Inflammation II Flashcards by tcarlso 3

What are the two major processes of phagocytosis?

Recognition and attachments via complement

2. Engulfment

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What is the function of complement?

Attach to microbes and macrophages

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What is the process of engulfment?

Pseudopods surround object, forming, phagosome fusing with lysosome

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Phagosome + lysosome = ?

Phagolysosome

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What are the two types of mechanisms of microbe killing?

Oxygen dependent

2. Oxygen independent

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What are the three steps of oxygen dependent killing?

Oxygen is reduced to superoxide via NADPH oxidase
Superoxide is then converted to H2O2 by superoxide dismutase
Myelo-peroxidase from PMNs granules catalyzes rxn b/t Cl and H2O2, forming HOCl

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What are the oxygen-independent ways to kill microbes? (2)

Leukocytes granule proteins, and enzymes

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What are the four outcomes of leukocyte activation?

Production of arachidonic acid metabolites
Degranulation and secretion of lysosomal enzymes
Secretion of cytokines
Modulation of leukocyte adhesion molecules

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Where do mediators come from? What is their function?

plasma or granules of cells

Bind to specific receptors on target cells to stimulate other cell response

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What are the three sequential phases of chemical mediators that leukocytes express?

Initiation
Amplification
Termination

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Why are mediators short lived?

To prevent over reaction, since most have potential to cause harm

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What are the two major vasoactive amines? What are their functions (3)?

Histamine and serotonin

arteriolar dilation
constriction of large arteries
Increase permeability of postcapillary venules

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Where are vasoactive amines stored?

Preformed granules of mast cells or others

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What are the first mediators likely to be released in response to damage?

Vasoactive amines

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What stimulates mast cells? (5)

Trauma
Platelet aggregation
IgE activation
Complement
Cytokines

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What are the three plasma protein systems?

Complement
Kinin
Clotting

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What activates the classical pathway of complement activation?

binding of an IgG or IgM complex to C1 (“GM makes C1assic cars”)

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What activates the alternate pathway of complement activation?

C3 directly activated by bacterial endotoxins, or aggregated IgA

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What activates the lectin pathway of complement activation?

C1 activation by binding of mannose-binding lectin to carbs on microbes

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What is the essential pathway of complement activation (where all three pathways converge)?

C3 activation (cleavage)

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What is the function of C3a, C4a, and C5a?

Stimulate histamine release from mast cells

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What is the function of C5a specifically?

chemotaxis of monocytes and granulocytes via increased expression of leukocytes CAM which activates lipoxygenase pathway

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What is the function of C3b specifically?

Opsonization with recognition by receptors on PMNS

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What is the function of C5-9?

Membrane attack complex

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What is the function of Factor XII (Hageman factor)? How is it activated?

Triggers the kinin system, fibrinolytic system, and the clotting cascade Activated by direct contact with endotoxins, collagen, or basement membrane

Activated Hageman factor (XII) does what in the kinin system, specifically?

Converts prekallikrein to Kallikrein

What is the function of Kallikrein after it is activated via Hageman factor (XII)?

amplifies hageman factors activation Cleaves kinins, including bradykinin Converts plasminogen to plasmin

What is bradykinin?

A **short lived** vasoactive peptide that increases vascular permeability, and**causes pain**

What inactivates bradykinin?

Plasma kininase

What is the coagulation-fibrinolytic system?

Cascade of reaction resulting in a fibrin clot which is then dissolved by the fibrinolytic system

What is the function of thrombin?

Cleaves fibrinogen to insoluble fibrin

Why is thrombin significant in terms of the inflammatory system?

Links the coagulation system and the inflammatory system

What is the function of plasmin? (2)

Lyses fibrin clots to form fibrin split products Cleaves C3 to C3a

What activates Hageman factor (XII)?

Collagen, basement membrane, activated platelets

What is arachidonic acid?

Lipid normally bound to cell membrane phospholipids and is released by the action of cellular phospholipases

What are the two pathways that activate arachidonic acid?

