Hypersensitivity Type 1 Flashcards
What is a hypersensitivity reaction?
An immune response that results in bystander damage to self
What is hypersensitivity the pathological basis for?
Many diseases including allergy and autoimmunity
What is type 1 hypersensitivity?
Immediate hypersensitivity
IgE mediated
Allergy
What is an allergy?
IgE mediated antibody respose to an external antigen.
Give some examples of allergic diseases?
Asthma, hayfever, urticaria (hives), Angioedema (lip swelling) atopic eczema, food allergy, drug allergy, allergic rhinitis and anaphylaxis
What is the hygiene hypothesis?
Improved sanitation and decreased incidence of infectious disease has resulted in a world that is too clean.
Changes in microbial stimuli influences the maturation of the immune response.
General decrease in infectious burden during early life and variations in GI flora lead to increased predisposition to allergic conditions during childhood.
At birth our CD4+ T cells will inherently mature into T helper 2 cells. What happens if we:
1) live in a clean sterile environment?
2) live in an environment exposed to many different antigens?
1) T helper 2 cells are formed which secrete histamine => allergies and antibody mediated immunity
2) CD4+ T cells will preferentially differentiate into T helper 1 cells which secrete interferon gamma => no allergies and cell mediated immunity.
What are the generic features of a type 1 hypersensitivity response?
1) Occurs quickly after exposure to allergen (1-2 minutes)
2) Responses are stereotyped
3) Presentation is influenced by site of contact
4) Maybe associated with more than one organ system
5) Threshold for reactions can be influenced by factors such as exercise, alcohol and infection.
Which immune cells are associated with hypersensitive type 1 reactions and what do they release?
T helper 2 cells which release histamine and provide B cell activation to make IgE
B cells that recognise antigen and produce antigen specific IgE
Mast cells, Eosinophils and Basophils which release vasoactive substances
Explain the pathophysiology of type 1 hypersensitivity reactions?
1) Antigen presenting cell (dendritic cell) activates CD4+ T cells and B cells within a lymph node.
2) T helper 2 cells will start to produce cytokines which diffuse into the germinal centre.
IL5 activates eosinophils
IL4 and IL13 activate mast cells
IL4, IL5 and IL13 activate B cells
Which interlukin released by T helper 2 cells means B cells that were secreting IgM will secrete IgE
IL4
Where are mast cells found?
Resident in tissues, especially at the interface with the external environment
What do mast cells secrete?
Vasoactive substances:
1) Histamine, Tryptase and heparin
2) Leukotrienes and prostaglandins
3) Proinflamatory cytokines including IL4 and TNF alpha
How do mast cells orchestrate the inflammatory cascade?
Increase blood flow and dilation of smooth muscle
Increase vascular permeability and secretions at mucosal surfaces
What is the normal function of mast cells?
Important defence against parasites
Basophils and eosinophils are similar to mast cells but what sets them apart?
Mast cells reside in tissues
Eosinophils and basophils reside in the blood stream
What is the role of mast cells in unwanted allergic reactions?
1) Express receptors for the Fc region of IgE antibodies on their surface.
2) On first encounter with allergen, B cells produce antigen specific IgE antibodies => clearance of allergen
3) Residual IgE antibodies bind to circulating mast cells via Fc receptors (where they remain for months/years)
4) When the allergen is re-encountered, the allergen binds to IgE on mast cells and disrupts the cell membrane => degranulation
5) Preformed vasoactive substances are released and there is increased transcription of cytokines and leukotrienes.
What are the manifestations of asthma?
Muscle contraction, mucosal inflammation and inflammatory cell infiltrates
What are the manifestations of urticaria?
Lesions appear on the skin within 1 hour and last for 2-6 hours
What are the manifestations of angioedema?
Non pitting oedema, self limiting localised swelling of subcutaneous tissue
What are the manifestations of anaphylaxis?
Wheezing, swollen throat/eyes, low blood pressure, tachycardia, sense of impending doom, conjunctivitis, itchy feet, dysphagia, abdominal pain, nausea, vomiting, rash, SOB, stridor
Why is it important to diagnose allergic disease?
Identify causative agents- modification of lifestyle and antigen avoidance
Determine risk of severe reaction and appropriateness of therapy
What elective investigations can you do for allergy?
Skin pick test
Quantitate specific IgE to causative allergen
Challenge test- supervised exposure to antigen
What investigations can be carried out during anaphylaxis?
Tryptase level will indicate mast cell degranulation
Histamine levels rise and fall so fast that you cannot measure these
How are IgE mediated allergic reactions managed?
1) Allergen avoidance
2) Block mast cell activation using sodium chromoglycate
3) Prevent effects of mast cell activation using antihistamines, leukotriene receptor antagonists
4) Antiinflamatory agents- steroids inhibit the formation of many inflammatory mediators
5) Anaphylaxis management- IM adrenaline to constrict arterial smooth muscle and dilate bronchial smooth muscle
6) immunotherapy if allergen is unavoidable
Give an example of a leukotriene receptor antagonist?
Montelukast
Steroids inhibit the formation of many inflammatory mediators. Give 3 examples of these?
Cytokines
Protaglandins
Platelet activating factor
How is sodium chromoglycate used?
Topical spray for prophylaxis of allergic rhinitis, conjunctivitis and asthma.
Prevents the release of inflammatory mediators from mast cells
