L4 - Hypersensitivity Flashcards
What 3 diseases contribute to the atopic triad?
Rhinitis
Asthma
Atopic Dermatitis
What does skin prick testing diagnose?
allergies
What do you measure in a skin prick test?
Size of weal - measurement of allergen specific IgE
What is dual allergen exposure hypothesis?
- Tolerance occurs in babies through high dose of oral exposure.
- Allergy occurs through low dose cutaneous exposure e.g disrupted skin barrier.
What physiological effects does Histamine have?
- blood clots
- gastric acid secretion
- vasodilation
- bronchoconstriction
- increased permeability of capillaries
- release of adrenaline
- swelling and inflammation
- inc in heart rate
What 3 ways does the complement system destroy pathogens?
Opsonisation
Membrane Attack Complex (MAC)
Enhancing inflammatory process
Which complement protein causes opsonisation and initiates formation of MAC?
C3b
Which complement protein is a chemotactic agent which enhances the inflammatory process?
C3a
Describe Type 1 Hypersensitivity?
- IgE
- mast cell and basophil degranulation
- release of preformed and de novo inflammatory mediators
- rapid onset
- weal and flare
- late phase response mediated by eosinophils and Th2 T cell
What is the primary response of allergen exposure in Type 1 hypersensitivity?
Release of preformed mediators:
- Histamine
- Proteases
- Chemotactic factors (induce inflammatory cell infiltration)
What is the secondary response/late phase of allergen exposure in Type 1 hypersensitivity?
Release of newly formed mediators:
- Prostaglandin
(platelet activating factor/prolonged airway hyperactivity) - Leukotrienes
(chemoattractant, sustained bronchoconstriction and oedema)
What is the secondary/late phase response of type 1 hypersensitivity mediated by?
- Th2 Cells
- recruitment of eosinophils
Describe Anaphylaxis?
- medical emergency
- rapid onset
- severe type 1
NB: to provoke anaphylaxis the allergen must be systemically absorbed (ingestion/injection)
Describe Type 2 hypersensitivity?
- cytotoxic
- antibodies attach to cell bound antigen/self structures (autoantibodies)
- triggered by endogenous antigens
- IgG/IgM
- happens at cell surface
- cell lysis and necrosis
Example of diseases resulting in type 2 hypersensitivity?
- good pastures nephritis
- blood transfusion reaction
Describe Type 3 Hypersensitivity?
- immune complex
- IgG/IgM against soluble antigen
- onset 3-8 hours
- cause: serum sickness
- feature: vasculitis
Disease associated withy Type 3 hypersensitivity?
SLE
Systemic Lupus Erythematus
- widespread inflammation of connective tissues in organs aggravated by sunlight
- antibody recognises DNA/self as foreign = colonial B expansion
- small immune complexes result, stick to blood vessel wall, C1-9 binds = increased permeability of vessels
= Fluid leaks out (oedema).
Describe type 4 hypersensitivity?
- interaction between activated sensitised CD4+ and CD8+
- delayed onset 48-72h
- erythema induration
Diseases associated with Type 4 Hypersensitivity?
contact dermatitis
Describe type 5 hypersensitivity?
Type 5 is a subtype of type 2 - instead of the antibodies acting against cell surface components, antibodies act against cell receptors.
which type of sensitivity is mediated by IgG/IgM antibodies?
- type 2 (cytotoxic)
- type 3 (immune complex)
which type of sensitivity is described as cytotoxic?
type 2
which type of sensitivity is described as anaphylactic?
type 1
which type of sensitivity is described as a immune complex?
type 3
which type of sensitivity is described as delayed?
type 4
Which type of sensitivity has an exogenous antigen involved?
type 1
Which type of sensitivity has an cell surface antigen involved?
type 2
Which type of sensitivity has a soluble antigen involved?
type 3
Which type of hypersensitivity involves weal and flare and mast cell degranulation?
Type 1
Which type of hypersensitivity involves lysis and necrosis?
type 2
what is hypersensitivity?
a normal immune response directed against innocuous antigens in a presensitised host
- undesirable
- damaging
- uncomfortable
- fatal
what does innocuous mean?
not harmful or offensive
how would mild anaphylaxis present?
- itchy eyes or nose
- cutaneous pruritus
- flushing
- urticaria
- oral tingling/pruritus
- abdo pain/nausea/vomiting
- runny nose, sneezing
how would moderate-severe anaphylaxis present?
- Diffuse urticaria and angioedema
- Severe abdominal pain, vomiting diarrhoea
- Hoarseness, cough
- SOB
- Wheezing and cyanosis
- Hypotension
- Dizziness, loss of consciousness
how are we sensitised to allergens?
for example breathed in allergen or its gained access via a break in the skin
- picked up by APC cells (e.g. dendritic cell)
- APC presents it to naive T cell in the lymph nodes
- exposure to allergen and IL-4 causes naive T cell to differentiate into Th2 cell
- Th2 cell releases more IL-4 and IL-13 which causes B cells to undergo class switching to IgE
= memory B cells with IgE to that allergen
what is meant by a naive T cell?
not seen a particular antigen before
which cytokines push naive T cells to differentiate into Th2 cells?
IL 4
which cytokines are produced by Th2 cells to push B cells to undergo class switching?
IL-4
IL-13
can you inherit allergies?
- no
- allergies are polygenic diseases
- not sufficient for disease only susceptibility
what is the highest food allergy prevalence in infants?
milk
what is the highest food allergy prevalence in adults?
shellfish
features of rhinitis
- allergic/non allergic
- can be perennial or seasonal
- treatment: nasal steroids and antihistamines
- symptoms incl blocked nose, runny nose
features of asthma
- inflammation and hyperactivity of the small airways
- immediate symptoms are IgE mediated
- damage to airways due to late phase response
what does MAC (membrane attack complex) result in?
focused target cell lysis
what does the complement protein C3b do?
opsonises (make more susceptible to phagocytes) immune complexes for waste disposal
what is the difference between type 2 and type 3 hypersensitivity?
type 2: anybody against an antigen attached to a cell (not an immune complex)
type 3: antibody attached to free antigen/floating about/soluble (immune complex)
which complement system proteins are anaphylatoxins?
C5a
C4a
C3a
increase vascular permeability
Name 3 chemical mediators produced by a mast cell.
- Histamine
- Proteases
- Chemotactic factors
