Immune Response to Infections

Immune Response to Infections - Gatekeepers & Guards

• Innate Immunity (First Line): Rapid, non-specific.
  • Barriers: Physical (skin, mucosa), chemical (lysozyme, pH), biological (flora).
  • Key Cells:
    • Phagocytes: Neutrophils (early), Macrophages (APC, late).
    • NK Cells: Cytotoxic; target viral/tumor cells (no prior sensitization).
• Recognition & Signaling:
  • PRRs (e.g., TLRs, NLRs): Detect PAMPs (Pathogen-Associated) & DAMPs (Damage-Associated).
• Complement System: Proteins activated via Classical, Alternative, Lectin pathways.
  • Functions: Opsonization (C3b), Lysis (MAC: C5b-C9), Inflammation (C3a, C5a). 📌 CALM.

![Complement system activation pathways](https://ylbwdadhbcjolwylidja.supabase.co/storage/v1/object/public/notes/L1/Pathology_Immunopathology_Immune_Response_to_Infections/48181e13-0799-4a64-8f21-3631cde9749a.jpg)
> ⭐ **TLR4** recognizes Lipopolysaccharide (LPS) on Gram-negative bacteria, a key PAMP.

Immune Response to Infections - Special Forces Strike

Adaptive immunity: "Special Forces" (T & B lymphocytes) for targeted elimination & memory. APCs present antigens via MHC for activation.

• Cell-Mediated Immunity (CMI): T-cell driven; combats intracellular pathogens (viruses, Mycobacteria) & tumor cells.

  • CD4+ T Helper (Th) Cells: Orchestrate.
    • Th1: IFN-γ → Potent macrophage activation (vs. intracellular microbes); granuloma formation.
    • Th2: IL-4, IL-5, IL-13 → B-cell switching to IgE, eosinophil activation (helminths, allergy).
  • CD8+ Cytotoxic T Lymphocytes (CTLs): Directly kill virus-infected/tumor cells (perforins/granzymes); MHC-I restricted.

• Humoral Immunity: B-cell driven; antibodies neutralize/eliminate extracellular microbes & toxins.

  • B-cells → Plasma cells → Antibodies (IgM, IgG, IgA, IgE).
  • Key Antibody Actions: Neutralization, opsonization (enhances phagocytosis), complement activation.

⭐ IFN-γ, secreted by Th1 cells and NK cells, is pivotal for macrophage activation and effective clearance of intracellular pathogens like Mycobacterium tuberculosis.

Immune Response to Infections - Know Your Enemy

Host defense mechanisms are tailored to specific pathogen classes.

• Innate Immunity: Rapid, non-specific first line.
  • Cells: Phagocytes (Neutrophils, Macrophages), NK cells.
  • Soluble: Complement, Interferons (IFNs), Cytokines.
• Adaptive Immunity: Specific, develops memory.
  • Humoral (B-cells): Antibodies → Extracellular pathogens.
  • Cell-Mediated (T-cells): CTLs (cytotoxic T lymphocytes), Th1 (intracellular pathogens), Th17 (fungi, extracellular bacteria), Th2 (helminths).

Immune Response to Infections - Masters of Disguise

• Microbial Evasion Strategies:
  • Antigenic variation: Altering surface antigens (e.g., Influenza, HIV, Neisseria).
  • Complement inhibition: Preventing opsonization/lysis.
  • Resistance to phagocytosis: Capsules (e.g., S. pneumoniae), toxins.
  • Blocking IFN pathways: Dampening antiviral responses.
  • Establishing latency: Persisting silently (e.g., Herpesviruses, HIV).
• Immunopathology (Damage by Immune Response):
  • Cytokine storm: Excessive inflammation (e.g., Sepsis, ARDS).
  • Immune complex deposition: Glomerulonephritis, vasculitis.
  • Molecular mimicry: Cross-reactive antibodies triggering autoimmunity (e.g., Rheumatic fever).
  • Granuloma formation: Walling off pathogens, but causing fibrosis (e.g., TB).

⭐ Antigenic variation in Trypanosoma brucei involves sequential expression of variant surface glycoproteins (VSGs), enabling chronic infection by evading host antibodies.

High‑Yield Points - ⚡ Biggest Takeaways

• Innate immunity: first defense via phagocytes (neutrophils, macrophages), NK cells.
• Adaptive immunity (T/B cells): specific, long-lasting protection, immunological memory.
• T-helper (CD4+) cells: orchestrate responses, activate B cells & cytotoxic T cells.
• Cytotoxic T (CD8+) cells: kill virus-infected and tumor cells.
• Antibodies: neutralize toxins, opsonize pathogens, activate complement.
• Granulomatous inflammation: characteristic of intracellular pathogens (e.g., TB).
• Microbes use immune evasion (antigenic variation, latency) to persist.