Lecture 28-30 (Types of Hypersensitivity)

what is hypersensitivity?

what is hypersensitivity?

a state of altered reactivity in which the body reacts with an exaggerated immune response to what is perceived as a foreign substance

hypersensitivity is a reflection of ____________ or ___________ immune responses

excessive or aberrant

*Immune Reactant: IgE

*Important Cells Involved: Mast cells (& eosinophils)

*Mechanism of Damage: TH2 response, degranulation of mast cells & eosinophils; inflammation

which hypersensitivity?

type I hypersensitivity

*Immune Reactant: IgG (& IgM)

*Important Cells Involved: Neutrophils, Macrophages

*Mechanism of Damage: Antibodies made against cell surface antigens or extracellular matrix antigens; opsonization, phagocytosis, etc.

which hypersensitivity?

type II hypersensitivity

*Immune Reactant: IgG (&IgM)

*Important Cells Involved: Neutrophils & Mast Cells

*Mechanism of Damage: Immune complexes of antigen and antibody aren't removed by phagocytosis; deposited in vascular basement membranes, etc.

which hypersensitivity?

type III hypersensitivity

*Immune Reactant: TH1 & CTLs

*Important Cells Involved: T Cells, APCs, Macrophages

*Mechanism of Damage: CD4+ activating macrophages and producing cytokine-mediated inflammation or CD8+ causing direct target cell lysis

which hypersensitivity?

type IV hypersensitivity

which hypersensitivity is exemplified by all of the following:

-allergic rhinitis
-food allergies
-bronchial asthma
-systemic anaphylaxis
-vaccine reactions

type I hypersensitivity

which hypersensitivity is exemplified by all of the following:

-Immune Mediated Hemolytic Anemia (IMHA)
-Immune Thrombocytopenia (ITP)
-Hemolytic Disease of the Newborn (HDN)
-Myasthenia Gravis
-pemphigus vulgaris
-drug reactions
-Acute Rheumatic Fever

type II hypersensitivity

which hypersensitivity is exemplified by all of the following:

-Systemic Lupus Erythematosus (SLE)
-Purpura (Little bruises on the skin)
-Recurrent Airway Obstruction (RAO)
-Blue Eye
-Farmer's Lung (Hypersensitivity Pneumonitis)
-serum sickness
-Rheumatoid arthritis (Non-Erosive)
-Glomerulonephritis associated with Rheumatic Fever

type III hypersensitivity

which hypersensitivity is exemplified by all of the following:

-allergic contact dermatitis
-Tuberculin reaction (used for Tb test)
-type 1 diabetes
-erosive arthritis
-Multiple sclerosis

type IV hypersensitivity

what cells are responsible for the acute inflammatory response in the early phase of type 1 hypersensitivity?

a. pre-formed Mast Cells
b. T cells (Like TH17)
c. neutrophils & macrophages

a. pre-formed Mast Cells

what cells are responsible for the second wave late phase reaction in a type 1 hypersensitivity 6-12 hours post exposure? (characterized by redness, edema, pruritus)

a. pre-formed Mast Cells
b. T cells (Like TH17)
c. neutrophils & macrophages

b. T cells (Like TH17)
c. neutrophils & macrophages

exaggerated TH2 response & exaggerated IgE production are characteristic of which hypersensitivity?

type I hypersensitivity

the exaggerated TH2 response & exaggerated IgE production seen in Type 1 Hypersensitivity is called:

atopy

what is type I hypersensitivity?

a form of acute inflammation that results from the interaction of antigens with mast cell-bound IgE

type I hypersensitivity:

binding of antigens with mast cell-bound IgE leads to...

