Inflammatory Mediators

Question 1

effect of histamine release

Answer 1

dilation of arterioles and increased permeability of venules by producing interendothelial gaps due to retraction of endothelial cell

Question 2

how is histamine mediated?

Answer 2

binding to H1 receptors on microvascular endothelial cells

Question 3

what does production of histamine induce

Answer 3

induces synthesis of prostacyclin and nitric oxide (smooth muscle relaxants and vasodilation)

Question 4

what are things that stimulate release of histamine from mast cells

Answer 4

trauma, cold, heat, binding of Ab to mast cell, C3a and C5a, IL-1, IL-8, substance P, histamine releasing proteins from WBC

Question 5

where are histamines stored

Answer 5

preformed and stored in granules and released immediately

Question 6

what is the source of serotonin?

Answer 6

platelets and some neuroendocrine cells

Question 7

when is serotonin released?

Answer 7

released with histamine during platelet aggregation

Question 8

what does serotonin do

Answer 8

vasoconstrictor and is a neurotransmitter in the GI tract

Question 9

what do steroids do

Answer 9

inhibits phospholiases that are needed for the arachidonic acid pathway. reduce transcription of genes encoding COX-2, phospholipase A2, proinflammatory cytokines and iNOS

Question 10

what is produced in the arachidonic acid pathway

Answer 10

1. cylooxygenases

2. 5-lipooxygenase

Question 11

what does prostacyclin do (PGI2)

Answer 11

vasodilation, inhibit platelet aggregation

Question 12

what does thromboxane A2 do?

Answer 12

vasoconstriction, promote platelet aggregation

Question 13

what does PGE/PGD do

Answer 13

vasodilation, increased vascular permeability

Question 14

what pathway makes prostaglandins and thromboxanes?

Answer 14

cyclooxygenase (COX)

Question 15

what do aspirin, indomethacin do?

Answer 15

inhibit COX1 and COX2 (inhibit making of prostaglandins and thromboxanes)

Question 16

how is leukotriene B4 made?

Answer 16

5-lipooxygenase makes 5-HETE which makes leukotriene B4

Question 17

what makes leukotriene C4, D4, and E4

Answer 17

5-lipooxygenase

Question 18

what do leukotrienes C4, D4, and E4 do

Answer 18

bronchospasm and increased vascular permeability

Question 19

what does PGE2 do?

Answer 19

pain and fever

Question 20

what are the main causes of pain in inflammation

Answer 20

PGE2 and bradykinin

Question 21

what are ecosinoids

Answer 21

arachidonic acid metabolites (lipid products)

Question 22

how are ecosinoids made

Answer 22

membrane amino acids are rapidly converted by enzymes into prostaglandins and leukotrienes when cells are activated by diverse stimuli

Question 23

what do phosphoplipases do

Answer 23

release membrane amino acids into cell cytoplasm to be metabolized by 1 of 2 enzymatic pathways

Question 24

what do steroids do

Answer 24

inhibit phospholipases that release membrane AA into cell cytoplasm to enter lipooxygenase or cyclooxygenase pathways

Question 25

what does the cyclooxygenase pathway produce?

Answer 25

prostaglandins and thromboxane

Question 26

what does the lipooxygenase pathway produce?

Answer 26

leukotrienes and lipoxins

Question 27

what do PGD2, PGE2, PGF2 do

Answer 27

1. vasodilation | 2. potentiate edema by enhancing vascular permeability effects of other mediators

Question 28

what does PGE2 do specifically

Answer 28

mediates pain and is involved in cytokine induced fever with infections

Question 29

what does PGI2 do? prostacyclin

Answer 29

is released from endothelium and vasodilates and inhibits platelet aggregation

Question 30

what does thromboxane A2 do

Answer 30

released from platelets and vasoconstricts and promotes platelet aggregation

Question 31

cyclooxygenase pathway products

Answer 31

1. PGI2 prostacyclin 2. thromboxane A2 3. PGD2, PGE2, PGF2

Question 32

lipooxygenase pathway products

Answer 32

1. leukotriene B4 (LTB4) 2. leukotriene C4, D4, E4 3. lipoxins A4 and B4

Question 33

what does leukotriene B4 do

Answer 33

neutrophil chemotaxis

Question 34

what does leukotriene C4, D4, and E4 do

Answer 34

increase vascular permeability by endothelial cell contraction, vasoconstriction, bronchospasm

Question 35

what do lipoxins A4 and B4 do

Answer 35

inhibitors of inflammation

Question 36

what 2 cells are required for lipoxin synthesis

Answer 36

1. leukocytes (neutrophils) produce intermediates in lipoxin synthesis 2. platelets convert these intermediates to lipoxins

Question 37

what do lipoxins actually do

Answer 37

inhibit neutrophil adhesion and chemotaxis, play role in resolution of inflammation

Question 38

what eicosanoids do vasodilation

Answer 38

prostaglandins PGI2 (prostacyclin), PGE1, PGE2, PGD2

Question 39

what eicosanoids do vasoconstriction

Answer 39

thromboxane A2 and leukotrienes C4, D4, E4

Question 40

what eicosanoids do increased vascular permeability

Answer 40

leukotrienes C4, D4, E4

Question 41

what eicosanoids do chemotaxis and leukocyte adhesion

Answer 41

leukotrienes B4 and HETE

Question 42

what eicosanoid causes bronchospasm?

