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Flashcards in Hypersensitivity Clinical Correlations Deck (46):
1

Hypersensitivity reactions

Excessive, undesirable reaction produced by the normal immune system
- exaggerated and harmful response
- mild to life threatening

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Sensitizaiton

Initial exposure to an antigen
- subsequent exposure to the same antigen results in hypersensitivity

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Type 1

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

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Type 1 - phase 1

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

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Type 1 - phase 1 example

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

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Type 1 - phase 1 summary

- mediated by IgE
- primary cellular component is the mast cell

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Type 1 - phase 2

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

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Mast cell degranulation

Release of cytokines (IL-4,5,6 and inflammatory mediators)
- results in pruritus, bronchoconstriction, and vasodilation

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Type 1 active substances

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

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Clinical consequence of mast cell degranulation

Immediate hypersensitivity (occurs within 15-20 min)
- vasodilation/vascular permeability = tissue edema
- bronchoconstriction (smooth muscle contraction)
- interaction with local nerves = pruritis
- platelet aggregation

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Type 1 - late phase

Occurs 4-24 hrs after antigen exposure
- recruitment of eosinophils and macrophages into the tissue

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Presence of ______ is the hallmark of type 1 hypersensitivity

Eosinophils!

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Majority of type 1 reactions are ______

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

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Type 1 - systemic reactions

Often involve drugs or insect stings
- causes anaphylactic reaction

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Anaphylactic reaction signs

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

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Anaphylactic reaction treatment

- epinephrine
- fluids
- oxygen
- antihistamines
- steroids
- supportive care

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Feline Asthma

Lower airway disease, limiting airflow due to reduced airway diameter
- airway inflammation
- accumulating airway mucus
- airway smooth muscle contraction

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What 2 cells play an important role in feline asthma?

Interactions between T cells and eosinophils

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Feline asthma treatment

Need to address inflammation and bronchoconstriction
- steroids and bronchodilators

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Adverse vaccine reactions

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

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Type 2 hypersensitivity

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

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Type 2 - antibody production

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)

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Type 2 - pathophysiology

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

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Type 2 - examples

- IMHA
- transfusion reactions
- myasthenia gravis
- pemphigus

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IMHA

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

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Intravascular hemolysis leads to _____ and ______

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

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Extravascular hemolysis

Destruction of RBCs by spleen/liver macrophages

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What is the hallmark of IMHA?

Autoagglutination

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How do you treat IMHA?

Immunosuppressive medications

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Blood transfusion in cats

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

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Type A cat receiving type B blood

Minor risk, but possible for transfusion reactions

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Type B cat receiving type A blood

Much greater risk for transfusion reaction

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Myasthenia gravis

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

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Pemphigus foliaceus

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

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Type 3 hypersensitivity

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

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Type 3 - pathophysiology

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

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Immune complexes are comprised of

Antibodies, antigens, platelets, and neutrophils

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Type 3 - signs

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

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Where do the immune complexes deposit?

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

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Vasculitis

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

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Type 3 - cause

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

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Immune-mediated polyarthritis

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

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Type 4 hypersensitivity

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

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Type 4 - pathophysiology

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)

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What causes direct damage in type 4?

Cytotoxic T cells
- recruited by helper T cells

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What is the most significant type 4 manifestation?

Contact allergy
- inappropriate inflammatory response at cutaneous site of challenge