step predisposes to infection, autoimmunity, or immunodeficiency.