Allergic Disease 1 + 2 (5/02) Flashcards
1
Q
LO’s
A
- Describe the role of histamine in the inflammatory process
- Describe the terms allergy, atopy, anaphylaxis
- Describe with clinical examples the basis of the cellular mechanisms underlying types I, II, III and IV hypersensitivity reactions
- Describe the differences between allergy and intolerance
- Describe the causes of anaphylaxis
- Describe the emergency management of anaphylaxis
- Describe the treatments available for allergic disease
- Describe the techniques used in the investigation of allergic disease
2
Q
What is the function of the immune system?
A
- To defend against infections.
- Surveillance of damaged/old/malignant cells.
3
Q
What is an allergy?
A
- A hypersensitivity reaction, triggered by an immune response.
4
Q
Define Allergen?
A
- An antigen that causes an immune reaction.
- Must be able to gain entry or contact with the body.
- Small molecules can diffuse into the skin.
- Mediated through degranulation of mast cells and eosinophils.
- Rapid onset: minutes.
- EG: bee sting, posionous plants, pollen, medication, nuts and latex.
5
Q
What is hypersensitivity?
A
- An allergy is a type of hypersensitivity reaction.
- When exposure to a stimulus causes reproducible symptoms. Exposure to this does of the stimulus has no effect on normal people.
- It can happen in response to bacteria, allergens in the enviroment or self antigens.
- Hypersensitivity is classified according to the pathway of immune response it causes → Gell and Coombs Classification.
6
Q
How is hypersensitivity classified?
A
- By the Gell and Coombs classification.
- Type 1 involves the degranulation of mast cells (early phase) and eosinophils (late phase) come to site of infection. release more cytokines and cause tissue damage.
- Type 2 involves the interaction of IgG with Antigens present on a cell surface, the Ig then interacts with macrophages or complement eg drug induces haemolysis.
- Type 3 involves the formation of an immune complex between IgG and Ag, which then is deposited and causes tissue damage.
7
Q
Describe T1 Hypersensitivity
A
- Two components: early and late phases
- Early Phase
- An allergen is phagotisosed by a dendritic cell.
- The dendritic cell presents the antigens to a T cell.
- The T cell causes a Th2 cell to releases cytokines IL4, IL5, IL13.
- The IL cause a B cell to release the antigen specific antibody (IgE).
- Mast cells and eosinophils express receptors for IgE. The IgE antibodies are placed on them. The allegen/antigen attatch to the antibodies (two antibdies for one allegen) and cause mast cell degranulation.
- This releases prostaglandins and leukotrienes which increase vascular permeability and vasodilation.
- The local symptoms: changes are restricted to site of allergen entry. For example, if allergen inhaled, like pollen, the get rhinitic (inflammation of the nose’s mucase membrane) causing a runny nose and sneezing. Leukotrienes also cause increased mucus secretion. If have asthma, leukotrienes cause smooth muscle constriction, so airway obstruction too.
- The systematic symptoms: BP drop and angiodema (skin).
- Late phase: chemokines released in the early stage recruit leukocytes esp eosinophils to the site of reaction. These further release of cytokines and mediators causing tissue damage. Can lead to chronic inflammation.
8
Q
What is uticaria?
A
- Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps.
9
Q
What is angiodema?
A
- Swelling of the skin.
- Hives are itchy and only involve the top layer of skin, whereas angiodema involes deeper layers.
10
Q
Describe histamine?
A
- Predominantly produced by mast cells
- Stored in granules
- Bind to H1, H2, H3 or H4 receptors on target cells
- H1: increased vascular permeability, smooth muscle contraction, mucus production, increased heart rate, leukocyte chemotaxis (signalls for lekocytes).
- Other mediators include enzymes like tryptase – elevated levels can be detected in anaphylaxis???
11
Q
What is Atopy?
A
- Atopy refers to the genetic tendency to develop allergic diseases, because these individuals produce IgE in response to low doses of allergens.
- 20-30% of the population have this tendancy.
- Includes: atopic asthma, allergic rhinitis and atopic dermatitis and IgE-mediated food allergies.
- All caused by a hypersensitivity to certain stimuli.
- People who are atopic produce IgE in response to low doses of allergens.
12
Q
Describe the Atopic March
A
- Often, people have different types of allergy at different times in their lives.
- Eczema can be present from birth.
- Food allergies tend to appear from 2y.
- Rhinitis (hayfever) tends to appear from 3y.
- Asthma tends to appear from 7y.
13
Q
Describe type 2 hypersensitivity?
A
- This happens in some drug allergies, like penicillin.
- In T2H the allergen is already bound to a cell.
- For example, penicillin can act as a hapten (small antigen) and stimulates IgG production. This is the sensitisation process,
- On re-exposure to penicillin, IgG, binds to penicillin, which is bound to RBCs.
- This causes drug-induced haemolysis
- The IgG/antigen complex causes macrophages, complement and NK cells to be activated, and cause inflammation.
14
Q
Describe type 3 hypersensitivity?
A
- Sensitisation to an allergen happens, so the allergen specific IgG antibody is produced.
- IgG binds to antigen in circulation.
- Can cause damage at the site of production or circulate and cause damage elsewhere.
- EG: Poststreptococcal glomerulonephritis (kidney disease that develops 10 to 14 days after a skin or throat infection).
- In PSGN IgG antibodies become trapped in the filters of the kidneys called the glomerulus. This causes inflammation, which slows down the filters of the kidneys, making it harder for them to make urine and get rid of the waste.
15
Q
Describe type 4 hypersensitivity?
A
- Sensitisation happens (see allergic contact dermatitis to nickel).
- Antigen interacts with antigen-specific T lymphocytes – stimulates a Th1 response →IFNγ – activates macrophages
- T-cells and macrophages release inflammatory and cytotoxic substances (TNF)
- These attract other white blood cells and result in inflammation and tissue injury.
