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Immunology Lecture 5
Innate Immunity & Complement System
27
Immunology
Graduate
10/21/2012

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Term
What is the role of innate immunity in bacterial infections?
Definition
Innate immunity serves to phagocytose extracellular pathogens with the use of acute phase proteins produced in the liver. Acute phase proteins are produced in response to IL-6 which is secreted by macrophages
Term
What is the role of innate immunity in viral infections?
Definition
innate immunity functions to lyse virally infected cells via natural killer cells and activating cytotoxic T cells. Macrophages secrete IL-12 and INF I, which activates natural killer cells and T helper cells (1) which activate cytotoxic T cells
Term
Macrophages role in mediating mechanisms of innate immunity
Definition
secrete cytokines
Term
Neutrophils role in mediating mechanisms of innate immunity
Definition
engulf, degrate and destroy via pathogens via intracellular granules
Term
Natural Killer cells role in mediating mechanisms of innate immunity
Definition
lyse virally infected cell and produce cytokines
Term
IL-6
Definition
Stimulates synthesis of acute-phase and complement proteins in the liver
Term
TNF alpha
Definition
Systemic (fever) and Local (tumor, rubor, calor, dolor) inflammation
Term
IL-1 beta
Definition
Lymphocytes’ activation, Production of IL-6
Term
CXCL8
Definition
Chemotaxis: accumulation of inflammatory cells in the center of reaction
Term
INF1 and IL-12
Definition
NK and T helper cell 1 activation
Term
chemotaxis
Definition
Chemotaxis is the accumulation of inflammatory cells in the center of the reaction
Term
chemokines
Definition
control cell trafficking
Term
cell trafficking
Definition
regulated by CAMs and chemokines
Term
cell homing
Definition
white blood cells to the site of infection
Term
Phagocytic receptor function of the macrophage
Definition
Phagocytic receptors are Lectins (recognize carbohydrates) or Scavenger receptor (recognize negatively charged ligands). There is a Mannose receptor, a Glucan receptor, and a LPS receptor
Term
signaling receptor function of the macrophage
Definition
Toll like receptor activation results in triggering of the cascade of the signaling pathway leading to the release of the transcriptional factor NF(kappa)B which induces expression & transcription of the inflammatory and immune responses genes, detects microbial components
Term
complement receptor function of the macrophage
Definition
CR3 and CR4
Term
Alternative Pathway
Definition
Part of Innate immunity
1) C3 is cleaved in plasma into C3a and C3b
2) C3b attaches to pathogen surface
3) factor B binds C3b
4) factor D binds to C3b, and causes factor B to be cleaved into Bb and Ba
5)Bb attaches to C3b and factor D leaves
6) C3bBb is alternative C3 convertase
7) C3 convertase cleaves C3 into C3b and C3a
8) C3b can attach to pathogen surface OR attach to C3 convertase to create C5 convertase
9) C5 convertase cleaves C5 into C5b and C5a
10) C5b initiates membrane attack complex
Term
Lectin Pathway
Definition
Part of Innate Immunity
1) MBL binds to carbohydrates on the pathogen surface
2) MASPs becomes active via binding
3) MASPs cleave C4 into C4a and C4b, C4b attaches to pathogen surface
3a) MASPs cleave C2 into C2a and C2b, C2b attaches to C4b on surface
4) C4bC2b complex = classical/lectin C3 convertase
5) C3 convertase cleaves C3 into C3b and C3a, C3b binds to cell surface or binds to C3 convertase to turn it into C5 convertase
6) C5 convertase cleaves C5 into C5a and C5b, C5b initiates membrane attack complex
Term
Classical Pathway
Definition
Part of adaptive and innate immunity
1) C reactive proteins or Ab bind to pathogen surface
2) C1 bind to C reactive proteins or Ab, C1 becomes active protease
3) C1s cleaves C4 into C4a (anaphylaxis) and C4b and C2 into C2a and C2b
4) C4b binds to pathogen surface, C2a binds to C4b (C4bC2a convertase aka C3 convertase)
5) C3 convertase can cleave C3 molecules into C3a and C3b, C3b attaches to C3 convertase to create the C3/C5 convertase
6) C3/C5 convertase cleaves C3 into C3a and C3b, C3b attaches to cell surface to induce phagocytosis
6a) C3/C5 convertase cleaves C5 into C5a and C5b, C5b initiates membrane attack complex
Term
C3bBb complex
Definition
produced in the alternative pathway from factor D causing the cleavage of factor B into Bb and Ba. Bb associates with C3b on pathogen surface

C3 convertase cleaves C3 into C3b and C3a. C3b attaches to pathogen surface or associated with C3 convertase to create C5 convertase
Term
C4bC2a complex
Definition
produced in the classical pathway from C1s cleaving C4 and C2 and C4b and C2a binding to pathogen surface

produced in the lectin pathway from MASP protease cleaving both C4 and C2, and C4b and C2b associating and binding to cell surface

C3 convertase aka C4bC2a protease cleaves C3 into C3a and C3b. C3b binds to C3 convertase and creates C3/C5 convertase.
Term
C5b fragment
Definition
initiates membrane attack complex
Term
Function of alternative convertases
Definition
C3bBb: continues cleavage of the soluble C3 molecules while bound to the pathogen surface
Term
Function of classical convertases
Definition
C4bC2a: component of both the lectin & classical pathways of complement activation. It binds & cleaves C3 to yield C3b fragment attached to the pathogen surface
Term
Role of C3a fragment
Definition
fragment acts as a chemoattractant which recruits phagocytes from blood circulation
Term
Role of C5a fragement
Definition
fragments are termed anaphylatoxins because sometime these inflammatory reactions can generalize & cause anaphylactic shock
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