CP10 - Allergy Flashcards
what is allergy/hypersensitivity?
undesirable, damaging, discomfort producing and sometimes fatal reactions produced by the normal immune system directed against innocuous antigens in a pre-sensitised host.
what does atopic mean?
allergic
what does innocuous mean?
not harmful
which types of hypersensitivity are most commonly observed in a clinical context?
types I and IV
which types of hypersensitivity are mediated by antibodies?
I, II, III
which types of hypersensitivity are cell mediated?
IV
what is the immunopathology of type I hypersensitivity?
- processed by APC
- presented to T cells
- t cell activation to form Th1,2,17 or Treg (in allergies, thought to only activate the
- the cells generate IL4
- IL4 stimulates B cells to produce IgE
- IgE binds to the allergen
- next time, IgE is already in the system bound to the receptors on sensitised mast cells
- binding of allergen to IgE causes cross linking
- sends the signal to mast cells to release mediators eg. histamine
- 2,d stage is regulated by the arachidonic acid pathway which produces leukotrienes and prostaglandins (late phase)
what are the clinical features oh type I hypersensitivity?
fast onset - 15-30 mins
called wheal and flare, but short lived
what is the immunopathogenesis of type II hypersensitivity?
IgG/IgM response against self or foreign antigen that has adhered to the cell surface (solid medium) , leading to complement activation and phagocytosis or ADCC (antibody dependent cell-mediated cytotoxicity)
what are the clinical features of type II hypersensitivity?
slightly delayed onset - minutes to hours. causes cell lysis and necrosis
which antigen commonly causes type II hypersensitivity?
penecillin
which diseases are associated with type II hypersensitivity?
- Erythroblastosis fetalis - difference in Rh between mum and fetes sensitises her in the first pregnancy and in the second pregnancy, if there is a difference too, her body will react
- Goodpasture’s nephritis
what is the immunopathogenesis of type III hypersensitivity?
IgG/IgM against soluble antigen, not bound to cell leads to formation of immune complexes, which are unable to pass into small blood vessels, causing vasculitis and cell damage in that area
what are the clinical features of type III hypersensitivity?
delayed onset of 3-8 hours, causes vasculitis
what are the common triggers of type III hypersensitivity?
serum sickness, when they injected horse serum as protection from tetanus
which autoimmune condition is associated with type III hypersensitivity?
Systemic Lupus Erythematosus (SLE)
what is the immunopathophysiology of type IV hypersensitivity reactions?
no antibodies involved. APC presents antigen to T cells which develop defences against the antigen and learn to recognise it in later stages
what are the clinical features of a type IV hypersensitivity reaction?
delayed response, 48-72h
erythema induration
which antigens can trigger a type IV hypersensitivity reaction?
metals eg. nickel, causing a tuberculin reaction
which condition is associated with type IV hypersensitivity?
contact dermatitis - reaction caused due to patch testing carried out by dermatologists
how does genetics affect allergies?
- at the level of sensing allergens
- poor barriers (SPINK5 for eczema)
- immune response
- tissue response
are allergies genetic or environmental disorders?
multifactorial, genetics only increases susceptibility
which organs respond to allergens?
- eye - allergic conjunctivitis
- nose - allergic rhinitis
- mouth - oral allergy syndrome
- airways - allergic asthma
- skin - atopic dermatitis
- GI tract - food allergy
what was the initial function of IgE in our body?
to fight parasitic infections
why does our body exhibit severe symptoms when faced with a parasitic infection?
D&V to quickly get rid of an organism that would have otherwise been difficult to remove from the body
what is thought to increase the prevalence of allergies?
less infectious drive
how does parasitic disease impact blood?
- eosinophilia
- mastocytosis - abnormal increase of mast cells in multiple organs
- basophil infiltration
- tissue inflammation
- secretion of IL4, IL5, IL13, by CD4 t cells
what is the hygiene hypothesis?
stimulation of the immune system by microbes is protective. competition between allergens and infectious agent and the absence of infectious agents is thought to make allergies more predominant
which types of t helper cells manage which conditions?
th1 - infections
th2 - allergies
what is immunoregulation?
a method by which the body controls the response of the immunee system and prevents it from doing too much damage
what are allergens?
antigens that initiate an IgE mediated response. the first encounter leads to sensitisation rather than an actual response
what is the role of the th2 cell?
- releases multiple cytokines which activate other cells
- activates innatee cells eg. macrophages via cytokines
- supports b cells to produce IgE
what is the atopic triad?
a triad of 3 commonly seen conditions -
- asthma - type I
- Rhinitis - type I
- Eczema - type IV
what happens in asthma and rhinitis?
allergens cause irritation in the mast cells within the nasal mucosa and airway epithelium
what are the 2 types of rhinitis?
- allergic
i. perennial
ii. seasonal
depending on the occurrence of allergens - non-allergic
what is the clinical presentation of allergic rhinitis?
blocked nose
runny nose
often eye symptoms
what are the triggers of allergic rhinitis?
house dust mites
animal danders
pollens
how is allergic rhinitis treated?
antihistamines
nasal steroids
what is the clinical presentation of asthma?
bronchoconstriction of airways due to hyper-reactive response to allergic stimuli
what are the triggers to asthma?
similar to allergic rhinitis, but house dust mite is key
what is the clinical presentation of dermatitis?
intense itching, blistering, cracking of skin
clue is in the history
why does the itching cause a vicious cycle in dermatitis?
development of th2 cells stimulates the release of IL31 (t cell derived itch-mediator), which makes one want to scratch, causing barrier disruption
what are the types of dermatitis?
- atopic - idiopathic, commonly eczema
- contact
a. allergic - type IV
b. non-allergic - irritant
what is anaphylaxis?
acute potentially life threatening, IgE mediated systemic hypersensitivity reaction. it is a multi systemic syndrome, with an immediate onset.
how is allergy diagnosed in clinics?
- history - important to gauge time relation between exposure and onset of symptoms
- specific IgE levels measuring >0.35 signifies allergy, but patient may be tolerant to substances with a higher IgE count too
- skin prick tests
- intradermal tests
- oral challenge test
- basophil activation test
what happens in an intradermal test?
going deeper into the skin. high sensitivity, low specificity
what is an oral challenge test?
gold standard, if skin prick and intradermal are inconclusive. give increasing concentrations of the substance to patients and check for a reaction
what are the advantages of a specific IgE test?
safe
what are the advantages of a skin prick test?
quick
satisfies the patient
