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PathSattar > 2 - Inflammation, Inflammatory Disorders, And Wound Healing > Flashcards

2 - Inflammation, Inflammatory Disorders, And Wound Healing Flashcards

1
Q

What are the mediators of acute inflammation?

A 
TLRs
Arachidonic acid metabolites
Mast cells
Complement
Hageman factor XII
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2
Q

In TLRs, what is involved in the activation of pathogen associated molecular patterns (PAMPs) that are commonly shared by microbes?

A

CD14 (TLR4 co-receptor) on macrophages recognizes lipopolysaccharides (PAMP) on outer membrane of gram negative bacteria

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3
Q

TLR activation results in upregulation of?

A

NF-kB

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4
Q

AA released from phospholipid cell membrane by phospholipase A2 is acted upon by COX and results in?

A

Prostaglandin (D I E)

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5
Q

AA released from phospholipid cell membrane by phospholipase A2 is acted upon by 5-lipoxygenase and results in?

A

Leukotrienes (B C D E)

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6
Q

What PG mediates pain and fever?

A

PGE2

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7
Q

PGI2, PGE2, and PGD2 mediates what?

A

Vasodilation and increased vascular permeability

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8
Q

What LT attracts and activates neutrophils?

A

LTB2

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9
Q

LTC2, LTD2, and LTE2 mediate what?

A

Vasoconstriction, bronchospasm, and increased vascular permeability

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10
Q

What are the 4 key neutrophil mediators?

A

LTB4
C5A
IL8
Bacterial products

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11
Q

Mast cells are activated by what 3 things?

A

Tissue trauma
Complement ptns C3a and C5a
Cross linking of cell surface IgE by antigen

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12
Q

The delayed mast cell response involves what AA metabolite?

A

Leukotrienes

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13
Q

What is the classical pathway for complement activation?

A

C1 binds to IgG and IgM

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14
Q

What is the alternative pathway for complement activation?

A

Microbial products

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15
Q

What is the MBL pathway for complement activation?

A

Mannose binding lectin binds to mannose

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16
Q

What factor is involved in DIC especially in severe gram negative sepsis?

A

Hageman factor (XII)

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17
Q

What mediates vasodilation, increased vascular permeability and pain?

A

Bradykinin

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18
Q

What are the key mediators of rubor and calor?

A

Vasodilation and increased blood flow

Histamine, prostaglandins, and bradykinin

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19
Q

What are the key mediators of tumor?

A

Leakage of fluid from postcapillary venules into the interstitial space
Histamine and tissue damage

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20
Q

What are the key mediators of dolor?

A

Bradykinin and PGE2 sensitize nerve endings

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21
Q

What is the pathophysiology of fever?

A

Pyrogens cause MACROPHAGES to release IL-1 and TNF which increase COX activity in the perivascular cells of the hypothalamus. Increased PGE2 raises temperature setpoint

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22
Q

Acute inflammation arises in response to?

A

Infection or tissue necrosis

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23
Q

In margination of leukocytes, vasodilation slows blood flow where?

A

Post capillary venules

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24
Q

In inflammation, what are the 3 key players?

A

Fluid
Neutrophils (24h)
Macrophages (2-3 days)

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25
Q

7 Steps in Neutrophil Arrival and Function?

A 
Margination
Rolling (selectins)
Adhesion
Transmigration and Chemotaxis
Phagocytosis
Destruction of Material
Resolution
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26
Q

In rolling of leukocytes, ___ is upregulated on endothelial cells

A

Selectins

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27
Q

P-selectin is released from?

A

Weibel-Palade bodies

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28
Q

P-selectin release from WPb is mediated by?

A

Histamine

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29
Q

E-selectin is induced by?

A

TNF and IL-1

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30
Q

Selectins bind ____ on leukocytes

A

Sialyl Lewis X

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31
Q

In adhesion of leukocytes, ___ are upregulated on endothelium

A

CAMs (ICAM, VCAM)

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32
Q

CAM upregulation depends on ___

A

TNF and IL-1

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33
Q

Integrins are upregulated on leukocytes by ___

A

C5a and LTB4

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34
Q

Interaction between ___ and ___ results in firm adhesion of leukocytes to the vessel wall

A

CAMs and Integrins

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35
Q

Leukocyte adhesion deficiency is due to an autosomal RECESSIVE defect of ___ (___ subunit)

A

Integrins

CD18 subunit

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36
Q

Clinical features of leukocyte adhesion deficiency

A

Delayed separation of umbilical cord
Increased circulating neutrophils
Recurrent bacterial infections that lack pus

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37
Q

In chemotaxis, neutrophils are attracted by what

A

C5a
LTB4
IL-8
Bacterial products

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38
Q

Phagocytosis is enhanced by?