mast cell degranulation

t/f: granule content causes acute inflammation

true

immediate hypersensitivity

a) type I hypersensitivity
b) type II hypersensitivity
c) type III hypersensitivity
d) type IV hypersensitivity

a) type I hypersensitivity

antibody-mediated hypersensitivity

a) type I hypersensitivity
b) type II hypersensitivity
c) type III hypersensitivity
d) type IV hypersensitivity

b) type II hypersensitivity

immune complex-mediated hypersensitivity

a) type I hypersensitivity
b) type II hypersensitivity
c) type III hypersensitivity
d) type IV hypersensitivity

c) type III hypersensitivity

T-cell mediated hypersensitivity

a) type I hypersensitivity
b) type II hypersensitivity
c) type III hypersensitivity
d) type IV hypersensitivity

d) type IV hypersensitivity

excessive production of IgE is called __________ and affected individuals are said to be ____________

atopy; atopic

development of atopy and type I hypersensitivity depends upon the interaction of...

genes and environmental factors

what are the two important features of type I hypersensitivity?

-exaggerated TH2 response
-excessive IgE production

what is the role of IL-4 in an IgE response such as in type 1 hypersensitivity reactions?

a) produced by TH1; promotes more TH1; promotes IgE
b) produced by TH2; promotes more TH2; promotes IgE
c) produced by TH1; promotes more TH1; inhibits IgE
d) produced by TH2: promotes more TH2; inhibits IgE

b) produced by TH2; promotes more TH2; promotes IgE

which of the following inhibit IL-44?

1. IFNα/β or IFNγ?
2. IL-2 or IL-12?

1. IFNγ
2. IL-12

what is Il-4 produced by?

TH2 cells

type I hypersensitivity:

once IL-4 is produced by TH2 cells, it promotes the development of more TH2 cells and promotes ______ responses

IgE

the response to IL-4 is inhibited by _________ and __________

IFNγ and IL-12

what causes degranulation upon a second exposure to allergen?

a) co-stimulation by B7 to stimulate mast cells
b) cross binding of allergen by IgE bound to mast cells

b) cross binding of allergen by IgE bound to mast cells

IgE binds to what on mast cells?

a) CD152
b) Fas
c) FcεRI receptor
d) TLR

c) FcεRI receptor

the allergy loop:

dendritic cells express trimeric ____________ and as a result can bind antigen-IgE complexes

*this antigen, once processed, stimulates TH2 responses and promotes the IgE response

FcεRI receptor

what is stimulated to cause the switch to IgE in the first exposure to an allergen?

a) TH1 cells
b) TH2 cells
c) TH17 cells
d) Treg cells

b) TH2 cells

IgE is associated with rapid degranulation. Which immunoglobulin is associated with normal gradual degranulation?

IgG

stimulation of α adrenergic receptors causes:

-[enhanced/suppressed] degranulation of mast cells

-[contraction/relaxation] of smooth muscle

-[constriction/dilation] of blood vessels

-enhanced degranulations of mast cells

-contraction of smooth muscles

-constriction of blood vessels

stimulation of β adrenergic receptors causes:

-[enhanced/suppressed] degranulation of mast cells

-[contraction/relaxation] of smooth muscle

-[constriction/dilation] of blood vessels

-suppressed degranulation of mast cells

-relaxation of smooth muscles

-dilation of blood vessels

to treat allergic reactions by reducing edema and raising blood pressure we use:

a) α agonist
b) β agonist

a) α agonist

α stimulators cause vasoconstriction and may be of use in treating severe ________ _________, reducing _____________, and raising _________ ________

-treating severe allergic reactions
-reducing edema
-raising blood pressure

β stimulators mediate smooth muscle relaxation and may therefore reduce the severity of...

smooth muscle contraction

epinephrine (or adrenaline) has both _____ and _____ adrenergic activity

α and β

Epinephrine has...

a) α adrenergic activity
b) β adrenergic activity
c) both α & β adrenergic activity
d) neither α or β adrenergic activity

c) both α & β adrenergic activity

what is the interleukin for eosinophils?

