Lecture 2 - Aetiology and immunopathogenesis of autoimmune disease Flashcards
what is autoimmunity?
Autoimmunity is a breakdown of mechanisms responsible for self tolerance and induction of any immune response against components of the self. a Autoimmune Disease is A specific and sustained adaptive immune response directed against self which causes tissue damage to the host.
what are some common autoimmune disease?
Rheumatoid arthritis
SLE
Psoriasis
Uveoretinitis
What can be causes in autoimmune diseases?
genetic factors, infectionn and environmental exposure, age, gender, immune regulation, diet, social and economic status.
Women are 2.7 times more likely than men to develop an autoimmune disease
what age population has a higher incidence of autoimmune diseases?
Autoantibodies are more prevalent in older people perhaps due to less stringent immunoregulation by the aging immune system, e.g. less Treg cells
what effect do genetic components have on autoimmune diseases?
MHC genes have an important role in controlling susceptibility to autoimmune disease
A defect in a single gene can be associated with autoimmune disease
Defects in genes regulating immune responses such as cytokine production or signalling that can lead to autoimmunity
For example, an individual who has HLA-B27 is 90 times more likely to develop ankylosing spondylitis.
outline the basic concept of MHC genotype with autoimmune diseases.
The association of MHC genotype with autoimmune disease is not surprising because autoimmune responses involve T cells, and the ability of T cells respond to a particular antigen depends on MHC genotype.
describe ALPS
ALPS is an autoimmune condition resulting from genetic mutation in the FAS gene which regulates cell death in immune cells. the key problem in ALPS is the failure of apoptosis in self reactive T cells and B cells. the cells are supposed to be eliminated but due to mutation, they survive and can lead to autoimmune resposne.
in the case of Ellen Ohara; there is a uncontrolled lymphocyte proliferation in the absence of infection or cancer
features and symptoms of ALPS;
splenomegaly
lemphadnopahty
increased lymphocytes and immunoglobulins in blood
father and grandfather familial history
descrie IPEX
IPEX; Immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome. there is a Lack of both CD4CD25 cells and CD4Foxp3 positive cells.
Mutation of foxp3 gene. case of a defect in peripheral tolerance leading to dermatitis, diarrhea and diabetes
what can lead to autoimmunity?
defects in cytokine production or signalling such as over expression or under expression can lead to autoimmunity
explain how external factors eg infection can cause autoimmune syndrome.
infection can lead to autoimmunity by providing and environment that promotes lymphocyte activation or through cross reactivity between foreign molecules on pathogens and self molecules
give an example of how a virus infection breaks tolerance in mice models.
- hybrid gee created by combining NP from LCMV with rat inclusion promoter region
- mice genetically engineered to express hybrids even only in pancreatic beta cells (where insulin made)
- NP is expressed only in beta cells and provokes no T cell response
- transgenic mice infected with LCMV and NP specific CD8 T cells are activated
- CD8 T cells attack pancreatic B cells expression NP, leading to diabetes
what can cause failure of central or peripheral tolerance?
defects on AIRE, INS, PTPN22, CTLA-4, CD25, HLA genes
explain the balance between immunity and regulation
Regulatory factors that suppress the immune system to prevent it from attacking the body’s own tissues. immunity factors that activate the immune system to defend against pathogens.there Sia fine balance between immune regulation versus pathogenesis.
immunity components; Pathogenic CD4 and CD8 T cells, pathogenic B cells, and activating dendritic cells part of the immune response that defends against pathogens. regulatory components; Regulatory T cells, B cells, and dendritic cells produce factors that keep the immune response in check to avoid damaging the body’s own tissues
the balance can be disrupted by genes and environmental factors which can cause autoimmune diseases
how can external factors like trauma or infection can lead to autoimmune responses through two mechanisms
1) Disruption of the tissue or cell barrier : the release of isolated foreign antigens leads to the activation of immune cells which are intolerant to them. an example is sympathetic ophthalmic
2) molecular mimicry: the presence of foreign antigens that resemble self antigens can lead to cross reactive antibodies or T cells. examples are rheumatic fever, reactive arthritis and Lyme arthritis
