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Veterinary Immunology > Lecture 4 - Inflammation > Flashcards

Lecture 4 - Inflammation Flashcards

1
Q

What are the proinflammatory things produced by sentinel cells as early response

A

-IL-1
-IL-6
-TNF-a
-HMGB-1 (DAMP)

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2
Q

What are the effects of the proinflammatory cytokines/DAMP on the hypothalamus

A

fever, anorexia, sleepiness, depression

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3
Q

What are the effects of the proinflammatory cytokines/DAMP on the liver?

A

increased synthesis of acute-phase proteins, iron sequestration

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4
Q

Why is iron sequestration important

A

makes freely available iron unavailable to pathogens

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5
Q

What are the effects of the proinflammatory cytokines/DAMP on bone marrow

A

increased WBC production

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6
Q

What is inflammation

A

tissue reaction that rapidly delivers mediators of host defense to the sites of infection and tissue damage

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7
Q

What 3 essential roles does inflammation play in combating infection

A
  1. deliver additional effector molecules and cells to sites of inefection to augment the killing of invading microbes by the front-line macrophages
  2. provide a physical barrier preventing the spread of infection
  3. promote the repair of injured tissue
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8
Q

What is the main purpose of inflammation

A

focus the immune response to the site of infection or injury

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9
Q

Acute inflammatory response pathway:
1. ______ and other pro-inflammatory mediators are produced by cells in response to _____ and ____
2. These mediators increase the _________ of blood vessels, leading to entry of plasma proteins into the tissues and promote the movement of ____ from blood into tissue.
3. _____ destroy microbes, clear damged cells, promote more ____, and repair

A

cytokines, microbial products, damged host cells; permeability, leukocytes; leukocytes, inflammation

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10
Q

What allows fluid, protein, and inflammatory cells to leave blood and enter tissue

A

vasodilation and increased vascular permeability

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11
Q

What are the stages of neutrophil adhesion and emigration from blood vessels

A

rolling, adherance, emigration

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12
Q

What is rolling mediated by

A

selectin (by PAMPs and DAMPs)

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13
Q

What is adherance mediated by

A

integrin (by PAMPs and DAMPs)

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14
Q

What does emigration lead to

A

chemotaxis

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15
Q

What is an autosomal recessive immunodefinciency in Holstein calves

A

Bovine Leukocyte Adhesion Deficiency (BLAD)

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16
Q

What is BLAD characterized by

A
  1. recurrent bacterial infections
  2. oral ulcerations, gingivitis, periodontis
  3. chronic pneumonia
  4. stunted growth
  5. delayed wound healing
  6. peripheral lymphadenopathy
  7. persisten extreme neutrophilia
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17
Q

What calves are affected by BLAD

A

holstein

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18
Q

When do calves affected by BLAD die

A

2 and 7 months of age

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19
Q

Why is BLAD so deadly

A

calves have large number of intravascular neutrophils that can’t exit blood vessels to reach infection site because there is a point mutation in the integrin gene, neutrophils cannot attach to vascular endothelial cells or emigrate from blood vessels

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20
Q

What gene is mutated in calves with BLAD

A

integrin

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21
Q

Inflammation at the site of infection is initiated by ….

A

response of macrophages to pathogens

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22
Q

Characteristics of inflammation

A

pain, redness, heat, swelling

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23
Q

Why is there redness during inflammation

A

increased blood flow to area of injury

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24
Q

Why is there edema during inflammation

A

increased extravascular fluid and phagocyte infiltration to the damaged area

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25
Q

Why is there heat during inflammation

A

increased blood flow and action of pyrogens

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26
Q

What are pyrogens

A

fever-inducing agents

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27
Q

Why is there pain during inflammation

A

local tissue destruction and irritation of sensory nerve receptors

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28
Q

What happens if a whole organ or tissue is involved in inflammation

A

loss of function

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29
Q

What are the 6 pro-inflammatory mediators

A
  1. cytokines
  2. chemokines
  3. vasoactive amines
  4. vasoactive peptides
  5. vasoactive lipids
  6. coagulation system
30
Q

When do sentinel cells synthesize and secrete cytokines

A

when exposed to infectious agents or their PAMPs

31
Q

What are the 3 major cytokines

A

TNF a, IL-1, IL6

32
Q

Major functions of IL-1

A
  1. promotes inflammation
  2. kills cells
  3. affects leukocytes
  4. affects metabolism
  5. affects blood flow
  6. affects cell growth
33
Q

How can proinflammatory cytokines allow more cells to get to infection site

A

increase expression of adhesion molecules (integrins) on endothelium for cells to bind and exit