IL-5

______________ exacerbate the inflammation triggered first by mast cells via a complex array of molecules that contribute to the acute inflammatory response

eosinophils

clinical signs of type I hypersensitivity result from abrupt and excessive release of inflammatory mediators from...

mast cells, basophils, and eosinophils

type I hypersensitivity:

if the rate of release of vasoactive molecules exceeds its ability to adjust changes in the vascular system, an animal will undergo ________ ___________ and may die

allergic anaphylaxis

severe urticaria

a) type I hypersensitivity
b) type II hypersensitivity
c) type III hypersensitivity
d) type IV hypersensitivity

a) type I hypersensitivity

what is the shock organ in dogs?

hepatic veins (the liver)

treatments of type I hypersensitivity (4)

-prevent exposure to the offending allergens
-epinephrine for allergic anaphylaxis
-corticosteroids for local inflammation
-desensitizing injections of allergens

for local inflammation we use:

a) corticosteroids
b) epinephrine

a) corticosteroids

for anaphylaxis/systemic type 1 we use:

a) corticosteroids

b) epinephrine

b) epinephrine

what is the shock organ of most animals other than the dog?

respiratory tract

what 3 animals have the intestines as an additional shock organ?

horse, pig, and cat

type I hypersensitivities, also called immediate hypersensitivity, are mediated by __________ attached to mast cells

immunoglobulin E (IgE)

t/f: the clinical signs of allergic disease depend in large part on the route by which antigens (allergens) enter the body

true

"IgG or IgM Mediated Cytotoxic Hypersensitivity" is another name for which type of hypersensitivity?

type II hypersensitivity

type II hypersensitivity occurs when antibodies and complement attach to normal cells and cause ___________ and ___________ of cells

opsonization and phagocytosis

what are the 3 effects of type II hypersensitivity reactions?

1. Complement/FcR mediated inflammation
2. opsonization & phagocytosis
3. abnormal physiologic responses without tissue injury (Ex: Myasthenia gravis)

blood antigens are controlled by _________ and __________

genes and inherited

RBCs express cell surface molecules, usually glycoproteins or glycolipids, that act as antigens and are called...

blood group antigens or erythrocyte antigens (EA)

t/f: animals may possess antibodies against foreign blood group antigens even when never previously exposed to foreign red cells

true

what are the 2 results of IgM binding donor RBC antigens?

agglutination & hemolysis

the action of an antibody when it cross-links multiple antigens producing clumps of antigens

a) agglutination
b) hemolysis

a) agglutination

antibody + complement - creates MAC and puts holes in RBC membrane causing hemoglobin to leak out

a) agglutination
b) hemolysis

b) hemolysis

severity of blood transfusion reactions ranges from mild febrile response to rapid death - depends mainly on the amount of...

incompatible blood transfused

a large number of lysed RBCs trigger ______________ and __________

blood clotting and DIC

if a reaction is suspected while giving a blood transfusion what should you do?

-transfusion must be stopped immediately
-maintain urine flow with fluids and a diuretic

how do you prevent a blood transfusion reaction?

cross-matching

what is hemolytic disease of the newborn (HDN)?

-fetal RBCs leak into the bloodstream of their dams through the placenta

-if they have incompatible blood antigens the dam makes antibodies to the fetal RBCs

-in sensitized females, these anti-fetal RBC antibodies are concentrated into their colostrum

-when a newborn suckles, colostrum antibodies are absorbed through the intestinal wall and cause rapid destruction of fetal RBCs

what four conditions must be met for HDN to occur?

