2 - Inflammation, Inflammatory Disorders, And Wound Healing Flashcards
(140 cards)
1
Q
What are the mediators of acute inflammation?
A
TLRs Arachidonic acid metabolites Mast cells Complement Hageman factor XII
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
3
Q
TLR activation results in upregulation of?
A
NF-kB
4
Q
AA released from phospholipid cell membrane by phospholipase A2 is acted upon by COX and results in?
A
Prostaglandin (D I E)
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)
6
Q
What PG mediates pain and fever?
A
PGE2
7
Q
PGI2, PGE2, and PGD2 mediates what?
A
Vasodilation and increased vascular permeability
8
Q
What LT attracts and activates neutrophils?
A
LTB2
9
Q
LTC2, LTD2, and LTE2 mediate what?
A
Vasoconstriction, bronchospasm, and increased vascular permeability
10
Q
What are the 4 key neutrophil mediators?
A
LTB4
C5A
IL8
Bacterial products
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
12
Q
The delayed mast cell response involves what AA metabolite?
A
Leukotrienes
13
Q
What is the classical pathway for complement activation?
A
C1 binds to IgG and IgM
14
Q
What is the alternative pathway for complement activation?
A
Microbial products
15
Q
What is the MBL pathway for complement activation?
A
Mannose binding lectin binds to mannose
16
Q
What factor is involved in DIC especially in severe gram negative sepsis?
A
Hageman factor (XII)
17
Q
What mediates vasodilation, increased vascular permeability and pain?
A
Bradykinin
18
Q
What are the key mediators of rubor and calor?
A
Vasodilation and increased blood flow
Histamine, prostaglandins, and bradykinin
19
Q
What are the key mediators of tumor?
A
Leakage of fluid from postcapillary venules into the interstitial space
Histamine and tissue damage
20
Q
What are the key mediators of dolor?
A
Bradykinin and PGE2 sensitize nerve endings
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
22
Q
Acute inflammation arises in response to?
A
Infection or tissue necrosis
23
Q
In margination of leukocytes, vasodilation slows blood flow where?
A
Post capillary venules
24
Q
In inflammation, what are the 3 key players?
A
Fluid
Neutrophils (24h)
Macrophages (2-3 days)
25
7 Steps in Neutrophil Arrival and Function?
```
Margination
Rolling (selectins)
Adhesion
Transmigration and Chemotaxis
Phagocytosis
Destruction of Material
Resolution
```
26
In rolling of leukocytes, ___ is upregulated on endothelial cells
Selectins
27
P-selectin is released from?
Weibel-Palade bodies
28
P-selectin release from WPb is mediated by?
Histamine
29
E-selectin is induced by?
TNF and IL-1
30
Selectins bind ____ on leukocytes
Sialyl Lewis X
31
In adhesion of leukocytes, ___ are upregulated on endothelium
CAMs (ICAM, VCAM)
32
CAM upregulation depends on ___
TNF and IL-1
33
Integrins are upregulated on leukocytes by ___
C5a and LTB4
34
Interaction between ___ and ___ results in firm adhesion of leukocytes to the vessel wall
CAMs and Integrins
35
Leukocyte adhesion deficiency is due to an autosomal RECESSIVE defect of ___ (___ subunit)
Integrins
| CD18 subunit
36
Clinical features of leukocyte adhesion deficiency
Delayed separation of umbilical cord
Increased circulating neutrophils
Recurrent bacterial infections that lack pus
37
In chemotaxis, neutrophils are attracted by what
C5a
LTB4
IL-8
Bacterial products
38
Phagocytosis is enhanced by?
Opsonins - IgG and C3b
39
Chediak-Higashi syndrome is an autosomal RECESSIVE ____
Protein trafficking defect - microtubule defect
40
Clinical features of Chediak-Higashi syndrome
```
Increased risk of pyogenic infections
Neutropenia (intramedullary death of neutrophils)
Giant granules in leukocytes
Defective primary hemostasis
Albinism
Peripheral neuropathy
```
41
Chronic granulomatous disease is characterized by poor O2 dependent killing due to ___ defect
NADPH oxidase defect (X-linked or autosomal RECESSIVE)
42
Chronic granulomatous disease leads to recurrent infection and granuloma formation with ___ organisms
```
Catalase positive
Staphylococcus aureus
Pseudomonas cepacia
Serratia marcescens
Nocardia
Aspergillus
```
43
What test is used for chronic granulomatous disease?
Nitroblue tetrazolium test
44
Nitroblue tetrazolium test turns blue if ___ can convert O2 to Superoxide
NADPH oxidase
45
Catalase producing organisms ___ H2O2
Destroy
46
Myeloperoxidase deficiency presents as ___
Nothing. Asymptomatic but with increased risk for Candida infections
47
O2 independent killing (less effective than O2 dependent) occurs via enzymes present in leukocyte secondary granules like...