COX | LOX

What are the AA metabolites produced in the COX pathway?

``` TXA2 PGI2 PGE2 PGD2 PGF2 PGE ```

What is the function of TXA2? (2)

Potent platelet aggregator and vasoconstrictor

What is the function of ASA in treating an MI specificalLy?

inhibits production of TXA2, thus inhibits platelet aggregation and vasoconstriction

What is the function of PGI2?

Vasodilator and inhibitor of platelet aggregation

What is the function of PGE2?

Sensitizes skin to painful stimuli and fever

What is the function of PGD2, PGF2, and PGE2?

Vasodilation/edema

What are the metabolites of the LOX pathway?

LTB4 | LTC4, D4, E4

What is the KEY function of LTB4?

Potent chemoattractant causing PMN aggregation and adhesion to endothelial cells

What are the functions of LTC4, D4, and E4?

Causes intense vasoconstriction and bronchospasm

What are lipoxins?

Endogenous **negative** regulators of Leukotriene action

What is the function of lipoxin A4 and B4?

Inhibit PMN adhesion to endothelium and PMN chemotaxis

What is the function of steroids in treating asthma?

Inhibit phospholipases that produce AA

What are the two pathways that AA can go down?

Cyclooxygenase (COX) | Lipoxygenase (LOX)

What is the MOA of ASA?

Inhibits Cyclooxygenase

What generates platelet activating factors (PAF)?

basophils, PMNs, etc

What is the main function of PAF? What is this dependent on?

Vaso/bronchoconstriction at high[C], BUT opposite at low [C]

What is the other, more minor functions of platelet activating factor (PAF) mentioned in class?

Stimulates prostaglandin & leukotriene synthesis

What are cytokines and chemokines?

Polypeptide which function as "cellular hormones", that participate in intricate networks to achieve their effects

What are the key cytokines?

IL-1 IL-8 and TNF-alpha

What produces IL-1 and TNF-alpha? (or cytokines in general)

activated macrophages

What are the acute phase effects of IL-1 and TNF-alpha?

Fever, sleep, shock, neutrophilia and hemodynamic effects

What are the three endothelial effects of IL-1 and TNF-alpha?

1. Increase leukocyte adherence 2. Produces IL-1 3. Increases Procoagulant activity

What is the major fibroblastic effects of IL-1 and TNF-alpha?

Increased collagen synthesis

What are the leukocyte effects of IL-1 and TNF-alpha?

Increase cytokine secretion (IL-1, IL-6)

What is the function of chemokines?

Stimulates leukocyte recruitment in inflammation

Almost all chemokines are what type of molecule?

Cysteine residues with some other amino acids in there somewhere

What is the function of C-X-C (or alpha) chemokines?

Act primarily on PMNs | IL-8

What is the function of C-C (or beta) chemokines?

Attract cells BESIDES neutrophils

What is the function of C or Gamma-chemokines?

Specific fo lymphocytes

What is the function of CX3C chemokines?

Strong attractant for monocytes and T cells

What are the two functions of NO?

Vasodilation | Reduces platelet aggregation

What are the two places that NO are prodced?

Endothelial cells | Macrophages

What are the effects of ROS? (3)

1. Endothelial cell damage 2. Inactivation of antiproteases 3. Injury to other cells

What is substance P? Neurokinin A?

Both are neuropeptides, and act to cause pain, increases vascular permeability

Vasodilation is caused by what two chemicals?

PG, NO

Vascular permeability is produced by what?

Vasoacive amines, | C3a, C5a Leukotrienes (C4 D4 and E4) substance P

Chemotaxis and leukocyte activation is produced by what?

C5a, leukotriene B4, chemokines

Fever is produced by what?

IL-1, IL-6, TNF-alpha, and PG

Pain is produced by what?

PG and bradykinin

What produces tissue damage?

Lysosomal enzymes Oxygen metabolites NO

Why is it that you do not develop a severe allergic reaction to a substance upon first exposure?

Because IgE needs to bind to mast cells (via Fc region) and "prime" it for next time

What is the main constituent of bee venom? What does this cause?

Bradykinin= pain

What are the three systems that activation of the Hageman factors sets in motion (4)

1. Kinin cascade 2. Fibrinolytic system 3. Complement cascade 4. Clotting cascade

What is the cause of the bronchoconstriction seen in an allergic reaction?

Production of LTC4, D4, and E4

What are the endogenous inhibitors of leukotrienes?

Lipoxins

What are the major chemicals that inhibit neutrophil adhesion to the endothelium and neutrophil chemotaxis?

Lipoxin A4 and B4

What does the COX pathway produce?

Prostaglandins

What does the LOX pathway produce?

Leukotrienes

What is the **really** general function of lysosomal enzymes of leukocytes? Why is this bad if left unchecked?

Destroy stuff, and that's bad

Inflammation II Flashcards

(85 cards)