34
Q

What effect do proinflammatory cytokines have on cytokine production and eosinophils

A

increase TH2 production and degranulates eosinophils

35
Q

What cells do proinflammatory cytokines enhance the growth of

A

fibroblasts, keratinocytes, vascular smooth muscles

36
Q

How do profinflammatory cytokines promote inflammation

A

enhanced collagen synthesis, fibroblast activity, chrondrocyte activity

37
Q

4 major functions of TNF a

A
  1. promotes inflammation
  2. enhances fibroblast growth, collagen syn., bone resorption
  3. toxic effects
  4. activates cells
38
Q

What happens when proinflammatory cytokines are produced in low quantities

A

local inflammation, which includes macrophage activation, endothelium activation, complement activation

39
Q

What happens when proinflammatory cytokines are produced in moderate quantities

A

local and systemic effects, including fever, lethargy, loss of appetite from effects on hypothalamus, production of acute-phase proteins from actions on the liver, and neutrophilia resulting from action on the bone marrow

40
Q

What happens when proinflammatory cytokines are produced in high quantities?

A

systemic vasodilation, increased vascular permeability. This leads to a drop in blood pressure and low cardiac output, vascular injury, thrombosis and disseminated intravascular coagulopathy (DIC), pulmonary edema, air spaces fill with fluid, and leads to acute respiratory distress syndrome (ARDS)

41
Q

When can septic shock occur in cows

A

cows with gram-negative bacterial mastitis because endotoxin produces high quantities of proinflammatory cytokines

42
Q

Proinflammatory cytokines are necessary in low quanities and ______ in high quantities

A

LETHAL

43
Q

What are chemokines a family of

A

50 small chemotactic cytokines

44
Q

What do chemokines coordinate the migration of?

A

cells and dictate the course of many inflammatory and immune responses

45
Q

What are chemokines produced by

A

sentinel cells including macrophages and mast cells

46
Q

What is the function of IL-8

A

chemokine that is produced by macrophages or mast cells that attract and activate neutrophils

47
Q

What is CXCL2

A

chemokine that is secreted by macrophages and attracts neutrophils

48
Q

Where do vasoactive molecules derived from

A

inactive precursors in plasma, macrophages, mast cells, neutrophils, basophils, platelets, or damaged tissue cells

49
Q

3 major types of vasoactive molecules

A
  1. vasoactive amines
  2. vasoactive peptides
  3. vasoactive lipids
50
Q

What is the most important vasoactive molecule (amine) released by mast cells

A

histamine

51
Q

What happens when histamine binds to its receptors on endothelial cells

A

stimulates them to produce nitric oxide, potent vasodilator

52
Q

What does histamine stimulate the production of

A

nitric oxide- potent vasodilator

53
Q

What does histamine cause

A

blood vessel leakage, leading to fluid escape into tissues and local edema

54
Q

What does histamine upregulate

A

TLR expression on sentinel cells

55
Q

What is serotonin chemically

A

5-hydroxytryptamine (5HT)

56
Q

What is serotonin a derivative of

A

tryptophan

57
Q

What effect does serotonin have

A

vasoconstriction that results in rise in BP (vasodilator in cattle)

58
Q

What are the 2 vasoactive amines

A

histamine and serotonin

59
Q

What are vasoactive peptides producted by

A

proteolysis of inactive precursors

60
Q

What are the C5a and C3a (vasoactive peptides) considered

A

anaphylotoxins

61
Q

What do C5a and C3a promote

A

histamine release from mast cells

62
Q

C5a is a potent attractant for what?

A

neutrophils and monocytes

63
Q

Mast cell granules contain proteases called …..

A

kallikreins

64
Q

What do kallikreins do

A

act on kininogens to generate kinins

65
Q

What is the most important kinin

A

Bradykinin

66
Q

What are the 4 roles of kinins

A
  1. increase vascular permeability
  2. stimulate neutrophils
  3. trigger pain receptors
  4. have antimicrobial properties
67
Q

When is the coagulation system activated

A

when fluid leaks from blood vessels

68
Q

What is the main clotting enzyme, which is generated after the coagulation system activates

A

thrombin

69
Q

What does thrombin do

A

act on fibrinogen in tissues and plasma to form insoluble fibrin

70
Q

What happens to fibrin after its formed

A

deposited in the inflamed tissue forming a physical barrier to the spread of infection

71
Q

What do system is also activated with the coagulation system

A

fibrinolytic system

72
Q

What does the fibrinolyitc system do

A

destroys fibrin and releases peptide fragments that attract neutrophils

Veterinary Immunology (20 decks)

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