T-cell maturation / immuno week 6 Flashcards
What is the first step of T-cell maturation when the cell reaches the thymus?
rearrange TCR genes (specifically beta chain)
after beta chain rearranges, you make pre-TCR
What does pre-TCR signal?
starts proliferation / double positive expression on T-cells
What happens after proliferation in the thymus?
positive selection
T-cells express both CD8 and CD4
occurs in thymic cortex
*make sure TCR recognize antigens presented by MHCs
What happens after positive selection?
negative selection at the cortex-medullary boundary (medullary more)
cells only positive for CD8 OR CD4
selects for TCR that attacks MHC + self with a low binding affinity (never receive a signal for apoptosis)
MHC-restricted
T-cells are MHC-restricted after they pass positive and negative selection
can only bind to peptide antigens in the context of the MHC molecules presented by their hosts
Where do T-cells go after the thymus?
to secondary lymphoid organs (lymph nodes + spleen)
Immune tolerance
refers to the ability of immune system to recognize a wide variety of potentially pathogenic microorganisms and react to self-structures
need to discriminate self from not-self
Central tolerance
tolerance to self antigens that is established in lymphocytes during development in primary lymphoid organs (thymus or bone marrow)
removes strongly autoreactive lymphocytes
Peripheral tolerance
tolerance to antigens encountered by mature lymphocytes in peripheral tissues
AIRE
involved in self-tolerance
transcription factor
turns on expression of self proteins in the thymus
APECED
a severe and fatal autoimmunity causes by mutations in the AIRE gene
What happens if an antigen binds strongly to self-cell presented by AIRE transcription factors?
the T-cell is deactivated
What happens if a T-cell binds moderately to self-antigen?
cells develop into regulatory T-cells (Tregs)
What transcription factor is essential for Treg development and function?
Foxp3
Where does B-cell central tolerance occur?
in the bone marrow
List the 4 peripheral tolerance mechanisms
Anergy
Activation induced cell death (AICD)
Suppression by regulatory Treg and Breg
Immune privilege
Anergy
state of non-responsiveness to antigen
peripheral tolerance mechanism
IPEX Syndrome
mutation in Fox3p gene
leads to multiple autoimmune diseases in infancy
no Tregs
How do Tregs work?
they can regulate overactive T-cells
secrete anti-inflammatory cytokines that inhibit T-cells or other immune cells
immunologically privileged sites
sites in the body where the immune system is dampened down
Examples of immunologically privileged sites
brain, eye, testis, uterus
3 ways immune privileged sites work”
- not surrounded by conventional lymphatics + tissue barriers
- use non-inflammatory Th2 responses
- expression of Fas ligand by tissues of privilege. induce apoptosis in Fas-bearing lymphocytes that try to enter these sites
What do you need to develop an autoimmune disease?
combination of genes and environment
Are autoantibodies always cause of disease?
no, sometimes they are the symptoms of a disease
