Chapter 2 - Inflammation, Inflammatory Disorders and Wound Healing Flashcards
1
Q
What 2 things characterize acute inflammation?
A
- Edema
- Neutrophils
2
Q
What 2 things cause acute inflammation?
A
- Infection
- Tissue Necrosis
3
Q
What 5 things mediate acute inflammation?
A
- Toll-like receptors (TLRs)
- Arachidonic Acid (AA) Metabolites
- Mast Cells
- Complement
- Hageman Factor (Factor XII)
4
Q
What activates TLRs?
A
Pathogen-Associated Molecular Patterns (PAMPs)
5
Q
What receptor recognizes LPS?
A
CD14 on Macrophages
6
Q
How does activation of TLRs activate the immune response?
A
Upregulation of NF-κB which activates the immune response.
7
Q
What are the two pathways for AA?
A
Cyclooxygenase (COX) and 5-Lipoxygenase (LOX)
8
Q
What does the COX pathway produce (be specific)
A
PGI2
PGD2
PGE2
9
Q
What functions do PGI2, PGD2, and PGE2 share?
A
Vasodilation at arteriole
Increased vascular permeability at postcapillary venuole
10
Q
What two functions are unique to PGE2?
A
Pain and Fever
11
Q
What does the 5-LOX pathway produce?
(be specific)
A
LTB4
LTC4
LTD4
LTE4
12
Q
What are the functions of the Leukotrienes?
A
Vasoconstriction
Bronchospasm
Increased Vascular Permeability
13
Q
What 4 things attract and activate Neutrophils?
A
- LTB4
- C5a
- IL8
- Bacterial Products
14
Q
What 3 things activate mast cells?
A
- Tissue Trauma
- C3a and C5a
- Cross-linking of cell-surface IgE by antigens
15
Q
What is the immediate response of Mast cells?
A
Release of preformed histamine granules
16
Q
What is the delayed response of Mast cells?
A
Production of AA metabolites, especially Leukotrienes
17
Q
What are the 3 ways to activate Compliment?
A
- Classical Pathway (IgG or IgM + antigen)
- Alternative Pathway (Microbial Products)
- Mannose-Binding Lectin (MBL) Pathway (MBL + Mannose actives compliment)
18
Q
Which two compliment proteins cause mast cell degradation?
A
C3a and C5a
19
Q
Which Compliment protein is an opsonin?
A
C3b
20
Q
What activates Hageman Factor?
A
Exposure to subendothelial or tissue collagen
21
Q
What does Hageman Factor activate?
A
- Coagulation
- Complement
- Kinin System
22
Q
What are the functions of Bradykinin?
A
Vasodilation
Increased Vascular Permeability
Pain
23
Q
What is the mechanism behind Redness and Warmth in inflammation?
A
Vasodilation due to Prostaglandins, Bradykinin and Histamine
24
Q
What is the mechanism behind Pain in inflammation?
A
Bradykinin and PGE2 sinsitize nerve endings
25
What is the mechanism behind Swelling in inflammation?
leakage of fluid from postcapillary venules due to **histamine.**
26
What is the mechanism behind Fever in inflammation?
Pyogens cause **macrophages** to release TNF which **increases COX activity in perivascular cells of the hypothalmus**.
PGE2 increases temperature set point.
27
Is this Acute or Chronic inflammation?
Acute
28
What are the 7 steps of Neutrophil arrival and funtion?
1. Margination
2. Rolling
3. Adhesion
4. Transmigration and Chemotaxis
5. Phagocytosis
6. Destruction of phagocytosed material
7. Resolution
29
What are the 3 phases of acute inflammation?
1. Fluid
2. Neutrophil
3. Macrophage
30
What is the mechanism of Margination?
**Vasodilation** slows blood flow in _postcapillary veins_
31
What is the mechanism of Rolling (Step 2)?
**Selectin** is upregulated on endothelial cells.
Selectins bind **sialyl Lewis X** on leukocytes
32
What are the two types of Selectin and where do they come from?
**P-Selectin** (comes from Weibel-Palade bodies)
**E-Selectin** (induced by TNF and IL-1)
33
What is the mechanism of Adhesion (Step 3)?
**Cellular Adhesion Molecules (CAMs)** on endothelial cells bind to **Integrins** on leukocytes and adhere them to the vessel wall.
34
What upregulates CAMs?
TNF and IL-1
35
What upregulates Integrins?
