autoimmunity Flashcards
what is autoimmunity
Defined as the presence of immune responses against self-antigens
what does autoimmunity cause a huge potential for
Huge potential for generation of autoreactive B cells (and T cells) in primary lymphoid tissues during normal lymphocyte development
how are antibodies generated
Antibodies are generated by the production of heavy chain (HC) and light chain (LC) polypeptides that are synthesized from two separate immunoglobulin (Ig) genes
gene segments
both heavy chains and light chains are composed of them, it creates lots of variation as they’re randomly selected
heavy chain rearrangement
loose the intervening segments. creates a unique VDJ region
how is the 3D shape of an antibody formed
the VDJ and VJ region creates the 3D form that recognises a specific antigen. completely random
how are self reactive cells made
Antigen receptor gene rearrangement in developing T cells and B cells is RANDOM. therefor some self reactive cells are made by accident these are usually killed during development but in some situations they arent
How does the immune system deal with the presence of autoreactive T cells and B cells?
Specific ‘tolerance’ mechanisms are used to kill or inactive auto-reactive lymphocytes
what are the tolerance mechanisms
Deletion of self-reactive lymphocytes in primary lymphoid tissues (central tolerance)
Regulatory T cells (TREG cells) can help inactivate auto-reactive lymphocytes in peripheral tissues that escape central tolerance (peripheral tolerance)
What are regulatory T cells ?
they inactivate lymphocytes to stop excessive reactions. they are crucial for the suppressing hyper-reactive or auto-reactive T cells
how to Treg cells stop hyper reaction
via the production of anti inflam cytokines
how does autoimmune disease occur
genetic susceptibility > initiating event (could be infection) > breakdown of immune tolerance to self-antigens > can lead to autoimmune phenomena or disease
genetic influences in autoimmune disease
Monogenic disorders - single gene defects causing autoimmune diseases are rare (IPEX syndrome). or a complex genetic interplay (HLA genes)
IPEX syndrome
A rare genetic disorder of immune dysregulation, Severe infections, Intractable diarrhoea, Very early onset insulin dependent diabetes.
what are the treatments for IPEX syndrome
Cure: hematopoietic stem cell transplantation (HSCT)
Supportive care: immunosuppressive drugs plus total parental nutrition
science behind IPEX syndrome
condition is X linked, causes of peripheral tolerance mechanisms due to absence if Treg cells
what are normal HLA molecules
MHC molecules in humans are also referred to as HLA molecules. T cells only see peptides exhibited on a defined framework. HLA molecules are able to present many peptides
HLA alleles
certain HLA alleles have been linked to increased (or decreased) risk of developing autoimmunity. some are better at binding self peptides than others so have a higher chance of autoimmunity
sex differences in autoimmunity
there’s a clear sex bias in certain autoimmune diseases. eg sex hormones are known to influence lymphocyte function on males versus females
pregnancy and autoimmunity
alterations in disease severity for some autoimmune diseases are known to occur during pregnancy. as fetal developed effects immune system autoimmunity
environmental influences
Several environmental factors can trigger autoimmunity in genetically predisposed individuals
eg infections, smoking, hormone level, tissue damage
mechanisms to do with environmental autoimmunity
molecular mimicry, alterations to self antigens
example of molecular mimicry
acute rheumatic fever after strep infection. some antibiotics cross react with heart tissue causing rheumatic fever
tissue injury and antigen sequestration
Self-antigens normally sequestered from the immune system can become exposed and cause an autoimmune reaction during infections/trauma
