Immunological Tolerance & Autoimmunity

Question 1

lymphocytes in development could potentially recognize?

Answer 1

self Ag

Question 2

healthy IS can discriminate btwn?

failure to do so?

Answer 2

self and non-self

autoimmunity

Question 3

IS recognition of commensal microbes

failure?

Answer 3

must discriminate these from non-commensal

failure to do so is chronic inflammation

Question 4

particular Ag will result in what responses

Answer 4

immunological or tolergenic

Question 5

central/peripheral tolerance diagrammed

Answer 5

Question 6

Principal mechanisms of central T cell tolerance

Answer 6

occurs at the thymus: negative selection or development of t regulatory cells

Question 7

Principal mechanisms of peripheral T lymphocyte tolerance

Answer 7

anergy
deletion
supression via regulatory t cell

Question 8

usual T cell response diagram

many of the Ag presented are what?

Answer 8

many are self Ag, could allow a self recognizing t cell to react

Question 9

t cell anergy
which cells?
how can this occur?

Answer 9

CD4 and CD8 cells
two possible ways:
1. TCR does not send activating signal without costimulators present
2. T cell engages an inhibitory receptor (CTLA-4 or PD-1)

Question 10

how can CTLA-4 act on B7 in anergy

Answer 10

possesses higher affinity than CD28, non-activated APC with self Ag will have less B7 so it will mainly bind CTLA 4 causing removal

Question 11

t cell supression

Answer 11

occurs with CD4 cells via regulatory cells

Regulatory T cells develop in the thymus or peripheral tissues (LN) on recognition of self-antigens and suppress the activation of lymphocytes that also recognize these self-antigens

can inhibit the t cells but also other cells such as NK and b cells, will prevent naive activation, suppress activated t cells

Question 12

Regulatory T cells suppress immune responses by:

Answer 12

1. Cytokine signaling inhibits activation of target cells
2. CTLA-4 expression remove B7 from APCs
3. High amount of IL-2 receptor depletes IL-2 in local area

Question 13

deletion of self reactive t cells in periphery

Answer 13

t cell engages APc with self Ag, no costimulators present= activation of apop mechanisms without these

Anti-apoptotic mechanisms activated by costimulators (e.g.B7)
and cytokines from APCs during a response to foreign antigens (vs. self antigens)

Question 14

Principal mechanisms of central B lymphocyte tolerance
relation to T cells?
types of Ag recognized?

Answer 14

B cells can be activated by T cells in germinal centers, could potentially be self reactive t cells which could cause Ab production against self Ag
can also recognize more than just pro Ag

Question 15

Principal mechanisms of peripheral B lymphocyte tolerance

Answer 15

Question 16

commensal microbes and their protection
what cells help to protect?
physical protection?

Answer 16

do not want to destroy
TLR of DC can produce inhibitory signal in response to these microbes Ag
T reg cell can also use IL-10 to inhibit responses to these
physical separation of these microbes from lymphoid tissues (microbes usually in lumen)

Question 17

Postulated mechanisms of autoimmunity

Answer 17

usually genetic susceptibility which creates an error in self tolerance= self reactive t cells escape
this is then followed by some response to the environment such as injury and APC activation causing self reactive t cells to recognize self Ag and have efector response to self tissue = autoimmunity

Question 18

Mechanisms by which microbes may promote autoimmunity

Answer 18

microbe could induce costimulators on APCs with self Ag= self-reactive t cells are activated= autoimmunity
microbe may also use molecular mimicry to to have a similar Ag to a self Ag causing self reactive t cell to activate and autoimmunity to occur