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SGU Immuno # 11 - Inflammation
SGU Immuno # 11 - Inflammation
73
Medical
Professional
12/27/2012

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Term
What is inflammation ?
Definition
Events that either occur locally, following trauma or infection and leading to rhep (redness, heat, edema, pain) or occur systematically.
Term
Markers of inflammation ?
Definition
rhep p
Redness, heat, edema, pain, and sometimes pus
Term
Heat and redness in inflammation reflect what ?
Definition
Vasodilatation (or increased blood flow) and extravasation
Term
Edema in inflammation is caused by ?
Definition
Leakage of fluid from circulation into tissues (increased vascular permeability)
Term
Pain in inflammation is due to?
Definition
Stimulation of nerve endings by bradykinin
Term
Pus in inflammation is ?
Definition
The accumulation of dead phagocytes and bacteria along with byproducts of tissue destruction
Term
3 classical inducers of inflammation are ?
Definition
TMT
Tissue damage, microbial infections, or toxic agents
Term
Some of the things that happen during inflammation ?
Definition
Tissue damage
Deposition of C3b (if infection)
Phagocytosis by tissue macrophages
Increase dendritic cells for endocytosis
Antigen particles migrate to lymph node
Term
Tissue damage, regardless of initiating agent, triggers what ?
Definition
Activation of coagulation pathway contact system
Contact system is composed of 4 proteins: Factor 12, Factor 11, prekallikrein, and high molecule weight kininogen
Term
What two things serve as target for Factor 12 binding ?
Definition
Collagen
Platelet membranes
Term
Activated Factor 12 does what ?
Definition
Converts prekallikrein to active kallikrein
Term
What does kallikrein do ?
Definition
Cleaves kininogen to release bradykinin (vasodilator that increases vascular permeability) and cleaves C5 to make C5a (anaphylatoxin that binds onto basophils and mast cells to induce degranulation and histamine release)
Term
Other than cleaving kininogen to release bradykinin, Kallikrein activates what cell ?
Definition
Neutrophils
Term
Vasodilatation leading to increased blood flow in inflammation is due to what 3 things ?
Definition
B H L
Bradykinin, Histamine, Leukotriene B4
Term
Mast cell activation or degranulation results in ?
Definition
Exocytosis of intracellular granules liberating histamine and other inflammatory mediators
Term
What occurs to a selectin following histamine binding to the vascular endothelium ?
Definition
P-selectin is rapidly translocated to the plasma membrane from cytoplasmic stores
Term
What are selectins ?
Definition
Selectins are monomeric proteins that bind carbohydrate molecules, producing transient and weak adhesion b/w two cells which lead to leukocyte rolling on the endothelium
Term
In presence of infection, what complement pathway is started ?
Definition
C3b is deposited on activating surface and triggers activation of alternative pathway of complement
Term
Activ. of complement by alternative pathway of complement generates what anaphylatoxins ?
Definition
C3a and C5a
Term
Interaction of C3a and C5a anaphylatoxins with their receptors causes what ?
Definition
Mast cell degranulation and release of histamine
Term
What cell type are the first responders in mediating clearance of necrotic tissue and/or invading organisms present at inflammatory sites ?
Definition
Macrophages (leukocytes)
Term
Activation of macrophages leads to what during inflammation ?
Definition
Recruitment of neutrophils and monocytes to site of inflammation
Term
Other than cytokines and chemokines, activated macrophages also secrete what 2 things ?
Definition
Matrix metalloproteinases (proteins that degrade basement membrane to allow cell migration) and TIMPS (tissue inhibitors of matrix metalloproteinases)
Term
What are matrix metalloproteinases ?
Definition
Proteins that degrade basement membrane to allow cell migration
Term
Are cell adhesion and firm rolling critical for inducing an inflammatory response ?
Definition
Yes
Term
CRP release due to IL-6 secretion has what role ?
Definition
Induces expression of VCAM-1, ICAM-1, and E-Selectin on human endothelial cells
Term
TNF and IL-1 induce vascular endothelial cells to secrete what chemokines ?
Definition
IL-8 and MCP-1
Term
MCP-1 and RANTES are chemotactic for ?
Definition
Monocytes and lymphocytes respectively
Term
RANTES is chemotactic for ?
Definition
Lymphocytes
Term
IL-8 is chemotactic for ?
Definition
Neutrophils
In early phase of inflammatory response, C5a and PAF (platelet activating factor) are also chemoattractants for neutrophils
Term
Leukocyte rolling is mediated by ?
Definition
Selectins
Term
Selectin family members include ?
Definition
LEP
L-selectin
E-selectin
P-selectin
Term
What selectin is expressed on circulating lymphcytes in "non-inflammatory" state ?
Definition
L-selectin
Term
E-selectins and P-selectins are expressed where ?
