Chapter 4 ( Innate Immune Response ) Flashcards
Rolling is the result of interaction of ?
E-selectin molecules on the endothelium with mucin-like adhesion molecules on phagocyte membrane
The results of activation of phagocyte by chemoattractants ?
They trigger G protein mediated activating signal , this signal induces a conformational change in integrin molecules in the phagocyte membrane that increases their affinity for immunoglobulin-superfamily adhesion molecules on the endothelium
Leukocyte adhesion deficiency mechanism ?
Absence of CD 18 ( the common Beta2 chain of a number of integrin molecules )
Chemoattractive molecules ?
IL-8
C5a
Leukotriene B4
Formyl methionyl peptides
Proinflammatory cytokines ? Their effect ?
IL-1
IL-6
TNF-alpha
Have systemic effect on tissues leading to :
Fever
Production of acute phase proteins as CRP , mannose binding protein and complement components
Leukocytosis
Opsonins ?
IgG
C3b
Oxygen independent degradative materials ?
1- Lysozyme : digests bacterial cell wall by cleaving peptidoglycans
2- Defensins : forms channels in bacterial cell membrane
3- Lactoferrin : chelates iron
4- hydrolytic enzymes
Catalase positive organisms ?
Staphylococcus
Klebsiella
Serratia
Aspergillus
Investigations for CGD ?
Nitroblue tetrazolium reduction test
The Dihydrorhodamine test
Specialized intra-epithelial lymphocytes which are part of the innate immunity ?
Gamma delta T cells
pH of the skin ?
Slightly acidic
Mechanism of INF alpha and beta as an antiviral interferons ?
By transiently inhibiting nascent protein synthesis in cells
Examples for PAMPs ?
Bacterial LPS
N-formyl peptides
Activation of the inflammasome results in secretion of ?
IL-1 beta
IL-18
Mutation in signaling molecules effecting TLRs result in ?
Recurrent severe bacterial infection
Gain of function mutations in inflammasome result in ?
Gout
Atherosclerosis
Type ll DM
NOD-2 mutations results in ?
IBD
IL-12 receptor deficiency and INF-gamma receptor deficiency results in ?
Recurrent infections with intracellular bacteria ( Mycobacterium )
Pathways for macrophage activation ?
1- Classic M1 : induced by innate immunity ( TLRs , INF-gamma )
Phagocytosis and initiates inflammatory response
2- Alternative pathway M2 : induced by IL-4 , IL-13
Tissue repair and control of inflammation
Ways for activation of mast cells ?
1- innate TLRs
2- antibody-dependent IgE
Functions of the complement system ?
1- mediate inflammation by recruitment of inflammatory cells and anaphylatoxins ( function of C3a , C4a , C5a )
2- enhance phagocytosis by opsonization and clearance of immune complexes ( function of C3b )
3- cause lysis of particles by membrane pore formation ( function of MAC )
How the MBP of the complement system is activated ?
By binding to carbohydrates on the pathogen
How interferon inhibits viral protein synthesis ?
1- activation of an RNA endonuclease , which digests viral RNA
2- phosphorylation of protein kinase , which inactivates eIF2 , inhibiting viral protein synthesis
TNF-alpha actions ?
It acts on :
1- hypothalamus —> fever
2- liver —> stimulates the production of acute phase proteins
3- Endothelial cells —> increases expression of ICAMs
4- Neutrophils —> activation
5- tumor cells —> apoptosis
6- fat and muscle —> cachexia
IL-8 actions ?
Act on leukocytes causing induction of :
Adherence to endothelium
Chemotaxis
Extravasation
IL-15 action ?
Proliferation of NK cells
IL-18 action ?
Stimulation of INF-gamma synthesis
IL-10 actions ?
It acts on macrophages and dendritic cells causing :
1- inhibition of IL-12 production
2- decreased expression of costimulatory molecules
3- decreased class ll MHC expression
INF-alpha and INF-beta actions ?
Acts in all cells causing transient inhibition of protein synthesis and increased class l MHC expression
Acts on NK cells causing activation
INF-beta is secreted by ?
Fibroblasts
INF-alpha is used in the ttt of which cancers ?
Hairy B cell leukemia
CML
Kaposi sarcoma
INF-beta is used in the ttt of ?
MS
INF-gamma is used in the ttt of ?
CGD
Side effects of INF therapy ? How to counter them ?
Fever
Chills
Fatigue
Acetaminophen
