Pathoma - Acute Inflammation

Question 1

What co-receptor for TLR4, is responsible for recognizing LPS (on outer membrane of gram negative bacteria)

Answer 1

CD14

Question 2

What is the “on-switch” for acute inflammatory response, when TLR binds PAMP

Answer 2

NF-KB

Question 3

What are the effects of prostaglandins?

Answer 3

Vasodilation (at arteriole)

Increased vascular permeability (at post-capillary venule)

Question 4

Which molecule mediates pain and fever

Answer 4

PGE2

Question 5

What 4 molecules attracts and activates neutrophils

Answer 5

LTB4 (leukotriene)
C5a
IL-8
Bacterial products

Question 6

What are the effects of leukotrienes?

Answer 6

(Increased smooth muscle contraction)

Vasoconstriction
Bronchospasm
Increased vascular permeability

Question 7

What are 3 methods by which mast cells are activated?

Answer 7

(1) Tissue trauma
(2) C3a and C5b
(3) cross-linking of cell-surface IgE by antigen

Question 8

What is the acute and delayed response of mast cells?

Answer 8

Acute - histamine release

Delayed - production of leukotrienes

Question 9

What are 2 effects of histamine released by mast cells?

Answer 9

(1) Vasodilation of arterioles

(2) Increased vascular permeability in post-capillary venule

Question 10

What are the 3 pathways of complement activation?

Answer 10

(1) Classical pathway - C1 binds IgG or IgM bound to antigen (GM makes classic cars)
(2) Alternative - microbial products directly activate complement
(3) Mannose-binding lectin - MBL binds to mannose on microorganisms and activates complement

Question 11

What is Hageman factor (Factor XII)

Answer 11

Inactive pro-inflammatory protein produced by the liver and activated upon exposure to subendothelial or tissue collagen

Question 12

What is the effects of C3a

Answer 12

Trigger mast cell degranulation

Question 13

What are the effects of C5a

Answer 13

Trigger mast cell degranulation

Chemotactic for neutrophils

Question 14

What is the effects of C3b

Answer 14

Opsonin for phagocytosis

Question 15

What are the key mediators of rubor and calor?

Answer 15

Things that induce vasodilation:
Histamine
Prostaglandins
Bradykinin

Question 16

What are the key mediators of swelling

Answer 16

Things that induce vascular permeability:
Histamin
Tissue damage

Question 17

What are the key mediators of pain

Answer 17

Bradykinin and PGE2

Question 18

Describe the mechanism behind fever development

Answer 18

Pyrogens (e.g. LPS form bacteria) cause macrophages to release IL-1 and TNF

IL-1 and TNF travel to the perivascular cells of the hypothalamus adn increase COX activity

Increased COX leads to increased PGE2, which is a mediator of fever

Question 19

Where does most neutrophil entry occur

Answer 19

Postcapillary venues (blood flow is slowed here due to vasodilation in the arterioles, and permeability is increased here)

Question 20

What are the players in neutrophil “rolling”

Answer 20

Selectin “speed bumps” on endothelial cells

Sialyl Lewis X on leukocytes

Question 21

What is responsible for upregulation of P-selectin and E-selection

Answer 21

P-selectin release from Weibel-Palade bodies is mediated by histamine

E-selectin induced by TNF and IL-1 (same things that precipitated fever)

Question 22

What are the main player of neutrophil adhesion

Answer 22

Cellular adhesion molecules (CAM) on endothelium

Integrins on leukocytes

Question 23

What is responsible for upregulation of integrins and CAMs

Answer 23

CAMs upregulated via TNF and IL-1 (same things that upregulated E-selectin)

Integrins upregulated by C5a and LTB4 (2/4 things that attract neutrophils)

Question 24

What is the problem in Leukocyte adhesion deficiency?

Answer 24

Defect in the CD18 subunit of integrins

Question 25

What are some of the clinical features of Leukocyte adhesion deficiency?

Answer 25

Delayed separation of the umbilical cord

Increased circulating neutrophils

Recurrent bacterial infections with lack of pus formation

Question 26

What are the molecules that are chemotactic for neutrophils?

Answer 26

bacterial products
IL-8 (from macrophages)
C5a
LTB4

Question 27

What are the opsonins that enhance phagocytosis by neutrophils

Answer 27

IgG and C3b

Question 28

What is the problem in Chediak Higashi syndrome?

Answer 28

Protein-trafficking defect (phagosome cannot be directed to the lysosome)

Question 29

What are some of the clinical features of Chediak Higashi syndrome?

Answer 29

Increased risk of pyogenic infection (impaired phagolysosome formation)

Neutropenia (impaired replication because protein trafficking products needed for division)

Giant granules in leukocytes (they cannot travel out to the periphery)

Defective primary hemostasis (platelet granules need trafficking proteins)

Albinism (melanin from melanocytes cannot be passed to keratinocytes)

Peripheral neuropathy

Question 30

What are the steps of O2-dependent killing within the phagolysosome?

Answer 30

O2 converted to O2- via NADPH oxidase

O2- converted to H2O2 via superoxide dismutase

H2O2 converted to HOCl (bleach) via myeloperoxidase (MPO)

Question 31

What is the problem in chronic granulomatous disease (CGD)

Answer 31

NADPH oxidase defect

Question 32

How does the nitroblue tetrazolium test work?

Answer 32

It will turn blue if NADPH oxidase can convert O2 to O2-

Will be colorless in CGD

Question 33

What part of O2 dependent killing is effected by MPO deficiency

Answer 33

H2O2 to HOCl

Question 34

How do macrophages do most of their killing?

Answer 34

O2-independent killing via enzymes, such as lysozyme

Question 35

What are the anti-inflammatory cytokines produced by macrophages

Answer 35

IL-10 and TGF-B

Question 36

What is the cytokine produced by macrophages that calls in more neutrophils?

Answer 36

IL-8