Definition
Not expressed on circulating cells but
on post capillary venules during inflammatory states
Term
Each selectin interacts with distinct
Definition
carbohydrate ligands
Term
Preferential expression of P and E selectins on postcapillary venules correlates with what ?
Definition
Greater migration of leukocytes into inflammatory sites
Term
Which selectin is not induced by TNF and IL-1 secretion ?
Definition
P-selectin
Term
Firm adhesion b/w leukocytes and endothelium is mediated by ?
Definition
Integrins (adhesive molecules)
Term
Integrins are classed into families based on ?
Definition
the beta chain they express
Exs) Integrins that have a B2 polypeptide belong to B2 integrin family, and integrins that have a B1 polypeptide belong to the B1 integrin family
Term
What is gelatinase B ?
Definition
A member of family of zinc-binding matrix metalloproteinases which degrades Type 4 collagen in reconstituted membranes
Term
Inhibitors of gelatinase B or elastase do what ?
Definition
Inhibit leukocyte transmigration across the reconstituted membranes
Term
Subendothelial basement membrane is normally a barrier to ?
Definition
Entry of leukocytes into tissues
Term
What happens to basement membrane under inflammatory conditions ?
Definition
Enzymes degrade the basement membrane permitting leukocyte (WBC) entry into tissues
Term
Interaction of PECAM on leukocytes with endothelial cells allows for what ?
Definition
Transmigration of cells in-between the endothelial cells
Term
Steps leading to diapedesis/transmigration of leukocytes to site of inflammation are ?
Definition
12 steps starting with expression of P-selectin on vascular endothelium and ends with migration of leukocytes into inflamed tissue
Term
Which two cytokines act on the hypothalamus to induce fever ?
Definition
TNF and IL-1
Term
Macrophage activity is enhanced by what cytokines ?
Definition
TNF and IFNgamma
Term
What things serve as an opsonin for phagocytosis ?
Definition
C3b and IgG
Term
Activated and memory lymphocytes express high concentrations of which integrins ?
Definition
LPAM and VLA-4
Term
Another name for pro-gelatinase A and pro-gelatinase B ?
Definition
MMP-2 and MMP-9
Term
When are pro-gelatinase A and pro-gelatinase B secreted ?
Definition
During inflammation, pro-gelatinase A is secreted
Secretion of pro-gelatinase B is induced by vasoactive intestinal peptide and interaction of VLA-4 on activated memory lyphocytes with endothelial VCAM-1
Term
Conversion of pro-gelatinases to their active form is mediated by ?
Definition
Elastase and other MMP family members secreted by macrophages and other inflammatory cells
Term
What two cytokines are potent activators of macrophages and lead to enhanced phagocytosis ?
Definition
IFNgamma and TNF
Term
What are some cytokines that inhibit development of Th1 response ?
Definition
IL-4
IL-10
TGFbeta
Term
LFA-3 on APCs binds to what on T-cells ?
Definition
CD2
Term
CD154 on T-cells binds to what on APCs ?
Definition
CD40
Term
Another name for MAC-1 ?
Definition
(CD11b and CD18)
Term
Another name for LFA-1 integrin ?
Definition
(CD11a and CD18)
Term
VCAM-1 on activated vascular epithelium binds to what on leukocytes and eosinophils ?
Definition
VLA-4 (CD49d and CD29)
Term
E-selectin and P-selectin on activated vascular endothelium binds to what on leukocytes and eosinophils ?
Definition
Cognate counter molecule
Term
MHC Class 2 on APCs binds to what on T-cells ?
Definition
CD4
Term
MHC Class 1 on APCs binds to what on T-cells ?
Definition
CD8
Term
Another name for CD80 and CD86 ?
Definition
(B7-1 and B7-2)
Term
B7-1 and B7-2 on APCs binds to what on T-cells ?
Definition
CD28 and CD152 (CTLA-4)
Term
Another name for CTLA-4 ?
Definition
CD152
Term
CTLA-4 binds to what on APCs ?
Definition
CD80 and CD86 (B7-1 and B7-2)
Term
LFA-1 on T-cells binds to what on APCs ?
Definition
ICAM-1, ICAM-2, ICAM-3
Term
What is effect of CD28 binding to CD80 and CD86 ?
Definition
Enhanced transcription of IL-2 gene, stabilization of IL-2 mRNA, costimulation
Term
Effect of CD8 binding to MHC Class 1 is what ?
Definition
Costimulation
Term
Affect of PECAM binding to PECAM is what ?
Definition
Adhesion for transmigration
Term
CD40 binding to CD40L (CD154) has what effect ?
Definition
Isotype Switching in B cells
Term
(Extra) What antibody plays a role in anaphylatic shock ?
Definition
IgE
Term
(Extra) Which cytokine plays a key role in fungal infections and extracellular bacterial infections?
Definition
IL-17
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