Atopy and hypersensitivity Flashcards
What is the term for secreted proteins that bind to specific receptors and play a role in intercellular communication among leukocytes?
Interleukins
What cytokines are produced by Th2 cells?
IL-4, 5, 13, 31
What cytokines are released by damaged epithelial cells and contribute to the development and intensity of Th2 responses/inflammation?
TSLP
IL-25
IL-31
IL-33
What immune cells are the primary producers of IFN-gamma?
Th1 cells
What type of cell produces cytokines that are important in the immune response to helminths?
Th2
What cytokines are produced by Th17 cells?
IL-17A
IL-17F
IL-6
IL-8
TNF-alpha
IL-22
IL-26
What is the major role of Treg cells in hypersensitivity?
Allergen tolerance
Where are ILCs active?
Mucosal surfaces
What cytokines are produced by epithelial cells when they sense allergens?
IL-1alpha
IL-25
IL-33
TSLP
GM-CSF
What cytokines are produced when epithelial cells sense viruses?
type I interferons
GM-CSF
RANTES
What is the role of IL-1RA?
Anti-inflammatory via inhibition of IL-1 signaling (it acts as a “dummy” IL-1)
What two interleukins can produce high levels of IFN-gamma when combined?
IL-12
IL-18
What cytokine downregulates filaggrin expression and can impair barrier function?
IL-33
Is IL-38 pro- or anti-inflammatory?
Anti
What cytokine is essential for the development of Treg cells?
IL-2
What cytokine serves as a major stimulus of Th2 cell development?
IL-4
What is the effect of IL-4 on type I immunity?
It suppresses type I immunity
The receptor for which cytokine serves as a marker for ILCs?
IL-7
What is the effect of IL-9 on Th1 cells?
Reduces Th1 cytokine secretion
What is the effect of IL-9 on B-cells?
Promotes IgE production
Is IL-10 pro- or anti-inflammatory?
Anti
What is the effect of IL-10 on B cells?
Promotes their survival and proliferation
Increases IgG production
What is the effect of IL-20 on the skin?
Hyperkeratosis, epidermal thickening
What cells express IL-24?
Melanocytes
T-cells
Monocytes
What is the major function of IL-24?
Tumor suppression
What type 2 cytokine contributes to proliferation and activation of eosinophils?
IL-5
What cytokine is found in bronchoalveolar lavage fluid in asthmatic patients?
IL-5
What cells produce IL-31?
Activated CD4+ T-cells (CD8+ T-cells produce lower levels)
What cells express the IL-31 receptor?
KCs
epithelial cells
dorsal root ganglia
eos
basophils
monocytes
What cytokine does TSLP resemble structurally?
IL-7
What type of inflammatory response is promoted by TSLP?
Th2
What is the major function of IL-8?
activation and recruitment of neutrophils
Is IL-17 pro- or anti-inflammatory?
Pro
IL-14 promotes proliferation of what cell type?
B-cells
In what organ is IL-34 most abundant?
spleen
Does IFN-gamma promote a Th1 or Th2 cell response?
Th1
What cytokine plays a role in embryonic development?
TGF-beta
What cytokine plays a key role in the defense against intracellular pathogens?
TNF-alpha
A local increase in which cytokine causes the 5 cardinal signs of inflammation?
TNF-alpha
What is the average size of cytokines?
25 kDa
Are cytokines usually found in circulation?
No (rare)
Do cytokines act in a widespread or local manner?
Local
What cytokine shares similar properties to IL-4?
IL-13
What are the primary roles of Th17 cytokines?
Inflammation
Extracellular pathogens
What are the major roles of Th1 cytokines?
Viruses
Intracellular pathogens
What are the major roles of Th2 cytokines?
Parasites (extracellular organisms)
Allergy
What is the role of DC1 dendritic cells?
Anti-tumor activity
What T cell subset can be activated by DC1 dendritic cells?
Th1
What cytokines are produced by DC1 dendritic cells?
IL-1alpha
IL-1beta
IL-6
IL-12
IL-23
What T-cell subset is activated by DC2 dendritic cells?
Th2
What cytokines are produced by DC2 dendritic cells?
IL-4
IL-5
IL-10
What cytokines/chemokines are produced when Langerhans cells are stimulated by TSLP?
IL-16
IL-8
CCL22/MDC
CCL17/TARC
What chemokine is considered a biomarker for atopic dermatitis?
CCL17/TARC
What receptor does TARC bind to attract Th2 cells?
CCR4
What cells produce TARC?
Langerhans cells
Keratinocytes
What cells produce MDC/CCL22?
Macrophages
T-cells
Langerhans cells
What cytokines induce CCL2 expression?
IL-4
IL-13
What cells produce IL-8?
Langerhans cells
Endothelial cells
Macs
What is the function of IL-16?
CD4+ T-cell chemotaxis
What cytokine binds to nerves to stimulate itch?
TSLP
What cells are activated by IL-33?
ILC2
Eos
Basophils
Mast cells
Macs
What cells are activated by IL-33?
Mast cells
Th2 cells
What cytokines have receptors on peripheral nerves?
TSLP
IL-25
What cytokine is critical in equine allergy?
IL-5
What pro-inflammatory cytokine is a major inducer of acute phase proteins in the liver?
IL-6
What cytokine has similar activities to IL-1?
IL-6
What are the 3 primary pro-inflammatory cytokines?
