Acute & Chronic Inflammation and Hypersensitivity Flashcards Preview

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Flashcards in Acute & Chronic Inflammation and Hypersensitivity Deck (68)
1

What are Toll-like receptors?

TLRs are surface receptors that respond to patterns on extracellular microbes. Activation leads to release of TNF.

2

What are inflammasomes

Inflammasomes are intracellular receptors that detect fragments of dead cells and some microbes. Activation of the inflammasome leads to activation of caspase-1, which in turn activates release of IL-1.

3

Vasodilation is mediated by what?

Histamine and nitric oxide (NO)

4

Vascular permeability is mediated by what?

histamine and bradykinin

5

Histamine: what is it released by and what does it mediate?

Released by: mast cells (stimulated by IL-1 and other inflammatory cytokines) Produces vasodilation and increases vascular permeability

6

Nitric oxide: what is it released by and what does it mediate?

Released by: endothelial cells in response to injury Increases vasodilation

7

Bradykinin: what is it released by and what does it mediate?

Bradykinin is a plasma protein produced by the liver. It is activated by factors expressed on injured epithelial cells. Bradykinin increases vasodilation, increases vascular permeability, and causes pain

8

Define edema

excess fluid in the interstitium

9

Compare/contrast: Trasudate vs. Exudate

Transudate: SG < 1.012, protein-poor ultrafiltrate of blood plasma due to increased hydrostatic pressure or lowered plasma osmotic pressure. Non-inflammatory. Exudate: SG > 1.02, protein and inflammatory cell rich fluid released due to increased vascular permeability. Due to inflammatory process.

10

What is pus?

Purulent exudate -> exudate rich in neutrophils (PMNs)

11

List the major steps in leukocyte recruitment

  1. margination
  2. rolling
  3. adhesion
  4. transmigration
  5. chemotaxis

12

Name the receptor associated with each of the following steps of leukocyte recruitment:

  1. rolling
  2. adhesion
  3. transmigration

  1. selectins
  2. ICAM-1
  3. PECAM-1 (CD31)

13

Selectins are expressed on endothelial cells in response to what?

Histamine, thrombin, etc

14

ICAM-1 is expressed on endothelial cells in response to what?

TNF and IL-1 secreted by macrophages at the site of injury

15

What is diapedesis?

Movement of a leukocyte through the epi/endothelial barrier

16

Killing and degradation of microbes/tissues at the site of injury is driven by what two processes?

  1. ROS (within phagolysosome)
  2. Enzyme release (example: elastase, extracellular)

17

Name the principal mediators of the following features of inflammation:

  1. Vasodilation
  2. Increased vascular permeability
  3. Chemotaxis and leukocyte recruitment
  4. Fever
  5. Pain
  6. Tissue damage

  1. histamine and nitric oxide
  2. histamine and bradykinin
  3. TNF, IL-1, bacterial products
  4. TNF, IL-1
  5. bradykinin
  6. ROS, NO, lysosomal enzymes

18

Name four major morphologies of acute inflammation

  1. serous
  2. fibrinous
  3. suppurative
  4. ulcerative

19

Describe serous acute inflammation

  • mildest form of acute inflammation
  • consists mostly of transudate from injured serious tissues
  • example: pleural/pericardial/peritoneal effusion due to chronic heart failure or fluid overload
  • example: skin blistering from friction, burn, trauma, or viral infection due to leaky epi/endothelia

20

Describe fibrinous acute inflammation

  • usually secondary to a more severe injury
  • larger vascular leaks, allowing passage of fibrinogen and conversion to fibrin
  • examples: fibrous pericarditis, fibrous peritonitis with ascites, acute rheumatoid fever (ARF)

21

Describe suppurative acute inflammation

  • suppurative = purulent (pus)
  • S. aureus is common
  • formation of an abscess: central necrotic tissue with PMNs enclosed by fibroblasts
  • examples: acute appendicitis, acute bronchopneumonia, acute meningitis

22

Describe ulcerative acute inflammation

  • local defect on surface of organ or tissue
  • sloughing of surface and necrotic tissue
  • examples: peptic ulcer, skin ulceration (common with diabetes)

23

A friction rub on cardiac auscultation may be indiciative of what type of inflammation?