A

Opsonins - IgG and C3b

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39
Q

Chediak-Higashi syndrome is an autosomal RECESSIVE ____

A

Protein trafficking defect - microtubule defect

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40
Q

Clinical features of Chediak-Higashi syndrome

A 
Increased risk of pyogenic infections
Neutropenia (intramedullary death of neutrophils)
Giant granules in leukocytes
Defective primary hemostasis
Albinism
Peripheral neuropathy
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41
Q

Chronic granulomatous disease is characterized by poor O2 dependent killing due to ___ defect

A

NADPH oxidase defect (X-linked or autosomal RECESSIVE)

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42
Q

Chronic granulomatous disease leads to recurrent infection and granuloma formation with ___ organisms

A 
Catalase positive
Staphylococcus aureus
Pseudomonas cepacia
Serratia marcescens
Nocardia
Aspergillus
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43
Q

What test is used for chronic granulomatous disease?

A

Nitroblue tetrazolium test

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44
Q

Nitroblue tetrazolium test turns blue if ___ can convert O2 to Superoxide

A

NADPH oxidase

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45
Q

Catalase producing organisms ___ H2O2

A

Destroy

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46
Q

Myeloperoxidase deficiency presents as ___

A

Nothing. Asymptomatic but with increased risk for Candida infections

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47
Q

O2 independent killing (less effective than O2 dependent) occurs via enzymes present in leukocyte secondary granules like…

A

Lysozyme in macrophages

Major basic protein in eosinophils

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48
Q

Macrophages predominate after neutrophils and peak after ___ days after inflammation begins

A

2-3 days

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49
Q

Macrophages are derived from what type of cell?

A

Monocytes

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50
Q

Macrophages ingest organisms via phagocytosis and destroy material using what enzyme (O2 independent killing)?

A

Lysozyme

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51
Q

Anti-inflammatory cytokines produced by macrophages

A

IL-8 and TGF B

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52
Q

Macrophage recruit additional neutrophil by what?

A

IL-8

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53
Q

Chronic inflammation is characterized by the presence of?

A

Lymphocytes and plasma cells

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54
Q

Stimuli of chronic inflammation

A 
Persistent infection
Infection with viruses, mycobacteria, parasites, and fungi
Autoimmune disease
Foreign material
Some cancers
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55
Q

Where are T lymphocytes produced and where do they develop?

A

Produced in bone marrow

Develop in thymus

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56
Q

What do T cells use for antigen surveillance?

A

TCR complex (TCR and CD3)

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57
Q

Activation of T cells requires

A

1 - binding of antigen/MHC complex

2 - additional 2nd signal

58
Q

CD4 T cell recognizes what kind of antigen?

A

Extracellular

59
Q

CD8 T cell recognizes what antigen?

A

Intracellular antigen

60
Q

What is the 2nd activation signal for CD4 helper T cells?

A

B7 (on APC) binds CD28 (on CD4 T cell)

61
Q

Activated CD4 T cells secrete cytokines that help inflammation and are divided into ___ subsets

A

Two subsets - TH1 and TH2

62
Q

CD4 T cell TH1 subset secretes what?

A

IFN-y (activates macrophage)

IL-2 (T cell growth factor, CD8 T cell activator)

63
Q

CD4 T cell TH1 subset helps what cell?

A

CD8 T cell

64
Q

CD4 T cell TH2 subset helps what cell?

A

B cell

65
Q

CD4 T cell TH2 subset secretes what?

A 
IL-4 (promotes class switching to IgG and IgE)
IL-5 (eosinophil chemotaxis and activation; class switching to IgA)
IL-10 (anti-inflammatory)
66
Q

What is the 2nd activation signal of CD8 T cell?

A

IL-2

67
Q

How does CD8 T cell kill cells?

