Path Mechanisms II 1: PMNs and Inflammatory Disease Flashcards
What are PMNs designed to do?
Chemotaxis
Phagocytosis
Bacterial Killing
What is LAD Deficiency?
Diminished Neutrophil rolling and recurrent bacterial infections….severe periodontitis in children
What PMN and monocyte cell receptors are missing in LAD patients?
Mac1
LFA1
What is Chediak-Higashi Syndrome
Chemotaxis defect with increased oxygen consumption and increased H202 production. Sever periodontitis and ulceration due to recurrent pyogenic S. aureus infections
What is Neutropenia Agranulocytosis Myelosuppression?
Diminished number of phagocytes which leads to severe, life threatening infections and severe PD
What is Hyper-IgE or Job’s Syndrome
Chemotaxis defect due to cytokine dysfunction.
Leads to PD with oral ulcerations
Higly elevated IgE
What Th produced inflammatory PMN responses?
Th17
Why is IL-17 such a problem for PD?
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
What enzymes do PMNs produce that can destroy host tissues?
MMP-8
Acid hydrolases
Why do PMNs produce oxygen radicals that can leak out and destroy host tissue?
For use in their lysosomes
What do PMNs also synthesize that are also pro-inflammatory response?
Platelet activating factor
Thromboxane
Leukotrienes
What is PMN hyperactivity?
When PMNs are overloaded by bacteria that they are trying to kill. Their enzymes, inf factors, and o2 rads build up and become toxic.
PMNs are the first responders, what comes next in the immune response?
Monocytes and Activated Macrophages
What do Monocytes and activated Macrophages release when they encounter endotoxin?
TNF
IL-1
What do TNF and IL-1 do
They further inflammation related tissue damage
What cells produce MMPs
PMNs
Fibroblasts
Macrophages
What does the drug resolvyx target?
IL-17
IL-23
What are lipoxins, resolvins, and protectins?
They are mediators produced by PMNs that actually stop the inflammatory response
What can low dose aspirin induce?
lipoxin production
How can neutrophils help to resolve inflammation?
by changing phenotype and producing resolving factors
What fat molecules are protectins, resolvins, and lipoxins produced from?
PUFAs
What does RvE1 do?
Restores bone loss due to P.gingivalis in mice
What is RvE1?
A resolvin
What pro-inflammatory mediator can be turned into RvE1
Leukotrienes
What do Th1 Cells do?
Increase macrophage production
What do Th2 Cells do?
Increase antibody production
How do Th1 and B Cells lead to PD destruction?
Can release inflammatory cytokines that call for more Macrophages
How do T Cells lead to PD damage?
Produce cytokines that lead to osteoclast activity
How do Th-17 Cells lead to PD damage
Secrete cytokines that enhance inflammatory response and promote autoimmunity
What chemical signal allows Th1 Cells to recruit macrophages?
INF gamma
What other signal can T-cells and B-Cells produce that directly affects bone resorption?
RANK-L
What cells are the primary source of RANK-L in PD patients?
T and B Cells
What are the 3 disease modifiers?
Diabetes
Genotype
Smoking
