L11- Hypersensitivity Flashcards
What are the 4 hypersensitivity reactions of immunology?
- Type I- IgE antibody-mediated (involves mast cell responses)
- Type II- Cytotoxic
- Type III- Immune Complex (causing autoimmune diseases)
- Type IV- Cell-mediated (delayed)
Describe type I hypersensitivity
It is an IgE- mediated response
IgE is bound to mast cells via its Fc portion. When an allergen binds to these antibodies, cross-linking of IgE induces degranulation e.g. histamine
Response: causes localised and systemic anaphylaxis, seasonal allergies including hay fever, food allergies such as shellfish and peanuts, hives and eczema.
Explain Type 1 hypersensitivity in greater detail
APC finds antigen usually in the periphery and migrate to lymph nodes and other important immune sites and presents it to CD4+ via MHC class II.
- Driven to TH2 cells producing IL-4 and IL-5 and GM-CSF. These go on to promote firstly allergy such as asthma involving eosinophils.
- TH2 cells bind to B cells and release IL-4 and IL-13 cytokines. This activates class switching of B cells into IgE specific to antigen. IgE binds to mast cells or basophils. They are then primed and ready for when they encounter antigen again. When they do, they cross link at Fc receptor with IgE to release (degranulation) by a process of exocytosis to release pre-formed mediators such as histamines, cytokines, proteases, PGD2 and LTC4.
Describe the bodies initial and late phase response to type I hypersensitivity
Initial:
Vasodilation, vascular leakage and smooth muscle spasm
Late phase: Mucosal oedema (liquid coming into the mucosa or skin), mucus secretion e.g. in the lungs, leukocyte infiltration, epithelial damage and in case of lungs bronchospasm or an asthma attack.
List some examples of type I hypersensitivity disorders.
- Anaphylaxis
- Urticaria (hives)
- Eczema (atopic dermatitis)
- Conjunctivitis
- Angioedema
- Gastroenteritis
- Rhinitis
- Food allergy
What prevalence of food allergies affects Australians?
5-10% of population
What parts of the body are affected by food allergy?
Sensitisation through oral or skin routes
Affects skin, respiratory tract, gut
What is the treatment for food allergies?
Immunotherapy, medications (e.g anti-histamines), avoidance
Mechanisms suppressing clinical reactivity include IgA neutralisation, IgG4 and Treg cells to suppress TH2 or mast cells
Food allergies can be linked to genetic factors linked with barrier dysfunction. What is the important molecule that is necessary for the epidermal barrier?
Filaggrin
What is filaggrin and what is it’s relationship to food allergy?
Strengthens the barrier between epidermal squamous cells to prevent microbes from entering and preventing inflammation. In terms of food, filaggrin dysfunction can lead to food intolerance and type 1 hypersensitivity to occur.
What gut microbiome may be responsible for inducing food allergy?
Clostridium spp.
What nutritional factors may be responsible for food allergy?
Protective factors: vitamin D, vitamin A, AHR ligand and long chain FA
High risk factors:
High fat diet, medium chain TG > these factors could change gut flora and might not be as protective leading to an inflammatory type gut where the barrier dysfunction gets worse leading to type 1 hypersensitivity.
List some of the factors that might contribute to food allergy
- Genetics e.g. barrier dysfunction- filaggrin
- Route of exposure e.g skin allergy can induce eczema and lead to food allergy
- Early life exposure- during pregnancy, as a neonate, as a young toddler
- Nutrition and gut flora
- IgG mediated activation of neutrophils with immune complexes (type III hypersensitivity)
- Complex issues e.g. multiple allergens, ther immune pathways, non-immune driven (e.g. toxicity), mixture of factors
Describe some toxic adverse reactions to food that can lead to allergy
- Non-immune mediated
- Enzymatic damage e.g. lactose intolerance
- Pharmacological e.g. vasoactive amines, methylxanthines, capsaicin, ethanol
Describe some non toxic adverse reactions to food.
- Immune mediated
- Adaptive immune responses
- Type I: IgE and/or T cells (IgE-associated food allergy)
- Type IV: T cells (e.g. celiac disease, food protein-induced enterocolitis)
•Innate immune responses e.g. complement, toll-like receptors, innate immune cells
Describe Type II hypersensitivity
IgG- mediated cytotoxicity hypersensitivity:
Cells are destroyed by bound antibody, either by activation of complement or by a cytotoxic T cell with an Fc receptor for the antibody (ADCC)
Response: RBC destroyed by complement and antibody during a transfusion of mismatched blood type or during erythroblastosis fetalis.
What are the two main mechanisms to the Type II hypersensitivity?
• Cell mediated cytotoxicity
- Production of antibodies specific to antigen e.g. self antigen IgM or IgG bind to receptors on own cells which you can then have binding of cytotoxic T cells which can release their perforin and cause cellular cytotoxicity
• Activates complement
-Antibodies binding to receptors on target cells directly and activate compliment to cause lysis via pore forming complex
What is ADCC?
Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system actively lyses a target cell, whose membrane-surface antigens have been bound by specific antibodies.
List some Type II hypersensitivity example
- ABO blood incompatibility
- Myasthenia gravis (acetylcholine receptor)
- Grave’s disease (thyrotropin receptor)
- Goodpasture’s syndrome (collagen typeA4)
- Adverse drug reactions (eg. penicillin)
What is an example of a Type II hypersensitivity towards ABO blood compatibility
Haemolytic disease of the newborn
What is Haemolytic disease of the newborn?
Maternal blood antigen specific (anti-Rhesus) antibodies cross the placenta and destroy foetal cells
- Rh + father
- Rh - mother carrying her first Rh + fetus
- Rh antigens from developing fetus can enter mother’s blood during delivery
- In response to Rh antigens, the mother will produce anti-Rh antibodies
- If woman becomes pregnant with another Rh + fetus, her Rh antibodies will cross the placenta and damage fetal RBC’s causing erythroblastosis fetalis
How common is Haemolytic disease of the newborn?
Quite rare (8 in 10,000 births)
How can you prevent and treat Haemolytic disease of the newborn?
- Screening to find Rh: mothers
- RhD antibody prophylaxis (routine in Australia for all Rh- pregnant women)
- Intravascular red blood cell infusions (to newborns)
What is Type III hypersensitivity?
Immune complex-mediated hypersensitivity
Antigen-antibody complexes (IgG or IgM) are deposited in tissues, and particularly small vessels causing activation of complement which attracts neutrophils to the site causes inflammation and ultimately damages cells
