hypersensitivity and autoimmunity Flashcards
define organ specific autoimmune disease
one in which an immune response is directed toward antigens in a single organ
e. g. thyroid: Hashimoto’s thyroiditis, primary myxoedema, thryotoxicosis
stomach: pernicious anaemia
adrenal: Addison’s disease
define non-organ specific autoimmune disease
autoimmune activity is widely spread throughout the body
e. g. muscles: dermatomyositis
skin: scleroderma
kidneys: SLE
joints: rheumatoid arthritis
what is loss of tolerance due to in AI disease
abnormal selection or lack of control of self-reactive lymphocytes
hypersensitivity responses
hyper response from the immune system that is harmful and may cause tissue injury or serious disease
I, II, III (V) - antibody mediated
IV - T cell mediated
autoimmune diseases usually fall into II, III and IV depending on the damage associated with the disease
type I antibodies
IgE - soluble antigen
allergy
type II antibodies
IgG - cell matrix or antigen
rheumatic fever
type III antibodies
IgG - soluble antigen
rheumatoid arthritis
type IV cells
Th1 - soluble antigen
Th2 - soluble antigen
CTL - cell antigen
type I diabetes
type I hypersensitivity
allergen is taken up and presented by a dendritic cell to a naive T cell
drives B cell response
IgE produced and binds to Fc receptor
allergen cross links the antibody and activates the mast cell
pro-inflammatory mediator (propagate the inflammatory response) and cytokines are generated very quickly
early phase response in allergy
IgE mediated effects
vasodilation, oedema, vascular congestion
occurs within minutes
preformed mast cell mediators
late phase reaction in allergy
newly synthesised mediators (prostaglandins, leukotrienes)
Th2 cytokines
eosinophil mediators
atopy
predisposition to allergy
depends on IgE levels
high = likely to develop at least one allergy
type II hypersensitivity
body’s antibodies bind to antigens on its own cell surfaces
antibodies are produced in response to the antigens on the cell surfaces
IgG and IgM antibodies trigger the complement system causing cell lysis
type III hypersensitivity
characteristed by the formation of immune complexes (clumps of antibodies that have stuck together)
low conc of antibody coupled with a large conc of antigen causes small complexes to form
type IV hypersensitivity reactions
A) cytokine mediated: APC presents fragments of protein to CD4 T helper cells, recognise the foreign antigen and produce cytokines which drives pro-inflammatory responses, leading to tissue injury
B) T cell mediated: T cells recognise antigens demonstratedy by normal epithelial cells, leading to tissue injury
type V hypersensitivity reactions
stimulate the receptor, inappropriate increase in function response e.g. myasthenia gravis - Ach cant bind to receptor on muscle, loss of muscle function
define the pathophysiology of immune complex formation in localised type III hypersensitivity
causes localised inflammation and can be cleared away by macrophages
define the pathophysiology of immune complex formation in systemic type III hypersensitivity
complexes are deposited in tissues and organs such as the skin, joints, kidneys and blood vessels
define the term autoimmune disease
a large group of clinical disorders characterised by tissue or organ damage mediated by incorrect immune mechanisms targeted at self antigens
illustrate the factors involved in the aetiology of AI disease
caused by interaction of: genetics, immune regulatory factors, hormonal, environmental and ‘other’ factors
describe the pathogenic mechanisms involved in AI disease
cell mediated antibody mediated antibody and complement immune complex mediate recruitment of innate compounds
Fc receptors
antibody receptor involved in antigen recognition which is located at the membrane of certain immune cells including B lymphocytes, natural killer cells, macrophages, neutrophils, and mast cells. Such receptors recognize Fc fragment of antibodies
immune tolerance
Tolerance is the prevention of an immune response against a particular antigen.
how does immunological tolerance develop
T cells, possessing receptors which strongly bind onto one of the body’s own peptides bound to an endogenous MHC molecule, are triggered to undergo apoptosis
