Hypersensitivity and Autoimmunity Flashcards
(41 cards)
What is the lifespan of a neutrophil?
1-2 days
What is hypersensitivity and what are the four types which exist?
Hypersensitivity is an unwanted immune response.
It can be caused by infection, environmental substances, self-antigens.
Broadly, what are the hypersensitivity reactions?
II, III, IV - diseases characteristic of autoimmune disease.
What are allergens?
- Antigens which cause allergy are called allergens.
- They are small proteins
- There is no clear feature shared by all allergens but many are a specific type of enzyme called a protease.
- Exposure is generally through inhalation, ingestion or administered as drugs.
- Most allergens promote a Th2 immune response.
What are the characteristics of a type 1 hypersensitivity reaction?
IgE & The Mast Cell
What is Allergy and Atopy?
- Allergy only occurs as a result of repeated exposure to an allergen which generates an IgE mediated immune response.
- Atopy is the term used to describe a predisposition for an IgE mediated immune response.
How does IgE bind to mast cells?
- IgE binds to mast cells via the IgE receptor (FceR1)
- IgE not the most abundant antibody, but performed and loaded onto Mast cell makes this a really potent response (pre loaded, increases the half-life of IgE)
What is the mechanism of allergy?
- Cross-linking of two IgE molecules on the surface of mast cells results in granule release and the release of mediators of inflammation.
- Immediate reaction
- Late reaction
- Mediators of inflammation: Histamine, herparin and tripdase
The mast cells don’t stop there - they are capable of stimulating leukotrienes and producing cytokines
What is immediate I hypersensitivity reaction?
Characterised by release of mast cell mediators:
Histamine:
- Causes smooth muscle contraction of lungs, gut and blood vessels promoting oedema:
- Acts as chemoattractant to other WBCs - particularly neutrophils and eosinophils.
- Causes skin itching.
Cytokines:
- Pro-inflammatory induce inflammation (e.g. TNFalpha)
Enzymes e.g. Tryptase
- Activate complement
Leukotrienes - bronchial and gut contraction and chemotaxis and eosinophils and neutrophils
Prostaglandins - vasodilation, increased vascular permeability and constriction of gut and bronchial smooth muscle.
Th2 cytokines - IL-4 to activate Th2 cells and Il-3 and IL-5 to induce eosinophil activation.
What is the late hypersensitivity reaction?
- Occurs hours after exposure
- Migration of leukocytes espcially eosinophils.
- Eosinophils release peroxidase and other mediators which cause further tissue damage
What are the effects of mast cell activation?
What is allergic rhinitis?
Treatment:
- Reduced exposure
- Intranasal corticosteroids
- Anti-histamines
- Some instances: immunotherapy
What are Leukotrienes?
Leukotrienes are a family of inflammatory mediators produced by leukocytes by the oxidation of arachidonic acid and EPA.
Explain the pathology of asthma
- Histamine plays less of a role in asthma than other allergic diseases.
Treatment:
- Reliever Inhalers (Salbutamol - B2 agonist)
- Preventatibe Inhalers - corticosteroids
- Leukotriene receptor antagonists
- Theophylines (inhibit leukotriene synthesis)
What is allergic eczema?
- Itchy, dry, red and cracked skin.
- Barrier dysfunction - protein called filaggrin
- Treatment:
- Reducing Scratching
- Emollients (moisturising)
- Topical corticosteroids
What is Urticaria? (T1 hypersensitivity)
- Raised red itchy bumps or wheals
- Response to histamine release within the skin
- Treatment:
- Trigger avoidance
- Anti-histamines
- Corticosteroids
- Leukotriene receptor antagonists
- Ciclosporin
- Omalizumab (anti-IgE therapy)
What is anaphylaxis (T1 hypersensitivity)
- Systemic response to an allergen via any exposure route
- Rapid synthesis of prostaglandins and leukotriene
- Systemic vasodilation and increased vascular permeability
- Fluid enters extravascular space
- Fall in blood pressure
- Severe bronchiole constriction, oedema and shock
- Similar to systemic inflammation
- Anaphylaxis should always be treated as a medical emergency
What is Type II hypersensitivity?
- Antibody mediated - IgG or IgM
- Cytotoxicity to tissues:
1. Antibody dependent cellular cytoxicity (ADCC)
2. Complement dependent cytotoxicity (CDC) - Cellular receptor modifying (Type V hypersensitivity)
Can be a reaction to cause cytotoxicity to tissues, or can also be to modify cell/receptor function.
In Type II hypersensitivity, the antibodies produced by the immune system bind to the patient’s own cell surfaces.
These cells are recognised by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.
An example of Type II hypersensitivity is ABO blood incompatibility.
What is Rhesus Disease/Haemolytic disease of the newborn?
- Baby with big spleen & abdomen
- High levels of bilirubin, rash on face due to platelet response
- A Rh D- mother if exposed to RhD+ RBC from a foetus will develop anti-D IgG antibodies - sensitisation.
- In subsequent pregnancies IgG can cross the placenta to induce haemolysis of foetal RBC - Rhesus disease of the newborn.
Explain the process of drug induced haemolytic anaemia
- Antibodies can also target our own cells - this is seen in the case of drug induced haemolytic anaemia
- Binding of drugs to cells can induce an immune response
- Antibodies recognise drug in combination with cells
- Drug acts as immunological hapten.
e. g. penecillin
Explain Goodpasture Syndrome
- IgG antibodies recognise collagen within the kidney basement membrane
- IgG binding to basement membrane results in complement activation
- Treatment:
- Oral immunosuppressants
- Plasmpheresis
- Complement + Subsequent activation
Explain Myasthenia Gravis
- Antivodies block the acetylcholine receptor at neuromuscular junctions preventing nerve impulse transmission.
- Presents at muscle weakness especially of the eyes and face but all muscles can be affected
Treatment:
- Pyridostigmine - blocks acetylcholinesterase which suppresses AcH
- Corticosteroids
- Immunosupressants
- Thymectomy
- Biologics - B cell depleting therapy
What is Graves Disease
- Antibodies bind the Thyroid hormone receptor causing activation of the receptor and increased thyroid hormone production.
Treatment:
- Thionamides
- Radioactive Iodine Therapy
- Surgery
