W31 Allergy and Hypersensitivity Flashcards
What is hypersensitivity?
- An exaggerated response of the immune system to ‘foreign’ antigen causing tissue damage
- Damage is mediated by the same attack mechanisms that mediate normal immune responses to pathogens
- Mediated by the Adaptive Immune System
- Not seen on 1st contact with antigen but appears on subsequent exposure – “senitisation” step
-Allergy and hypersensitivity are used interchangeably
What are the 4 groups pf hypersensitivity?
Type I: Immediate, IgE monomers, Anaphylaxis
Type II: Cytotoxic, IgG/IgM monomers, Drug-induced haemolysis
Type III: Immune Complex, IgG/IgM complexes,
Serum sickness
Type IV: Delayed, T-cells, Contact dermatitis
1960s – still used (although probably now a simplification)
Type 1 hypersensitivity:
What are the names for this? (2)
Which antigen mediates this?
What are the associated conditions?
- Also called Immediate or Anaphylactic
- IgE mediated
- Immune cell: Mast Cell
- Release mediators such as histamine and
leukotrienes
-Inflammatory response - Hay fever
- Allergic asthma
- Allergic rhinitis
- Atopic dermatitis (eczema)
- Urticaria
- Anaphylaxis
Type 1: phases
Type 1: phases
1. Sensitization
* Antigen contact,
* Often low-dose via mucous membranes
(respiratory, GI)
* Primary IgE production
2. Elicitation (Re-exposure)
* Pre-formed IgE (allergen-specific) triggers mast
cell activation
* Mediator release immediate (mast cell
degranulation) and then early and late-phase
synthesis of other inflammatory mediators
House dust mite / fecal pellets
(bottom left)
Pollen grains (top left)
Roitt’s essential immunology
Delves, Peter J. ; Roitt, Ivan M. (Ivan Maurice).
2011 ; 12th ed.
Hypersensitivity: Sensitisation
What are the steps?
What is secreted?
- Antigen (allergen) is presented on dendritic cells
- This Activates helper T cells
- T helper cells secrete Th2 cytokines
- Activates B-cells
-B-cells differentiate into plasma cells to produce IgE
-Plasma cell – secretes antibodies: IgE (driven by Th2 cytokines)
* Memory B and T cells also formed
- IgE immediately binds to their Fc receptor on
mast cells
-These are Granulocyte / which can release
mediators eg histamine
-IgE remains bound to mast cell (stays there + persists) - May be no symptoms during sensitisation
phase (as mast cells may not degranulate-release histamine)
Why is a type of cell called Helper T cells? (for info)
They can promote subsequent immune responses
Can differentiate into either B cells or Cytotoxic T cells
Mast cell degranulation (effector phase)
What is the process?
- Re-exposure to allergen
– Allergen binds to IgE on mast cell
– Cross linking IgE receptor
– Causes mast cells to degranulate
– Release of histamine and other inflammatory mediators - IMMEDIATE – EARLY PHASE (MINUTES)
- Histamine
- Other chemokines / cytokines
-Leukotrienes, prostaglandins - LATE PHASE (HOURS LATER)
-Other inflammatory mediators
-Often stimulated by early phase
-Eg attraction of eosinophils
Type 1:
Early and late phase
When you are first exposed to an antigen (after a skin-prick test or an injection)
- Wheal-and-flare reaction
- (lasts up to 30 min post injection)
- Raised, red and itchy
Late-phase reaction
* (develops approximately eight hours later and persists several hours)
* Painful lump
What is Allergic Rhinitis?
- Nearly 10% of the population suffer from allergies involving localized
- IgE-mediated anaphylactic reactions
- Most common manifestation is allergic rhinitis – hayfever
- Target organs: mucus membranes of the nose and eyes
- Congestion, itchiness and sneezing
- eyes red and watery
What is Atopy?
- Individuals said to be atopic
- Atopy: clinical presentation of Type I
hypersensitivity
-Usually occur in individuals with family history
-Show immediate wheal-flare skin reactions to the intradermal injection of common environmental allergens
-Raised level of serum IgE an atopic individual
=although a normal IgE serum level does not exclude atopy - Effects of IgE mediated allergic reactions vary with the site of mast cell activation
What medications are given for allergic rhinitis?
- Chromoglycate / Nedocromil –
-inhalational products (asthma)
-mast cell stabilisers - Leukotriene receptor antagonists (asthma)
-Singulair® / Monteleukast, Accolate® - Antihistamines (H1 receptor)
- Steroids
Sodium cromoglicate function: (Opticrom eyedrops) - for info
cromoglycate- mast cell stabilisers
- Works by stabilising the membrane of mast cells and stops mast cells degranulating (thus releasing their stored chemicals such as histamine) in response to allergens
- By stabilizing mast cells, sodium cromoglicate prevents or reduces the release of inflammatory substances, which helps to prevent allergic symptoms such as itching, swelling, and redness
Type II sensitivity:
What are the names for this?
What are the mechanisms?
Also called “Cytotoxic” or “cytolytic” hypersensitivity
* An appropriate immune reponse to antigen
* But where antigen is inappropriately situated
* Damage caused by specific IgG or IgM
Mechanisms
* Complement-mediated cytolysis (CMC)
* Antibody-dependent cell mediated cytotoxicity
(ADCC)
What is Complement-mediated cytolysis (CMC)?
- Antibodies (IgM and IgG) can bind to target cells and activate C1 from the Classical Complement pathway.
- causing target cell destruction by direct membrane damage
What is Antibody-dependent cell mediated cytotoxicity (ADCC)?
What are examples of effector cells? (3)
- Antibodies (host IgG or IgM) bind to target cells and direct effector cells via Fc receptors (opsonise cells).
- Effector cells –
- Phagocytic cells macrophages, neutrophils, eosinophils,
- Non phagocytic cells – Natural Killer (NK) cells
- Cells removed by phagocytes or killed by NK cells
