L50: hypersensitivities

what are the mediators for type 1 hypersensitivity?

IgG and mast cell histamine

what are the mediators for type 2 hypersensitivity?

1. IgG

2. IgM

3. +/- complement

what are the mediators for type 3 hypersensitivity?

1. IgG

2. IgM

3. IgA

what are the mediators for type 4 hypersensitivity?

1. Th1/CD4+

2. CTL (CD8+)

what does a type 1 hypersensitivity lead to?

exaggerated Th2 response to antigens leading to excessive IgE production

what is the term for when there is excessive IgE production?

atopy

where does IgE bind to during the first encounter with an allergen?

Fc receptors on mast cells

what happens when there is a re-exposure to the allergen?

1. the allergen binds to the IgE

2. cross-linking of IgEs

3. mast-cell degranulation and release of histamine

what is the immediate clinical response with a type 1 hypersensitivity?

mast cell degranulation for 30 minutes → fluid leakage

what occurs during the late stage of a type 1 hypersensitivity reaction?

leukotrienes, chemokines, and eosinophils released in 6-8 hours

describe the process of opsonization and phagocytosis during a type 2 hypersensitivity

Macrophages and neutrophils recognize the Fc or complement fragments bound to the target cell and phagocytize it

describe the process of complement activation during a type 2 hypersensitivity

Formation of the membrane-attack complex (MAC) and lysis of the target cell

what does the type 2 hypersensitivity reaction result in?

Leads to the lysis and removal of host cells

what are the clinical findings of a type 2 hypersensitivity?

1. icterus

2. hemolysis

3. hemoglobinuria

4. spherocytes

5. agglutination (positive Coomb’s test)

what is a type 3 hypersensitivity reaction?

soluble antigens combine with IgG and IgM antibodies to form immune complexes while in circulation

what are the common sites of deposition for a type 3 hypersensitivity reaction?

1. kidney

2. joints

3. skin

what cells process the antigen in a type 4 hypersensitivity reaction?

1. Langerhan cells

2. dendritic cells

which hypersensitivity reaction has no antibody involvement?

type 4

what do CD4+ helper T cells do during a type 4 hypersensitivity reaction?

release cytokines and activate macrophages → inflammation, swelling, and tissue damage

what do CD8+ cytotoxic T cells do during a type 4 hypersensitivity reaction?

directly attack antigen-presenting cells using perforins and granzymes

what are examples of type 1 hypersensitivity reactions?

1. systemic anaphylaxis

2. hives

3. redness

what are examples of type 2 hypersensitivity reactions?

1. IMHA

2. neonatal isoerythosis

3. IMT

what are examples of type 3 hypersensitivity reactions?

1. immune complex vasculitis

2. pupura hemorrhagica

3. wet form of FIP

4. blue eye

what are examples of type 4 hypersensitivity reactions?

1. contact dermatitis

2. dry form of FIP

3. TB test

what are examples of local type 1 hypersensitivity reactions?

1. allergic rhinitis

2. atopy or hives

3. eosinophilic granuloma complex

4. ectoparasite allergies

what are examples of systemic type 1 hypersensitivity reactions?

1. asthma

2. food allergies

3. generalized angioedema

4. anaphylaxis

what are the effects of histamine?

1. vasodilation

2. increased vascular permeability

3. smooth muscle contraction

4. mucus hypersecretion

what is the shock organ of cats?

lungs

what is the shock organ in dogs?

liver

what do we use for the treatment of anaphylaxsis?

epinephrine

A horse develops severe urticaria and mild respiratory distress 20

minutes after eating freshly cut alfalfa hay. The horse has experienced

similar signs after alfalfa exposure in the past. What immunologic event

is most responsible for the onset of the clinical signs in this horse?

allergen cross-linking of mast cell bound IgG causing degranulation

radioimmunosorbent test (RIST)

measures TOTAL IgE

why can radioimmunosorbent tests have false positives?

1. non-specific IgE measurement

2. high IgE levels with parasitism

radioallergosorbent test (RAST)

measures patient IgG specific to allergen using anti-dog IgE

what are the clinical signs of atopy?

1. erythema of feet and face

2. pruritis

3. scratching

4. biting

5. alopecia

explain the process for hyposensitization for atopy

Repeated low-dose allergen exposure induces blocking IgG antibodies

describe the mechanism for hyposensitization for atopy

1. IgG binds allergen before it can cross-link IgE on mast cells

2. promotes Th1 response

3. Th2 activity suppressed

4. decreased IL-4 and IgG production

5. reduced allergic reaction

what are the treatments for a mild type 1 hypersensitivity reaction?

1. antihistamines

2. corticosteroids

what are the treatments for a moderate type 1 hypersensitivity reaction?

1. antihistamines

2. corticosteroids

3. IV fluids if vomiting or diarrhea present

what are the treatments for a severe type 1 hypersensitivity reaction?

1. epinephrine

2. IV fluids

3. oxygen therapy

4. bronchodilators

5. H2 blockers

6. corticosteroids in LATE PHASE

how long do we monitor for a mild type 1 hypersensitivity reaction?

1-2 hours

how long do we monitor for a moderate type 1 hypersensitivity reaction?

3-4 hours

how long do we monitor for a severe type 1 hypersensitivity reaction?

12-24 hours

what is the prognosis for mild to moderate type 1 hypersensitivity reactions?

excellent with prompt treatment

what is the prognosis for severe type 1 hypersensitivity reactions?

guarded to good depending on how quickly treatment is initated

answer the MCQ

Perform immediate sedation and oral examination, with epinephrine and oxygen support ready

what is a type 2 hypersensitivity reaction?

Antibody/complement mediated removal or destruction of erythrocytes and/or platelets

what would an example of a drug-induced hemolytic anemia for a type 2 hypersensitivity reaction?

penicillin in horses

what do we use for the diagnosis of type 2 hypersensitivity reactions?

1. coombs test

2. flow cytometry test for surface antibodies

what is the treatment for neonatal isoerythrolysis?

1. transfuse mare’s packed washed red blood cells

2. withhold mare’s colostrum for 24-30 hours

3. start foal on milk supplement through feeding tube

pupura hemorrhagica

immune complex damage to vessels leads to necrosis of tissues

why can there be chronic granulomatous inflammation with type 4 hypersensivity reaction?

persisten Th-1 macrophage activation

how is contact dermatitis a type 4 hypersensitivity?

stimulates CTLs to induce apoptosis of keratinocytes

what is the diagnosis for type 4 hypersensitivity reactions?

clinically based on timing and lesion distribution

what is the treatment for type 4 hypersensitivity reactions?

1. remove antigen

2. topical or systemic corticosteroids

3. hyposensitization normally ineffective

Two weeks after recovering from a Streptococcus equi (strangles) infection, a

horse develops distal limb edema, petechiae on the mucous membranes, fever,

and depression. Serologic testing shows high antibody titers to S. equi.

What immunologic mechanism best explains these clinical signs?

immune-complex mediated hypersensitivity

A dog develops erythematous, pruritic, weeping skin lesions 48 hours after a topical

ointment containing penicillin was applied to its ears. No systemic signs of

anaphylaxis are observed. What immunologic mechanism is most responsible for these skin lesions?

Th-1 cell mediated delayed inflammatory response

what are the common causes associated with glomerulonephritis in type 3 hypersensitivity reactions?

1. Boriela

2. Diofilara

what is the key diagnostic finding for glomerulonephritis in a UA?

proteinuria

in hyposensitization for atopy, which “blocking antibody” is stimulated?

IgG

how long does the sensitization period typically last?

7-10 days