Hypersensitivity Clinical Correlations

Question 1

Hypersensitivity reactions

Answer 1

Excessive, undesirable reaction produced by the normal immune system

• exaggerated and harmful response
• mild to life threatening

Question 2

Sensitizaiton

Answer 2

Initial exposure to an antigen

- subsequent exposure to the same antigen results in hypersensitivity

Question 3

Type 1

Answer 3

Immediate!

• minor symptoms to death
• present 15-30 min after antigen exposure

Question 4

Type 1 - phase 1

Answer 4

Sensitization

• antigens encountered at mucosal and cutaneous surfaces
• IgE production to inital encounter
• asymptomatic

Question 5

Type 1 - phase 1 example

Answer 5

DC within the bronchial epithelium encounters an inhaled antigen
--> DC travels to lymph node to signal Th2 --> IL-4, 13 induces a humoral response --> B cells are directed to a class switch to IgE production --> IgE binds to tissue mast cells, where they reside at mucosal/cutaneous surfaces at the original site of encounter = sensitization

Question 6

Type 1 - phase 1 summary

Answer 6

• mediated by IgE

- primary cellular component is the mast cell

Question 7

Type 1 - phase 2

Answer 7

Re-exposure

• exposure to the same allergen = cross linking (occurs when antigen is bound by 2 or more IgE)
• initiates signal pathway in mast cells and triggers degranulation

Question 8

Mast cell degranulation

Answer 8

Release of cytokines (IL-4,5,6 and inflammatory mediators)

- results in pruritus, bronchoconstriction, and vasodilation

Question 9

Type 1 active substances

Answer 9

• histamine!
• heparin
• leukotrienes
• prostaglandin D2
• platelet activating factor
• eosinophil chemotactic factor

Question 10

Clinical consequence of mast cell degranulation

Answer 10

Immediate hypersensitivity (occurs within 15-20 min)

• vasodilation/vascular permeability = tissue edema
• bronchoconstriction (smooth muscle contraction)
• interaction with local nerves = pruritis
• platelet aggregation

Question 11

Type 1 - late phase

Answer 11

Occurs 4-24 hrs after antigen exposure

- recruitment of eosinophils and macrophages into the tissue

Question 12

Presence of ______ is the hallmark of type 1 hypersensitivity

Answer 12

Eosinophils!

Question 13

Majority of type 1 reactions are ______

Answer 13

Localized

• skin: dermatitis
• respiratory: asthma, allergic rhinitis
• intestinal tract: food allergy

Question 14

Type 1 - systemic reactions

Answer 14

Often involve drugs or insect stings

- causes anaphylactic reaction

Question 15

Anaphylactic reaction signs

Answer 15

• bronchoconstriction and dyspnea
• hypotension
• tachycardia
• vomiting/diarrhea
• dizziness

Question 16

Anaphylactic reaction treatment

Answer 16

• epinephrine
• fluids
• oxygen
• antihistamines
• steroids
• supportive care

Question 17

Feline Asthma

Answer 17

Lower airway disease, limiting airflow due to reduced airway diameter

• airway inflammation
• accumulating airway mucus
• airway smooth muscle contraction

Question 18

What 2 cells play an important role in feline asthma?

Answer 18

Interactions between T cells and eosinophils

Question 19

Feline asthma treatment

Answer 19

Need to address inflammation and bronchoconstriction

- steroids and bronchodilators

Question 20

Adverse vaccine reactions

Answer 20

Due to IgE mediated degranulation of mast cells located in the skin = histamine and leukotriene release to deeper skin layers
- causes angioedema, urticaria, and pruritis

Question 21

Type 2 hypersensitivity

Answer 21

Aka cytotoxic or antibody mediated hypersensitivity

• affects variety of organs
• involves destruction of a target cell and the sensitization is to an antigen displayed on the surface of that target cell

Question 22

Type 2 - antibody production

Answer 22

Produced to endogenous antigens or exogenous substances (haptens) which attach to cell membranes and cause subsequent tissue damage
- mediated by IgG or IgM (with or without complement involvement)

