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Basics of Path > Inflammation, Inflammatory Disorders, and Healing > Flashcards

Inflammation, Inflammatory Disorders, and Healing Flashcards

1
Q

What is the main inflammatory cell involved in acute inflammation?

A

Neutrophils (polys)

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2
Q

What are the two main stimuli of acute inflammation?

A

Infection and tissue necrosis

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3
Q

Acute inflammation is an _________ response with _______ specificity.

A
  1. Immediate

2. Limited (innate immunity)

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4
Q

Where are TLR’s found?

A

Macrophages and dendritic cells

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5
Q

CD14

A

A TLR on macrophages - recognizes LPS on the outer membrane of GN bacteria

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6
Q

TLR activation results in upregulation of ______

A

NF-kB

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7
Q

True or False: TLRs are only present on cells of innate immunity.

A

False. TLRs are present on lymphocytes and play a role in mediating chronic inflammation as well.

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8
Q

Cyclooxygenase acts on arachidonic acid to generate what? What do these mediate?

A

PGI2, PGD2, PGE2 - vasodilation (arteriole) and inc. vasc. perm (post. cap venule)
PGE2 - fever and pain

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9
Q

5-lipooxygenase acts on AA to produce what? What do these mediate?

A

LTB4 - attracts/activates neutrophils

LTC4, LTD4, LTE4 - vasoconstriction, bronchospasm, and inc. vasc. perm

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10
Q

What are the 4 key mediators that attract and activate neutrophils?

A
  1. LTB4
  2. C5a
  3. IL-8
  4. Bacterial products
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11
Q

Mast cells are activated by which 3 things?

A
  1. Tissue trauma
  2. C3a and C5a
  3. Cross-linking of cell-surface IgE by antigen
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12
Q

Once activated, mast cells release ___________, that mediates _____________ and _________________.

A
  1. Histamine granules
  2. Vasodilation of arterioles
  3. Inc. vasc. perm at post. cap venule
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13
Q

What is the delayed response of mast cells?

A

Production of AA metabolites – leukotrienes

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14
Q

Classical complement pathway

A

C1 binds to IgG or IgM that is bound the antigen

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15
Q

Alternative complement pathway

A

Microbial products directly activate complement

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16
Q

Mannose-binding lectin pathway

A

MBL binds mannose on microorganisms and activates complement

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17
Q

What is the result of the activation of complement?

A
  1. C3 convertase
  2. C5 convertase
  3. Formation of MAC
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18
Q

What role does C3b play?

A

Opsonin for phagocytosis

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19
Q

Hageman factor

A

Inactive proinflammatory protein made in liver - activated upon exposure to subendothelial or tissue collagen

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20
Q

What does Hageman factor activate? What can this cause?

A
  1. Coagulation and fibrinolytic system - DIC in GN sepsis
  2. Complement
  3. Kinin system –> bradykinin (VD, VP, pain)
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21
Q

What are the cardinal signs of inflammation?

A
  1. Redness & Warmth
  2. Swelling
  3. Pain
  4. Fever
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22
Q

What mediates redness and warmth?

A

VD of arteriole - histamine, PGI2, PGD2, PGE2, and bradykinin

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23
Q

What mediates swelling?

A

Leakage of fluid from postcap venule into interstitial space - histamine & tissue damage

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24
Q

What mediates pain?

