Hypersensitivity Flashcards
(40 cards)
What is an allergen?
An allergic reaction provoked by re-exposure to a specific type of antigen
What are examples of type 1 hypersensitivity?
asthma, allergic rhinitis and atopic dermatitis.
What antigens are type 1 responses mediated by?
Antigen specific IgE antibodies
What do non-allergic individuals predominately make IgE in response to?
- Parasitic infections
- V potent venoms
What do individuals with allergies produce?
- antibodies against common multivalent (which means the antigen has multiple sites at which an antibody can attach or antigen can be produced) environmental antigens
- these antigens have become known as allergens, and include things such as foods (e.g. peanuts), plants (e.g. timothy grass, birch trees), animal dander (e.g. cats, dogs), drugs (e.g. penicillin, sulphonamides) and insect products (e.g. bee venom, house dust mites).
What are prick of skin tests?
expose skin to small amount of allergen and look at inflamed tissue to diagnose allergy
What is the initial sensitisation of the immune response to allergens that cause IgE production?
- complex
- Factors such as genetics, age environment involved
What is the end result of sensitisation of imminent response to allergens that case IgE production?
- Generation of type 2 helper CD4 T cells and B cell helper follicular CD4 T cells which produce the type 2 cytokines IL-4 and IL-13; when these act on B cells they can promote B cell to switch to producing antigen specific IgE.
- Interestingly unlike other antibodies IgE is very rarely found in the circulation, even in allergic individuals
What happens once IgE is production?
It is rapidly bound to surface of innate immune cells, especially mast cells and basophils
What do these granulocytic cells express?
- a high affinity IgE receptor, Fc epsilon receptor I (FcεRI)
- If an allergen is encountered by cell bound IgE it results in rapid crosslinking and degranulation of the mast cell or basophil
- For perspective this happens much faster, and across a much broader site, even a low antigen levels, than is seen during normal inflammation based activation of mast cells (see the summary figure below and the table of mediators released).
What is the end product of the reactions?
- release of histamine a host of cytokines and can recruit other cells and promote further Th2 differentiation and highly active smooth muscle contraction molecules such as leukotrienes and prostaglandins
- The variety of molecules released during type I responses results in “phases” of response
What early phase?
-The early phase, a result of bioactive small molecules produced directly by mast cells, occurs within minutes of allergen exposure
What is a later phase?
-A later response, often seen within a few hours is the result of the recruitment of early inflammatory cells such as neutrophils
What is a third phase?
-A third phase, or late response, is often peaks 3-4 days after exposure where high frequencies of eosinophils are recruited and Th2 cells are present
What does type II hypersensitivity include?
-otherwise known as antibody-mediated cytotoxic hypersensitivity, involves the destruction of cells by IgG or IgM antibody bound to antigens present on the surface of the cells
What could mismatched blood transfusions?
-mismatched blood transfusion could be considered one such hypersensitivity with antibodies recognising different, non-self, carbohydrate groups of the transfused red blood cells resulting in immune induced destruction of those red blood cell, inflammation and tissue damage
What are other examples of type II hypersensitivity?
-Other examples include haemolytic disease of newborns, where maternal antibodies can cross the placenta and destroy fetal red blood cells if the foetus and the mother have mismatched Rh D alleles
What is immune thrombocytopenia disease?
- Where antibodies develop against platelet surface proteins
- Graves disease where patients develop thyroid stimulating antibodies that bind the thyrotropin receptor resulting in secretion of thyroid hormones
What can type II sensitisation can involve?
- Exposure to a foreign antigen (for example some drugs can bind to the surface of cells in the blood, or non-self antigens blood transfusions or organ transplants)
- The aberrant response to a self-antigen resulting in IgGs or IgMs that recognise cell surface structures
What are the different mechanisms that antibodies cause disease?
- Anti-receptor activity – blocking or activating its function
- Antibody dependent cell-mediated cytotoxicity (abbreviated to ADCC)
- Classical activation of the complement cascade
What is a complement cascade?
-Is a complex process by which antibody on the surface of cells is recognised by the complement components, ultimately leading to the formation of the membrane attack complex (MAC) in the surface of the cell, and cell death due to loss of osmotic integrity
What does activation of the classical complement pathway cause?
inflammation, opsonisation and recruitment and activation of immune cells
What happens in ADCC?
-In ADCC antibody-antigen complexes on the surface of cells are bound by Fc receptors (which bind the constant, not antigen specific, tail regions of IgM and IgG antibodies) expressed by cells such as granulocytes and NK cells lead to directed lysis of the target cell, but also the release of inflammatory mediators, chemokines and cytokines.
What can type II hypersensitivity result in?
-multiple mechanisms of tissue injury including local or systemic inflammation, cell depletion leading to a loss of function or imbalance in organ function.
