Unit 3 - Autoimmunity Flashcards
What is autoimmunity?
Immune response against self (auto-) antigen
How does autoimmunity progress?
Development of autoimmunity reflects a combination of susceptibility genes and environmental triggers
What causes autoimmune diseases?
Different autoimmune diseases may be systemic or organ specific
- may be caused by different types of immune reactions
- antibody
- T-cell-mediated
What are the two mechanisms to induction of self tolerance?
- central mechanisms
- peripheral mechanisms
What are the central mechanisms which induce self-tolerance?
Deletion of lymphocytes reacting to self
- clonal deletion in thymus or bone marrow of lymphocytes reacting to self-antigen
What are the peripheral mechanisms which induce self-tolerance?
Direct induction of peripheral lymphocyte tolerance
- endothelial barrier segregates T cells from self-antigens
- low levels of antigen will render B cells unresponsive by down regulation of surface IgM expression these B cells are short-lived - clonal anergy
Which is the first organ to be populated with lymphocytes in the unborn child?
Thymus
Which type of cells are in the thymic epithelium?
Reticular cells
What is the cortex of the thymus comprised of?
Almost all lymphocytes - mostly small resting types, packed tight
New arrivals from the marrow are larger and appear mostly under the capsule
What is the medulla of the thymus comprised of?
Forms a continuous unit
In addition to epithelium and small lymphocytes as in the cortex - there’s more of a mix of cell with some fibrous tissue extending from the vessels and a variable number of macrophages (both major types), eosinophils, plasma cells
What type of selection processes happen in the thymus?
Positive selection
Negative selection
How does positive selection take place in the thymus gland?
Selects T cells that are able to interact with MHC class I and II molecules - selecting those lymphocytes that are able to interact with self MHC
How does negative selection take place in the thymus gland?
Deletes cells that recognise self antigens expressed in conjunction with MHC class I or II molecules on thymic dendritic cells or macrophages
- if the interaction is of high affinity - T cells will be deleted
- if the interaction is of low affinity - T cells may escape negative selection
Deleting those lymphocytes that are able to interact with self MHC and respond to self antigen
What is clonal deletion?
The process of destroying B and T cells that react to self antigens
What causes alterations in the state of ‘immunological silence’?
- injury causes access to normally sequestered autoantigen
- induction of MHCII on cells not normally expressing these molecules could lead to presentation of ‘self-antigens’. Coupled with the production by these cells of necessary ‘co-stimulatory’ signals for activation of lymphocytes
What causes cross-reactivity - mimicry of microbial antigens?
- T-cell stimulation by microbial antigen mimicking self-antigen. Once primed by microbial antigen then high avidity primed T-cell could be chronically stimulated by autoantigen e.g. Streptococcal infection of throat leading to auto-antibodies against heart valves (Rheumatic fever)
- another possibility is that anergic T-cells may be converted to a responsive state by local high concentrations of cytokines released during infectious/inflammatory response
Give two examples of genetic factors that cause autoreactivity
- familial incidence
- HLA linkage
Give two examples of familial incidence of autoreactivity
- insulin-dependent diabetes
- association of thyroid antibodies with X chromosome
Which HLA specificities are common in organ-specific autoimmune disease?
HLA-B8
HLA-DR3
Which HLA specificities are common in rheumatic heart disease?
HLA-DR7
Which HLA specificities are common in rheumatoid arthritis?
HLA-DR4
Which HLA specificities are common in insulin-dependent diabetes?
HLA-DR3
HLA-DR4
What is Myasthenia gravis?
Progressive muscle weakness caused by auto-antibodies against acetylcholine receptors in motor end plates of neuromuscular junctions
Interferes with ACh neuromuscular transmission
- may lead to reduction in number of receptor as a result of increased endocytosis
Results
- failure of muscle to respond to normal neural impulses
- progressive muscle weakness
Treatment
- anticholinesterases which prolong the action of ACh by inhibiting acetylcholinesterases
- corticosteroids
- azathioprine
What is Hashimoto’s disease?
Autoimmune hypothyroidism
