Condensed Quiz 7 Flashcards
What causes the redness in psoriasis?
vasodilation and inflamed endothelial cells
What causes the skin thickening in psoriasis?
hyper-proliferation of keratinocytes
What causes the white scales in psoriasis?
parakeratosis
Because of the dysfunction of skin in psoriasis what 3 things occur making it a skin barrier dysfunction disease?
improper skin stacking
improper secretion of lipids
improper adherence of keratinocytes
What are the 4 histological changes in psoriasis?
corneum becomes thick and broken
epidermis is much larger than normal
dermis has enlarged blood vessels
immune infiltrates (DC and T cell clusters)
Are keratinocytes or T cells the driving force of psoriasis and why?
T cells
Decreased T cells = decreased psorasis
What molecule produced by keratinocytes causes new of blood vessels?
VEGF
What 4 ways do keratinocytes aid in barrier protection?
hyper-proliferation
recruit immune cells
produce AMP
produce VEGF
LC–Cd1a produces ______
Th17
pDCs produce __________
a lot of IFN-a
TH1 cells produce _____
TNF-a
keratinocytes produce _____, ____, and ______
IL-1
IL-6
TNF-a
What are the polarizing and effector cytokines for TH17?
polarizing: IL-1, IL-6, IL-23, TGF-B
effector: IL-17, IL-22
What are the polarizing and effector cytokines for TH1?
polarizing: IL-12, IFN-a, IL-18
effector: IFN-a, TNF
What is the target of DAB389 IL-2 (TOX)?
activated T cells expressing IL-2R alpha
A proposed mechanism of psoriasis is that specific HLA class I alleles are expressed what other mechanism backs up this claim?
CD8+ cells (T17 or T1 cells) found in lesions
HLA I C___ and B___ are common in psorasis patients
C06
B07
What are 4 characteristics of IFN-a?
pleiotropic (multiple functional cytokine)
anti-viral
immunomodulator (up-regulates MHC)
anti-proliferative (shuts down protein synthesis)
What signaling cascade does IFN-a R1 and 2 use?
TYK2/JAK
What are 3 psoriasis therapeutics we talked about that targets IFN-a?
TYK2 inhibitor
anti-IFNa R1 Ab
anti BCDA2 Ab
How does TYK2 inhibitor prevent psoriasis?
blocks IFN-a receptor signaling pathway in cells (preventing anti-viral state)
How does anti-IFNa R1 Ab prevent psoriasis?
blocks all IFN signaling because it cannot bind to its receptor
How does anti BCDA2 Ab prevent psoriasis?
prevents them from activating and secreting IFN
What are 3 ways to measure IFN signaling?
measure MHC up-regulation
measure STAT phosphorylation
detect expression of ISG (IFN stimulated gene)
What are 3 pieces of evidence what pDCs are important in psorasis?
psoriatic skin has active IFN-a signaling pathways
excessive IFN signaling
treatment with IFN-a will make psoriasis worse
What are 2 markers for pDCs?
BDCA-2/CD123
CD86
How do pDCs recognize self-DNA if its inside the endosome in the cell?
LL37 binds with self-DNA , causing it to aggregate and cluster, triggering TLR-7 in endosome
LC DC + CD1a sense improper lipid secretion in psoriasis and activate __________
Th17
In APECED patients they have a decrease in _____ and ____ causing them to be prone to yeast infections
IL-17 and IFN-a
What 3 things do keratinocytes produce?
IL-1
IL-6
TNF-a
What is the major function of pDC?
produce lots of IFN-a
What is the overall function of IFN-a?
induce viral state
What does anti-CD80/86 prevent and how ?
T cell activation
binding to B7 on APC so T cells cannot
What does anti-CD20R prevent and how?
B cell activation
chimeric Ab activating complement (MAC) to kill B cells
What does anti-IL1B prevent and how?
prevents Th17 activation (polarizing cytokine)
binding to IL-1
What does anti-IL-6R prevent and how?
prevents Th17 activation (polarizing cytokine)
binding to IL-6R on T cells
What does anti-12R prevent and how?
inhibits IL-12 and 23 from activating Th1 and Th17 (polarizing cytokines)
binds to IL-12R
What does anti-TNF-a prevent and how?
prevents TNF-a from binding to Th1 cells and activating them (effector cytokine)
binds to TNF-a
What does anti-IL-17 prevent and how?
prevents Th17 activation (effector cytokine) and and neutrophils
binds to IL-17
