Hypersensitivity - Type I Flashcards

1
Q

What are the principal cells and antibodies that mediate Type I Hypersensitivity?

A

APC w/ allergen on MHC-II and B7 costim bind to Naive CD4+ cell’s CD4 and CD28—>IL-4 floatin’ around—>maturation into Th2-cell—>induce B-cell (plasma cell) class ∆ing—>”IgE (usually); other immunoglobulins e.g. IgG4

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2
Q

Which Hypsensitivity Types are Ab-mediated? Which are cell-mediated?

A

I, II and III are Ab-mediated. IV is cell-mediated

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3
Q

Define atopy

A

presence of specific IgE directed against environmental allergens

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4
Q

Name 3 majors processes in anaphylaxis

A

dilation and leakage of post-capillary venules (causing edema, life-threatening hypotension and cardiovascular collapse) and constriction of airway smooth muscles, (bronchoconstriction, which can result in hypoxia and death).

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5
Q

Contrast first and second exposures in Type 1.

A

First exposure = sensitization where IgE “arms” the FcER1 receptors and basophils and mast cells.

2nd exposure: allergen cross-links these and causes release of immediate hypersensitivity mediators

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6
Q

Define mast cell role in Type 1

A

releases granules full of mediators when allergens bind the allergen-specific IgEs that are residing in its FcεR1 receptors

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7
Q

histamine

A

most common vasoactive amine; stored in granules of mast cells and basophils; causes increase vasc permeability, (Abbas: also vasodilation), SMM constriction and incr mucous prod in goblet cells, via H1 receptors.

increases gastric secretions via H2 receptors (target of some heartburn meds!)

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8
Q

basophil

A

Orig. in marrow and circulate in blood responding to chemotactic stim.; have FcεR1 receptors; release mediators

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9
Q

IgE

A

Ab that mediates Type I; plasma [IgE] incr in atopic individuals; made predom. in GI and resp. epith. plasma cells; binds FcεR1 on: mast cells, eosinophils, basophils, lymphocytes and monocytes; dunno what it’s for totally, think defense against helminthes and some protozoans

you only need tiny bit (10^-10 IgEs will sat. 1/2 all FcεR1s)

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10
Q

FcεR

A

receptor for IgE; found on mast cells, eosinophils, basophils, lymphocytes and monocytes

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11
Q

prostaglandin D2

A

lipid mediator that causes periph. vasodilation, coronary vasoconstriction, bronchoconstriction, inhibits platelet agg, and attracts neutrophils; made in response to cross-linking of IgE in FcεR on surface of ?basophils and ?mast cells

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12
Q

allergen

A

an antigen that causes a Type I hypersensitivity rxn in an atopic pt.

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13
Q

hyposensitization

A

(a.k.a. immunotherapy) tx for atopic pts; give grad. incr. doses of allergen either subQ or SL; idea: will incr IgG and IgA to allergen

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14
Q

lekotriene

A

lipid mediator (from arachadonic acid 1°ly): bronchoconstr., vasodilator and incr vasc perm —> edema; incr mucous, constriction coronary and cerebral aa., decr contractility and incr gastric acidity

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15
Q

sensitization

A

initial exposure to allergen that causes initial generation of IgE against allergen and then coating of FcεR-bearing cells with that IgE

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16
Q

anaphylaxis

A

a severe, whole-body allergic reaction resulting from the sudden release of mast cell- and basophil-
2
derived mediators into the circulation

17
Q

LTB4

A

Leukotriene B4: Binding to a different receptor from SRS-A, LTB4 causes neutrophil
chemotaxis, adhesion of neutrophils to endothelium of post capillary venules, and neutrophil degranulation. LTB4 also induces leakage of post capillary venules, leading to edema.

18
Q

SRS-A

A

Slow Reacting Substance of Anaphylaxis (SRS-A): SRS-A is an older name for the cysteinyl-leukotrienes (LTC4, LTD4, LTE4).

19
Q

describe the time course and clinical consequences of Type I hypersensitivity reactions.

A
  1. Sensitization
  2. 2nd exposure:
    —initial rxn (few mins.) = Immediate Hypersens. (e.g. anaphylaxis)
    ——caused by pre-formed mediators in granules
    —later (6-24hrs) = Late Phase Rxn: cytokines attract leukocytes in inflamm.
    ——caused by newly-formed gene products (cytokines) and lipid metabolites (prostaglandins and leukotrienes)

allergic rhinitis, bronchial asthma, urticaria, GI allergy, and anaphylaxis 2° to drugs, foods and venoms.
–anaphylaxis is the prototype reaction. occurs after prior sensitization; obvious within mins. in a sensitized individual. small amt of antigen can elicit deadly response.
pathophys ∆s include mast cell degranulation, infiltration of eosinophils and neutrophils, contraction of smooth muscle, increased vascular permeability and finally, infiltration of mononuclear cells.
Clinical symptoms may involve:
a) skin: pruritis (itching); edema (swelling); wheal and flare (raised skin with radiating redness) = urticaria (hives).
b) Pulm: bronchospasm, mucosal edema with airway obstruction, laryngeal edema.
c) Cor: hypotension, arrhythmias, cardiovascular collapse
d) GI: cramps, vomiting, diarrhea.

20
Q

hypersensitivity

A

inflammation due to an exaggerated, inappropriate or ineffective immune response to antigens that, in the absence of immunity, are usually innocuous (eg. pollen)

21
Q

Txs to inhibit mediator action

A
  • H1 antagonists (e.g. diphenhydramine, chlortrimeton) work for sneezing, rhinorrhea, itchy eyes
  • leukotriene receptor antagonists (motelukast) or antibody to IgE for chronic asthma and syst. anaphyl.
  • epi and long-acting beta2 recept. agonists (e.g. salmeterol) for bronchospasm and hypotension
22
Q

Txs to inhibit inflamm. mediator production

A

glucocorticoids (e.g.dexamethasone, beclomethasone, and fluticasone) = potent inhibitors of inflamm. cytokine prod.; inhibit leukotriene synthesis

cromolyn blocks hist release

ziletuon blocks leukotriene synth

Omalizumab (Xolair) = Anti-IgE subQ

23
Q

SCIT/SLIT Mechanism

A

subQ or SL immunotherapy works by hyposensitization; increase Treg and Th1 proliferation

24
Q

explain genetic and environmental factors that influence predisposition to allergy

A

air pollution, water pollution, pesticides, C-section, bottle feeding, hygiene hypoth

genetic: female sex (auto-imm more common in females); heredity (concordance: DZ twins = ~35% MZ = ~55%)

25
Q

CLICKER QUESTION:
IgE that is bound to a mast cell in a person with type I hypersensitivity is most likely to be…
A) monospecific B) monoclonal C) polyclonal D) complement-activating E) mono-allotypic

A

correct answer: C; the only time you would have monoclonal antibodies in your body would be if you had (cancerous) myeloma in which you have a clonal expansion of a single B cell

26
Q

What critical cell type, CD molecule and cytokine favor the production of IgE rather than IgG?

A

B-cell’s CD40 interacts w/ TH2’s CD40L (a.k.a. CD154, wtf immunologists) —> TH2 releases IL-4 —> B-cell class ∆ing to IgE

27
Q

Why bother with IgE at all?

A

(we think) to kill helminths, schistosomes, etc. via ADCC (Ab-dependent cellular cytotoxicity): opsonization w/ IgE binds high-affininty FcεR1 on eosinophil

28
Q

T/F?: Chocolate consumption increases the likelihood of winning the Nobel Prize?

A

Likely true; high correlation. =)