Lesson 50 - Hypersensitivity Reactions

What is the purpose of the Type I hypersensitivity?

1. self-eliminate roundworms in the gut

2. eliminate allergen from mucocutaneous surfaces

What occurs with the first exposure in Type I?

1. Th2 cells activate B cells to produce IgE antibodies to allergens

2. IgE binds Fc receptors on Mast cells

What occurs with the second exposure in Type I?

1. antigen binds to IgE on mast cells

2. cross-linking of IgEs

3. mast cells degranulate releasing histamine

What does histamine cause?

1. vasodilation

2. increased vascular permeability

3. smooth muscle contraction

4. mucus secretion

What is the immediate result of second exposure in Type I?

1. mast cell degranulation causing fluid leakage in 30 minutes

2. local angioedema

What is involved with the late phase result of second exposure in Type I?

1. leukotrienes

2. chemokines

3. eosinophils

4. 6-8 hours

What are the local Type I hypersensitivity clinical syndromes?

1. allergic rhinitis

2. allergic inhalant dermatitis (atopy) & urticaria

3. eosinophilic granuloma complex

4. ectoparasite allergies

What are the systemic Type I hypersensitivity clinical syndromes?

1. anaphylaxis

2. asthma

3. food allergies

4. generalized angioedema

What can bind to host-cell antigens in Type II?

1. IgG

2. IgM

3. complement proteins

What is the mechanism of Type II?

1. opsonization and phagocytosis

2. complement activation

What is the timeline of Type II?

hours to days after exposure

What hypersensitivity is immune response to foreign antigen on RBCs and platelets?

Type II

What organ can the Type II mechanism occur in the body?

spleen

What is the mechanism of opsonization and phagocytosis in Type II?

macrophages and neutrophils recognize the Fc or complement proteins bound to target cell and phagocytose it

What is the mechanism of complement activation in Type II?

formation of membrane-attack complex and lysis of the target cell

What are some clinical syndromes associated with type II?

1. immune-mediated hemolytic anemia

2. immune-mediated thrombocytopenia

3. drug-induced hemolytic anemia

4. red blood cell transfusion reaction

5. hemolytic disease of the newborn

What are typical results seen with Type II?

1. anemia

2. thrombocytopenia

3. hemoglobinuria

4. spherocytes

5. agglutination

6. icterus

What hypersensitivity is associated with a positive Coombs test?

Type II

What infections are associated with type III?

1. FIP

2. Streptococcus equi

What is the mechanism of type III?

1. antibody made to foreign antigen of prior infections makes immune complex

2. complexes deposit in vessels

3. complement activation

What is the result of complement activation in Type III?

1. vasculitis

2. neutrophil infiltration

3. activation of mast cells

4. necrosis and fibrosis of vessel wall

What is the timeline with Type III?

2-8 hours after re-exposure

What antibody is typically involved with Type III?

IgG

What are the clinical syndromes seen with Type III?

1. purpura hemorrhagica

2. wet form of feline infectious peritonitis

3. blue eye

4. glomerulonephritis

What is purpura hemorrhagica?

dermal or lung vasculitis secondary to prior strangles infection

Why is the wet form of FIP considered Type III?

vasculitis of peritoneum causes fluid to leak into the cavity

What is blue eye?

vasculitis in the eye causing corneal edema in puppies following adenovirus vaccination

What infections can cause glomerulonephritis and Type III?

1. dirofilaria

2. borrelia

What is the mechanism of Type IV?

1. Th1 cell produces IFN-gamma which activates macrophages

2. activation of CD8 can lead to epithelial cell damage

What is the timing for Type IV?

24-72 hours after exposure

What hypersensitivity has no antibody involvement?

Type IV

What lesion forms with Type IV?

granuloma

What clinical syndromes are associated with Type IV?

1. contact dermatitis

2. positive tuberculin skin test

3. dry form of FIP

4. transplant rejection

5. chronic granulomatous inflammation

What antibody is typically involved with Type I?