C5a and LTB4
36
What is Leukocyte Adhesion Deficiency?
An Autosomal Recessive Defect of Integrins
(subunit CD18)
37
What are the clinical features of Leukocyte Adhesion Deficiency?
1. **Delayed separation of unbilical cord**
2. increased circulating neutrophils
3. recurrent bacterial infections that lack pus
38
Where do leukocytes transmigrate?
Postcapillary Venules
39
What are the 2 opsonins in the text?
IgG and C3b
40
What is Chediak-Higashi Syndrome?
An Autosomal Recessive **Protein Trafficking Defect** characterized by **impared phagolysosome formation**
41
What are the 6 clinical features of Chediak-Higashi Syndrome?
1. Increased risk of pyogenic infection
2. Neutropenia
3. Giant Granules in Leukocytes
4. Defective Primary Hemostasis
5. Albinism
6. Peripheral Neuropathy
42
Is O2 dependent or O2 independent killing more effective?
Dependent
43
How is O2 used to kill organisms in O2 dependent killing?
It is converted to HOCl- (Bleach)
44
What are the reactions and enzymes used to convert O2 into HOCl-
O2 → O2- (NADPH Oxidase)
O2- → H2O2 (Super Oxide Dismutase)
H2O2 → HOCl- (Myeloperoxidase aka MPO)
45
What is Chronic Granulomatous Disease (CGD)?
An **NADPH Oxidase defect** characterized by poor O2 dependent killing.
(X-linked or Autosomal Recessive)
46
To what type of microorganisms are people with CGD susceptible?
(Whic 2 of them were emphasized?)
Catalse Positive Microorganisms
(*Staph aureus* and ***Pseudomonas cepacia)***
47
What symptoms are characteristic of MPO deficiency?
**Inreased risk of Candida infections**, but most patients are **Asymptomatic**
48
What test is used for CGD?
Nitroblue Tetrazolium (NBT) test
| (turns blue if NADPH Oxidase works)
49
If a patient has MPO deficiency, but **not** CGD, what color will an NBT test be, and what does that mean?
Blue (NADPH Oxidase works normally)
50
What is the mechanism of O2 independent killing?
**Enzymes** present in leukocyte secondary granules
(Macrophages = Lysozyme)
(Eosinophils = Major Basic Protein)
51
What is the mechanism of Resolution (Step 7)?
**Neutrophils undergo Apoptosis** within 24 hours of resolution of infection.
52
What are macrophages derived from?
Monocytes in the blood
53
How do macrophages enter tissues?
The same as neutrophils
(margination, rolling, adhesion, transmigration)
54
How do macrophages kill phagocytized organisms?
**Lysozyme** (and other enzymes)
O2 independent
55
What are the 4 main outcomes that Macrophages can promote in the inflammatory process?
(think managing)
1. Resolution and Healing
2. Continued Acute Inflammation
3. Abscess
4. Chronic Inflammation
56
How do macrophages promote resolution and healing?
IL-10 and TGF-β
57
How do macrophages recruit more neutrophils to continue acute inflammation?
IL-8
58
What is an abscess?
Acute inflammation surrounded by fibrosis
59
How do macrophages promote chronic inflammation?
Presenting antigen to activate CD4+ and Helper T-Cells
60
After how much time is Acute Inflammation considered Chronic Inflammation?
FALSE
The differentiation is not based on time, but on the presence of neutrophils vs lymphocytes
61
Is this Acute or Chronic Inflammation?
Chronic
62
What are the 5 common cuases of Chronic Inflammation?
1. **persistent infection**
2. viruses, mycobacteria, parasites, fungi
3. autoimmune diseases
4. foreign material
5. some cancers
63
Where do T cells mature?
Thymus
64
What is the difference between the TCR on CD4+ and CD8+ cells?
**CD4+** recognizes antigen on **MHC class II** (extracelllar)
**CD8+** recognizes antigen on **MHC class I** (intracellular)
65
What is required for T cell activation?
1. binding of antigen/MHC complex
2. an additional 2nd signal
66
What is the second signal to activate CD4+ cells?
B7 on APC binds to CD28 on CD4+ cell
| ( 28 / 7 = 4 )
67
What do Th1 cells secrete?
(What are the functions of the secretions?)
**IL-2** (T cell growth and CD8+ activator)
**IFN-γ** (macrophage activator)
68
What do Th2 cells secrete?
