Lecture 8 - Immunological Tolerance and Autoimmune Disease (Powell) Flashcards
Where does central tolerance occur?
bone marrow and thymus
Central tolerance involves…
immature lymphocytes recognizing self antigen
Peripheral tolerance involves…
mature self-reactive lymphocytes (that somehow escaped central tolerance)
Positive selection happens in…
cells can’t recognize MHC & are deleted
CORTICAL region of thymus
Negative selection happens in…
cells bind antigen too tightly & are deleted
MEDULLARY region of thymus
What Ig do immature B cells express?
IgM
Mechanisms of Peripheral Tolerance
- Clonal deletion/apoptosis
- Clonal anergy (functionally inactivated)
- Supression of these self-reactive T cells by interaction with other cells
- Ignorance (cells don’t respond to antigen)
B cells can undergo FOLLICULAR EXCLUSION (a type of peripheral tolerance.
They are excluded from enter the follicle of the speen, a very enriching area that B cells need to develop.
self-reactive B cells enter a state of anergy when T cells see the antigen, but they don’t respond w/ costimulatory molecule (CD40L/CD40 interaction) because the antigen is SELF and therefore the B cell does not become activated
okay.
Which two receptors are on a T cell?
CD28 (activate T cell)
CTLA-4 (shut T cell down)
What do CD28 and CTLA-4 bind to?
B7 on APCs
Which has higher affinity for B7, CD28 or CTLA-4?
CTLA-4 (T cell inhibitory costimulator)
What happens if no IL-2 is present?
T cell apoptosis. They NEED IL-2.
Oral administration of Ag _____ tolerance
favors
Subcutaneous Ag favor _____
immune responses