A

Secretion of perforin and granzyme —> apoptosis

FasL —> apoptosis

68
Q

What is the key mediator of apoptosis?

A

Caspase

69
Q

What are the three ways in which caspase is activated?

A

1 - intrinsic mitochondrial (cytochrome c leakage)
2 - extrinsic receptor (FasL, TNF)
3 - CD8 —> granzyme, perforin

70
Q

B cell activation occurs via

A

Antigen binding by surface IgM or IgD

B cell antigen presentation to CD4 T cell

71
Q

What is the 2nd activation signal for B cell?

A

CD40 receptor on B cell binds CD40L on T cell

72
Q

What happens after 2nd activation signal of B cell?

A

Helper T cell secretes IL-4 and IL-5 to induce isotype switching

73
Q

What is the hallmark of a granuloma?

A

Epithelioid histiocytes

74
Q

What characterizes epithelioid histiocytes?

A

Macrophages with abundant pink cytoplasm

75
Q

Noncaseating granuloma etiologies?

A 
Reaction to foreign material
Sarcoidosis
Beryllium exposure
Crohn disease
Cat screatch disease
76
Q

Caseating granuloma etiologies?

A

Tuberculosis (AFB stain)

Fungi (silver stain, GMS)

77
Q

Histologic hallmark of crohn disease?

A

Noncaseating granuloma

78
Q

Histologic hallmark of ulcerative colitis

A

Crypt abscesses

79
Q

How are granulomas formed?

A

Macrophages present antigen to CD4 T cell —> macrophages then secrete IL-12 —> differentiate into TH1 subtype —> IFN-y which converts macrophages to epithelioid histiocytes

80
Q

DiGeorge syndrome is the developmental failure of?

A

3rd and 4th pharyngeal pouches

81
Q

DiGeorge syndrome is due to ___ microdeletion

A

22q11 microdeletion

82
Q

DiGeorge Syndrome presents with

A

T cell deficiency and hypocalcemia

Abnormalities of the heart, great vessels, and face

83
Q

Severe combined immunodeficiency is characterized by defective…

A

Humoral and cell mediated immunity

84
Q

Etiologies of SCID?

A 
Cytokine receptor defects
ADA (adenosine deaminase) deficiency
MHC class II deficiency
85
Q

SCID treatment

A

Sterile isolation and stem cell transplantation

86
Q

Complete lack of immunoglobulin due to disordered B cell maturation?

A

X linked agammaglobulinemia

87
Q

X linked agammaglobulinemia is due to mutated ___

A

BTK (bruton tyrosine kinase)

88
Q

X linked agammaglobulinemia presents after ___ months of life

A

6 months of life

89
Q

X linked agammaglobulinemia presents with recurrent ____ infections

A

Bacterial
Enterovirus
Giardia lamblia

90
Q

Low immunoglobulin due to B cell or T cell defects

A

CVID (combined variable immunodeficiency)

91
Q

CVID (combined variable immunodeficiency) presents as increased risk for what type of infections?

A

Bacterial
Enteroviral
Giardia lamblia

92
Q

CVID (combined variable immunodeficiency) presents as increased risk for what type of disease?

A

Autoimmune disease and lymphoma

93
Q

Most common immunoglobulin deficiency

A

IgA deficiency

94
Q

Most common IgA deficiency

A

Celiac disease

95
Q

Elevated IgM

A

Hyper-IgM syndrome

96
Q

Hyper IgM syndrome is due to mutated ___

A

CD40L or CD40 receptor (class switching cannot occur)

97
Q

In hyper IgM syndrome, low IgA, IgG and IgE result in

A

Recurrent pyogenic infections (from low IgG mostly bc of opsonins)

98
Q

Characterized by TIE
Thombocytopenia
Infections
Eczema

A

Wiskott Aldrich Syndrome

99
Q

Major cause of death in wiskott aldrich syndrome?

A

Bleeding

100
Q

What gene is affected in wiskott aldrich syndrome?

A

WASP gene; X linked

101
Q

C5-C9 complement deficiencies result in increased risk to what type of infections?

A

Neisseria infection

102
Q

C1 complement inhibitor deficiency results in?

A

Hereditary angioedema

103
Q

What involves loss of self tolerance?

A

Autoimmune disorders?

