Type I hypersensitivity (start test 3)

immediate

Type I hypersensitivity is a ______________________ hypersensitivity

IGE, mast cell

Type I hypersensitivity is ______ and _________ mediated

true

true/false: type I hypersensitivity needs prior sensitization to occur

extracted, antigen specific T cells, IgE, mast cells

After first exposure to an antigen, the antigen is _____ and activated ________________. Then the production of ______ and the binding of this to ___________ occurs to prep for future exposure.

nature of the antigen, route of exposure, predominant Th pathway, genetic predisposition

what factors affect the development of a type I hypersensitivity?

small soluble proteins, Th2

what is the nature of an antigen that will cause type I hypersensitivities?

What is the predominant Th pathway?

sensitization

what is the first exposure of an immune response called?

antigen presenting cells, helper T cells, TH2 cells, IgE antibodies,

Sensitization: Allergen enters the body, and __________display fragments of it to ______________.

•In genetically predisposed individuals, these differentiate into_____________ and promote B cells to produce large amounts of _________________specific to that allergen.

basophils, mast cells, no symptoms

during sensitization:

After IgE is produced, they attach to high-affinity receptors (FcεRI) on the surface of ______________ and ___________ which are potent inflammatory cells. The individual is now "sensitized", and experiences what type of symptoms?

IgE antibodies, degranulate, inflammatory mediators

•Upon re-exposure to an allergen, it binds to and cross-links the _______________ on the surface of the sensitized cells.

•This cross-linking causes the cells to __________ and release preformed and newly synthesized __________________.

histamine, tryptase, proteoglycans

what are the preformed inflammatory mediators released?

prostaglandins, leukotrienes

what are the newly synthesized innflammatory mediators?

vasodilation, pruritis, bronchoconstriction

What are the symptoms caused by the second exposure to an allergen?

immediate phase, late phase response

Almost immediately after exposure, allergens cause clinical signs (_________________ phase type I response) and then usually subside.

But they can resurface between 4-20 hours later in what is called the ______________________ phase response

preformed mediators, histamine, serotonin

During the immediate phase response ________________ such as ______ and _______ predominate and cause mucous secretion and smooth muscle contraction

mast cell degranulation, T helper 2 cells

during immediate phase responses:

In addition to preformed mediators, ____________ triggers recruitment of other cells from the circulation, notably _______________

increased mucus secretion, smooth muscle contraction (causing airway obstruction)

what effects do the preformed mediators have on the body?

cytokines, IL-4, IL-5, eosinophils

As the T helper 2 cells enter the area, they begin to produce _________ such as _____ and ______. These recruit additional cells such as ______ which degranulate, releasing additional proteins and enzymes that contribute to the overall response

(THIS IS THE LATE PHASE/CHRONIC RESPONSE)

true

true/false: clinical manifestations of mast cell degranulation can be localized or systemic

increased vascular permeability (movement of fluid/proteins into tissue)

mucous secretion, bronchoconstriction (difficulty breathing)

fluid secretions, peristalsis (diarrhea, vomiting)

What effect does mast cell granulation have on the blood vessels?

On the respiratory tract?

On the GI?

mast cells, eosinophils

_____________ and ______________ have products that promote type I hypersensitivity

degranulation, leukotriene and prostaglandin synthesis, cytokine production

like everything else, mast cell degranulation is triggered by signal transduction, specifically cross linking two IgE molecules with antigens leading to ______________, ______________ and ____________________

histamine, serotonin, tryptase, kallikreins, proteases, proteoglycans

granule exocytosis

What are released from mast cell cranules within seconds of degranulation? (6 but I think only the first two are genuinely important)

And what is this called?

leukotrienes, prostaglandins, platelet activating factor

eicosanoid synthesis and secretion

What does the mast cell synthesize within minutes of degranulation (3 but I think theyre ALL important)

and what is this called?

IL 4, IL 5, IL 6, IL 13, TNF-a, MIP-1a

Cytokine synthesis and secretion

What does the mast cell synthesize within hours of degranulation? and what is this process called?

