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Pathoma High Yield > 2. Inflammation, Inflammatory Disorders, and Wound Healing > Flashcards

2. Inflammation, Inflammatory Disorders, and Wound Healing Flashcards

1
Q

What activates TLRs?

A

PAMPs

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2
Q

What is the TLR4 co-receptor on macrophages that recognizes LPS (gram negative bacteria)?

A

CD14

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3
Q

What is the role of prostaglandins (E2, D2, and I2)?

A

vasodilation and increased vascular permeability

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4
Q

What is the more specialized role of PGE2?

A

mediates Fever and Pain

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5
Q

What is the role of LTC4, LTD4, and LTE4?

A

Vasoconstriction, bronchospasm, increased vascular permeability

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6
Q

What are the 4 mediators of neutrophil migration?

A

LTB4
C5a
IL-8
Bacterial products

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7
Q

In what 3 ways are mast cells activated?

A
  • Tissue trauma
  • Complement C3a or C5a
  • Crosslinking of cell-surface IgE by Ag
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8
Q

What are the actions of histamine?

A

Vasodilate arterioles

Increase vascular permeability (at post capillary venules)

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9
Q

What allows for delayed and prolonged response to histamine?

A

Leukotrienes

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10
Q

What can Hageman factor (Factor XII) lead to?

A

DIC (gram negative sepsis)

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11
Q

What are the roles of bradykinin?

A

Mediates vasodilation
Increased vascular permeability
Pain mediating

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12
Q

What causes the rubor and calor of inflammation?

A

vasodilation

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13
Q

What causes the tumor of inflammation?

A

increased vascular permeability and tissue damage

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14
Q

What causes the fever of inflammation?

A

Macrophages release IL-1 and TNF which increase COX activity from the hypothalamus and increase PGE2 to raise the temperature set point

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15
Q

What molecules lead to “rolling” of neutrophils?

A

selectins

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16
Q

From where are P-selectins released and what is the stimulus?

A

histamine causes release of P-selectin from Weibel Palade bodies

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17
Q

What induces the release of E-selectins?

A

TNF and IL-1

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18
Q

To what do selectins bind on leukocytes?

A

sialyl Lewis X

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19
Q

What molecules lead to adhesion of the leukocytes?

A

ICAM and VCAM (upregulated by TNF and IL-1)

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20
Q

What is the cause of Leukocyte adhesion deficiency?

A

AR defect of integrins (CD18 subunit)

18 yo LADs have no INTEGRity

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21
Q

Into what type of vessels do leukocytes transmigrate across?

A

postcapillary venules

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22
Q

What is the underlying problem in Chediak-Higashi Syndrome?

A

protein trafficking defect due to decreased microtubule system (so no phagolysosomes can be formed)

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23
Q

In the O2 dependent killing pathway, what defect will NOT show blue NBT dye?

A

Chronic granulomatous disease

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24
Q

What is the underlying cause of chronic granulomatous disease?

A

AR or XL NADPH oxidase defect

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25
Q

What type of bacterial infection is seen in chronic granulomatous disease?

A

Catalase Positive bacteria

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26
Q

List the most high yield catalase positive bacteria.

A

Staph Aureus
Pseudomonas cepacia
Serratia marcescens

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27
Q

In the O2 dependent killing pathway, what defect will show blue NBT dye?

A

MPO deficiency (because there is a normal NADPH oxidase)

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28
Q

What is the presentation of a patient with NADPH oxidase deficiency?

A

Candida infections (but mostly asymptomatic)

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29
Q

What happens to neutrophils post inflammation?

A

they undergo apoptosis

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30
Q

How do macrophages destroy phagocytosed bacteria?

A

enzymes (ex. lysozyme) in secondary granules that use O2 dependent killing

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31
Q

List the two anti-inflammatory cytokines released from macrophages during resolution and healing.

A

IL-10

TGF-beta

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32
Q

What cytokine released by macrophages recruits additional neutrophils for “continued acute inflammation”?

A

IL-8

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33
Q

What type of T cell recognizes MHC class I?

A

CD8+

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34
Q

What type of T cell recognized MCH class II?

A

CD4+

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35
Q

What is the secondary activation signal for CD4+ T cells?

A

B7 on APC binds to CD28 on the T cell

36
Q

What is secreted by Th1 cells?

A

INF-gamma

IL-2

37
Q

What is secreted by Th2 cells?

A

IL-4
IL-5
IL-13
IL-10

38
Q

What is the secondary activation signal for CD8+ T cells?

A

IL-2 from CD4+ Th1 cells

39
Q

How do CD8+ T cells kill cells?

A

Perforin makes pores, granzyme enters, activation of caspase, apoptosis

OR

Express FasL which binds to Fas on target cells

40
Q

B cells present antigen to what kind of T cell?

A

CD4+ T cells

41
Q

What is the second activation signal that B cells give to their CD4+ T cells?