Lysozyme in macrophages
| Major basic protein in eosinophils
48
Macrophages predominate after neutrophils and peak after ___ days after inflammation begins
2-3 days
49
Macrophages are derived from what type of cell?
Monocytes
50
Macrophages ingest organisms via phagocytosis and destroy material using what enzyme (O2 independent killing)?
Lysozyme
51
Anti-inflammatory cytokines produced by macrophages
IL-8 and TGF B
52
Macrophage recruit additional neutrophil by what?
IL-8
53
Chronic inflammation is characterized by the presence of?
Lymphocytes and plasma cells
54
Stimuli of chronic inflammation
```
Persistent infection
Infection with viruses, mycobacteria, parasites, and fungi
Autoimmune disease
Foreign material
Some cancers
```
55
Where are T lymphocytes produced and where do they develop?
Produced in bone marrow
| Develop in thymus
56
What do T cells use for antigen surveillance?
TCR complex (TCR and CD3)
57
Activation of T cells requires
1 - binding of antigen/MHC complex
| 2 - additional 2nd signal
58
CD4 T cell recognizes what kind of antigen?
Extracellular
59
CD8 T cell recognizes what antigen?
Intracellular antigen
60
What is the 2nd activation signal for CD4 helper T cells?
B7 (on APC) binds CD28 (on CD4 T cell)
61
Activated CD4 T cells secrete cytokines that help inflammation and are divided into ___ subsets
Two subsets - TH1 and TH2
62
CD4 T cell TH1 subset secretes what?
IFN-y (activates macrophage)
| IL-2 (T cell growth factor, CD8 T cell activator)
63
CD4 T cell TH1 subset helps what cell?
CD8 T cell
64
CD4 T cell TH2 subset helps what cell?
B cell
65
CD4 T cell TH2 subset secretes what?
```
IL-4 (promotes class switching to IgG and IgE)
IL-5 (eosinophil chemotaxis and activation; class switching to IgA)
IL-10 (anti-inflammatory)
```
66
What is the 2nd activation signal of CD8 T cell?
IL-2
67
How does CD8 T cell kill cells?
Secretion of perforin and granzyme —> apoptosis
| FasL —> apoptosis
68
What is the key mediator of apoptosis?
Caspase
69
What are the three ways in which caspase is activated?
1 - intrinsic mitochondrial (cytochrome c leakage)
2 - extrinsic receptor (FasL, TNF)
3 - CD8 —> granzyme, perforin
70
B cell activation occurs via
Antigen binding by surface IgM or IgD
| B cell antigen presentation to CD4 T cell
71
What is the 2nd activation signal for B cell?
CD40 receptor on B cell binds CD40L on T cell
72
What happens after 2nd activation signal of B cell?
Helper T cell secretes IL-4 and IL-5 to induce isotype switching
73
What is the hallmark of a granuloma?
Epithelioid histiocytes
74
What characterizes epithelioid histiocytes?
Macrophages with abundant pink cytoplasm
75
Noncaseating granuloma etiologies?
```
Reaction to foreign material
Sarcoidosis
Beryllium exposure
Crohn disease
Cat screatch disease
```
76
Caseating granuloma etiologies?
Tuberculosis (AFB stain)
| Fungi (silver stain, GMS)
77
Histologic hallmark of crohn disease?
Noncaseating granuloma
78
Histologic hallmark of ulcerative colitis
Crypt abscesses
79
How are granulomas formed?
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
DiGeorge syndrome is the developmental failure of?
3rd and 4th pharyngeal pouches
81
DiGeorge syndrome is due to ___ microdeletion
22q11 microdeletion
82
DiGeorge Syndrome presents with
T cell deficiency and hypocalcemia
| Abnormalities of the heart, great vessels, and face
83
Severe combined immunodeficiency is characterized by defective...
Humoral and cell mediated immunity
84
Etiologies of SCID?
```
Cytokine receptor defects
ADA (adenosine deaminase) deficiency
MHC class II deficiency
```
85
SCID treatment
Sterile isolation and stem cell transplantation
86
Complete lack of immunoglobulin due to disordered B cell maturation?
X linked agammaglobulinemia
87
X linked agammaglobulinemia is due to mutated ___
BTK (bruton tyrosine kinase)
88
X linked agammaglobulinemia presents after ___ months of life
6 months of life
89
X linked agammaglobulinemia presents with recurrent ____ infections
Bacterial
Enterovirus
Giardia lamblia
90
Low immunoglobulin due to B cell or T cell defects
CVID (combined variable immunodeficiency)
91
CVID (combined variable immunodeficiency) presents as increased risk for what type of infections?
Bacterial
Enteroviral
Giardia lamblia
92
CVID (combined variable immunodeficiency) presents as increased risk for what type of disease?
