Tolerance and Autoimmunity Flashcards
What causes primary immunodeficiency?
Primary immunodeficiency is caused by an inherited defect in the immune system. Can affect adaptive or innate systems. Results in overwhelming or opportunistic infections.
What causes secondary immunodeficiency?
Secondary immunodeficiency is caused by predisposition and disease from infection, malnutrition, aging, immunosuppression or chemotherapy.
What is an example of secondary immunodeficiency?
An example of secondary immunodeficiency is AIDS arising from HIV-I, which causes a depletion of CD4+ t-cells. This results in susceptibility to opportunistic infections, secondary neoplasms (abnormal mass of tissue) and neurologic manifestations.
What occurs when there is too much of an immune response?
Too much of an immune response leads to syndromes alike allergies and autoimmune disease. This is normally prevented by immune tolerance, but can occur with acute or chronic inflammation hypersensitivities. This leads to self-antigens being targeted by the immune response.
What is self-tolerance?
Self-tolerance is a lack of an immune response to one’s own tissues/ antigens.
What causes an autoimmune disease?
An autoimmune disease is a breakdown of self-tolerance.
What is central t-cell tolerance?
Central t-cell tolerance is the presentation of self-antigens and MHCs to CD4/CD8 cells by antigen presenting cells, in the thymus.
How does central t-cell tolerance occur?
Central t-cell tolerance occurs as developing t-cells are presented alongside MHCs to CD4/CD8 thymocytes. If no signalling occurs as there is no MHC = apoptosis. If there is weak MHC and t-cell reactivity then these cells surive and mature. If there is strong MHC and self peptide binding, apoptosis occurs.
Why does peripheral tolerance occur? H
Occurs as not all self-antigens are in the thymus.
What are the mechanisms of central tolerance?
Anergy - T-cell can’t respond to the antigen as the two signals for activation don’t occur, as co-stimulatory molecule isn’t expressed on the antigen presenting cell. CTLA-4 must compete for B7
Suppression - Regulatory lymphocytes express FoxP3 transcription factor to ensure tolerance and cytokines are secreted that dampen the t-cell response.
Deletion - Strong recognition of self-antigen = death.
Ignorance - Antigens are hidden from circulation.
What occurs during the gene rearrangement of b-cell tolerance?
- B-cell comes across a strong linking antigen in the bone marrow
- B-cell will undergo gene rearrangement, so it doesn’t have to die
- The receptor is edited and the self-reactive light chain is deleted/ replaced
What happens when gene rearrangement fails?
If gene rearrangement fails, the autoreactive b-cell is eliminated by apoptosis (deletion).
What are the processes of central tolerance?
Ignorance - Low access, weak binding or low concentration of the self-reactive antigen
Anergy - Antigen is permanently unresponsive and doesn’t survive.
Deletion
*these occur with aid from t-cells
What are the mechanisms of autoimmunity?
The mechanisms of autoimmunity are..
- Inheritance of susceptibility genes (HLA and non-MHC genes which affect amount of auto-antibodies, control activation of lymphocytes and AIRE development).
- Environmental triggers which promote self-reactive lymphocytes to activate
What is AIRE?
AIRE is an autoimmune regulator and transcription factor that induces the expression of peripheral tissue antigens in the thymus.
*Mutations in AIRE will cause an autoimmune disease