12/22/2010

cytotoxicity

Cytotoxic agents are toxic to cells:
● Cytotoxic physical agents
___ ● thermal (excessive heat or cold)
___irradiation

● Cytotoxic drugs and chemicals have cytolytic, carcinogenic, mutagenic and/or teratogenic potential. Direct contact may cause tissue irritation, ulceration, and necrosis.
___ ● antineoplastic and immunosuppressive therapeutic agents
___ ● free radicals
___ ● strong acids and alkalis
___ ● secreted digestive enzymes and antimicrobials – lysozyme, phospholipase, defensins
___ ● secreted cytolytic molecules • FasL, granzymes, granulysin, perforin
___phagocytosis-promoting opsoninsC3b of complement cascade, pulmonary surfactants

● Cytotoxic cellular immune responses
_ ● Antibody-dependent cell-mediated cytotoxicity (ADCC) is mediated by antibody-marking
_ ● Complement-dependent cytotoxicity (CDC) is mediated by the complement system (opsonin-induced phagocytosis performed by macrophages and neutrophils, anaphylatoxin induced histamine release by basophils and mast cells).
_ ● Lymphocyte-mediated cytotoxicity ('LMC') requires is independent of antibody-marking and the complement system

__killer cells
___ ● non-specific 'attack' cells – eosinophils (IgE, CD67), macrophages (IgG, CD14), K cells (IgG), LAK cells (IL-2 activated cytolysis cells, lymphokine-activated killer cells), NK cells (CD16, CD56)
___ ● natural killers cells (NK) of innate immune system – have activating receptors and killer inhibitory receptors (KIR) – secrete cytolytic granzymes and perforin ('LMC')
___ ● natural killer T cells (NKT) – have αβ TCR plus some of the cell-surface molecules of NK cells – respond to glycolipid antigens presented by the cell-surface molecule CD1d (ADCC) – secrete IFN-γ (Th1 cytokine) plus IL-4 and IL-13 (Th2 cytokines)
___ ● cytotoxic T cells • (CD8 +) Tc matures into CTL (killer T cells) following activation (ADCC)
___phagocytic cells engulf pathogens, often after pathogen coating by opsonins (CDC)

Tables  Fc receptors  Immune Cytokines  Immunoglobulins

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