Question 23

Type 2 - pathophysiology

Answer 23

Rapid destruction occurs via activation of classical complement pathway and formation of MAC
- takes longer when target cell destruction involves NK cell destruction or macrophage phagocytosis of the antibody dependent cell mediated pathway

Question 24

Type 2 - examples

Answer 24

• IMHA
• transfusion reactions
• myasthenia gravis
• pemphigus

Question 25

IMHA

Answer 25

Antibodies coat RBC and induce destruction - leads to severe damage by antibodies and complement = intravascular hemolysis - macrophages recognize Fc portion of antibody and remove the targeted RBC

Question 26

Intravascular hemolysis leads to _____ and ______

Answer 26

Hemoglobinemia and hemoglobinuria | - build up of hemoglobin due to RBC destruction

Question 27

Extravascular hemolysis

Answer 27

Destruction of RBCs by spleen/liver macrophages

Question 28

What is the hallmark of IMHA?

Answer 28

Autoagglutination

Question 29

How do you treat IMHA?

Answer 29

Immunosuppressive medications

Question 30

Blood transfusion in cats

Answer 30

Type A - no or low levels of pre-formed anti-B alloantibodies Type B - high levels of pre-formed anti-A alloantibodies

Question 31

Type A cat receiving type B blood

Answer 31

Minor risk, but possible for transfusion reactions

Question 32

Type B cat receiving type A blood

Answer 32

Much greater risk for transfusion reaction

Question 33

Myasthenia gravis

Answer 33

Generalized muscle weakness that worsens with exercise, and megaesophagus - antibodies against Ach receptors - treat with cholinesterase inhibitors

Question 34

Pemphigus foliaceus

Answer 34

Most common autoimmune disease of dogs - causes lethargy, febrile, lymphadenopathy - widespread distribution over head, face, ears - treat with immunosuppressive steroids

Question 35

Type 3 hypersensitivity

Answer 35

Immune complex hypersensitivity | - formation of soluble immune complexes in the blood and subsequent tissue deposition and tissue damage

Question 36

Type 3 - pathophysiology

Answer 36

Excessive production of antigen specific IgG antibody with sensitization - re - exposure causes antibody binding to antigen in circulation and formation of antigen/antibody complexes

Question 37

Immune complexes are comprised of

Answer 37

Antibodies, antigens, platelets, and neutrophils

Question 38

Type 3 - signs

Answer 38

Occur once immune complexes are deposited into tissues - inflammatory response - complement activation - recruitment of inflammatory cells to site of inflammation (neutrophils and macrophages)

Question 39

Where do the immune complexes deposit?

Answer 39

Within the walls of the capillaries of differing tissues - kidneys - skin - joints

Question 40

Vasculitis

Answer 40

Complement fixation and triggering of inflammatory pathways within the vascular walls - leads to: joint pain, cutaneous lesions, and protein losing nephropathy

Question 41

Type 3 - cause

Answer 41

Antigenic cause is often not determined | - idiopathic or immune-mediated

Question 42

Immune-mediated polyarthritis

Answer 42

Inflammatory disease where microbial organisms cannot be cultured from the joints and where the immune system plays an important role in the pathogenesis

Question 43

Type 4 hypersensitivity

Answer 43

Cell mediated, or "delayed" type - prolonged onset of action (24-72 hrs) - sensitization leads to generation of antigen specific T lymphocytes (Th1)

Question 44

Type 4 - pathophysiology

Answer 44

Subsequent exposure leads to activation of sensitized Th1 cells and movement to site of exposure - release of cytokines and recruitment of inflammatory cells (macrophages, Th cells, Tc cells)

Question 45

What causes direct damage in type 4?

Answer 45

Cytotoxic T cells | - recruited by helper T cells

Question 46

What is the most significant type 4 manifestation?

Answer 46

Contact allergy | - inappropriate inflammatory response at cutaneous site of challenge