A

Bradykinin and PGE2 - sensitize sensory nerve endings

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25
What mediates fever?
Pyrogens cause macrophages to release IL-1 and TNF --> Inc. COX activity in perivascular cells of hypothal --> Inc. PGE2 raises temp set point
26
Margination
VD slows blood flow in postcap. venule -- cells marginate from center of flow to periphery
27
Rolling
Endothelial cells upregulate selectin to slow down neutrophils
28
P-selectin
Released from Weibel-Palade bodies, mediated by histamine
29
E-selectin
Induced by TNF and IL-1
30
Selectins bind ____________ on leukocyte, which results in ________ of leukocytes along the vessel wall.
1. Sialyl Lewis X | 2. Rolling
31
Leukocytes
Neutrophils and macrophages
32
What upregulates cellular adhesion molecules and what do they bind?
1. TNF and IL-1 | 2. Integrins on the leukocyte
33
What triggers upregulation of integrins on the leukocytes?
LTB4 and C5a
34
What interaction results in a firm adhesion between leukocytes and the endothelium?
Cellular adhesion molecules and integrins
35
Leukocyte Adhesion Deficiency
Autosomal recessive defect of integrin (CD18) --> | Delayed separation of umbilical cord, inc. circ. neutrophils, recurrent bacterial infections that lack pus
36
Leukocytes transmigrate across the endothelium of the ____________.
Post capillary venules
37
Neutrophils are attracted by which 3 things?
IL-8, C5a, and LTB4
38
Neutrophil phagocytosis is enhanced by which opsonins?
IgG and C3b
39
How do neutrophils phagocytose necrotic cells and pathogens?
Pseudopods from leukocytes extend to form phagosomes which are internalized and merge with lysosomes --> phagolysosome
40
Chediak-Higashi Syndrome
Protein trafficking defect - MT defect (ARec) Inc. risk of pyogenic infection, neutropenia, giant granules in leukocytes, defective primary hemostasis, albinism, peripheral neuropathy
41
How do neutrophils destroy phagocytosed material?
1. O2 dependent | 2. O2 independent
42
O2-dependent killing
O2 converted to HOCl via oxidative burst to destroy organism - most effective mechanism
43
What converts O2 to O2- (superoxide)?
NADPH oxidase - "Oxidative burst"
44
What converts O2- (superoxide) to hydrogen peroxide?
Superoxide dismutase (SOD)
45
What converts H2O2 to HOCl (bleach)?
Myloperoxidase (MPO)
46
Chronic Granulomatous Disease
Poor O2-dependent killing - NADPH oxidase defect (X-linked or A. Rec.)
47
What infections do pt w/ CGD typically get?
``` Catalase-positive - S. Aureus P. cepacia Nocardia Aspergillus S. Marcescens ```
48
Why are pts with CGD susceptible to catalase positive bacteria?
Catalase destroys bacterial H2O2 - can't use it in lieu self-generated H2O2 (other bacteria produce some H2O2)
49
Nitroblue tetrazolium test
Turns blue if NADPH can convert O2 to O2-
50
What does a colorless nitroblue tetrazolium test indicate?
NADPH oxidase is defective - CGD
51
DHR (Dihydrorhodamine) test for CGD **preferred**
Whole blood stained w/ DHR and stimulated to produce O2- which then oxidizes DHR to rhodamin
52
MPO deficiency
Can't produce bleach - asymptomatic - inc. risk for candida infections - NBT test is normal
53
O2 independent killing
Less effective - occurs via enzymes present in leukocyte secondary granules e.g. lysozyme and major basic protein
54
Neutrophils undergo _________ and disappear within _______ after resolution of inflammatory stimulus
Apoptosis | 24 hours
55
Macrophages peak ______ after inflammation begins.
2-3 days
56
Monocytes arrive via the _________, rolling, adhesion, and ______________ sequence.
1. Margination | 2. Transmigration
57
How do macrophages destroy material?
1. Phagocytosis | 2. O2 independent - enzymes in secondary granules - Lysozyme
58
How do macrophages induce resolution and healing?
IL-10 and TGF-beta (anti-inflammatory)
59
How do macrophages induce continued acute inflammation?
IL-8
60
Abscess formation
Macrophages create a wall of fibrosis around area of infection to wall off acute inflammation.
61
Macrophages can call in _________________ by presenting on _______.
1. Chronic inflammation | 2. MCH II
62
Chronic inflammation is characterized by what?
Presence of lymphocytes and plasma cells in tissue Delayed More specific - Adaptive
63
What things stimulate chronic inflammation?
1. Persistant infection 2. Viruses, mycobacteria, parasites and fungi 3. Autoimmune disease 4. Foreign material 5. Some cancers
64
T cells develop in the ________ and undergo _______________ becoming CD4 and CD8 T cells.
1. Thymus | 2. TCR rearrangement
65
Activation of CD4 T cells requires what 2 things?
1. Extracellular antigen:MHC II | 2. B7(APC):CD28(CD4)
66
What 2 ways do CD8 T cells kill cells?
1. Secrete perforins and granzyme | 2. FasL expression to bind Fas on target cell
67
Naive B cells express ____ and ____.
IgM and IgD
68
What is the 2nd signal involved when B cells present to CD4 T cells?
CD40(Bcell):CD40L on T cell
69
What are the 2 ways a B cell can be activated?
1. IgM binds antigen | 2. B-cell presents to CD4 w/ 2nd signal - IgG
70
Granulomatous inflammation is characterized by a _________.
Granuloma
71
What is the key cell that characterizes a granuloma?
Epitheloid histiocytes (Macrophages w/ abundant pink cytoplasm)
72
What other things are seen in a granuloma
Giant cells w/ rim of lymphocytes
73
Noncaseating granulomas lack ______________.
Central necrosis - cells all have their nuclei
74
Noncaseating granulomas arise in reaction to what 5 things?
1. Reaction to foreign material 2. Sarcoidosis 3. Beryllium exposure 4. Crohn disease 5. Cat scratch disease
75
Caseating granulomas exhibit ___________ and are characteristic of ____ and _____________.
1. Central necrosis 2. TB (AFB stain) 3. Fungal infections (GMS stain)
76
How are granulomas formed?
1. Macrophages present to CD4 2. Macrophages secrete IL-12 --> Th1 3. Th1 cells secrete IFN-gamma which converts the macrophages to epithelioid histiocytes and giant cells
77
True or False: Both caseating and noncaseating granulomas are formed via the IL-12 from macrophages and IFN-gamma from Th1 cells?
True
78
DiGeorge Syndrome
22q11 microdeletion - developmental failure of the 3rd and 4th pharyngeal pouches

Basics of Path (5 decks)

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