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CELL MEDIATED IMMUNE RESPONSE

Purpose: Killing intracellular micro-organisms & tumor cells
Mediated by:
  • (a) Cytotoxic T-cell (Tc cell)
  • (b) NK cells
  • (c) ADCC (NK cells, Macrophages, Neutrophils, Eosinophils)

(a) Cytotoxic T-cell (Tc / CD8+ T-cell)

Activation Pathway:
  1. Processed Ag loaded on MHC-I of APC / any nucleated cell binds to TCR of CD8 T-cell (Tc cell)
  2. CD28 of Tc cell binds to B7 of APC (co-stimulatory signal)
  3. Cytokine signal - IL-2 from T_H1
  4. Tc cell gets activated → cytosolic tail of CD8 molecule has tyrosine kinase activity
  5. Causes phosphorylation of tyrosine residues of ITAM (Immunoreceptor Tyrosine Based Activation Motif)
  6. ITAM now acts as docking site for ZAP-70
  7. ZAP-70 (Zeta Associated Protein Kinase) becomes active → generates multiple intracellular signals
  8. Gene expression:
    • Perforins - Produce pores in target cell membrane
    • Granzymes - Enter through pores and induce APOPTOSIS of the cell

(b) NK Cells

  • Non-MHC restricted cells, no memory
  • Markers: CD16, CD56, CD99
  • Kill tumor cells & virus-infected cells
Mechanism of killing:
StepEvent
1Tumor/virus-infected cells show reduced MHC-I expression
2Inhibitory signal to NK cell is lost
3NK cells recognise ligands on such cells via activation receptors (CD16)
4NK cells activated → secrete Perforins & Granzymes
5Apoptosis of target cell
Why are normal cells NOT killed by NK cells?
  • Normal cells express MHC-I normally
  • NK cell receptors bind MHC-I → causes inhibitory signal → suppresses NK cell activity

(c) ADCC - Antibody Dependent Cellular Cytotoxicity

Steps:
  1. Virus-infected cells are coated by Fab portion of IgG immunoglobulins
  2. Effector cells (NK cell / Macrophage / Eosinophil / Neutrophil) bind to the Fc portion of IgG via their Fc receptors
  3. Cells get activated and release cytotoxic factors:
CellCytotoxic Factor
NK cellsPerforins & Granzymes
NeutrophilsLytic enzymes
EosinophilsPerforins & Lytic enzymes
MacrophagesLytic enzymes
  1. Lysis of the cell

Quick Exam Tips:
  • ZAP-70 = Zeta Associated Protein Kinase
  • ITAM = Immunoreceptor Tyrosine Based Activation Motif
  • CD8 T-cells are MHC-I restricted; NK cells are non-MHC restricted
  • Both Tc cells and NK cells kill via Perforins + Granzymes
  • ADCC uses antibody (IgG) to guide cellular killing

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A set of 4 exam flashcards on "Cell Mediated Immune Response" arranged in a 2x2 grid on a clean white background. Each card has a dark blue header with white question text and a light background answer section. Card 1 - Q: "What are the 3 mechanisms of Cell Mediated Immunity?" A: "a) Cytotoxic T-cell (Tc), b) NK cells, c) ADCC (NK cells, Macrophages, Neutrophils, Eosinophils)". Card 2 - Q: "What is ITAM and its role?" A: "ITAM = Immunoreceptor Tyrosine Based Activation Motif. After Tc activation, tyrosine residues of ITAM get phosphorylated → becomes docking site for ZAP-70". Card 3 - Q: "How does Cytotoxic T-cell kill a target cell?" A: "MHC-I + Ag → TCR binding + CD28-B7 co-stimulation + IL-2 → ZAP-70 activation → Perforins (pores) + Granzymes → Apoptosis". Card 4 - Q: "What is ZAP-70?" A: "Zeta Associated Protein Kinase. Docks to phosphorylated ITAM → generates multiple intracellular signals → gene expression of Perforins & Granzymes"

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A set of 4 exam flashcards on "NK Cells and ADCC" arranged in a 2x2 grid on a clean white background. Each card has a deep green header with white question text and a light background answer section. Card 1 - Q: "NK cell markers and key features?" A: "Markers: CD16, CD56, CD99. Features: Non-MHC restricted, No memory, Kill tumor & virus-infected cells". Card 2 - Q: "Why don't NK cells kill normal cells?" A: "Normal cells express MHC-I normally → NK cell receptor binds MHC-I → Inhibitory signal generated → NK cell suppressed". Card 3 - Q: "How do NK cells kill tumor/virus-infected cells?" A: "Reduced MHC-I on target → Inhibitory signal lost → CD16 activation receptor recognises ligands → Perforins & Granzymes secreted → Apoptosis". Card 4 - Q: "What is ADCC and which cells mediate it?" A: "Antibody Dependent Cellular Cytotoxicity. Mediated by: NK cells (Perforins+Granzymes), Neutrophils (Lytic enzymes), Eosinophils (Perforins+Lytic enzymes), Macrophages (Lytic enzymes)"

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