AUTOIMMUNITY AND AUTOIMMUNE DISEASES Flashcards
(47 cards)
DEFINE AUTOIMMUNITY
An immunological response against the body’s normal cells, tissues and body constituents
TOLERANCE CAN BE GROUPED INTO
Central tolerance and Peripheral tolerance
DEFINE CENTRAL TOLERANCE AND WHERE IT OCCURS
is a mechanism of eliminating any T or B cells with a high affinity for self-antigens. It occurs in the Primary Lymphoid organ
Give the primary lymphoid organs.
The bone marrow and the thymus
In the case of central tolerance it may be grouped into
T cell tolerance and B cell tolerance
Explain T cell central tolerance
T cell central tolerance consists if both negative and positive selection. It occirs in the thymus
T cells undergo positive selection to check whether they are able to recognize and bind to MHC molecules on cell. Those that bind MHC class I become CD8+ while those that bind class II become CD4+. This positive selection occurs in the thymic cortex.
T cell negative selection occurs to check the affinity of the T cells to self-antigens. The thymic epithelial cells display self-antigens to test them and those T cells that bind with a high affinity undergo apoptosis. This occurs in the cortico-medullary junction.
The T cells that do not undergo apoptosis proceed to the secondary lymphoid organs.
Differentiate between negative and positive selection
Negative selection occurs first and usually takes place in the PLO . This check to see which cells recognize and bind too strongly to self antigens . These are eliminated by apoptosis
Positive selection checks that the cells that are able to recognize and bind to foreign antigens mature and differentiate into functional cells. Takes place in the SLO
Explain peripheral tolerance
It occurs in the secondary lymphoid organs to ensure the self-reactive T and B cells that had escaped central tolerance do not escape peripheral tolerance and cause autoimmunity.
T cell activation usually requires two types of signals , explain
Signal one where TCR interact with the antigen on APC
Signal 2, interaction of costimulatory molecules i.e CD80/86 on APCs and CD28 on T cells.
Peripheral tolerance of T cells has three main mechanisms
1)anergy where the APC does not lead to induction of second signal
2)Ignorance where the antigens with very low concentrations are not sensed by the T cells.
3)Deletion
4) Suppression by Treg cells: cell to cell contact suppression or release of cytokines
In the case of B cells and central tolerance , the receptors and cells may undergo three outcomes .
1) Apoptosis
2) B cell receptor editing where genes are rearranged in the BCR to avoid self-antigen binding.
3)Induction of anergy
The Treg cells are generated in central or peripheral tolerance
Central tolerance
Three main mechanisms result in breakdown of self tolerance
Genetic predisposition - MHC , AIRE , cytokine pathways
Environmental factors - infection, microbiome, traumatic insult
Defective regulation - FOXP3, CTLA4, complement deficiency.
Give the causes of autoimmunity
1) Lymphocyte abonormalities
2) Cytokine dysregulation
3) Failure of central and peripheral tolerance
4) Molecular mimicry
5) Alteration in ag processing
6) Infection
7) Genetic factors
Give the examples of autoimmune diseases
SLE
Rheumatoid arthritis
Psoriasis
Diabetes type 1
Autoimmune hemolytic anemia
Grave’s disease
Myasthenia gravis
Vitiligo
Give several possible treatment for autoimmunity
Immunosuppresion (prednisone , cyclosporin a)
Removal of thymus ( Myasthenia gravis)
Plasmapheresis - removal and filtering of harmful antibodies from plasma
T cell vaccination
Anti CD4 monoclonal antibody
Define SLE
A chronic autoimmune disease in which the immune system attacks healthy tissues and may occur in different parts of the body thus a chronic systemic disease.
State in SLE
1) Peak age
2) Gender ratio
20-40 years
Women more affected than men (9:1)
The Etiology of SLE is a combination of which three main factors . Explain
Genetic susceptibility
-HLA - A1, B8 AND DR3
- Abnormal coomplement genes
Environmental factors
- UV light exposure
- Women taking estrogen contraceptives
- Certain medication such as isoniazid , Hydralazine and procainamide
Immune system abnormalities
Give the Immunopathology of SLE
In SLE there is loss of self-tolerance and the production of an array of antibodies against both nucleic and cytoplasmic antigens such as histones , dsDNA , lymphocytes , erythrocytes , platelets etc.
This may be in addition to dysregulation of both B and T cells where T cells become activated in response to self-antigens and produce cytokines that stimulate B cell to produce an array of autoantibodies.
During the immune reaction , immune complexes are formed and deposited in different part of the body leading to inflammation.
Autontibodies to which nuclear antigen represent the vast majority (70%) of autoantibodies in SLE
dsDNA
SLE represent what type of hypersensitivity reaction
Type III ( formation of immune complexes causes an inflammatory process)
Neonatal SLE occurs in what percentage of infants born to mothers with SLE
and resolves within?
8%
Resolves within 6-8 months
The major autoantibody associated with neonatal SLE
Anti-SSA / Anti - RO
