Autoimmune diseases Flashcards
Why is autoreactivity common?
- Its impossible to remove all dangerous autoreactive T cells in thymus
- Lymphocytes perfom recognition via Ig-receptor and T-cell receptor which are similar to human/microbial antigens
what is an autoimmune disease?
Disease in which the pathology is caused by adaptive immune response to self antigens
Its occurs in aggressive, pronounced and persistent autoimmune reactions. this can affect most organs of the body. Its either organ-specific or systemic.
What are the criterias for an autoimmune (antibody-mediated) disease?
- Is there an autoantigen that is the target for the autoantibodies?
- Are there autoantibodies that targets the autoantigen?
- Is there a passive transfer of the autoantibodies to the infant? (e.g. neonatal disease)
- Is there an experimental model that shows that if you add autoantibodies to a healthy individual the individual will get the autoimmune disease?
5 Is there an effect of immunosuppressive treatment? Meaning if you would dampen the
effects of the immune system, will the autoimmune disease be milder? If yes, that means that the disease is due to the immune system.
What is an example of a type 2 autoimmune disease?
Myastenia gravis;
Myasthenia gravis is an antibody mediated autoimmune disease (type 2b: antibodies against receptor). Antibodies bind to acetylcholine receptors so when acetylcholine is released into the synaptic cleft it can’t be taken up by its receptors. This leads to disturbed neuromuscular transmission and muscle weakness.
Describe the second type of immune reactions according to the combs and gell theory?
Its called IgG and IgM mediated cytotoxic hypersensitivity.
There are two types:
2a) Antibodies against cell bound antigen
Mechanism:
B-cells can produces antibodies that attaches to a bloods which can bind to a Fc-receptor or a complement factor which either leads to it being phagocytized or lysed by complement system.
2b) Antibodies against receptors (antagonism)
Mechanism: Blocks and restrains the receptors function
Describe the third type of immune reactions according to the combs and gell theory?
Its called Immune comples mediated hypersensitivity.
Immune complexes must be removed from tissues and kept from accumulating in blood circulation and forming deposits. If the immune system fails to do so => autoimmunity
What is a example of type 3 immune reaction?
An example of this is rhematoid arthitis in the joints
Describe the fourth type of immune reactions according to the combs and gell theory?
Its called T cell mediated hypersensitivity.
Autoantibody-mediated inflammation can lead to the release of autoantigens, particularly intracellular ones that are targets in SLE, stimulate B cells only when released from dying cells.
The result is the activation of autoreactive T and B cells and the
eventual secretion of autoantibodies.
What is a example of type 4 immune reaction?
Type 1 diabetes is an example of a type 4 immune reaction.
In type 1 diabetes there
is highly specific destruction of insulinproducing β cells in the pancreatic islets of Langerhans, sparing other islet cell types (α and δ).
What causes autoimmune diseases?
Its multifactoral:
- It could be hereditary or infections that induce (or protect?).
- It is maybe possible because of hormones or stress?
– Environmental factors, exposure?
How can autoantibodies cause damage to the body’s own cells?
Autoantibodies are antibodies created for self-antigens. This is harmful to the body because it causes
immune cells to react to our own tissues. If the autoantibodies targets cells(erythrocytes, thrombocytes) it will lead to opsonization, phagocytosis or complement activated lysis, in other words, destruction of the cell. If the autoantibodies target tissue, it will lead to complement and Fc-mediated inflammation and tissue damage.
Explain the role of heredity/genes in autoimmune disease. What significance does heredity
have, what genes could be of importance?
HLA association is common in autoimmune disease, most often HLA/MHC class II. A specific HLA allele
can increase the relative risk of autoimmune disease. HLA is responsible for antigen presentation to T-cells, shows autoantigen (but also other factors included).
There is an increased risk of getting an autoimmune disease if there is a family member that also has an
autoimmune disease.
What is Immunomodulating treatment?
Its an immunosuppressive treatment that selectively inhibits disease-inducing reactivity.
Certain examples of are:
- Blocking cell-trafficking(anti-VLA4)
- Blocking cytokines using
- Monoclonal antibodies against
TNF, IL1,or IL6
- Inhibition of signal transduction
(JAK)
- B-cell depletion (anti-CD20)
- T-cell inhibition (cyclosporin)
