L13: Hypersensitivity Reactions

a type 1 hypersensitivity is ___________-mediated

antibody (IgE)

a type 2 hypersensitivity is _________-mediated

antibody (IgE/IgM)

a type 3 hypersensitivity is ___________-mediated

antibody (IgG/IgM)

a type 4 hypersensitivity is _________-mediated

T cell (not antibody!)

a type 1 hypersensitivity is _______-onset and ___________

immediate, anaphylactic

a type 2 hypersensitivity __________ to cells

cytotoxic

a type 3 hypersensitivity form an _________ _________

immune complex

a type 4 hypersensitivity is _______-onset

delayed

the immune system is Th__ bias as a fetus

2

allergies may develop if there is a lack on infections during childhood growth years may maintain the Th__ bias

2

an allergen is a small, inhaled protein that stimulates ____ production in _______ individuals

IgE, atopic

to be considered an allergen, the protein must be carried on ____ particles

dry (ex: pollen, mold, pet dander)

non-atopic individuals respond _______ to allergens and produce mainly ______ antibodies

weakly, IgG (does not cause release of mediators)

atopic individuals are pre-disposed to develop type ___ allergic reactions as they will produce large quantities of ____ antibodies

1, IgE (they’ll release cytokines and mediators)

atopic individuals exposed to an allergen will release IL-___ cytokines which increase class-switching of B cells to produce more Ig___

4, E

atopic individuals exposed to an allergen will release IL-___ cytokines which produce more _____________ that are important in late phase rxns

5, eosinophils

in an initial exposure type 1 HSR, IgE that are specific to the Ag bind the _____ region on _______ cells

Fc, mast

an immediate reaction to an allergen is due to _________ and __________ mediators

mast cells and basophils

a late phase reaction to an allergen is due to _________ and ____________ cells that are recruited by mediators

eosinophils and neutrophils

a late phase reaction is cause by ____________ released from cell degranulation

mediators

a late phase reaction is caused by mediators released from cell __________

degranulation

a _________ allergic reaction is due to mediators that release inflammatory cells like eosinophils and neutrophils

late-phase

infections as a child illicit a Th___ response

1 (was Th2 bias as a fetus)

‘hygiene hypothesis’= dirtier you are as a kid, the more you are used to allergens

certain genes have been linked with certain allergic diseases due to an improper bias towards _____

Th2 (never changes from the fetal bias into the childhood Th1 bias)

the placenta secretes ____ and ____ that results in a Th___ bias in the mother and the fetus

IL-4 and IL-10, Th2

when children get infected, their memory cells will remember the allergen and remember the ____ that was there during the allergen’s exposure

Th1 (—> Th1 bias)

certain genes linked to allergic diseases result in mutant ____ receptors which the cross-link and make B cells produce excess ___

IgE

certain gene linked to allergic diseases result in _________ IgE receptors which cross-link and make ___ cells produce excess IgE

mutant, B

atopic individuals have defective ___-regulator responses

T (Tregs)

Tregs in atopic individuals are defective and therefore cannot suppress ___ ________ production

Th2, cytokine

_______ in atopic individuals are defective and therefore cannot suppress Th2 cytokine production

Tregs

which mediator in a type 1 HSR is similar to histamine but has a slower onset and is more persistent

Leukotrienes (Late phase rxns)

which one mediator released from mast cells during a type 1 HSR is responsible for all allergic symptoms

NONE! a bunch of mediators work together, not just a single one

_________ mediators released during a type 1 HSR bind to H1 receptors on endothelial cells and cause bronchospasm and vasodilation

histamine

histamine mediators released during a type 1 HSR bind to ___ receptors on endothelial cells and cause bronchospasm and vasodilation

H1

histamine mediators released during a type 1 HSR bind to H1 receptors on endothelial cells and cause broncho______ and vasodilation

spasm

prostaglandin mediators released during a type 1 HSR are part of the ___________ _____ cell membranes that cause bronchoconstriction

degranulated, mast

prostaglandin mediators released during a type 1 HSR are part of the degranulated mast cell membranes that cause broncho_______

constriction

____________ mediators released during a type 1 HSR are part of the degranulated mast cell membranes that cause bronchoconstriction

prostaglandin

which two cytokine mediators are released during a type 1 HSR to attract inflammatory cells and stimulate Th2 and IgE production

TNFa and IL-4

_____________ ___________ bind to leukotriene receptors and inhibit their formation to prevent airway edema, bronchoconstriction and inflammation

leukotriene modifiers (ex: Zafirlukast)

____________ drugs block cytokine production which decreases Ig production

corticosteroids (anti-inflammatory)

Omalizumab is an Ig treatment that grabs Fc region of IgE and prevents it from binding to _____ cells

mast

__________________ drugs decrease/prevent mast cell degranulation

mast cell stabilizers (Cromolyn)

specific immunotherapy to treat type 1 HSRs are only effective for allergens that enter ____________

circulation (ex: venom) (not airborne like pollen)

specific immunotherapy to treat type 1 HSRs attempts to shift the ___ bias to a ___ bias by gradually exposing the pt to an increasing dose of allergen

