2 - Inflammation Flashcards
What activates TLR?
PAMP
TLR activation results in up regulation of …, which activates immune response genes leading to production of multiple …?
NFKB; immune mediators
Inflammasomes sense dead cell products –> activates … –> which activates … –> resulting in …
caspase-1; IL-1; Leukocyte Recruitment
What are the cell-derived mediators of Acute Inflammation?
AA metabolites, Masts Cells, Cytokines, NO
What are the plasma-protein derived mediators of Acute Inflammation?
Complement, and Hageman Factor
AA is released from the phospholipid cell membrane by …
phospholipase A2
AA is acted upon by what?
cyclooxygenase OR 5-lipoxygenase
AA Metabolites: What does Cyclooxygenase produce?
Prostaglandins (PG) and Thromboxane A2 (TXA2)
AA Metabolites: What PGs mediate vasodilation and increased vascular permeability?
PGI2, PGD2, PGE2
AA Metabolites: What also mediates pain and fever?
PGE2
AA Metabolites: What inhibits platelet aggregation?
PGI2
AA Metabolites: What causes vasoconstriction, platelet aggregation?
TXA2
AA Metabolites: What does 5-lipoxygenase produce?
Leukotrienes (LT)
AA Metabolites: What attracts (chemotaxis) and activates neutrophils?
LTB4
AA Metabolites: What are slow reacting substances of anaphylaxis; mediate vasoconstriction, bronchospasm, and increased vascular permeability?
LTC4, LTD4, and LTE4
AA Metabolites: What inhibit neutrophil chemotaxis and adhesion?
Lipoxins
What do Corticosteroids (cortisones, prednisone) inhibit?
Phospholipase
What do NSAIDS inhibit?
COX
What is expressed in most tissues and increased during inflammation?
COX-1
What is absent from most normal tissues and is induced during inflammation?
COX-2
What are the COX-1 inhibitors? (3)
aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve)
What is the COX-2 inhibitor?
Celebrex
What are Lipoxygenase inhibitors (Singular) used to treat?
Asthma
What 3 things activate Mast Cells?
- tissue trauma
- C3a and C5a
- cross-linking of IgE by antigen
The Immediate Response of Mast Cells involves the release of what?
histamine granules
The Delayed Response of Mast Cells involves production of what?
AA metabolites, particularly LT (prolong the inflammatory response over hrs)
What Cytokines are the Acute Inflammation major players and what is their main role?
TNF, IL-1, IL-6
endothelial cell activation
What Cytokines are the Chronic Inflammation major players?
INF-g, IL-12
What is an example of a Chemokine = cytokine that acts as chemotactic agents for various inflammatory cells?
IL-8
What Cytokines exhibit negative feedback to downregulate inflammation?
IL-10, TGF-B
All Complement pathways result in production of what, which in turn, produces what?
C3 convertase –> C5 convertase
C5b complexes with C6-C9 to form what?
MAC (membrane attack complex)
Complement: What triggers mast cell degranulation?
C3a, C5a
Complement: chemotactic for neutrophils?
C5a
Complement: opsonin for phagocytosis?
C3b
Complement: lyses microbes by creating a hole in the cell membrane?
MAC
Hageman Factor (Factor XII) is produced in the liver, and activated upon exposure to sub endothelial or tissue …
collagen
Hageman Factor: activates Coagulation and Fibrinolytic Systems, Complement, and …
Kinin System
Hageman Factor: What does Kinin do?
cleaves HMWK –> bradykinin
Cardinal Signs of Acute Inflammation: Redness and Warmth, due to vasodilation, occurs via relaxation of arteriolar sm; what are the key mediators?
histamine, PGs, bradykinin
Cardinal Signs of Acute Inflammation: What mediates Pain (dolor)?
Bradykinin and PGE2, sensitize sensory nerve endings
Cardinal Signs of Acute Inflammation: What causes Fever?
Pyrogens and increased PGE2
Cardinal Signs of Acute Inflammation - Fever: Pyrogens cause macrophages to release what, which increase COX activity in perivascular cells of the hypothalamus
IL-1, TNF
What is the hallmark cell of acute inflammation?
neutrophils
Rolling: what is P-selectin mediated by?
histamine
Rolling: What induces E-selectin?
TNF, IL-1
What do Selectins bind to that results in rolling of leukocytes along vessel wall?
sialyl-Lewis X
What are the Cellular adhesion molecules?
ICAM and VCAM
Adhesion: what become high affinity and are unregulated by C5a and LTB4?
Integrins
Interaction of what results in firm adhesion of leukocytes to the vessel wall?
CAMs and integrins
Transmigration and Chemotaxis: Neutrophils are attracted by what bacterial products?
IL-8, C5a, LTB4
Phagocytosis: is enhances by what opsonins?
IgG and C3b
Chronic Granulation Disease is characterized by poor O2 dependent killing, due to what defect?
NADPH oxidase defect (X-linked or autosomal recessive)
What test is used to screen for CGD?
Nitroblue tetrazolium
What predominate after neutrophils and peak 2-3 days after inflammation begins?
Macrophages
What from macrophages recruits additional neutrophils?
IL-8
What kind of Inflammation is due to burn or viral infection, tend to be watery?
Serous inflammation
What kind of inflammation is common in bacterial infections
Purulent or suppurative inflammation
What kind of inflammation is rich in fibrin which makes it sticky, covering called a pseudomembrane; noted when inflammation occurs in a body cavity?
Fibrinous Inflammation
Classical Pathway - Macrophage Activation: induced by microbial products (LPS), T cell signals, foreign substances and …
IFN-gamma
What induces the Alternative Macrophage Activation Pathway?
IL-4, IL-13 from T cells and other cells
In the Alternative Macrophage Activation Pathway macrophages are not actively attacking microbes, instead they help in repair by secreting … to promote angiogenesis, fibroblast activation, collagen synthesis?
TGF-Beta
What produce IFN-gamma stimulate classical pathway for MACs?
Th1 cells
What secrete IL-4, IL-13 which activate eosinophils and stimulate alternative pathway for MACs; important in allergic inflammation and in defense against parasites?
Th2 cells
What secrete IL-17 recruits PMNs and monocytes?
Th17 cells
Found in inflammatory sites around parasitic infections and associated with Ig-E mediated immune reactions (allergies)
Eosinophils
