Immuno – Inflamation, Immunity

Master answer

Definition

Innate immunity is the body’s first line of defense, present from birth, and provides immediate, non-specific protection against a wide range of pathogens. It does not require prior exposure to pathogens and lacks immunological memory, meaning its response does not improve with repeated exposure.

Components of Innate Immune System

Comprises of three components: Physicochemical barriers, Humoral defences, Cellular defences

1. Physiocochemical Barriers

prevent pathogenic factors from gaining access to body

• Epithelial barriers (skin, GIT, respiratory tract, genitourinary tract)
  • Secretion of “antibacterial substances” (Eg. lysozyme in saliva, gastric HCl)
  • High turnover of epithelial membranes
  • High flow rates of urine, saliva and tears
  • Acidic environment (especially low pH of stomach)
  • Normal flora (prevents growth of foreign organisms)
  • Mucous membranes secrete mucous that trap foreign particles and remove them via ciliary action
• Innate reflex mechanisms (Eg. coughing, sneezing, vomiting, diarrhoea, Etc.)

2. Humoral defences

• Complements
  • Proteolytic system present in plasma.
  • Group of serum proteins produced by hepatic parenchymal cells and also macrophages at sites of inflammation.
  • Activated in a sequential manner via two separate pathways (classical and alternate), which come together in a final common pathway involving the breakdown of C3.
• Acute phase proteins – Plasma proteins produced by liver during acute
  inflammation/infection (Eg. CRP, Fibrinectin, α1AT, α2-macroglobulin) → aids in
  opsonisation, complement activation and regulation of the AIR
• Proteolytic enzymes (Eg. lysozyme) – Break down bacterial cell wall → lysis

3. Cellular defences

a) Granulocytes

• Neutrophils → main defence against bacteria and fungi as follows:
  • At site of infection, tissue damage releases mediators that activate
    circulating PMNLs and vascular endothelium and causes them to express
    adhesive proteins → results in “Margination” (PMNL to move along
    margin of endothelium) and “Diapedesis” (PMNL migrate through
    endothelium into tissues)
  • “Chemotaxis” – PMNL are drawn towards chemotactic factors (Eg. cytokines, complement, Etc.) in tissues
  • “Phagocytosis” – PMNL recognise foreign material (Eg. bacteria) using “surface receptors” (Eg. LPS) → leads to cellular ingestion. This process is enhanced by “Opsonisation”, whereby the foreign material is coated with an “Opsonin” (Eg. IgG or C3b)
  • “Killing/Digestion” – Phagocytosed material is incorporated into a “Phagosome” and destroyed by an O2-dependent process (via respiratory burst using H2O2, OH-and O2 generated from O2) and non-oxidative process (via lysosomal enzymes)
• Eosinophils
  • Mainly present in tissues (esp epithelial surfaces) cf. circulation
  • Mainly implicated in allergic and parasitic responses → via release of “basic” granular material
• Mast cells and Basophils
  • Basophils circulate in blood → become Mast cells when they enter tissue
  • Mainly implicated in allergic and parasitic responses → degranulate and release mediators (histamine, 5-HT, SRS-A, Etc.) when IgE binds to it

b) Monocytes and Macrophages

• “Monocytes” enter blood from BM for 3 days before entering specific tissues (esp the reticuloendothelial system) → once in tissue, they can stay there for months-years as “Tissue Macrophage” (Eg. Liver (Kupffer Cells), Lung (Alveolar and Interstitial Macrophages), Bone (Osteoblast), CNS (Microglia), Kidney (Mesangial), LN and Spleen (sinus macrophages), Skin (Langerhans cells))
• Actions of tissue macrophages
  • Phagocytosis and killing/digestion of IC pathogens (Eg. Listeria), mycobacteria, parasites (Eg. Trypanosomes), and fungi
  • Ag presentation to T-cells

c) NK Cells

• Large granular lymphocytes (resemble lymphocytes morphologically but lack TCR, CD3 and Ag clonal specificity)
• Actions:
  • Lyse viral-infected cells, tumour cells, and allogenic (graft) cells:
    • Possess receptors that allow it to identify target cells – recognises (i) downregulation of MHC I (Eg. viral infected cell) and (ii) IgG bound to target cells
    • Causes cell lysis via – (i) Apoptosis (nucleus of target cell is rapidly fragmented by endonucleases), and (ii) Release of Perforin/Granzyme granules onto the target cells
  • Release of cytokines (IFN-γ and TNF) that activate phagocytes and recruit T-cells

Bianca’s notes