-fetus must inherit a red cell antigen from its sire that's not present in its mother

-the mother must be sensitized to this antigen

-the mother's response must be boosted by transplacental hemorrhage/repeated pregnancies

-a newborn animal must ingest colostrum containing high-tiered antibodies to its red cells

what are horses blood groups? (7)

EAA
EAC
EAD
EAK
EAP
EAQ
EAU

in mules, hemolytic disease of the newborn (HDN) in foals is seen in about _____%

8-10%

in thoroughbreds and Standardbreds, hemolytic disease of the newborn (HDN) is ___%

2%

hemolytic disease is a problem in mares that have had...

several foals

the most severe form of HDN results from the production of antibodies against the ___ antigen of the EAA system

Aa

anti-Aa and anti-Qa accounts for a total of ____% of HDN in foals

90%

t/f: antibodies produced by mares cross the placenta

false - do not cross the placenta

how do antibodies produced by mares reach the foal?

through colostrum

HDN in foals:

earliest signs are ____________ and _____________

weakness and depression

HDN in foals:

mucus membrane of affected foals may be pale and may eventually show ___________

jaundice

how does HDN in calves differ from HDN in foals?

-HDN is rare

-usually see similar issue from vaccination containing RBCs from infected calves sensitizing the mother

how does HDN in pigs differ from HDN in foals?

-used to be associated with Hog Cholera vaccine
-true HDN is also rare

HDN in calves is rare but has resulted from vaccination against ____________ or __________

anaplasmosis or babesiosis

what is Bovine Neonatal Pancytopenia?

-hemorrhagic disease of newborn beef calves

-sudden onset of bleeding

-anemia and leukopenia

-bone marrow completely aplastic

-traced back to the use of BVD vaccine

Bovine Neonatal Pancytopenia:

studies showed that the colostrum of dams of these calves contained antibodies against the ____________ antigens of neonatal leukocytes and bone marrow stem cells

MHC I

HDN in pigs formerly occurred as a result of the use of ______ ________ vaccine containing pig blood

hog cholera

talk about type II hypersensitivity reactions to drugs

-drugs and antibodies may combine directly and activate Complement and RBCs will be destroyed

-some drugs (Penicillin) may bind to RBCs and cause hemolytic anemia

type II hypersensitivity, also called ___________ hypersensitivity, occurs when antibodies (and complement) destroy normal cells

cytotoxic

the destruction of transfused red blood cells when administered to a mismatched recipient is an example of type ____ hypersensitivity

II

some drugs may bind to blood cells and make them targets of antibodies in a type ____ hypersensitivity reaction

II

type III hypersensitivity develops when antigens and antibodies combine to form __________ _________, which if deposited in large amounts in tissues, trigger severe inflammation

immune complexes

type III hypersensitivity:

the prerequisite for the development of immune complex disease is the persistent presence of....

soluble antigen and antibody

type III hypersensitivity:

timing of the clinical manifestation is usually ____-____ after exposure

6-8 hours

type III hypersensitivity:

the most frequently affected sites include the...

lungs, kidneys, joints, and brain (i.e., where large capillary beds exist)

what cells and mediators are responsible for type III hypersensitivity?

-neutrophils: granule contents

-macrophages: phagocyte

-mast cells: granule contents

-complement: Anaphylatoxins (C3a, C5a)

_____ and ______ are also called anaphylatoxins since, when injected in sufficient amounts, they can kill an animal in a manner similar to anaphylaxis by causing mast cells to release histamine granules = pro-inflammatory

C3a and C5a

______________ release oxidants and enzymes that lead to acute inflammation and tissue destruction in a type III hypersensitivity reaction

neutrophils

what are the two major classifications of a type III hypersensitivity?

localized and generalized

what is a localized type III hypersensitivity?

-immune complexes are deposited in tissues & the reaction is seen at the site of the antigen entry

-the antigen is introduced into the tissue and preformed antibody in circulation binds to its antigen

what is a generalized or systemic type III hypersensitivity?

-there is excess antigen in the circulation

-antibody in the circulation (IgG) binds to circulating antigen and forms immune complexes

-immune complexes circulate and get deposited in blood filtration points

-local reaction seen in the skin after subcutaneous or intradermal injection of an antigenic substance (post-vaccination)

-type III hypersensitivity

-starts as red edematous swelling and eventually there is local hemorrhage and thrombosis; even necrosis possibly

what is this reaction called?

Arthus Reaction