Path Mechanisms II 1: PMNs and Inflammatory Disease

Question 1

What are PMNs designed to do?

Answer 1

Chemotaxis
Phagocytosis
Bacterial Killing

Question 2

What is LAD Deficiency?

Answer 2

Diminished Neutrophil rolling and recurrent bacterial infections….severe periodontitis in children

Question 3

What PMN and monocyte cell receptors are missing in LAD patients?

Answer 3

Mac1

LFA1

Question 4

What is Chediak-Higashi Syndrome

Answer 4

Chemotaxis defect with increased oxygen consumption and increased H202 production. Sever periodontitis and ulceration due to recurrent pyogenic S. aureus infections

Question 5

What is Neutropenia Agranulocytosis Myelosuppression?

Answer 5

Diminished number of phagocytes which leads to severe, life threatening infections and severe PD

Question 6

What is Hyper-IgE or Job’s Syndrome

Answer 6

Chemotaxis defect due to cytokine dysfunction.

Leads to PD with oral ulcerations

Higly elevated IgE

Question 7

What Th produced inflammatory PMN responses?

Answer 7

Th17

Question 8

Why is IL-17 such a problem for PD?

Answer 8

Its primary function is the call PMNs out of the blood. When the PMNs can’t get out, more and more IL-17 is secreted by Th Cells.

Problem is that IL-17 also promoted bone resorption

Question 9

What enzymes do PMNs produce that can destroy host tissues?

Answer 9

MMP-8

Acid hydrolases

Question 10

Why do PMNs produce oxygen radicals that can leak out and destroy host tissue?

Answer 10

For use in their lysosomes

Question 11

What do PMNs also synthesize that are also pro-inflammatory response?

Answer 11

Platelet activating factor
Thromboxane
Leukotrienes

Question 12

What is PMN hyperactivity?

Answer 12

When PMNs are overloaded by bacteria that they are trying to kill. Their enzymes, inf factors, and o2 rads build up and become toxic.

Question 13

PMNs are the first responders, what comes next in the immune response?

Answer 13

Monocytes and Activated Macrophages

Question 14

What do Monocytes and activated Macrophages release when they encounter endotoxin?

Answer 14

TNF

IL-1

Question 15

What do TNF and IL-1 do

Answer 15

They further inflammation related tissue damage

Question 16

What cells produce MMPs

Answer 16

PMNs
Fibroblasts
Macrophages

Question 17

What does the drug resolvyx target?

Answer 17

IL-17

IL-23

Question 18

What are lipoxins, resolvins, and protectins?

Answer 18

They are mediators produced by PMNs that actually stop the inflammatory response

Question 19

What can low dose aspirin induce?

Answer 19

lipoxin production

Question 20

How can neutrophils help to resolve inflammation?

Answer 20

by changing phenotype and producing resolving factors

Question 21

What fat molecules are protectins, resolvins, and lipoxins produced from?

Answer 21

PUFAs

Question 22

What does RvE1 do?

Answer 22

Restores bone loss due to P.gingivalis in mice

Question 23

What is RvE1?

Answer 23

A resolvin

Question 24

What pro-inflammatory mediator can be turned into RvE1

Answer 24

Leukotrienes

Question 25

What do Th1 Cells do?

Answer 25

Increase macrophage production

Question 26

What do Th2 Cells do?

Answer 26

Increase antibody production

Question 27

How do Th1 and B Cells lead to PD destruction?

Answer 27

Can release inflammatory cytokines that call for more Macrophages

Question 28

How do T Cells lead to PD damage?

Answer 28

Produce cytokines that lead to osteoclast activity

Question 29

How do Th-17 Cells lead to PD damage

Answer 29

Secrete cytokines that enhance inflammatory response and promote autoimmunity

Question 30

What chemical signal allows Th1 Cells to recruit macrophages?

Answer 30

INF gamma

Question 31

What other signal can T-cells and B-Cells produce that directly affects bone resorption?

Answer 31

RANK-L

Question 32

What cells are the primary source of RANK-L in PD patients?

Answer 32

T and B Cells

Question 33

What are the 3 disease modifiers?

Answer 33

Diabetes
Genotype
Smoking