104
Q

What is defective in T cells with loss of self tolerance?a

A

Negative selection

105
Q

What is defective in B cells with loss of self tolerance?a

A

Anergic (no 2nd signal)

106
Q

What is the etiology of autoimmune disorders?

A

Environmental trigger in genetically susceptible individuals

107
Q

SLE involves what type of hypersensitivity?

A

Type 2 and 3 (cytotoxic and antigen-antibody complex)

108
Q

In SLE, what is the most common type of renal damage and is it nephrotic or nephritic?

A

Diffuse proliferative glomerulonephritis; nephritic

109
Q

What is a classic heart finding in SLE?

A

Libman Sacks endocarditis - sterile deposits on both sides of the MITRAL valve

110
Q

What is the characteristic of drug induced SLE?

A

Anti-histone antibody

111
Q

What are the most common drugs that cause drug induced SLE

A

Phenytoin, hydralazine, isoniazid

112
Q

Anti-phospholipid antibody syndrome is associated with SLE. What are the most common antibodies involved?

A

Anti-cardiolipin and lupus anti-coagulant

113
Q

Anticardiolipin may result in?

A

False positive syphilis test

114
Q

Lupus anticoagulant may result in

A

Falsely elevated PTT lab studies

115
Q

Sjogren syndrome involves what type of hypersensitivity?

A

Type 4 - lymphocyte mediated damage

116
Q

Sjogren’s syndrome is characterized by

A

ANA and anti-ribonucleoprotein antibodies (anti-SSA/Ro; anti-SSB/La)

117
Q

Sjogren’s syndrome is often associated with other autoimmune diseases especially

A

Rheumatoid arthritis

118
Q

Sjogren’s syndrome has increased risk for what type of cancer?

A

B cell (marginal zone) lymphoma —> unilateral enlargement of the parotid gland late in the disease course

119
Q

Autoimmune disease characterized by activation of fibroblasts and deposition of collagen (fibrosis)

A

Scleroderma

120
Q

Localized scleroderma involves the skin only. Most common subtype is called?

A

Morphea

121
Q

Localized scleroderma is associated with antibodies to?

A

DNA topoisomerase II

122
Q

Limited type of scleroderma - prototype - CREST syndrome involves what

A 
Calcinosis/anti-Centromere antibodies
Raynaud phenomenon
Esophageal dysmotility
Scleroodactyly
Telangectasia
123
Q

Diffuse type of scleroderma involves what two types of antibodies?

A

ANA

Anti-DNA topoisomerase 1 (Scl 70) antibody

124
Q

Mixed connective tissue damage involves

A

Mixed features of SLE, systemic sclerosis, and polymyositis

125
Q

What antibody is involved in mixed connective tissue disease?

A

Antibodies against U1 ribonucleoprotein

126
Q

Labile tissues possess ___ that continuously cycle to regenerate the tissue

A

Stem cells

127
Q

Stable tissues are comprised of cells that are ____ but can reenter the cell cycle to regenerate tissue when necessary

A

Quiescent (G0)

128
Q

Hematopoietic stem cells have what marker on it?

A

CD34

129
Q

In acute tubular necrosis, ___ is regenerated???

A

Proximal renal tubule of kidney

130
Q

What tissue formation is the initial phase of repair?

A

Granulation tissue

131
Q

In scar formation, type ___ collagen is replaced with type ___ collagen

A

Type 3 is replaced by type 1

132
Q

What enzyme removes type 3 collagen? This enzyme needs ___ as a cofactor

A

Collagenase

Zinc

133
Q

Epithelial and fibroblast GF

A

TGF alpha

134
Q

Impt fibroblast growth factor; also inhibits inflammation

A

TGF beta

135
Q

Growth factor for endothelium, smooth muscle, and fibroblasts

A

PDGF

136
Q

What growth factor is important for angiogenesis and also mediates skeletal development

A

Fibroblast growth factor

137
Q

Delayed wound healing occurs in

A

Infection

Deficiencies - vitamin C, copper, zinc

138
Q

In wound healing: vitamin C is important for

A

Hydroxylation - allows cross linking

139
Q

In wound healing: copper is required for

A

Lysyl oxidase

Also important for cross linking collagen

140
Q

In wound healing: zinc is needed for

A

Collagenase

PathSattar (3 decks)

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