IgE

What are hypersensitivities?

exaggerated or inappropriate adaptive immune responses

What is the cats shock organ?

lungs

What is the dogs shock organ?

liver

How does anaphylactic shock occur in cats?

fluid and mucous accumulation in the airways

How does anaphylactic shock occur in dogs?

hepatic venoconstriction/portal hypertension causing GI signs

What occurs during anaphylaxis in the respiratory system?

1. epiglottal swelling

2. pharyngeal edema

3. compression of trachea

4. fluid collection in lung

5. hypovolemia

How do dogs get hypovolemia during anaphylactic shock?

fluid loss from GI vomiting and diarrhea and visceral pooling of blood in the liver

What are the diagnostic tests for Type I?

1. radioimmunosorbent test (RIST)

2. radioallergosorbent test (RAST)

3. intradermal skin testing

What Type I test measures total IgE?

radioimmunosorbent testing

Which Type I test can lead to more false positives?

radioimmunosorbent testing

Why does RIST cause more false positives?

its non-specific so breeds with high IgE or parasitism can cause false positives

What Type I test measures patient IgE specific to allergen?

radioallergosorbent testing

What is used in RAST?

radioactive or enzyme conjugated anti-dog IgE

What is the intradermal skin testing?

inject micro-amounts of allergens into the dermis and measure the swelling

What are the positive and negative control for intradermal skin testing?

1. positive is histamine

2. negative is saline

What are the clinical signs of inhalant allergic dermatitis?

1. erythema

2. pruritus

3. alopecia

What is hyposensitization therapy used for?

atopy

What is hyposensitization therapy?

1. low dose allergen immunization

2. stimulates blocking antibody IgG

3. phagocytosis of allergen

4. stimulation of Th1 cytokines which inhibit Th2

5. interferon gamma

What is the treatment for a mild Type I reaction?

1. antihistamines

2. corticosteroids

3. monitoring for 1-2 hours

What is the treatment for a moderate Type I reaction?

1. antihistamines

2. corticosteroids

3. IV fluids if V/D

4. monitoring for 3-4 hours

What is the treatment for a severe Type I reaction?

1. monitoring for 12-24 hours

2. corticosteroids

3. oxygen therapy

4. bronchodilators

5. epinephrine

6. H2 blockers

7. IV fluids shock dose

What is important to know about using corticosteroids for Type I reactions?

delayed onset

What are the signs of a mild Type I reaction?

1. localized urticaria

2. pruritus

3. mild facial swelling

What are the signs of a moderate Type I reaction?

1. widespread urticaria

2. vomiting

3. respiratory signs

What are the signs of a severe Type I reaction?

anaphylaxis

What is the prognosis for mild to moderate type I reactions?

excellent with prompt treatment

What is the prognosis for severe anaphylaxis?

guarded to good depending on how quickly treatment is initiated

What is important to tell the owner after severe anaphylaxis?

typically they recover fully but future exposures may trigger similar or more severe responses

What diagnostic is used for food allergies?

food trial

What is a common drug-induced hemolytic anemia?

penicillin hapten type in horses

What is the treatment for Type II?

1. remove trigger

2. immunosuppression

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 and substitute from another source

3. start on milk supplement through feeding tube and muzzling the foal

What do we not want to give a foal with neonatal isoerythrolysis?

1. mare's plasma

2. sire's red blood cells or plasma

What is the target with Type II?

host cells

What are clinical signs of Type II with strangles?

1. hemorrhage of mucous membranes

2. tissue necrosis

What is the prognosis of Type III?

guarded to poor if chronic organ damage occurs

What is the prognosis of Type IV?

good if cause is removed

What agents can cause a contact dermatitis?

1. nickel

2. formaldehyde reactions

3. poison ivy

4. penicillin

What diseases cause chronic granulomatous inflammation with Type IV?

1. Johne's disease

2. Tuberculosis

How does poison ivy cause contact dermatitis?

1. acts as a hapten

2. binds to skin proteins

3. stimulates CTLs to induce apoptosis of keratinocytes

What is the treatment for Type IV?

1. remove antigen

2. topical/systemic corticosteroids

What type is hyposensitization usually ineffective?

Type IV