A

CD40 on B cell binds to CD40L on T cell

42
Q

What is the defining characteristic of granulomatous inflammation?

A

epithelioid histiocytes

43
Q

What are the other two features of granulomas that are commonly seen (other than epithelioid histiocytes)?

A

giant cells and rim of lymphocytes

44
Q

List the top 5 causes of noncaseating granulomas.

A
  • Foreign material
  • Sarcoidosis
  • Beryllium exposure
  • Crohn disease
  • Cat-scratch disease (stellate shaped)
45
Q

What do you immediately do when you see a caseating granuloma?

A

AFB for Tb
GMS for fungal infections
(differentiate between the two causes)

46
Q

What is the first step a macrophage does to form a granuloma?

A

present antigen via MHC class II to CD4+ helper cell

47
Q

What does a macrophage do after presenting antigen via MHC Class II to CD4+ helper cell?

A

secretes IL-12 to induce the CD4+ to differentiate into Th1

48
Q

What do Th1 cells secrete to convert macrophages into epithelioid histiocytes?

A

IFN-gamma

49
Q

What is the developmental defect in DiGeorge syndrome?

A

failure of the 3d and 4th pharyngeal pouches to develop

50
Q

What is the chromosome mutation in DiGeorge?

A

22q11 microdeletion

51
Q

What is one of the underlying causes of SCID?

A

Adenosine deaminase (ADA) deficiency

52
Q

What is ADA?

A

necessary enzyme for deaminaion of adenosine and deoxyadenosine for excretion as waste products (if these are not excreted, they build up and are toxic to lymphocytes)

53
Q

What is mutated in XLA?

A

Bruton tyrosine kinase

54
Q

What are the 3 infections that occur due to lack of B cells?

A

bacterial (can’t opsonize)
Enterovirus (low mucosal IgA)
Giardia lamblia (low IgA in GI)

55
Q

People with CVID are at increased risk for what 2 conditions?

A

Autoimmune Disease

Lymphoma

56
Q

In what condiiton is IgA deficiency commonly seen?

A

Celiac disease

57
Q

What is the cause of Hyper IgM?

A

Mutated CD40L or CD40 receptor so helper T cells cannot get the secondary activation signal from B cells and no class switching occurs

58
Q

With what type of deficiency are Neisseria infections most common?

A

C5-C9 deficiencies

59
Q

What is the most common renal disease seen in SLE?

A

diffuse proliferative glomerulonephritis
OR
Membranous glomerulonephritis

60
Q

What is the characteristic auto-antibody seen in drug-induced SLE?

A

anti-histone antibody

61
Q

What 3 drugs cause drug-induced lupus?

A

hydralazine
procainamide
isoniazid

62
Q

How do you definitely diagnose Sjogren’s syndrome?

A

Biopsy of salivary glands shows lymphocytic sialadenitis

63
Q

What are the two types of scleroderma?

A

Limited

Diffuse

64
Q

Which type of scleroderma is associated with CREST?

A

limited

65
Q

What is CREST?

A 
Calcinosis (and anti-Centromere Ab)
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasias on skin
66
Q

Which type of scleroderma has a better prognosis?

A

limited

67
Q

Which type of antibodies are seen in diffuse scleroderma?

A

anti-DNA topoisomerase II

68
Q

What antibodies are seen in Mixed CT disease?

A

antibodies against U1 ribonucleoprotein and ANA

69
Q

What is the marker of hematopoietic stem cells?

A

CD34+

70
Q

Which type of tissue cannot repair and must scar?

A

permanent tissues (ex. myocardium, skeletal muscle, neurons)

71
Q

What goes on with collagen in healing?

A

Type III collagen is replaced by ype I collagen

72
Q

Type I collagen is seen in what tissues?

A

bONE

73
Q

Type II collagen is seen in what tissues?

A

cart2lidge

74
Q

Type III collagen is seen in what tissues?

A

granulation tissue, embryos

75
Q

Type IV collagen is seen in what tissues?

A

basement membrane

76
Q

Name the epithelial and fibroblast growth factor.

A

TGF-alpha

77
Q

Name the fibroblast growth factor that also inhibits inflammation.

A

TGF-beta

78
Q

Name the growth factor for endothelium, smooth muscle and fibroblasts.

A

PDGF

79
Q

List the growth factor used for angiogenesis and mediation of skeletal development.

A

FGF

80
Q

List the growth factor used for angiogenesis only.

A

VEGF

81
Q

How does a wound come together with secondary intention?

A

myofibroblasts contract the wound

82
Q

Why is Vitamin C needed for wound healing?

A

Procollagen needs Vit C for hydroxylation before it can be cross-linked

83
Q

Why is copper needed for wound healing?

A

needed by lysyl oxidase for collagen crosslinking

84
Q

Why is zinc needed for wound healing?

A

collagenase cofactor to remove type III collagen

85
Q

What is the name for a proliferation of type III collagen way out of proportion to a wound?

A

keloid

Pathoma High Yield (3 decks)

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