Asthma and allergy Flashcards
1
Q
What are the different types of hypersensitivity reactions?
A
- Type 1 = immediate hypersensitivity (acute allergy)
- Type 2 = Cytotoxic hypersensitivity
- Type 3 = Serum sickness and Arthus reaction
- Type 4 = delayed-type hypersensitivity, contact dermatitis
2
Q
Describe type 1 hypersensitivity
A
- Interaction between specific IgE and allergen
- Mast cells have specific IgE, allergen cross-links the IgE, causing mast cell activation and degranulation
- e.g. allergic rhinitis, asthma and anaphylaxis
3
Q
How can you test if someone is allergic to a substance?
A
- Skin prick test
- if mast cells have the specific IgE, it will recognise the allergen that you have pricked in the skin and produce a wheal response
4
Q
Describe a type II hypersensitivity
A
- Cytotoxic hypersensitivity
- IgG anti-drug antibodies
- Drug binds to RBC
- IgG binds to the drug
- Antibody-bound cells are cleared by cells such as macrophages and complement
- e.g. Some drug allergies such as penicillin
- Also special cases where IgG Abs are directed at cell-surface receptors; disrupting the normal functions of the receptor by uncontrollable activation or blocking receptor function
5
Q
Give an example of a type II reaction
A
- Graves - Ab recognises TSH receptor, induces production of thyroxine -> thyrotoxicosis
Myasthenia gravis - immune response reacts to Ach receptor, blocking synaptic transmission causing a type of paralysis
Haemolytic disease of the newborn
6
Q
What is haemolytic disease of the newborn?
A
- Caused by rhesus incompatibility
- During birth, rhesus +ve foetal erythrocytes leak into maternal blood after breakage of the embryonic chorion
- Maternal B cells are activated by the Rh antigen and produce large amounts of anti-Rh antibodies
- Rh antibody titre in mother’s blood is elevated after first exposure
- Rh antibodies are small enough to cross the chorion and attack foetal erythrocytes
7
Q
Describe a Type III reaction
A
- IgG and soluble antigen form immune complexes
- Immune complexes are cleared by phagocytosis/ complement
- e.g. Arthus reaction and serum sickness
8
Q
How does Arthus reaction occur?
A
- Locally injected antigen in immune individual forms immune complex with IgG antibody
- These bind to Fc receptors on mast cells, activating them and releasing inflammatory mediators
- Inflammatory cells invade the site, and blood vessel permeability and blood flow are increased
- Platelets also accumulate, leading to occlusion of the small blood vessels, haemorrhage and the appearance of purpura
9
Q
What is serum sickness?
A
- Caused by large IV dose of soluble antigens (drugs)
- IgG antibodies produced form small immune complexes with the antigen in excess
- Immune complexes get deposited in tissues/ blood vessel walls
- Tissue damage is caused by complement activation and subsequent inflammatory responses
10
Q
What is farmer’s lung?
A
- Farmers can become sensitised to moulds in the hay
- They inhale it and form complexes in the lung
- This can lead to severe pathology over many years
11
Q
What determines the pathology observed in type III hypersensitivity reactions?
A
- Antigen dose and route of delivery determine the pathology
- IV = vasculitis (vessel walls), nephritis (renal glomeruli), arthritis (joint spaces)
- Subcutaneous = arthus reaction (perivascular area)
- Inhaled = farmer’s lung (alveolar/ capillary interface)
12
Q
Describe type IV reactions
A
- Delayed-type hypersensitivity
- Antigen either acts on Th1 or Th2 cells
- Th1 when bound releases IFN-gamma, which activates macrophages, causing the release of chemokines, cytokines and cytotoxins - e.g. contact dermatitis
- Th2 releases IL-4,5 and eotaxin, which activate eosinophils, causing the release of proteins, enzymes and cytokines - e.g. chronic asthma, chronic allergic rhinitis
13
Q
What is IgE?
A
- Originally the first line of defence against worms - however we dont have them now so we react to things in the environment we wouldnt usually react to
- Binds to the Fc receptors on mast cells
- It pre-arms the mast cells to react when in the presence of antigen
14
Q
What is the hygiene hypothesis?
A
We live so cleanly these days that we arent exposed to enough dirt to combat allergens
15
Q
How does filaggrin?
A
- Filaggrin links skin integrity and allergen
- When it is defective, atopic dermatitis is greater
- This is due to the access of allergens
16
Q
What makes dendritic cells pro-allergenic?
A
- Langerhans are dendritic cells (APCs)
- When the skin is damaged, cytokine production is increased
- These langerhans go to the lymph nodes to present the antigens to Th2 cells
17
Q
What is the effector mechanism of the allergic immune response?
A
- We become sensitised after exposure to pollen
- Th2 cells release IL-4, which drives B cells to produce IgE in response to pollen antigens
- Pollen specific IgE binds to mast cells, priming them
- Second exposure to pollen
- mast cells are activated and release their inflammatory mediators -> allergic rhinitis
- Also IL-4 acts on eosinophils and IL-5 acts in mast cells - these cause chronic allergic reaction
18
Q
What causes the wheal and flare responses?
A
- Allergic responses have an early (wheal) and late phase (flare)
- Early is mediated by mast cells - allergen exposure triggers degranulation
- Late is mediated by T cells - activated T cells, eosinophils and basophils go to the site of allergen exposure
19
Q
What do each of the specific mediators produced by mast cells do?
A
- Histamine = increase vascular permeability and cause smooth muscle contraction
- Leukotrienes = increase vascular permeability, cause smooth muscle contraction and stimulates mucus secretion
- PGs = chemoattractants for T cells, eosinophils and basophils
- Cytokines - IL-4/13 = promotes Th2 and IgE formation. TNFa = promotes tissue inflammation
20
Q
What does mast cell activation and granule release do to different areas of the body?
A
- GIT = increased fluid secretion, increased peristalsis -> expulsion of GI contents (diarrhoea and vomiting)
- Airways = decreased diameter, increased mucus secretion -> congestion and blocking of airways, swelling and mucus secretion in nasal passages
- Blood vessels = increased blood flow and permeability -> increased fluid in tissue causing increased flow to lymph, increased cells and protein in tissues, and increased effector response in tissues.
21
Q
What are the two effector functions of eosinophils?
A
- Release highly toxic granule proteins and free radicals upon activation -> kill MOs/ parasites and cause tissue damage in allergic reactions
- Synthesise and release PGs, LTs and cytokines in order to amplify the inflammatory response by activating epithelial cells and recruiting lymphocytes
22
Q
What is allergic asthma?
A
- Asthma brought on be allergic reaction to: pollen, plants, some foods etc
23
Q
What causes the acute response in allergic asthma?
A
- Occurs within seconds of allergen exposure
- Results in airway obstruction and breathing difficulties
- Caused by allergen-induced mast cell degranulation in the submucosa of the airways
24
Q
What causes the chronic response in allergic asthma?
A
- Chronic inflammation of the airways
- Caused by activation of eosinophils, neutrophils, T cells and other leukocytes
- Mediators released by these cells cause airway remodelling, permanent narrowing of the airways and further tissue damage
25
Q
How do we treat allergy in the clinic?
A
- Blockage of effector pathways:
- Inhibit effects of mediators on specific receptors (anti-histamines)
- Inhibit mast cell degranulation (NSAID)
- Inhibit synthesis of specific mediators (lipoxygenase inhibitors)
- Steroids - act on DNA to increase transcription of anti-inflammatory mediators (IL-10) and decrease transcription of pro-inflammatory mediators
- B2 agonists
- Immunotherapy - reverses the sensitisation to allergen
