L 35 Flashcards
What is tolerance for T1DM?
Prevention of an immune response against an antigen causing a state of immunological unresponsiveness
Why does tolerance exist in T1DM?
Because lymphocytes have self-reactive receptors.
What are self-reactive lymphocytes?
Lymphocytes that recognise self tissue as requiring an immune response
Why do we have self reactive lymphocytes?
T cell and B cell receptors need to identify all pathogens for our survival in this world.
What is somatic recombination?
Random recombination means receptors formed randomly with different diversity by mixing up with different genes. Then they make different types of gene to bind with them and kill pathogens.
How are self-reactive lymphocytes formed? What is the adaptational benefit of this process?
Formed by somatic recombination.
Benefit = huge diversity produced to increase ability to recognise pathogens so we don’t get killed.
What should happen to self reactive lymphocytes? What are the 2 processes that do this?
They should be destroyed or controlled
Done via deletion or tolerance induced (respectively)
What is the process of deletion?
What is deletion also known as?
Aka negative selection or central tolerance.
Process: During early T and B cell development, the most self-reactive lymphocytes undergo apoptosis or die.
Peripheral tolerance: how do they occur?
It usually happens when self reactive cells escape from deletion. 3 ways i)Ignorance ii)Energy iii)Suppression
What are some limitations of the deletion process?
Not all peptides are present in the bone marrow or thymus at this stage, or sometimes only the strongly selective ones are weeded out. B cells mature in the ... T cells mature in the ... B cells mature in the bone marrow T cells mature in the thymus
What is ignorance
Lymphocytes are separated from immune privileged site however the sites also produce immunosuppressive cytokines.
What is anergy?
How does it work?
A lack of response or reactivity due to no costimulatory signal activating the T cell.
T cells need 2 signals to become activated. 1 from the antigen being presented as a result of the infection process. Then the antigen will response and produce antibody
2nd one is if there is no real infection but the antigen presenting cell calculated it mistakenly then, the 2nd signal won’t be occurring therefore there is no response to the self-antigen.
What is suppression/regulation?
Process whereby a suppressive cytokine (turns off immune response) or regulatory lymphocyte acts on a T cell to stop autoimmune reactions from occurring
What is autoimmunity?
Why does …. break down?
Autoimmunity is a breakdown of self tolerance.
Tolerance breaks down due to genetics and environment
What genes are involved in autoimmunity?
Polygenic.
Most important genes: ones involved in determining T cell activation - e.g MHC genes and cytokines.
What are the 2 ways that infection can cause tolerance to breaking down?
- Molecular mimicry
2. Bystander activation
What is molecular mimicry?
Why does it occur?
The peptide presented mimics a self-peptide that is also present in our body. T cell reacts with self-peptide because it is similar to another peptide.
Occurs as the peptides are very short (8-10 aa’s) therefore easy to mimic.
What is bystander activation?
Why does it occur?
The self-peptide cell has not been infected itself but is nearby. Cytokines in the area will activate the T cell because it is nearby and therefore causes self-reactivity.
The T cell must present a self-cell if there is no infectious antigen around to present.
3 types of autoimmune disease.
What is the difference between them?
T cell-mediated
Antibody-mediated
Immune complex-mediated
Difference: the self-reactive molecule being recognized is different (otherwise the process is the same)
T1DM is a … caused by …
T1DM is a chronic autoimmune disease caused by the immune destruction of B islet cells.
Pathogenesis of B islet cell destruction
T cells recognize antigens presented by B islet cells and destroy all B islet cells.
Why are NZ’s T1DM rates increasing so much? + examples
Environmental influences e.g climate, diet, social conditions, vitamin D