(What are the functions of the secretions?)
**IL-4** (B-cell slass switching to IgG and IgE)
**IL-5** (eosinophil chemotaxis/activation, maturation of B cells to plasma cells, class switching to IgA)
**IL-10** (inhibits Th1 phenotype)
69
What is the second activatoin signal for CD8+ cells?
IL-2 from Th1 cells
70
How do Cytotoxic T-cells (CD8+) kill?
1. Secretion of perforin and granzyme (activate caspase)
2. Expression FasL (binds to Fas and induces apoptosis)
71
What do naive B cells express?
surface IgM and IgD
72
What happens when atigen binds to the surface IgM or IgD on naive B cells?
Matures into IgM or IgD secreting plasma cell
73
What are the 3 steps of the second (not IgM or IgD) method of activation of B cells?
1. **B-cell presents antigen to CD4+ cell**
2. **CD40 receptor on B cell binds CD40L on T cell** (second T cell activation signal)
3. **Th2 cell secretes IL-4 and IL-5** which mediates B cell isotype switching and maturation
74
What are the 4 characteristics of granulomatous inflammation?
1. a granuloma
2. **EPITHELIOD HISTIOCYTES** (macrophages with abundant pink cytoplasm)
3. giant cells
4. rim of lymphocytes
75
What is the difference between non-caseating and caseating granulomas?
Caseating granulomas have central necrosis
(non-caseating do not)
76
What are the 5 common etiologies of non-caseating granulomatous inflammation?
1. Foreign Material
2. Sarcoidosis
3. Beryllium exposure
4. Chron's disease
5. Cat Scratch disease (stellate granuloma)
77
BONUS ROUND
What is the histologic hallmark of Ulcerative Colitis?
Crypt Abscesses
78
BONUS ROUND
What type of stain is used for TB?
AFB stain
79
BONUS ROUND
What type of stain is used for fungal infections?
GMS stain
80
What are the 3 steps of granuloma formation?
1. **Macrophages** present antigen to **CD4+ cells**
2. Macrophages then secrete **IL-12** causing CD4+ cells to become Th1 cells
3. Th1 cells secrete **INF-γ** converting macrophages into epitheliod histiocytes and giant cells
81
What type of inflammation is this?
Caseating
82
What type of inflammation is this?
Non-Caseating
83
How does a patient develop DiGeorge Syndrome?
22q11 mutation
84
What is problem in DiGeorge Syndrome?
(i.e. what's missing or imporoperly developed?)
Failure of the 3rd and 4th pharyngeal pouches
(lack of thymus and parathyroids)
85
How does DiGeorge syndrome present?
Lack of T-cells
Hypocalcemia
Abnormalities of heart, great vessels, and face
86
What type of infections would expect to see in a person who has DiGeorge Syndrome?
Viral or Fungal
| (no T-cells to fight those infections)
87
What are the 3 main etiologies of Severe Combined Immunodeficiency (SCID)?
1. Cytokine Receptor defects
2. Adenosine Deaminase (ADA) deficiency
3. MHC Class II deficiency
88
What is the end result of the etiology of SCID?
(i.e. what isn't working, or what is missing?)
Defective **cell-mediated** and **humoral** immunity
89
Why do lymphocytes need ADA?
Buildup of Adenosine and Deoxyadenosine is toxic to lymphocytes.
(they must be deanimated and excreted as waste)
90
SCID is characterized by susceptibility to what 6 things?
1. Fungi
2. Bacteria
3. Viruses
4. Protozoa
5. Opportunistic infections
6. Live Vaccines
91
What is the treatment for SCID?
| (short term and long term)
Sterile Isolation (Short Term)
Stem Cell Transplantation (Long Term)
92
What is the etiology of X-Linked Agammaglobulinemia?
Mutated Bruton Tyrosine Kinase (BTK)
(Naive B cells cannot mature to plasma cells)
93
What is missing or not working in X-Linked Agammaglobulinemia?
ocmplete lack of immunoglobulin.
94
What 3 infections are characteristic of X-linked Agammaglobulinemia?
1. Recurrent Bacterial
2. Enterovirus
## Footnote
***Giardia lamblia***
95
At what age does X-Linked Agammaglobulinemia normally present?
Around 6 months
(because maternal antibodies are present up to about 6 months of age)
96
What is the dysfunction in Common Variable Immunodeficiency (CVID)?