Th2 —> Th1 (can take several years tho)

there are 3 mechanisms of a type 2 HSR: ________-mediated causes cell lysis through cascade/formation of MAC or through C3b/opsonization

complement

there are 3 mechanisms of a type 2 HSR: complement-mediated causes cell _______ through cascade/formation of MAC or C3b/opsonization

lysis

there are 3 mechanisms of a type 2 HSR: complement-mediated causes cell lysis through formation of _____ or C3b/________

MAC, opsonization

there are 3 mechanisms of a type 2 HSR: Ig-dependent cellular cytotoxicity happens when ___ coated cells are killed by cells with Fc receptors for that specific ___

IgG (—> T-cell apoptosis)

there are 3 mechanisms of a type 2 HSR: Ig-dependent cellular __________ happens when IgG coated cells are _______ by cells with Fc receptors for that specific IgG

cytotoxicity, killed (apoptosis)

there are 3 mechanisms of a type 2 HSR: Ig-mediated cellular dysfunction happens with the cell-bound receptor acts as a ___ and then there is an ___ against that receptor which binds to it

Ag, Ig

there are 3 mechanisms of a type 2 HSR: Ig-mediated cellular __________ happens with the cell-bound receptor acts as an Ag and then there is an Ig against that receptor which binds to it

dysfunction (anti-receptor Ig can’t destroy/kill the cell, they can just disrupt their function)

hemolytic anemia and ABO blood transfusion rxns are examples of _________-mediated type 2 HSRs

complement (d/t Ig binding to Ag on RBCs)

Rh incompatibility in fetal RBCs is an example of an Ig-mediated cellular ____________ type 2 HSR

cytotoxicity (can cause problems in a mom’s 2nd kid —> give mom anti-Rh antibodies to prevent)

Myasthenia Gravis is an example of a Ig-mediated cellular ____________ type 2 HSR that affects the muscle cell _____ receptors

dysfunction, Ach (impaired muscle contractions)

type 1 HSRs principle mediator is/are ___________ and the effect is _________

IgE (antibodies), immediate (Anaphylactic)

type 2 HSRs principle mediator is/are _______ and their effect is __________

IgG, Cytotoxic

type 3 HSRs principle mediator is/are _______ and their effect is ____________

IgG, formation of Immune complex

type 4 HSRs principle mediator is/are _______ and their effect is __________

T-cell, Delayed

in a type 3 HSR, rather than an Ag bound to a cell, the IgG responds to ______________ antigen

free floating (—> immune complex)

in a type ___ HSR, rather than an Ag bound to a cell, the IgG responds to free-floating antigen

3 (immune complex)

the clinical manifestations of a type 3 HSR depends on ______ the immune complex is deposited

where

the clinical manifestations of a type 3 HSR depends on where the ________ ________ is deposited

immune complex

an arthus reaction is ________ inflammation d/t a type 3 HSR

localized

serum sickness is a __________ inflammatory response d/t a type 3 HSR

systemic

rheumatoid arthritis or lupus is a type 3 HSR where the complexes are deposited in the ________ and inflammation occurs there

joints (synovial membranes)

a type 4 HSR could be initiated _____ to ______ after the initial infection

hours to days

a type 4 HSR occurs when the macrophage ingests the Ag and then _______________ to the Th1 cells

presents via MCH II

a type ___ HSR occurs when the macrophage ingests the Ag and then presents via MCH II to the Th1 cells

4 (delayed) (function of t-lymphocytes, not antibodies)

a contact hypersensitivity like poison ivy is an example of a type ___ HSR

4

ex: pt comes into ER with severe asthma exacerbation, but gets SABA & Epi and goes home feeling fine. —> 8 hours later he come back to the ER with another exacerbation. What is the most likely cause of his symptoms?

eosinophils =Late-phase reaction —> released pro-inflammatory mediators

a type 2 HSR involves ___-mediated __________ of cells

Ig, destruction (or damage/dysfunction)

the final damage to vessels in immune complex-mediated arthritis is due to what

lysosomal enzymes of polymorphonuclear leukocytes

in type 3 HSRs Ag-Ig immune complexes are deposited into tissues which activates complement —> then ____________ ________ are attracted to the site and release _________ enzymes —> results in tissue damage

polymorphonuclear leukocytes (PMNs), lysosomal

a positive delayed-type hypersensitive skin reaction involves the interaction of ______, ____________, and _________

Ag, Ag-sensitive T cells, macrophages (type 4 HSR recruits macrophages)

a type 4 HSR occurs when Th cells are sensitized by the Ag and then re-exposed to that Ag —> then _______ are released which causes inflammation and macrophage activation with mediator release

lymphokine

a type 4 HSR occurs when Th cells are sensitized by the Ag and then re-exposed to that Ag —> then lymphokines are released which causes inflammation and ___________  activation with mediator release

macrophage