Answer 42

leukotrienes C4, D4, E4

Question 43

what do cytokines do

Answer 43

mediate and regulate immune and inflammatory reactions

Question 44

what cells make cytokines

Answer 44

activated leukocytes, endothelial epithelial cells, and connective tissue cells

Question 45

what do IL-1 and TNF do

Answer 45

1. endothelial activation 2. activation of leukocytes and other cells 3. systemic acute phase response

Question 46

what is the systemic acute phase response

Answer 46

fever, cachexia (TNF), and sepsis syndrome

Question 47

how does IL-1 and TNF help with endothelial activation

Answer 47

increased adhesion molecules, increased procoagulant activity, increased mediators like cytokines, chemokines, GF, eicosanoids

Question 48

what is the critical step in complement activation

Answer 48

proteolysis of C3 by one of 3 different pathways (classical, alternative, lectin)

Question 49

what do the complement pathways lead to

Answer 49

formation of C3 convertase which splits C3 into C3a and C3b

Question 50

what forms the membrane attach complex

Answer 50

C5b - C9

Question 51

what is C3b

Answer 51

opsonin

Question 52

what is C3a and C5a

Answer 52

anaphylatoxins, stimulate release of histamine

Question 53

what is C5a

Answer 53

leukocyte chemotactic factor

Question 54

what are the important regulatory proteins of complement

Answer 54

1. C1 inhibitor 2. delay accelerating factor (DAF) 3. CD59

Question 55

what does CD59 do

Answer 55

inhibits formation of membrane attack complex

Question 56

what is deficient in paroxysmal nocturnal hemoglobinuria

Answer 56

CD55 and CD59 are deficient on red cells, red cells prone to lysis

Question 57

what does DAF do

Answer 57

is CD55 | prevents formation of C3 convertase

Question 58

what does C1 inhibitor do

Answer 58

block activation of C1

Question 59

what causes hereditary angioedema

Answer 59

inherited deficiency of C1 inhibitor

Question 60

what does platelet activating factor do

Answer 60

1. vasoconstriction, bronchoconstriction 2. increased leukocyte adhesion to endothelium, chemotaxis, degranulation, oxidative burst 3. boost synthesis of other mediators esp eicosanoids

Question 61

what does PAF do in low concentration

Answer 61

causes vasodilation and increased venular permeability with a greater potency than histamine

Question 62

what cells make PAF

Answer 62

platelets, basophils, mast cells, neutrophils, macrophages, endothelial cells

Question 63

when does clotting cascade occur

Answer 63

clotting and inflammation occur together | tissue injury that leads to clotting will lead to inflammation.

Question 64

what is kinin

Answer 64

vasoactive peptides derived from plasma proteins called kininogens

Question 65

what converts kininogen to kinin

Answer 65

killikrein protease

Question 66

what does killikrein do

Answer 66

cleaves high molecular weight kininogen (HMWK) into bradykinin

Question 67

what activates kinin cascade

Answer 67

activated factor XII in the clotting system (hageman factor)

Question 68

effects of bradykinin

Answer 68

1. vasodilation and increased vascular permeability 2. major contributor to pain that accompanies inflammation 3. bronchoconstriction

Question 69

what secretes neuropeptides

Answer 69

sensory nerves and some WBC

Question 70

what neuropeptides are secreted in the peripheral and central nervous system

Answer 70

substance P and neurokinin A

Question 71

where is substance P prominent

Answer 71

GI and lungs

Question 72

what does substance P do

Answer 72

transmits pain signals, regulate BP, stimulate endocrine gland hormone secretion, increase vascular permeability

Question 73

what substance may help initiate and regulate inflammation

Answer 73

neuropeptides

Question 74

what major mediators are responsible for vasodilation?

Answer 74

1. prostaglandins 2. histamine 3. kinins 4. PAF

Question 75

what major mediators cause increased vascular permeability?

Answer 75

1. leukotrienes 2. histamine 3. kinins 4. PAF

Question 76

what major mediators cause fever?

Answer 76

1. IL-1 2. TNF 3. prostaglandins 4. systemic cytokines

Question 77

what major mediators cause pain?

Answer 77

1. bradykinin | 2. PGE2/prostaglandins

Question 78

what major mediators cause tissue damage?

Answer 78

1. PAF 2. complement (C5a, C3a) 3. granulocytes 4. cytokines

Question 79

what major mediators cause chemotaxis

Answer 79

1. C5a 2. interleukins 3. TNF 4. leukotrieneB4 5. HETE 6. cytokines