Fibrinous inflammation

24

Acute appendicities is usually an example of what type of acute inflammation?

suppurative inflammation

25

Tissue macrophages are a hallmark sign of what type of inflammation?

Chronic inflammation

26

What is polymyositis?

Chronic inflammation (autoimmune) characterized by CTL destruction of skeletal myofibers

27

What type of inflammation is defined by the presence of epithelioid macrophages?

Granulomatous inflammation

example: sarcoidosis is defined by the presence of granulomatous inflammation

28

What is a multinucleate giant cell?

Fused epithelioid macrophages, induced by IFN-gamma

29

Caseous necrosis with multinucleated giant cells is definitively what disease until proven otherwise?

TB

30

What is SIRS?

a.k.a. Acute Phase reaction

Systemic reaction to inflammation that may include the following:

  1. Fever: in response to bacterial lipopolysaccharides (endotoxin), elevated endogenous pyrogens (IL-1, TNF), and increased release of prostaglandins (PGE2, increases setpoint of HT)
  2. Elevated acute phase protein release from the liver, stimulated by IL-6. Includes: c-reactive protein, fibrinogen, serum amyloid A protein, etc. Produces increased sedimentation (sed) rate.
  3. Leukocytosis: stimulated by TNF and IL-1. Produces accelerated release of leukocytes from bone marrow.

31

What is the "sed rate"

Fibrinogen released in response to inflammation binds to erythrocytes (RBCs), forming stacks. In lab tests, these stacks (due to their mass) 'sediment' faster.

Inflammation may increase sed rate (part of SIRS)

32

What is a leukemoid reaction?

Extreme leukocytosis (>20,000)

33

What is a "left-shift"?

Accelerated release of immature neutrophils

34

Give the conditions of the following leukocytoses:

  1. Neutropenia
  2. Lymphocytosis
  3. Eosinophilia
  4. Leukopenia

  1. bacterial infection -> may produce a left-shift
  2. viral infection
  3. allergy, asthma, parasites
  4. WBC sequestration in lymph nodes due to certain infections (examples: rickettsia, typhoid, etc)

35

Name the four types of hypersensitivity

  • Type I: Immediate, IgE-mediated
  • Type II: direct antibody-mediated cytolytic
  • Type III: immune-complex-mediated
  • Type IV: delayed type cell-mediated

36

What type of hypersensitivity reaction is Rhus Dermatitis?

Type IV

37

Describe the sensitization stage of Type I hypersensitivity

  1. Specific antigen taken up and presented by APC
  2. Presentation to Th2 cell
  3. Th2 cell secretes IL-4 and IL-6, inducing B-cell class-switching to IgE
  4. B-cell produces IgE against specific antigen
  5. Specific antigen IgE is taken up by mast cells

38

What is the difference between an allergen and an irritant?

  • Allergen: not dose-dependent, does not affect all individuals, IgE-mediated, affects only those previously sensitized
  • Irritant: dose-dependent effet, affects all individuals, not Ig-E mediated, tends to be a small molecule

39

What products are secreted by mast cells in the early phase of type I hypersensitivity reactions?

  • Histamine
  • tryptase
  • PGD2
  • thromboxane
  • LTC4

40

What products are released during the late phase of Type I hypersensitivity reactions?

  • LTB4, LTC4
  • PGD2, PGE2, PGF2-alpha
  • kinins
  • histamine (lower load than early phase)
  • GM-CSF, IL-5
  • Eosinophil products: MBP, ECP, EPO, etc

41

Testing for what mast cell product is a good diagnostic indicator of Type-I hypersensitivity reaction?

Tryptase

Lasts for ~4 hours

42

What is the difference between alpha-tryptase and beta-tryptase? What does tryptase do?

  • Alpha: released constituitively
  • Beta: released upon mast cell activation

Tryptase triggers remodeling of connective tissue in the ECM

43

What class of drugs are likely to produce a false-negative skin test?

