Hypersensitivity - Type 1 (allergy) - 2 Flashcards
what antigen causes type 1 reactions
IgE and mast cells
can affect different organs
will cause an immediate local reaction in inhaled or ingested
a sting or IV can cause a systemic reaction
Antigens are allergens
enviromental, non infectious antigens (protiens)
ie pollen, hair, dust ect
give some examples of allergens
• Seasonal exposure
o Tree and grass pollens
• Perennial exposure
o House dust mite
o Animal dander = cats and dogs
o Fungal spores
• Accidental exposure o Insect venom (wasp and bee stings) o Medicines - for example, the antibiotic penicillin o Chemicals such as latex o Foods: milk, peanuts, nuts, etc...
what is the type I mechanism ?
Abnormal adaptive immune response against the allergens
o T helper 2 (TH2) response (IL-4, IL-5, IL-13)
o IgE production - activates mast cells
• Mast cell activation - by IgE mechanism
o Sensitized individuals
o Different clinical allergic disorders depending on
mast cell location
briefly explain why allergies are less common in poor countries
more outside time, more people - “Hygiene hypothesis”
• Children exposed to animals, pets and microbes in the early postnatal period appear to be protected against certain allergic diseases
alot more exposure as a child - not kept inside
these kids get good TH1 response to allergens
rich indoor kids will get a TH2 - mast cell response
read - its trash
“Old friends hypothesis” or “biodiversity hypothesis”
• Western lifestyle induces alteration of the symbiotic relationships with parasites and bacteria leading to “dysbiosis” of the microbiome at mucosal surfaces (gut)
Dysbiosis = compositional and functional alterations of
microbiome
Microbiome = The complete genetic content of all the
microorganisms that typically inhabit in the body, such as the skin or the gastrointestinal tract.
this leads to a loss of microbiota diversity - less immunne system exposure when young
so more immune diseases can be triggered
where do we find mast cells
in strategic defensive locations
most mucosal and epithelial tissues - GI tract, Skin, respiratory epithelium
in connective tissue around blood cells
name some key mast cell mediators
tryptase - enzyme - it remodels the connective tissue matrix
histamine - toxic mediator - toxic to parasites - increase vasc perm, cause smooth muscle contraction
leukotirnes C4,D4,E4 - lipid mediator - smooth muscle contraction, increase vasc perm, stimulate mucus secretion
platelet activating factor - lipid mediator - attracts leukocytes, amplifies production of lipid mediators, activates netropuhils, eosinophils and platelets
outline the mechansim of allergic reaction
probs best to look at lec 2 image
allergen 1st exposure - TH2 response - inapropriate - TH1 good
get an antigen specific IgE
igE cross linking on second exposure
Ige will activate and degranulate mast cells
this causes release of granules - histamines, chemokines,
synth new mediators - leukotriens and prostoglandins
leads to increased vasc perm
vasodilation
bronchial consriction
oedema and SOB and low BP
how does skin and faces manifest allergic reactions
skin
Urticaria
Caused by mast cell activation within the epidermis
Mediators = Histamine and leukotrienes/cytokines
If prolonged and chronic exposure = atopic dermatitis and eczema
face
angioedema
swelling of lips, tounge, face, upper resp tract
Caused by mast cell activation in the deep dermis.
Mediators = Histamine and bradykinin
what is the systemic manifestation of allergic response
anaphylaxis
systemic activation of mast cells
Hypotension Cardiovascular collapse Generalized urticaria Angioedema Breathing problems
how to we treat an anaphylatic shock
Treatment of anaphylactic shock :
epinephrine (adrenaline) IM
• Reverses peripheral vasodilation and reduces oedema
and alleviates hypotension
- Reverses airway obstruction / bronchospasm
- Increases the force of myocardial contraction
- Inhibits mast cell activation
DO NOT DELAY TREATMENT!!!!
Monitor pulse, blood pressure, ECG, oximetry
Timesaver vs lifesaver
• IM vs SC administration
• Multiple doses may be required - you probs wanna give 2 dose minimum
• Proper use of epipen
type 1 hypersentiviy reactions are immediate - dont need a first exposure - as its IgE dont need to produce IgM
bonus - key point thou fam
Type I hypersensitivity:
therapy
• Abnormal adaptive immune response against the allergens
o TH2 response = do Allergen desensitization (oral
immunotherapy) - eat little bits ect
o IgE = give Anti-IgE monoclonal antibody
• Mast cell activation
o Anti-histamine - stops histamines response of vasdo dilation ect
o Leukotriene receptor antagonists
o Corticosteroids - anti inflammatory
Allergen desensitization or
immunotherapy
“It involves the administration of increasing doses of allergen extracts over a period of years, given to patients by injection or drops/tablets under the tongue (sublingual)”
90% effective in patients with bee and wasp venom anaphylaxis
Potential mechanisms • CD4+CD25 Regulatory T cells • Shift from TH2 to TH1 • Inhibitory anti-inflammatory cytokines • Allergen specific blocking IgG
