hypersensitivity and autoimmunity Flashcards
Contrast the mechanisms of Types I, II, III and IV hypersensitivity.
- Type 1,2,3 are mediated via antibodies
- Type 3 is a result of an abnormal deposition of an antigen-antibody complex in tissues.
- In Type 2 and 3 the response can be against self or non-self material
- Type 4 is not mediated through antibody production and occurs in response to an inert environmental substance ( with low molecular weight) bound to an RBC or in response to a microorganism.
- Type 1 usually occurs within a matter of minutes whilst type 4 occurs within 48-72 hours
Define the roles of allergen, IgE, mast cells, in ammatory cells, mediators and cytokines in Type I hypersensitivity.
IgE is the immunoglobulin which is produced in excess during type 1 hypersensitivity in response to an airborne, ingested,injected or skin contacted antigen.
Mast cells activated an release mast cell mediators.
Mediators trigger inflammation. two types:
-preformed: histamine, heparin, tryptase, chymase,eosinophil
-newly synthesised: leukotrienes, prostaglandins
Cytokines: released from mast cells
Explain the pathophysiology of early and late phase allergic reactions.
Early: Antigen-presenting cells are exposed to allergen and engulf it to expose their antigens on their cell-surface. They then expose this to T-cells and this triggers B-cells to produce IgE. The IgE then binds to specific receptors on the mast cells.
Latency: When the allergen is encountered again, it cross links with the IgE bound to the mast cell and leads to the release of mediators
Define atopy and allergy.
ATOPY: A type 1 hypersensitivity. It is thought to be due to genetic inheritance. A state of sub-clinical immune sensitisation.
sub-clinical meaning it is not severe enough to denote serious/ observable symptoms
ALLERGY: A clinical disorder
Define the roles of antibody, complement, Fc receptor bearing cells and ADCC in Type II hypersensitivity.
Antibodies: IgG and IgM inappropriate production are responsible for type 2 hypersensitivity. They bind to external antigens which are present on the c.s.m or are embedded within tissues.
Complement: antibody complement system is a method by which the antigen is attacked- REFER TO IMMUNOLOGY
Fc receptor: receptor to which antibody binds which triggers phagocytosis
ADCC: antibody dependent cytotoxicity. Antibody triggers the production of cytotoxic T cells.
Define the pathophysiology of immune complex formation in localised and systemic Type III hypersensitivity.
Due to deposition of antibody-antigen complexes in tissues. They are usually associated with an RBC and are soluble in blood.
Serum sickness: due to deposition from circulation into tissue
Arthus reaction: due to the formation of the complexes in tissues.
Explain the factors involved in formation of abnormal immune complexes
Antigens
Hosts
Define the roles of haptens, carrier proteins, Th1 cells, antigen presenting cells and monocytes/macrophages in Type IV hypersensitivity.
Haptens: inert environmental substance with low molecular weight which binds to an endogenous protein and triggers Th1 to stimulate antibody and cytokines.
Carrier proteins: bind to haptens
Th1 cells: Recognise hapten and stimulate cytokine production
monocytes/macrophages: engulf the hapten structures and become antigen-presenting therefore triggering the Th1 cells
Define the mechanisms by which immunological tolerance arises.
Process by which the immune system avoids producing a response to antigens.
Can arise either during maturation of T and B cells (central) or by inhibiting auto reactive cells which escape the central tolerance (peripheral)
Define autoimmune disease.
A group of clinical disorders which is characterised by tissue/organ damage mediated by a faulty immune system which directs response against auto antigens.
Illustrate the factors involved in the aetiology of autoimmune disease.
Genetic factors e.g. HLPA
environmental factors
hormone factors
immune regulatory factors
Describe the pathogenetic mechanisms involved in autoimmune disease.
genetic factor+ initiating event lead to the breakdown of self-tolerance- autoimmune response to self-antigen.
Autoreactivity triggered which can either be humeral or cellular and leads to tissue damage.
Responses triggered:
- immune complex formation
-cellular T and B cell response
-recruitment of innate factors e.g. phagocytes,NK cells
-complement inflammatory response
Contrast organ-specific and non-organ specific autoimmune disease.
organ- autoimmune endocrine disorders stomach- pernicious anaemia thyroid- thyrotoxicosis, Hashimoto's thyroiditis, primary myxoedoma Adrenal- Addison's disease non-organ- connective tissue disorder Skin- scleroderma Joints- rheumatoid arthritis Muscles- dermatomyotisis Kidneys-SLE Overlaps tend to occur at either end of the spectrum but not overlaps between the different types of diseases.
What is hypersensitivity?
A group of disorders which arise when components of the immune system which are usually beneficial are exaggerated and lead to an immune response against antigens which do not usually cause damage