IgE, Fc receptor, B cells, IgE, IL-4

_____ secreted by plasma cells binds to the high affinity ______ of mast cells.

Activated mast cells provide contact and secreted signals to __________ to stimulate ______ production.

This is mediated primarily by _______ secretion by the activated mast cell

True!

true/false: the long and short of the past couple terms is that eosinophils and mast cells (when active) will continue to recruit/activate each. Mast cells recruit eosinophils. Eosinophilic granules activate and recruit mast cells.

lipid mediators (prostaglandins, leukotrienes, PAF)

_____________________ promote vasodilation and increased vascular permeability

the allergic loop

_______________________ refers to a positive feedback loop in the immune system that reinforces and sustains the allergic response. Instead of resolving the inflammation, the ongoing cycle leads to persistent symptoms and reinforces the body's allergic reaction.

TH2, B cells, mast cells, eosinophils

the main types of cells in type 1 hypersensitivities (_____________, _______, _______, _________) all produce more IL-4 and other cytokines/inflammatory factors that spur each other on and contribute to an allergic loop

IgE antibodies

the allergic loop is linked to the level of _________________ present, which are overabundant in people with allergies

drives IgE production, activates mast cells and basophils, promotes Th2 cells differentiation, increases eosinophil recruitment

What 4 things are the primary roles of IL-4 in a type I hypersensitivity?

tissue remodeling

generally speaking, eosinophilic enzymes promote what physical change?

vascular

during the acute phase of type I hypersensitivities, _______ changes predominate

true

true/false: clinical manifestations of type I hypersensitivities include edema, hives, dermatitis, gastroenteritis, rhinitis, and systemic anaphylaxis

urticaria

______________: pruritic (itchy) raised welts or wheals on the skin, commonly called hives.

contact allergens, environmental allergens, food reactions, medication/vaccine reactions, insect bites

what are some of the common ways we see type I hypersensitivities in vet med?

(i don't care if you memorize these obviously, just get the idea... But obviously I don't care if you memorize ANY of this, I'm not your mom)

ear infections

Recurrent or persistent ______________ can be a major sign of an underlying allergy

Th2, IL-4, IL-5, IL-13, IgE, IgG1, MHC II, Treg, Th1 IFNy

Canine allergic dermatitis:

This is a _____ response, and is due to increased ______, ______ and _____ in skin lesions. (cytokines). There is also increased ______ and _______ (antibodies) and we see increased _______ expression by langerhans cells. This stems from a decreased _________ function. Later in the disease there will be increased ______ response with ______.

(breathe, it's a lot, but it's all the things put together mostly.)

[this is equally a note for future Liz, irritated with a big a** flashcard. My B girl.]

regulatory T cells are shut off, so the reaction runs rampant

what does it mean if there is "decreased Treg function"

excessive scratching, intense licking/chewing, restlessness, alopecia, red inflamed areas and red bumps/pimples

What are the symptoms of canine allergic dermatitis?

skin barrier dysfunction

____________________ is where the outermost layer of skin is defective in atopic dogs, allowing environmental antigens to penetrate easier

thymic stromal lymphoprotein (TSLP)

_______________________ is a specific protein released by damaged skin cells that promotes a strong Th2 response

intradermal skin testing

an allergen is injected under the skin. later the diameter of the injection site is measured.

What process is this describing?

wheal

_______: elevation of the skin due to vasodilation and congestion during intradermal skin testing

flare

________________ area of hyperemia surrounding the wheal in an intradermal skin test

true

true/false: the route of allergen exposure affects clinical manifestations. (SubQ = more localized, where IV would be a systemic response)

anaphylaxis

______________________ is a severe, life-threatening systemic reaction that can occur within minutes of exposure to an allergen

hepatic veins (viscera)

what is the target organ of anaphylaxis in dogs?

respiratory tract (and intestine in cats and horses)

What is the target organ of anaphylaxis in EVERYTHING EXCEPT DOGS

(feline, equine, bovine, human)