**Low immunoglobulin**
(due to B-cell or Helper T-cell defects)
97
For which 3 types of infections are patients with CVID at increased risk?
1. Recurrent Bacterial
2. Enterovirus
3. ***Giardia lamblia***
98
For which 2 diseases are patients with CVID at increased risk?
Autoimmune disease and lymphoma
99
What is the most common immunoglobulin deficiency?
IgA Deficiency
100
What are the symptoms for IgA Deficiency?
Asympomatic
(increased risk for mucosal infection. especially viral)
101
What is the etiology of Hyper-IgM Syndrome?
Mutated CD40L or CD40 receptor
102
What are the levels of the different immunoglobulins in Hyper-IgM syndrome (in relation to normal levels)?
IgM - high
IgD - ? ? ?
IgA - Low
IgG - Low
IgE - Low
103
To which type of infection(s) are patients with Hyper-IgM syndrom more susceptible?
Recurrent pyogenic infections (especially at mucosal sites)
104
What is the etiology of Wiskott-Aldrich Syndrome?
mutationin the WASP gene (X-linked)
105
Which three conditios are characteristic of Wiskott-Aldrich Syndrome?
1. Recurrent infections
2. Thryombocytopenia
3. Eczema
106
For what infection is someone with C5-C9 deficiency at risk?
***Neisseria***
107
What is characteristic of C1 Inhibitor deficiency
**Hereditray Angioedema**
(edema of the skin and mucosal surfaces)
108
What type of edema is most characteristic of Angioedema?
Periorbital
109
What condition does this patient have?
**Angioedema** (periorbital edema)
| (possibly C1 Inhibitor deficiency)
110
What percent of American's have autoimmune disorders?
1 %
111
What demographic most commonly has autoimmune disorders?
Women of child-bearing age
112
What is the etiology of autoimmune disorders?
1. Environmental Trigger
2. Genetic Susceptability
113
What is the mechanism of Systemic Lupus Erythematosus (SLE)?
Type II (Cytotoxic) Hypersensativity
Type III (Antigen-Antibody Complex) Hypersensativity
114
What are the 8 clinical features of SLE ?
(good luck..)
1. Fever and Weight Loss
2. **Malar 'butterfly' rash**
3. Arthritis
4. Pleuritis/Pericarditis (serosal surface involvement)
5. CNS Psychosis
6. **Renal Damage (Diffuse Proliferative Glomerulonephritis)**
7. Endocarditis, Myocarditis, Pericarditis
* **Libman-Sacks Endocarditis**
8. Anemia, Thrombocytopenia, leukopenia
115
What are the 2 most common causes of death in SLE?
Renal failure
infection
116
What is the classic finding in Liebman-Sacks endocarditis?
sterile deposits **on both sides** of the valve
117
What 2 antibodies are characteristic of SLE?
Which is the most specific for SLE?
Antinuclear Antibodies (ANA)
## Footnote
**Anti dsDNA (more specific)**
118
What antibody is characteristic of Drug-induced SLE?
Antihistone Antibody
119
What 3 drugs can cause Drug-Induced SLE?
1. Hydralazine
2. Procainamide
3. Isoniazid
120
What 2 antibodies are associated with Antiphospholipid antiobody sundrome?
Anticardiolipin and Lupus Anticoagulant
121
What can Anticardiolipin lead to?
False-Positive Syphilis test
122
How does Lupus Anticoagulant manifest clinically?
Falsely-elevated PTT
123
What effects can Antiphospholipid antiobody syndrome have?
Arterial and Venous Thromboses
(deep vein, hepatic vein, placental, stroke)
124
How is Antiphospholipid antiobody syndrome treated?
Lifelong anticoagulation
125
What is the etiology of Sjogren Syndrome?
**Type IV Hypersensitivity** with Fibrosis
126
What is attacked by the immune system in Sjogrens System?
Lacrimal and Salivary Glands
127
In what 3 ways does Sjogren Syndrome present clinically?
1. Dry Eyes
2. Dry Mouth
3. Recurrent Caries
128
If a patient complains that they "can't chew a cracker" or that they "have dirt in my eyes" they probably have what?
Sjogren Syndrome
129
What antibodies are characteristic of Sjogren Syndrome?
ANA and **Anti-Ribonucleoprotein Antibodies**
130
What other diseases is Sjogren Syndrome associated with?
Autoimmune diseases like **Rheumatoid Arthritis**
131
Sjogren Syndrome puts a patient at risk for what?
