Week 5/6 - C - Hypersensitivity - 1 (Tcells,IgE,mast cells), 2 (IgG,IgM v cell surface antigens), 3 (Immune complexes), 4 (T-cell ) Flashcards
What is the Gel and Coomb’s classification of hypersensitivity reactions?
ABCD Type 1 - Immediate hypersensitivity (Allergy, Anaphylaxis and Atopy) Type 2 - Direct cell effects (cytotoxic or stimulatory) - antiBody Type 3 - Immune Complex mediated Type 4 - Delayed type hypersensitivty - Tcell mediated
TYPE 1 HYPERSENSITIVITY REACTIONS What is the immunoglobulin in the type 1 hypersensitivity reactions? What type of conditions?
Type 1 hypersensitivity is an IgE mediated antibody response to external antigen Wide variety of conditions eg atopy (asthma, atopic eczema, allergic rhinitis), food allergy, drug allergy, anaphylaxis, hayfever
Sensitization stage What causes the production of IgE cells in type 1 hypersensitivity reactions? (from antigen exposure to IgE production) Give an example of an antigen presenting cell?
Antigen presenting cell bind to the antigen eg a dendritic cells. These cells express MHC Class II or MHC Class1 molecules for the binding of CD4+Tcells and CD8+ T cells respectively Once the CD4+Tcells (helper T cells) are activated (after binding to MHC Class II molecules) they divided into different subsets of T helper cell It is the Th2 cytokine producing cells that stimulate antibody switching to produce IgE cells
Which ctyokine do Th2 cells produce that stimulates eosinophil release from the bone marrow?
Th2 cells releases IL-5 that stimulates the bone marrow to produce and release eosinophils
Sensitisation stage What do the produced IgE antibodies bind to and what happens?
Mast cells, basophils and eosinophils express receptors for the Fc region of the IgE on their surface (Fc receptors) In the sensitisation stage for type 1 reactions, the allergen is cleared, and the resident IgE bind to these
Allergic stage What happens to the patient on rexposure to the allergen?
On re-exposure to the allergen, the allergen cross-links with the IgE cells that are bound tot he mast cells, basophils and eosinophils causing degranulation of these cells and release of inflammatory mediators
What is released from the mast cells and what does it cause?
Mast cells produce vasoactive inflammatory substances HISTAMINE, tryptase and heparin As well as leukotrienes and prostoglandsins And pro-inflammatory cytokines These cause vasodilation and permability, smooth muscle contraction 9airway constiction) and increased secretions at mucosal surfaces
What is the usual treatment of type 1 hypersensitivity reactions?
Avoidance of allergen Block mast cell activation / effect * Anti-histamines * Leukotriene receptor antagonist * Mast cell destabiliser eg sodium cromoglycate Corticosteroids to suppress inflamation Monoclonal antibodies eg against IgE
TYPE 2 HYPERSENSITIVITY REACTIONS Describe the pathogenesis of type 2 hypersensitivity reactions?
Type 2 reactions are an antibody mediated process in which IgG and IgM antibodies are directed against antigens on cells (such as circulating red blood cells) or extracellular material (such as basement membrane). This subsequently leads to cell lysis, tissue damage or loss of function through different mechanisms Due to the antibody/antigen being bound to the person’s normal tissue as well, it is damaged
What are the three immunological mechanisms that can lead to cell death in type II hypersensitivity reactions?
Binding of the antibody to the cell surface antigens results in complement activation and osmotic lysis of the cell Antibody bound to the cell surface antigen acts as an opsonin - molecule that enhances phagocytosis - phagocytosis of antigen+ve cells (eg red blood cells or basement membrane) Antigen dependent cellular cytoxicity - cells with bound antibody are recognized by NKcells leading to cell death
Give examples of Type II hypersensitivity reactions?
Abnormal antibodies (IgG and IgM) directed against antigens of target (self) organs cause destruction of the target (self) cell. Examples include * Autoimmune haemolytic anaemia * Goodpasture’s syndrome - antibodies attack the basement membrane of the lungs and kidneys * Grave’s disease * Myasthenia gravis * Idiopathic thrombocytopenia purupua (antibodies attack antigens on the self)
What are type V autoimmune reactions? (these are a subset of type 2 reactions)
Type 2 reactions can be split into * those that cause cell death or * Type V reactions- which work instead of binding to cell surface components, the antibodies recognise and bind to the cell surface receptors, which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand, thus impairing cell signalling.
What are examples of Type V hypersensitivity reactions and how do they work?
* Grave’s disease - in this disease, antibodies called thyroid stimulating immunuglobulin (TSI) are produced which bind to the thyrotopin receptors and mimic the effect of the ligand thyroid stimulating hormone (TSH) - therefore there is an increase in the production of thyroid hormones * Myasthenia gravis - in this disease antibodies are produced at the post-synaptic terminal acetylchoine receptors at the neuromuscular junction blocking or destroying them. This prevents acetylocholine acting on these receptors to stimulate muscle contraction.
TYPE 3 HYPERSENSITIVITY REACTIONS Describe the pathogenesis of type 3 reactions? (for now, how are the immune complexes formed, where do they deposit, are they soluble or insoluble)
In type 3 reactions, IgG and IgM antibodies form against soluble antigens forming insoluble immune complexes These immune complexes deposit in the basement membrane of different organs eg skin, joints, kidneys
What does the deposition of the immune complexes cause?
The deposition of the immune complexes in the basement membranes of the organs leads to * Activation of complement * Cell lysis & opsonisation Opsonisation leads to activation of phagocytosis Also infiltration of macrophages and neutrophils
Type 4 hypersensitivity reactions are often called delayed type as the reaction takes two to three days to develop. Unlike the other types, it is not antibody mediated but rather is a type of cell-mediated response. (Type 1-3 are antibody mediated and take minutes (type 1) to hours (type 2 and 3) What is the pathogenesis of type 4 reactions?
CD4+ T cells respond to tissue self-antigens expressing MHC Class II complexes. They promote differentiation of Th1 cells. On re-exposure to the antigen Th1 cells produce cytokines that stimulate inflammation and recruit /activate macrophages and neutrophils, leading to tissue injury . Activated cytotoxic T cell (CD8+Tcells) also can direct kill antigen cells expressing MHC Class1 complexes.
