Hypersensitivity Reactions and Allergic Disease Flashcards
What is an allergic disease?
The immune system reacting to non-harmful stimuli such as pollen or food.
What would increase your chances of getting an allergy?
Genetics
Environment
What is atopic march?
different types of allergies throughout your life
How many types of allergies is there and what causes them?
Type 1 - IgE mediated (immediate) hypersensitivity caused by mast cells, eosinophils and basophils and are involved in pollen, drug and food allergies.
Type 2 - IgG, IgA or IgM mediated involving complement phagocytes and is involved in autoimmune haemolytic anaemia.
Type 3 - Immune complex involving complement neutrophils involved in lupus.
Type 4 - cell mediated delyate hypersensitivity involving macrophages for things such as nickel and poison ivy.
Where can allergic disease come from?
inhalation, injection, eaten
When can you get a type 1 allergy?
Seasonal, continous, occasional
Describe how dust mite allergies occur?
The protease Derp1 is present in the pellets of mite faeces. These enter the cell by digesting occludin which maintains tight junctions. Once in the body dendritic cells uptake them and show them to the T-cells. These make IL-4 causing a class switch to IgE antibody.
This means the next time the body see dust mites there will be memory cells with the antigen known and therefore a quicker response.
What do antibodies normally only bind to?
Fc receptors
Why is IgE mediated allergy immediate after sensitisation?
IgE can bind FceR1 without an antigen to react.
Few IgE molecules need to bind to the IgE Fc-receptors for cross linking to make mast cells degranulate
Mast cell granules have preformed mediators for quick release
What causes the symptoms of allergies?
Mast cell release or basophils as these both have histamine
When is an allergy more severe?
If ingested or type 4 mast cell mediators cause symptoms
What are the routes of allergy and what do these cause?
Intravenous - IgE coated mast cells enters blood capillary causing anaphylaxis
Subcutaneous - IgE coated cells are in the epidermus causing wheal and flare
Inhalation - IgE coated cells in the lungs causing asthma
Ingestion - IgR coated cells in gut causing vomiting, diarrhea and anaphylaxis.
Describe the symptoms of anaphyclactic shock?
These can occur quickly after eating.
Include watery, red eyes, vomiting, diarrhoea, wheezing, shortness of breath, swollen tonguye and lips, rash, airway narrowing, difficulty swallowing, dizziness and a drop in blood pressure which can be fatal.
What can cause anaphylaxis and what can cause allergies but not anaphylaxis?
Shellfish, peanuts, penicillin, bees, wasps, latex, venom
Pollen, animal dander
How do you test for allergies?
Skin prick - insert histamine as a positive control and possible allergins under the skin and wait a 5 - 10 minutes to see if a lump (reaction forms) - if yes then there is an allergy, if no then no allergy.
Why do the symptoms wheal and flare arise?
These come from the mast cells secreting histamine which cause blood vessels to vasodilate and swell due to leakage of plasma into blood vessels.
How do you treat allergies?
Anti-histamines - reduces the histamine produced by the body.
Avoidance
Beta-2-adrenergic agonists - prevents asthma and bronchial contraction.
Epinephrine - stimulates alpha and beta adrenergic receptors to decrease vascular permeability which increases blood pressure and stops airway obstruction.
what are some ways you would use immunotherapy to desensitise someone from allergies?
Shots of allergin in a monitored environment to stimule Tregs, produce IL-10, reduce Th2 levles, reduce IL-4, reduce IgE and increase some IgG secretions.
Delivery pollen through the mouth which doesnt really contain mast cells, iduece Tregs, secrete IL-10, reduce Th2, reduce IgE, leading to reduced allergy.
Biologics can also interfere with Th2 pathway, and IgE binding to FceR1 receptor.
What is type 2 hypersensitivity and what can this cause or be found in?
Consequence of immunoglobin (IgG) or IgM binding to cell surface antigens which causes immune related haemolysis and activation of complement.
Antibodies can opsonise cells causing HDN or blood transfusion rejection. You can also get this is solid tumours.
Descirbe type 2 hypersensitivity - penicillan allergy?
When taken penicillin is can act as a haptin which allows for recognition of antigen and Ab production. In subsequent exposures the RBC will be opsonised and destroyed in the spleen.
What is type 3 hypersensitivity?
IgG bind antigens to make an immune complex
Type 3 hypersensitivity - describe farmers lung?
IgG antibodies are made against the proteins found in mould in the hay. Immune complexes form in the lung and after several hours this causes inflammation in the alveoli.
Can be treated by wearing masks.
What is type 4 hypersensitivity?
A delayed response response mediated by T-cells
What compounds are involved in a type 4 hypersensitivity response?
Th1, Th17, Macrophages are activated. CTL (CD8+ cytotoxic T cells). There is a delayed response because T cells take time to develop.
What is type 5 hypersensitivity?
Specific for cell surface receptors for hormone or neurotransmitter to interfere with physiology.
Desribe the development of Graves disease?
Pituitary gland secrete TSH encouraging the thyroid to secrete thyroid hormones. Autoimmune B cells make antibodies against the TSH receptor increasing the thyroid hormone in the body as there is normally a feedback loop keeping thyroid hormone in check
Symptoms of Graves disease?
Goitre, bulging eyes etc.
Can hypersensitive diseases have features of more than one type?
Yes