(What is the main symptom?)
B-cell Lymphoma
| (unilateral enlargement of the parotid)
132
What is Scleroderma?
Autoimmune tissue damage with activation of fibroblasts and deposition of collagen
133
What is affected by Diffuse Scleroderma?
Any organ
(Commonly the **esophagus** with **dysphagia for solids and liquids)**
134
What is Diffuse Scleroderma characterized by?
(what type of antibody?)
ANA
## Footnote
**Anti-DNA Toperisomerase I**
135
What is characteristic of Localized Scleroderma?
**CREST**
## Footnote
Calcinosis/**Anti-Centromere Antibodies**
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly
Telangiectasis of the skin
136
How does Mixed Connective Tissue Disease present?
Mixed features of
* SLE
* Systemic Sclerosis
* Polymyositis
137
What is characteristic of Mixed Connective Tissue Disorder?
Serum antibodies against **U1 Ribonucleoprotein**
138
When does healing begin (in relation to inflammation)?
Healing is intitiated when inflammation begins.
139
Tissues can be divided into 3 categories based on regenerative capacity. What are they?
1. Labile
2. Stable
3. Permanent
140
What is the definition of Labile tissues?
Possess stem cells that continuously cycle to regenerate the tissue
141
What are 3 examples of labile tissues?
| (Where are their stem cells located?)
1. Small and large bowel
* (mucosal crypts)
2. Skin
* (Basal Layer)
3. Bone Marrow
* Hematopoetic Stem cells
142
How are stem cells in bone marrow identified clinically?
Presence of CD34
143
What is the definition of a stable tissue?
(What is the main example?)
comprised of quiescent cells that can reenter the cell cycle to **regenerate tissue when necessary**
(Hyperplasia of the **liver**)
144
What is the definition of Permanent tissues?
Lack significant regenerative potential
145
What are the 3 types of permanent tissue?
1. Myocardium
2. Skeletal Muscle
3. Neurons
146
What is the definition of tissue repair?
Replacement of damaged tissue with a fibrous scar
147
What are the two situations when repair occurs?
1. When Regenerative Stem Cells are lost
2. When a tissue lacks regenerative capacity.
148
What is the initial phase of wound repair?
Granulation tissue
149
What 3 things make up granulation tissue?
Fibroblasts
Capillaries
Myofibroblasts
150
What causes the shift from granulation tissue to scar formation?
The shift from Type III Collagen to Type I Collagen
151
What enzyme is responsible for the change from Type III to Type I Collagen?
(What is the important cofactor?)
Collagenase
| (Zinc)
152
153
What type of signalling mediates regeneration and repair, paracrine, endocrine, or autocrine?
Paracrine
| (via Macrophage growth factors)
154
What are the 5 mediators of regeneration and repair?
1. TGF-α
2. TGF-β
3. Platelet-Derived Growth Factor (PDGF)
* Endothelium, smooth muscle, and fibroblasts
4. Fibroblast Growth Factor
* angiogenesis
5. Vascularendothelial growth factor (VEGF)
155
What is the difference between healing by Primary Intention versus Secondary Intention?
Edges are surgically approximated in Primary Intention
156
How is the wound closed in Secondary Intention?
Myofibroblasts contract to close the wound
157
What are the 6 things that cause delayed wound healing?
1. Infection (**the most common reason**)
2. **Vit C, Copper, or Zinc deficiency**
3. Foreign Body
4. Ischemia
5. Diabetes
6. Malnutrition
158
What is the definition of a Hypertrophic Scar?
excess production of scar tissue **localized to the wound**
(consists of **Type I Collage**)
159
What is the definition of a Keloid?
Excess production of scar tissue that is **out of proportion to the wound**
(Consists of **Type III Collagen**)
160
What demographic most often gets Keloids?
African Americans
## Footnote
**(Genetic Predisposition)**
161
What part of the body is most classically affected by Keloids?
**Earlobes**
| (also, face and upper extremeties)
162
Where are Types I - IV Collagen normally found?
I. Bone (high tensile strength)
II. Cartilage (car**_two_**lage)
III. Embryo, Blood Vessels, Granulation Tissue (pliable)
IV. Basement Membrane
163
How would you diagnose this scar?
Hypertrophic Scar
164
How would you diagnose this scar?
Keloid
165
What is the area outlined in red on this heart?
Fibrous scarring from infarct