Autoimmune disease and lymphoma
93
Most common immunoglobulin deficiency
IgA deficiency
94
Most common IgA deficiency
Celiac disease
95
Elevated IgM
Hyper-IgM syndrome
96
Hyper IgM syndrome is due to mutated ___
CD40L or CD40 receptor (class switching cannot occur)
97
In hyper IgM syndrome, low IgA, IgG and IgE result in
Recurrent pyogenic infections (from low IgG mostly bc of opsonins)
98
Characterized by TIE
Thombocytopenia
Infections
Eczema
Wiskott Aldrich Syndrome
99
Major cause of death in wiskott aldrich syndrome?
Bleeding
100
What gene is affected in wiskott aldrich syndrome?
WASP gene; X linked
101
C5-C9 complement deficiencies result in increased risk to what type of infections?
Neisseria infection
102
C1 complement inhibitor deficiency results in?
Hereditary angioedema
103
What involves loss of self tolerance?
Autoimmune disorders?
104
What is defective in T cells with loss of self tolerance?a
Negative selection
105
What is defective in B cells with loss of self tolerance?a
Anergic (no 2nd signal)
106
What is the etiology of autoimmune disorders?
Environmental trigger in genetically susceptible individuals
107
SLE involves what type of hypersensitivity?
Type 2 and 3 (cytotoxic and antigen-antibody complex)
108
In SLE, what is the most common type of renal damage and is it nephrotic or nephritic?
Diffuse proliferative glomerulonephritis; nephritic
109
What is a classic heart finding in SLE?
Libman Sacks endocarditis - sterile deposits on both sides of the MITRAL valve
110
What is the characteristic of drug induced SLE?
Anti-histone antibody
111
What are the most common drugs that cause drug induced SLE
Phenytoin, hydralazine, isoniazid
112
Anti-phospholipid antibody syndrome is associated with SLE. What are the most common antibodies involved?
Anti-cardiolipin and lupus anti-coagulant
113
Anticardiolipin may result in?
False positive syphilis test
114
Lupus anticoagulant may result in
Falsely elevated PTT lab studies
115
Sjogren syndrome involves what type of hypersensitivity?
Type 4 - lymphocyte mediated damage
116
Sjogren’s syndrome is characterized by
ANA and anti-ribonucleoprotein antibodies (anti-SSA/Ro; anti-SSB/La)
117
Sjogren’s syndrome is often associated with other autoimmune diseases especially
Rheumatoid arthritis
118
Sjogren’s syndrome has increased risk for what type of cancer?
B cell (marginal zone) lymphoma —> unilateral enlargement of the parotid gland late in the disease course
119
Autoimmune disease characterized by activation of fibroblasts and deposition of collagen (fibrosis)
Scleroderma
120
Localized scleroderma involves the skin only. Most common subtype is called?
Morphea
121
Localized scleroderma is associated with antibodies to?
DNA topoisomerase II
122
Limited type of scleroderma - prototype - CREST syndrome involves what
```
Calcinosis/anti-Centromere antibodies
Raynaud phenomenon
Esophageal dysmotility
Scleroodactyly
Telangectasia
```
123
Diffuse type of scleroderma involves what two types of antibodies?
ANA
| Anti-DNA topoisomerase 1 (Scl 70) antibody
124
Mixed connective tissue damage involves
Mixed features of SLE, systemic sclerosis, and polymyositis
125
What antibody is involved in mixed connective tissue disease?
Antibodies against U1 ribonucleoprotein
126
Labile tissues possess ___ that continuously cycle to regenerate the tissue
Stem cells
127
Stable tissues are comprised of cells that are ____ but can reenter the cell cycle to regenerate tissue when necessary
Quiescent (G0)
128
Hematopoietic stem cells have what marker on it?
CD34
129
In acute tubular necrosis, ___ is regenerated???
Proximal renal tubule of kidney
130
What tissue formation is the initial phase of repair?
Granulation tissue
131
In scar formation, type ___ collagen is replaced with type ___ collagen
Type 3 is replaced by type 1
132
What enzyme removes type 3 collagen? This enzyme needs ___ as a cofactor
Collagenase
| Zinc
133
Epithelial and fibroblast GF
TGF alpha
134
Impt fibroblast growth factor; also inhibits inflammation
TGF beta
135
Growth factor for endothelium, smooth muscle, and fibroblasts
PDGF
136
What growth factor is important for angiogenesis and also mediates skeletal development
Fibroblast growth factor
137
Delayed wound healing occurs in
Infection
| Deficiencies - vitamin C, copper, zinc
138
In wound healing: vitamin C is important for
Hydroxylation - allows cross linking
139
In wound healing: copper is required for
Lysyl oxidase
| Also important for cross linking collagen
140
In wound healing: zinc is needed for
Collagenase