Antihistamines

44

Name the drug(s) that blocks leukotriene synthesis by blocking the action of 5-lipoxygenase

zileuton

45

Name the drug(s) that block leukotriene receptors

montelukast / zafirlukast

46

Does psychological stress lower or raise the mast cell sensitivity threshold?

lower

47

Name 3 drugs or classes of drug that raise the sensitivity threshold of mast cells?

  1. Corticosteroids
  2. Antihistamines
  3. Cromolyn sodium

48

Describe the cytokines released by mast cells during the late phase reaction

  • IL-4 and IL-13: stimulate Th2 cells and IgE class switching
  • IL-3, IL-5, GM-CSF: activate and promote survival of eosinophils
  • TNF: endothelium activation and adhesion expression

49

Describe the major chemokines released by mast cells during the late phase

  • CCL3: macrophage and leukocyte chemotaxis
  • RANTES (CCL5) and eotaxin (CCL11): T-cell and eosinophil chemotaxis

50

Describe the major lipid mediators released by mast cells during the late phase reaction

  • LTC4, LTD4, LTE4: eosinophil migration, smooth muscle contraction, increased vascular permeability, mucus hypersecretion
  • PAF: attracts leukocytes, activates eosinophils/neutrophils/platelets

51

Name 5 major caused of increased eosinophil count (eosinophilia)

NAACP:

  1. neoplasia
  2. asthma
  3. allergy
  4. connective tissue disease
  5. parasite

52

Describe the mechanism by which corticosteroids suppress eosinophils

  1. Directly block IL-5, reducing eosinophil release from bone marrow and promoting eosinophil apoptosis
  2. Bind GR-alpha, inhibiting AP-1 and NFkB

53

Give 4 clinical examples of Type I hypersensitivity

  1. Allergic rhinitis
  2. asthma
  3. anaphylaxis
  4. urticaria

54

Why is early life viral infection significant in the context of hypersensitivity reactions?

Early childhood viral infections increases the risk of development of allergies

55

What cells type(s) infiltrates are commonly seen in asthma? Sudden-death asthma?

Asthma: eosinophils and lymphocytes

Sudden-death asthma: neutrophils

56

What is denudation?

Destruction of airway epithelium

57

Give the 5 major morphological features of asthma

  1. Denudation
  2. Mucus gland hyperplasia and hypersecretion
  3. smooth muscle hyperplasia
  4. submucosal edema and vascular dilation
  5. fibrin deposition and airway remodeling

58

Why must administration of a skin test wait 4-6 weeks after an allergic event?

Mast cells need time to 'reload'

59

What type of hypersensitivity reaction is Myasthenia Gravis?

Type II

60

What is the name for the Type II hypersensitivity reaction caused by Rh-factor mismatch between mother and child?

erythroblastosis fetalis

61

What type of hypersensitivity reaction generally features a soluble antigen? A matrix-bound antigen?

  • Type III
  • Type II

62

Name 4 major sites of immune complex deposition in Type III hypersensitivity reactions

  1. Kidney
  2. Skin
  3. joints
  4. blood vessels

63

What is the Arthus Reaction?

Skin reaction when sensitized individuals are exposed to a specific antigen. The reaction is caused by leukocyte activation via FC(gamma)III receptors with no complement involvement - therefore Type III

64

What is serum sickness?

Systemic reaction following injection of a large quantity of foreign antigen. Reaction occurs 7-10 days post-exposure (sweet spot of Ab:Ag complex formation).

Symptoms: flu-like condition (fever, vasculitis, arthritis, nephritis)

65

Farmer's Lung features what type of hypersensitivity reaction?

Type III - reaction to hay dust and mold spores

66

Systemic Lupus Erthematosus is what type of hypersensitivity reaction?

Type III

67

Describe Type IV hypersensitivity

  • Delayed-type, cell-mediated, does not generally involve antibodies
  • Process: antigen enters skin and binds self-protein, antigen-protein complex is presented to T-cells, resulting in T-cell proliferation
  • Cellular response is mediated by CD4+ Th1 cells and/or CD8+ CTLs

68

Name the plant-based chemical involved in Rhus Dermatitis?

pentadecacatechol