INNATE IMMUNITY

INNATE IMMUNITY rapid (minutes/hours), generalized response to injury FEATURES: primary response shares effectors w/ adaptive immunity; stimulates adaptive immunity recognizes MOLECULAR patters (as opposed to structural patterns) INVARIANT receptor classes (as opposed to recombined) appears in JAWED VERTEBRATES TARGETS: PAMS (pathogen-associated molecular patterns) invariant and specific to pathogen; necessary for pathogen survival (ex/ dsRNA, LPS, mannoprotein, f-Met, etc.) host has RECEPTORS: PRR’s (pattern recognition receptors) germline encoded; not arranged widely distributed (intracellular, cell surface, and secreted) varied functions – opsonization phagocytosis complement cytokine release apoptosis TLR’s – TOLL LIKE RECEPTORS transduce PAMP signal into effector cell trigger at least 2 signal transduction cascades MAPK inflammatory different TLR’s  different responses 2 – recognizes yeast 4 – LPS INNATE IMMUNE CELLS NEUTROPHILS MACROPHAGES short lived (days) long lived kill bacteria kill bacteria AND regulate inflammation ROI, degradative enzymes cytokine secretion can present antigens ROI and NO both arise from MYELOID progenitor cells (which came from pluripotent hematopeoetic stem cell) NEUTROPHILS – mature in bone marrow and released into blood adhere/diapedese through tissue kill pathogens by phagocytosis and use of ROS/degradative enyzmes all activities are cytokine regulated Defects: NEUTROPENIA – fatal due to bacterial/fungal infection Defects can occur in adherence chemotaxis killing MACROPHAGES – can live in tissue for >1 month interact w/ adaptive immune system can remodel tissue can kill pathogens LEUKOCYTE CIRCULATION/MIGRATION 1) Rolling (loose adhesion) mediated by SELECTINS (P/E) on epithelium; L on leukocytes LIGANDS are neutrophil CHO’s 2) CYTOKINE ACTIVATION of both leukocyte and epithelial cells 3) TIGHT adhesion  stops rolling Neutrophils: INTEGRINS Endothelium: CAM’s (cell adhesion molecules) 4) DIAPEDESIS migrates towards a junction and cytokine-mediated diapedesis 5) MIGRATION through tissue along chemotactic gradient towards i