Lecture 7- Mechanism of Tolerance Flashcards
(46 cards)
What is immunological tolerance?
-lack of immunological reactivity is induced and maintained to self, harmless antigens (food) and commensal microbiota
How do T Cells recognise antigens?
TCR/CDR - and have CD4 or CD8
What does CD4 and CD8 recognise antigens via?
CD8- MHC class I CD4- MHC class II
How does B cells produce antibodies?
- B Cell receptor (BCR) recognises non-self antigen
- produce antibodies (immunoglobulins)
How do T cell initiate an immune resposne?
- T cells do not recognise the native antigens
- Antigen must be presented
- APC process the protein and present into MHC
- T Cell recognise peptide with their TCR
what does the immunological equilibrium rely on?
-Balancing lymphocyte activation and control
How does the immune system learn to discriminate between self and non-self?
-Normal immune system does not exhibit self reactivity
Describe the pathway taken by B cells to come to B memory cells and plasma cells?
1) Antigen independent phase in bone marrow: progenitor B cell—>Ig-gene rearrangement selection —>Mature B cell
2) Antigen dependent phase (activation and proliferation)- peripheral lymphoid organ
- Naive B cell—>-Ag selection–>cell death
- Naive B cell—>+Ag —-> memory cells
-Naive B cells+Th cells —>affinity maturation and class switching —> plasma cell- secreted AB
describe the process of formation of CD4 and CD8 T cells
1) Thymocytes from bone marrow—->rearrangement of TCR genes—-> immature thymocytes
- death by apoptosis of the cells that do not interact with MHC molecules
2) Positive selection of cells whose receptor bind MHC molecules
3) Negative selection and death of cells with high affinity receptors for self MHC or self MHC+self antigen
4) formation of mature CD4+ Th cell
- CD8+Tc cell
where do the lymphoid progenitor migrate to develop into mature T cells?
from BONE MARROW to THYMUS
When does the Thymus develop and when does it increase in size?
fully develops before birth and increases in size during puberty
when does the thymus shrink?
atrophies with age and the degeneration is complete by 30
Why is a mechanism for repertoire selection and self tolerance needed?
- Generation of TcR repertoire involves random mechanisms to allow diversity
- The specificty of TcR in the immature repertoire us also random and will include cells with receptors that are:
1. Harmful - self antigen recognition- (Negative select)
2. Useless (Neglect)
3. Useful- foreign antigen recognition (positive select)
Which T cells mature and form the peripheral T cell pool?
T cells that bear antigen receptor with appropriate affinity for the peptide presented in self MHC complex
Where is the positive selection and negative selection of T cells occur?
Positive- Cortex
Negative- medulla
what is positive selection?
-Retention of the thympcytes expressing TcR that are RESTRICTED in their recognition of of antigen by self MHC
Which thymocytes survive?
thymocytes able to recognise self MHC expressed on the surface of the epithelial cell
What is negative selection?
Removal of thymocytes that express TcR that recognise self antigen presented by self MHC
Which APC cells at the cortico-medullary junction express MHC I and MHCII and self peptides?
Dendritic and macrophages
What happens if the Double positive T cell shows modest binding to MHC molecules?
T Cell Lives
What happens if the Double positive T cell shows STRONG binding to MHC molecules?
Possible autoimmunity- T cell dies via apoptosis- Known as negative selection
what is the name of the gene that helps to prevent autoimmunity?
Autoimmune regulator- (AIRE)
What does the mutation in this gene cause?
- Autoimmune poleyendocrinopathy
- ectodermal dysplasia
How is the tolerance established to antigens that cannot be expressed in the thymus?
T-cell bearing TcR reactive with proteins expressed in the thymus are deleted
- some self proteins are not expressed in the thymus
- Tolerance needs to be induced and maintained outside the thymus
