Flashcards in Exam 4: Dr. Archer Hypersensitivity Reactions Deck (63):
What are hypersensitivity reactions?
Excessive, undesirable reactions produced by the normal immune system
What do hypersensitivity reactions often involve?
Initial exposure or "sensitization" to an antigen
What does subsequent exposure to a specific antigen lead?
The inappropriately excessive response (or hypersensitivity reaction)
Describe Type I hypersensitivity
2 phases– sensitization and re-exposure
Describe phase I (sensitization) of type I hypersensitivity
Antigens often encountered at the mucosal and cutaneous surfaces
IgE production in response to initial antigen encounter
Often asymptomatic with initial encounter
What are examples of type I hypersensitivity?
Dendritic cell within the bronchial epithelium may encounter an inhaled allergen
Langerhan cell within the epidermis may capture a percutaneously absorbed antigen
What happens to the cells that can be involved in a type I hypersensitivity after encounter with antigen?
The cells travel to the regional lymph nodes, with preferential signaling towards Th2 and the promotion of a humoral immune response
What happens to B cells during a Type I hypersensitivity reaction?
They are directed to a class switch towards IgE production
What happens to antigen specific IgE in a type I hypersensitivity reaction?
It binds to tissue mast cells
The IgE coated art cells then reside at the mucosal and cutaneous surfaces where the antigen was originally encountered. The individual is now sensitized
What is type I hypersensitivity mediated by?
What is the primary cellular component of type I hypersensitivity reactions?
What is phase 2 (re-exposure) of type I hypersensitivity?
Subsequent exposure to the same allergen causes "cross-linking"
When does cross-linking occur?
When antigen is bound by two or more IgE molecules
What does cross-linking initiate?
A signaling pathway within mast cells and triggers the release (or degranulation) of active substances
What are the active substance involved in type I hypersensitivity?
Platelet activating factor
Eosinophil chemotactic facotr
Where does histamine come from?
Mast cells, as does eosinophil chemotactic factor
What is the clinical consequence of mast cell degranulation?
Vasodilation and vascular permeability of blood vessels, resulting in tissue edema
Contraction of smooth muscles
Interaction with local nerve endings
Describe the late phase response of type I hypersensitivity
Recruitment of eosinophils and macrophages into the tissue
Presence of eosinophils
What is the hallmark of type I hypersensitivity?
Presence of eosinophils
What are the majority of type I hypersensitivity reactions like?
Localized and affects only the tissues which come in contact with the allergen
What are examples of localized type I hypersensitivities of the skin?
Flea allergy dermatitis
Equine "sweet itch"
What are examples of localized type I hypersensitivities of the respiratory tract?
What are examples of localized type I hypersensitivities of the intestinal tract?
How can some type I hypersensitivities be classified?
Systemic, meaning they often cause an anaphylactic reaction
What are examples of systemic type I hypersensitivities?
Drugs or insect stings
Severe peanut allergy and seafood allergy in humans
What is feline asthma?
Lower airway disease limiting airflow
What can happen in feline asthma that limits airflow?
Accumulating airway mucus
Airway smooth muscle contraction
What happens in feline asthma that can reduce airway diameter?
Decreased airway pressure
Reduction in the volume of air through the airway
What plays an important role in feline asthma?
Interactions between T cells and eosinophils within airways
Describe vaccine adverse reactions
IgE mediated degranulation of mast cells in the skin
Histamine and leukotrienes are released to the deeper layers of the skin
What is a type II hypersensitivity also known as?
Cytotoxic or antibody mediated hypersensitivity
What does type II hypersensitivity involve?
The destruction of a target cell
What is the sensitization to in a type II hypersensitivity?
An antigen displayed in the surface of that target cell
What are antibodies produced to in type II hypersensitivities?
Endogenous antigens or exogenous substances which attach to cell membranes and cause subsequent tissue damage
What is type II hypersensitivity mediated by?
IgG (mostly) or IgM
What is the pathophysiology of type II hypersensitivity?
Rapid destruction can occur via activation of the classical pathway of complement and the formation of the membrane attack complex
Can take longer where the target cell destruction involves NK cell destruction or macrophage phagocytosis of the ADCC pathway
What are examples of type II hypersensitivities?
Immune-mediated hemolytic anemia (IMHA)
What happens in IMHA?
Antibodies coat RBC and induce destruction
What can cause intravascular hemolysis?
Severe damage by antibodies and complement
What can macrophages do in IMHA?
Recognize the Fc portion of the antibody and remove the targeted RBC from circulation
What is one of the hallmarks of IMHA?
Describe Type A cats
Either no or only low levels of pre-formed anti-B alloantiboides
Describe Type B cats
High levels of pre-formaed anti-A alloantibodies
What happens if a type A cat receives type B blood?
Minor risk, but possible for transfusion reactions
What happens if a type B cat receives type A blood?
Much greater risk for transfusion reaction
What is the diagnosis of myasthenia gravis?
Identification of antibodies against acetylcholine receptors
What is used to test for myasthenia gravis?
What is a type III hypersensitivity reaction also known as?
Immune complex hypersensitivity
What does a type III hypersensitivity involve?
The formation of soluble immune complexes in the blood and subsequent tissue deposition and tissue damage
What is the pathophysiology of type III hypersensitivity?
Excessive production of antigen specific IgG antibody sensitization
Re-exposure causes antibody binding to antigen in circulation and the formation of antigen/antibody complexes or "immune complexes"
What happens in a type III hypersensitivity once immune complexes are deposited or "settle out" into tissues?
Initiate inflammatory response
Recruitment of inflammatory cells to the site of inflammation
What can a high load of antigen re-exposure cause in type III hypersensitivity?
The formation of immune complexes within the circulation
How long do complexes circulate in the bloodstream in type III hypersensitivity?
Until the deposit within the wall of the capillaries of differing tissues (kidneys, skin, joints)
What can type III hypersensitivity be caused by?
Many infectious and inflammatory diseases
What can complement fixation and triggering of inflammatory pathways within the vascular walls lead to in type III hypersensitivities?
Protein losing nephropathy
What happens with antigenic causes in many cases of type III hypersensitivity?
It is not often determined and is described as "idiopathic" or "immune-mediated"
What is type IV hypersensitivity also known as?
Cell mediated or "delayed" type hypersensitivity
What does sensitization lead to in type IV hypersensitivity/
The generation of antigen specific T lymphocytes (Th1)
What does subsequent exposure lead to in type IV hypersensitivity?
Activation of sensitized T lymphocytes and movement of these T lymphocytes to the site of antigen exposure which can lead to the release of inflammatory cytokines and recruitment of inflammatory cells
What cells cause direct damage in type IV hypersensitivity?
Cytotoxic T cells
What do helper T cells do in type IV hypersensitivity?
Secrete cytokines which activate cytotoxic T cells and recruit and activate monocytes
What is the most significant manifestation of type IV hypersensitivity in humans and dogs?