Inflammatory Mediators Flashcards
CD14
Present on macrophages. Recognizes the PAMP LPR of gram neg bacteria. Co-receptor for TLR
NFkappaB
Nuclear transcription factor. Activated when TLR activated and lesads to activation of immune response and production of multiple inflammatory mediators
Phospholipase A2
Releases arachidonic acid from the phospholipid cell membrane
Prostaglandins
PGI2, PGD2, PGE2 mediate vasodilation and increased vascular permeability
PGE2 mediates pain and fever
Leukotrienes
Produced by arachidonic acid metabolism by 5-lipoxygenase
LTB4 attracts and activates neutrophils
LTC4, LTD4, LTE4 mediate vasoconstriction, bronchospasm, increased vascular permeability (slow reactors of anaphylaxis)
Four things that activate neutrophils
LTB4, C5a, IL-8, bacterial products
Three ways to activate mast cells
Tissue trauma
C3a and C5a
Crosslinking of IgE by antigen
HIstamine
Causes vasodilation and increased vascular permeability
Actions of mast cells
Immediate response: release of preformed histamine
Delayed response: production of luekotrienes from arachidonic acid maintaining acute inflammation
Alternate complement activation pathway
Microbial products directly activate complement
Mannose binding lectin pathway for complement
MBL binds mannose on microorganisms activating complement
C3a
Triggers mast cell degranulation (anaphylatoxic)
C5a
Triggers mast cell degranulation (anaphyatoxic) and chemotactic for neutrophils
C3b
opsonin for phagocytosis
Hageman factor
Actvated by exposure to subendothelial or tissue collagen. Turns on coagulation and fibrinolytic systems, complement, and kinin system
Bradykinin
Mediates vasodilation, increased vascular permeability, pain
Pain mediators
Bradykinin and PGE2
Mediators of fever
Macrophages release IL-1 and TNF which increase COX activity in perivascular cells of hypothalamus. This increases PGE2, raising temp set point
Weibel-Palade bodies
On endothelial cells. Contain von willebrand factor and P-selectin, which is involved in leukocyte rolling
Selectins
P-selectin from Weibel-Palade bodies. Released in response to histamine
E-selectin induced by TNF and IL-1
Responsible for leukocyte rolling
CD18
Component of integrins. Defective in leukocyte adhesion deficiency. Necessary for leukocyte adhesion to endothelium
Opsonins
IgG and C3b
Myeloperoxidase
Converts H2O2 to bleach
IL-10
Anti-inflammatory cytokine made by macrophages
TGF-beta
Anti-inflammatory cytokine made by macrophages
IFN gamma
secreted by Th1 cells. Activates macrophages. Promotes B cell class switching from IgM to IgG, promotes Th1 over Th2 phenotype
Th2 cell secretions
IL-4: B cell class switching to IgE
IL-5: eosinophil chemotaxis and activation, class switching to IgA
IL-13: similar to IL-4
IL-10: inhibits Th1
IL-2
From Th1 cell. Serves as second activation signal for CD8+ activation
CD8+ killing
Perforin and granzyme: activate apoptosis
FasL-Fas interaction: activates apoptosis
CD40
Receptor on B cells binds to lignand on Th cell providing second activation signal for B cell