Inflammation and Repair Part 2 Flashcards

1
Q

What are the 2 major sources of chemical mediators?

A

Cells (produced locally)

plasma (Produced elsewhere)

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2
Q

What are the 2 types of chemical mediators that are produced by cells?

A
Preformed (vasoactive amines)
Newly synthesized (Prostaglandins and cytokines)
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3
Q

What are the chemical mediators within plasma (3)?

A

Complement, kinins and coagulation system

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4
Q

Where are many of the plasma chemical mediator produced? Where are they activated?

A

Many produced in the liver

Activated at the site of injury

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5
Q

What is the major preformed vasoactive amine? What cells secrete it? Where is it found?

A

Histamine
Secreted by mast cells
Found in most tissues

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6
Q

What are the 3 major functions of histamine?

A
  • Causes vasodilatation of arterioles
  • increased venule permeability
  • Prominent in allergic response, edema
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7
Q

What is a vasoactive amine found in platelets? What is its major function?

A

Serotonin

Induces vasoconstriction during clotting

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8
Q

Arachidonic acid is considered a cell derived mediator. Where is it found in the cell? What activates it?

A

Found in the cell membrane

Activated by phospholipases

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9
Q

Regarding the arachidonic acid metabolites pathway, which enzyme is inhibited by steroids? Which is inhibited by NSAIDs?

A

Phospholipases inhibited by steroids

Cycloxygenase inhibited by NSAIDs

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10
Q

Regarding the cyclooxygenase pathway, what are the 2 major bioactive downstream products? What are their functions?

A
  • Prostacyclin - vasodilation, platelet inhibition

- Thromboxane - Vasoconstriction, platelet activation

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11
Q

What are the 2 major bioactive products of the lipoxygenase component of the arachidonic acid pathway? What are their functions?

A

Leukotrienes - Bronchospasm and increased vascular permeability
Lipoxins - Inhibit neutrophil adhesions and chemotaxis

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12
Q

What are the 4 mediators that are important for vasodilation?

A

PGI2, PGE1, PGE2 and PGD

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13
Q

What ae the 4 mediators that are important for vasoconstriction?

A

TXA2, Leukotrienes C4, D4 and E4

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14
Q

What are the cell derived mediators that increase vascular permeability?

A

Leukotrienes C4, D4 and E4

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15
Q

What are the cell derived mediators that promote chemotaxis and leukocyte adhesion?

A

Leukotriene B4 and HETE

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16
Q

What are the 4 major cytokines that are important for acute inflammation?

A

TNF
IL-1
IL-6
Chemokines

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17
Q

What are the 2 cytokines that are important for chronic inflammation?

A

Interferon gamma

IL-12

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18
Q

TNF and IL1 are produced by what 3 types of cells?

A

Activated macrophages
Endothelial cells
Mast cells

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19
Q

What is the major role of TNF and IL1?

A

Endothelial activation leading to increased permeability and expression of adhesion molecules

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20
Q

What are the 2 major functions of nitric oxide?

A

Vasodilation

Macrophage cytotoxicity

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21
Q

What are the sources of nitric oxide (2)?

A
Endothelial cells (chronic low levels) 
Macrophages (inducible, plays a role in killing of microorganisms)
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22
Q

What are the 2 antiinflammatory roles of nitric oxide?

A

Reduces leukocyte activity

Reduces platelet adhesion

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23
Q

Nitric oxide is short lived or long lived?

A

Short lived, made as needed

24
Q

True or false, nitric oxide is both proinflammatory and anti-inflammatory?

A

True

25
Q

What is another name for Hageman factor? Under what conditions is it activated?

A

Factor 12

Activated by exposed collagen, basement membrane or activated platelets (endothelial injury)

26
Q

From the point of view of activating inflammation, what 3 cascades does Factor 12 play a role in initiating?

A

Initiates the complement cascade, kinin and clotting

27
Q

What are the 3 ways that complement is activated?

A

Antibody antigen - Classical
Microbial surface antigen - Alternative pathway
Mannose binding lectin - Lectin Pathway

28
Q

What are 2 components of the complement cascade important in chemoattraction?

A

C3a and C5a

29
Q

What component of the complement cascade is important for opsonization? What about for cell lysis?

A

Opsonization - C3b

Cell lysis - MAC complex

30
Q

Regardining the complement system, what are the 2 components that are important for vasodilation and permeability?

