Hypersensitivity Clinical Correlations Flashcards
Hypersensitivity reactions
Excessive, undesirable reaction produced by the normal immune system
- exaggerated and harmful response
- mild to life threatening
Sensitizaiton
Initial exposure to an antigen
- subsequent exposure to the same antigen results in hypersensitivity
Type 1
Immediate!
- minor symptoms to death
- present 15-30 min after antigen exposure
Type 1 - phase 1
Sensitization
- antigens encountered at mucosal and cutaneous surfaces
- IgE production to inital encounter
- asymptomatic
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
Type 1 - phase 1 summary
- mediated by IgE
- primary cellular component is the mast cell
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
Mast cell degranulation
Release of cytokines (IL-4,5,6 and inflammatory mediators)
- results in pruritus, bronchoconstriction, and vasodilation
Type 1 active substances
- histamine!
- heparin
- leukotrienes
- prostaglandin D2
- platelet activating factor
- eosinophil chemotactic factor
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
Type 1 - late phase
Occurs 4-24 hrs after antigen exposure
- recruitment of eosinophils and macrophages into the tissue
Presence of ______ is the hallmark of type 1 hypersensitivity
Eosinophils!
Majority of type 1 reactions are ______
Localized
- skin: dermatitis
- respiratory: asthma, allergic rhinitis
- intestinal tract: food allergy
Type 1 - systemic reactions
Often involve drugs or insect stings
- causes anaphylactic reaction
Anaphylactic reaction signs
- bronchoconstriction and dyspnea
- hypotension
- tachycardia
- vomiting/diarrhea
- dizziness
Anaphylactic reaction treatment
- epinephrine
- fluids
- oxygen
- antihistamines
- steroids
- supportive care
Feline Asthma
Lower airway disease, limiting airflow due to reduced airway diameter
- airway inflammation
- accumulating airway mucus
- airway smooth muscle contraction
What 2 cells play an important role in feline asthma?
Interactions between T cells and eosinophils
Feline asthma treatment
Need to address inflammation and bronchoconstriction
- steroids and bronchodilators
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
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
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)
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
Type 2 - examples
- IMHA
- transfusion reactions
- myasthenia gravis
- pemphigus
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
Intravascular hemolysis leads to _____ and ______
Hemoglobinemia and hemoglobinuria
- build up of hemoglobin due to RBC destruction
Extravascular hemolysis
Destruction of RBCs by spleen/liver macrophages
What is the hallmark of IMHA?
Autoagglutination
How do you treat IMHA?
Immunosuppressive medications
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
Type A cat receiving type B blood
Minor risk, but possible for transfusion reactions
Type B cat receiving type A blood
Much greater risk for transfusion reaction
Myasthenia gravis
Generalized muscle weakness that worsens with exercise, and megaesophagus
- antibodies against Ach receptors
- treat with cholinesterase inhibitors
Pemphigus foliaceus
Most common autoimmune disease of dogs
- causes lethargy, febrile, lymphadenopathy
- widespread distribution over head, face, ears
- treat with immunosuppressive steroids
Type 3 hypersensitivity
Immune complex hypersensitivity
- formation of soluble immune complexes in the blood and subsequent tissue deposition and tissue damage
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
Immune complexes are comprised of
Antibodies, antigens, platelets, and neutrophils
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)
Where do the immune complexes deposit?
Within the walls of the capillaries of differing tissues
- kidneys
- skin
- joints
Vasculitis
Complement fixation and triggering of inflammatory pathways within the vascular walls
- leads to: joint pain, cutaneous lesions, and protein losing nephropathy
Type 3 - cause
Antigenic cause is often not determined
- idiopathic or immune-mediated
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
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)
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)
What causes direct damage in type 4?
Cytotoxic T cells
- recruited by helper T cells
What is the most significant type 4 manifestation?
Contact allergy
- inappropriate inflammatory response at cutaneous site of challenge
