Inflammation Mediators

Question 1

Toll-Like Receptors

Answer 1

Activated by PAMPs; upregulated NF-kB leading to activation of immune response genes to multiple immune mediators (also seen on lymphocytes for both acute and chronic)

Question 2

PGI2, PGD2, PGE2

Answer 2

Vasodilation and increased vascular permeability; PGE2 also mediates pain and fever

Question 3

LTB4

Answer 3

Attracts and activates neutrophils

Question 4

LTC4, LTD4, LTE4

Answer 4

Vasoconstriction, broncospasm, and increased vascular permeability (by contracting smooth muscle)

Question 5

Mast Cells

Answer 5

Activated by tissue trauma, C3a, C5a or cross-linking of cell surface IgE by antigen; release of histamine granules (vasodilation and increased vascular permeability)

Question 6

What are Rubor (redness) and Calor (warmth) due to?

Answer 6

Due to vasodilation, resulting in increased blood flow; mediated by histamine, bradykinin, and prostaglandin

Question 7

What is Tumor (swelling) due to?

Answer 7

Leakage of fluid from post-capillary venules into interstitial space (exudate); mediated by histamine (endothelial cell contraction) and tissue damage (endothelial cell disruption)

Question 8

What is Dolor (pain) mediated by?

Answer 8

Bradykinin and PGE2 that sensitive free nerve endings

Question 9

What is Fever mediated by?

Answer 9

Pyrogens (such as LPS) from bacteria that cause macrophages to release IL-1 and TNF, increases COX in perivascular cells of the hypothalamus

Question 10

What mediator raises set point temperature?

Answer 10

PGE2

Question 11

What causes margination?

Answer 11

Vasodilation, slowing down flow in POST-CAP VENULE; allowing cells to marginate from center to periphery

Question 12

What releases and mediates P-selectin?

Answer 12

Released from: Weibel-Palade bodies

Mediated by: histamine

Question 13

What induces E-selectin?

Answer 13

TNF & IL-1

Question 14

How does rolling occur?

Answer 14

Selectins bind to Sialyl-Lewis X found on leukocytes

Question 15

Where and how are I-CAM and V-CAM regulated?

Answer 15

Upregulated on endothelium by TNF and IL-1

Question 16

What do I-CAM and V-CAM interact with, what does it cause, and how does it happen?

Answer 16

I-CAM and V-CAM interact with Integrins on leukocytes; via C5a and LTB4 causing firm adheshion

Question 17

What is LAD due to, and what type of disease is it? (x-linked, autosomal dominant, autosomal recessive)

Answer 17

Autosomal recessive defect of Integrins (CD 18)

Question 18

How does LAD present?

Answer 18

First is delayed separation of umbilical cord, will see increased circulation of neutrophils, and recurrent bacterial infections that lack bus

Question 19

What are neutrophils attracted by?

Answer 19

IL-8, C5a, LTB4

Question 20

What do IgG and C3b do?

Answer 20

Phagocytosis; consumption of pathogens or necrotic tissue

Question 21

What is Chediak-Higashi due to, and what type of disease is it? (x-linked, autosomal dominant, autosomal recessive)

Answer 21

Autosomal recessive defect in protein trafficking leading to impaired phagolysosome formation

Question 22

How does Chediak-Higashi present?

Answer 22

Increased risk for pyogenic infections, neutropenia, giant granules in leukocytes, albinism, peripheral neuropathy

Question 23

Fill in the enzymes on top of the arrows:

O2 —> O2* —> H2O2 —> HOCl (bleach)

Answer 23

1. NADPH oxidase (oxidative burst)
2. Superoxide dismutase
3. Myeloperoxidase

Question 24

What is CGD due to, and what type of disease is it?

Answer 24

NADPH Oxidase deficiency leading to poor O2-dependent killing; x-linked recessive

Question 25

How does CGD present?

Answer 25

Infection and granuloma formation by catalase positive organisms such as Staph Aureus, Nocardia, etc.

Question 26

Results of nitroblue tetrazolium test in CGD?

Answer 26

Positive; means it’s colorless, if it turns blue, that would be the NORMAL.

Question 27

What is MPO deficiency due to and how does it present?

Answer 27

Myeloperoxidase enzyme missing; most patients are asymptomatic but at increased risk for Candida infections

Question 28

What do macrophages secrete for resolution and healing?

Answer 28

IL-10 & TGF-beta (anti-inflammator)

Question 29

What do macrophages secrete to continue an acute infection?

Answer 29

IL-8 (attracts neutrophils)

Question 30

What do macrophages secrete to form an abscess?

Answer 30

FGF & cytokines (fibrosis around inflammation)

Question 31

What are MHC-Class II linked to, and what type of antigen?

Answer 31

CD4+ T Cells; Extracellular

Question 32

What are MHC-Class I linked to, and what type of antigen?

Answer 32

CD8+ T Cells; Intracellular

Question 33

What does the Th1 subset of CD4+ T Cells secrete?

Answer 33

IL-2 (T-cell growth factor and CD8 activator), and IFN-gamma (activates macrophage)

Question 34

What does the Th2 subset of CD4+ T Cells secrete?

Answer 34

IL-4 (class switch IgG and IgE), IL-5 (eosinophil chemotaxis, and mature B-cell class switch to IgA), and IL-10 (inhibits Th1)

Question 35

How do CD8+ Cytotoxic T Cells kill?

Answer 35

Perforins and granzymes to induce apoptosis

Question 36

What is the characteristic cell of granuloma formation?

Answer 36

Epitheliod histiocytes (macrophages with abundant pink cytoplasm)

Question 37

What are the steps of a granuloma formation?

Answer 37

1. Macrophages process and present antigen via MHC Class II-CD4+ Helper T Cells
2. Interaction leads to macrophage secretion of IL-12 causing Helper T to form Th1
3. Th1 cells secrete IFN-gamma which differentiates macrophages into epithelioid histiocytes

Question 38

Where would you see a non-caseating granulatoma?

Answer 38

Reaction to foreign material, sarcoidosis, beryllium exposure, Chron’s, Cat Scratch

Question 39

Where would you see a caseating granuloma?

Answer 39

Tuberculosis and Fungi

Question 40

What causes Bruton’s and what do you expect to find?

Answer 40

Deficiency of IgG so opsinization through C3b only; recurrent infections from things such as Haemophilus, Strep, Hepatitis. Will have lymphoid hypoplasia (tonsils & adenoids)

SIGNIFICANT DROP IN ALL Ig LEVELS!

Question 41

What does the interaction of CD31 and PCAM-1 cause?

Answer 41

Diapedesis.