A

C3a and C5a

31
Q

Regardining the complement system, what component is an important chemotactic agent for neutrophils?

A

C5a

32
Q

Regardining the complement system, what 2 components act as opsonins (attach to bacterial cell wall and promote phagocytosis)?

A

C3b and C3bi

33
Q

Regardining the acute inflammtory response, what are the three chemical mediators that cause vasodilation?

A

Prostaglandins
Nitric Oxide
Histamine

34
Q

Increased vascular permeability during acute inflammation is mediated by _ (5)

A
Histamine 
Serotonin 
Complement 
Bradykinin 
Leukotrienes
35
Q

Leukocyte emigration is mediated by _ (5)

A
Complement components 
Leukotrienes 
Bacterial products 
Cytokines
Chemokines
36
Q

What are the 3 major mechanisms by which down regulation of acute inflammation occurs?

A

Cessation of proinflammatory stimuli
Anti inflammatory mediators
Immunoregulatory processes

37
Q

What are the 3 major anti-inflammatory mediators / mechanisms as referenced in the notes?

A

Lipoxin
Nitric Oxide
Anti inflammatory cytokines (IL10, TGF-beta)

38
Q

What are the 3 steps that have to occur for resolution of acute inflammation and what are responsible (where applicable)?

A

Return of vascular permeability to normal
Drain edema (lymphatics)
Remove debris and neutrophils (macrophages)

39
Q

An inflammation that goes on for weeks to years is termed _. What are the predominant cells?

A

Chronic

Macrophages and lymphocytes

40
Q

What are 3 processes that may be occuring simultaneously during chronic inflammation?

A

Active inflamnmation
Tissue injury
Attempts at healing

41
Q

What are 2 reasons why an acute inflammation can progress to a chronic inflammation?

A

Persistence of injurious agent

Interference with normal healing

42
Q

What are 2 forms of injury that engender a chronic inflammatory response from the onset?

A

Immunological reactions

Viral Infections

43
Q

What are the 2 bone marrow precursors of macrophages? What do they become when they get into the blood?

A

Stem cells and monoblasts ( in the bone marrow)

In blood, they are monocytes

44
Q

Where are macrophages activated? What is the morphology of its nucleus?

A

Reside in tissues, activated when needed there

Kidney bean shaped nucleus

45
Q

What are the 2 means by which macrophages can become activated?

A

Classical and alternative methods

46
Q

What are the 2 mediators of classical macrophage activation? What occurs after this type of activation?

A
  • Microbes and IFN-gamma activate macrophages classically
  • Leads to microbicidal activity (ROS, NO, lysozyme) and proinflammatory activity (IL1, IL12, IL23 and chemokine production)
47
Q

What are the 2 molecules involved in alternative activation of macrophages? What are their source? What is the net effect of alternative activation of macrophages?

A
  • IL13 and IL4
  • Produced by T cells
  • Net effect is tissue repair, scar formation and anti-inflammation
48
Q

How do activated T cells and Activated macrophages interact? What is the net effect?

A

Both feedforward to prolong and to maintain inflammation

- Increased accumulation of macrophages and lyphocytes in the tissues

49
Q

What are the 3 mechanisms by which macrophages accumulate in tissues?

A

Recruitment
Local proliferation and division
Cytokine driven immobilization at inflammation site

50
Q

What was the example disease of chronic inflammation characterized by lyphocytic inflammation and fibroblast proliferation in the lung?

A

Chronic interstitial pneumonia

51
Q

A distinctive pattern of chronic inflammation that is characterized by epithelioid macrophages is _. What are the 2 major causes of granuloma formation? What other cell type is very involved in this process?

A

Granulomatous inflammation
Foreign body or immune system
CD4+ T helper cells

52
Q

What are 3 types of microbes that can causes granulomatous inflammation?

A

Mycobacteria
Parasites
Yeast forms

53
Q

A central core of highly activated macrophaes surrounded by lymphocytes, with multinucleated giant cells describes _

A

Granulomas

54
Q

Multinucleated giant cells are associated with what type of process?

A

Granuloma formation

55
Q

What is the stain type used to identify giant cells containing mycobacterium as seen in tuberculosis?

A

Acid fast stain

56
Q

When a patient has an acute presentation of an inflammatory disease like lupus, what kinds of cells will mediate the reaction? Why?

A

Lymphocytes and macrophages

Even if acute, these are the cells that mediate immune mediated inflammatory disease