IL-1
IL-6
TNF-alpha
What is the major function of IL-17?
Activation of neutrophils
Is IFN-gamma a type I or type II intereron?
Type II
What cell type makes IFN-alpha?
Leukocytes
What cell type makes IFN-beta?
Fibroblasts
What cell types produce IFN-gamma?
T-cells (Th1)
NK cells
Macs
What are two major anti-inflammatory cytokines?
TGF-beta
IL-10
What T-cell subset produces TGF-beta
Treg
What cytokine is heavily implicated in canine leishmaniasis?
IL-17
What cytokines are produced by damaged keratinocytes and serve as alarmins?
IL-25
IL-33
TSLP
Is atopic dermatitis primarily Th1 or Th2-driven?
Th2
How does adult-onset AD differ from pediatric-onset AD?
Pediatric: low Th1, high Th2, preserved FLG expression
Adult: more upregulation of Th1 and Th17, less pronounced barrier defect
What ethnicity has the highest Th17 activation in AD?
Asian
What cytokines are considered the main drivers of AD pathogenesis?
IL-4
IL-13
What is the effect of IL-13 on dermal fibroblasts and how does this contribute to AD lesions?
It stimulates them to produce collagen –> AD-related skin fibrosis
Besides atopy, which condition is associated with increased IL-1 expression in the skin of humans?
Alopecia areata
What JAK subsets mediate signaling of IL-13?
JAK 1, JAK 2, TYK2
What JAK subsets mediated signaling of IL-31?
JAK1, JAK2
What receptor for IgE is over-expressed in AD skin?
FCεR1
What fibers are stimulated by histamine, triggering itch?
unmyelinated C fibers
Are cannabinoids considered agonists or antagonists of TRPV1?
Antagonists
What is released when C fibers are activated by TRPV1?
substance P
What are the keratinocyte-derived cytokines involved in AD?
TARC/CCL17
MDC/CCL22
TSLP
IL-33
What cytokine is constitutively expressed in epithelial tissues?
IL-33
True or false: TSLP is currently considered a relevant therapeutic target in cAD
False
What is the primary effect of TARC?
Recruitment of Th2 cells to the skin
What cytokine correlates with AD disease severity?
CCL17/TARC (this is why it is a biomarker for AD)
What is the receptor for CCL22/MDC?
CCR4 (same as CCL17/TARC)
What are the primary functions of IL-4?
Leukocyte survival in Th2 responses
IgE class-switching of B-cells
Is IL-4 considered more prominent in acute or in chronic AD?
Acute
When does IL-31 expression in the skin peak after allergen challenge?
24-48 hours
True or false: IL-31 expression in the skin and blood are highly correlated
False
What cytokines induce IFN-gamma secretion?
IL-12
IL-15
IL-18
What happens if IL-18 is present in the absence of IL-12?
Stimulates Th2 response (normally IL-18 + IL-12 stimulates Th1)
What are the representative cytokines produced by Treg cells (i.e. “immunosuppressive cytokines”)
IL-10
TGF-β
True or false: IL-10 and TGF-β secretion significantly change with ASIT
False (previously these were thought to be involved in the MOA of ASIT but a 2021 paper found no significant change in plasma levels of these cytokines after 1 year of ASIT)
What is the function of IL-22?
Activates keratinocyte proliferation
What cytokine is suspected to be involved in the lichenification seen in chronic cAD?
IL-22
How does IL-34 in human AD differ from canine AD?
IL-34 is decreased in the epidermis of humans with AD
IL-34 is higher in the serum of dogs with AD (but remained high despite clinical improvement so may play less of a role in dogs)
What medication serves as a NK-1R antagonist and decreased pruritus and skin lesions in cats?
Maropitant
Which neuropeptide is blocked from binding to its receptor by maropitant?
Substance P
What dog breeds are predisposed to cAD worldwide?
Boxer
Bulldog
Lab
Pug
WHWT
What short, single-stranded RNA molecules are suspected to play a role in the pathogenesis of allergies?
microRNAs (miRNA)
Name 4 environmental factors that are considered protective against AD in humans
Rural environment
Diet rich in fiber
High food diversity
Early contact with peers
What environmental factors have been associated with a decreased risk of developing cAD?
Rural environment
Walking in woods
Living with another dog
Living in detached house
Non-processed meat-based diet early in life
Birth in current household
What is the effect of D. farinae serine protease on cytokine expression?
Increased IL-33 expression
How is a “major” allergen defined?
If >=50% of patients allergic to the parent allergen have detectable positive IgE on serology or skin test
What are 5 known major allergens in dogs?
D. farinae (Der f2, Der f15, Der f18, Zen1)
Japanese cedar (Cry j1, Cry j3)
short ragweed (Amb a1)
M. pachydermatis
Ctenocephalides felis (Cte f1)
What is the most common cause of cAD worldwide?
House dust mites
What are the major HDM allergens for cAD?
Der f2
Der f15
Der f18
Zen1
What parameter has been most commonly used to indirectly assess the skin barrier?
TEWL
What 4 measurements have higher sensitivity when combined to assess the skin barrier integrity?
TEWL
pH
erythema
hydration
What is the correlation between pH and clinical sign severity in cAD?
Negatively correlated
What ceramides are usually altered in AD as compared to healthy controls?
ceramide 1
ceramide 9
cer[NP]