2. Self Recognition and Tolerance

Question 1

immune tolerance

Answer 1

specific induced UNresponsiveness towards a particular antigen; tolerance is induced by exposure to the antigen, it is not a lack of response

Question 2

tolerance can be induced to foreign __ and also prevents the immune system from attacking __

Answer 2

antigens, itself (self-tolerance has to be learned)

Question 3

when is self-tolerance learned

Answer 3

pre-/neo-natal period

Question 4

the immune system randomly generates a great diversity of ___ __, some of which are self reactive. __ and __ cells bearing these self reactive receptors must be eliminated.

Answer 4

antigen-specific receptors, T and B

Question 5

prevention of self-reactivity is not __ determined. self-reactivity is prevented by processes that occur during __ and __ cell development

Answer 5

genetically, T and B

Question 6

self vs nonself discrimination is __ during immune development

Answer 6

“learned”

Question 7

immunological “self” means

Answer 7

all epitopes encoded by an individual’s DNA, but the structure of a molecule itself does not define “self”

Question 8

central tolerance occurs during

Answer 8

development of T and B cells in primary lymphoid organs
- T cells in thymus
- B cells in bone marrow

Question 9

what does central tolerance result in

Answer 9

elimination of self-reactive cells

Question 10

in central tolerance, self-reactive cells that escape into the periphery can still be __ or __

Answer 10

“tolerized”, suppressed

Question 11

what is key to the development of self-tolerance

Answer 11

T cell-tolerance; T cells “learn” to recognize self

Question 12

when does T cell tolerance occur

Answer 12

during development of T cells from precursors in the thymus

Question 13

two rounds of thymic selection

Answer 13

• positive selection
• negative selection

Question 14

where does positive selection occur

Answer 14

thymic cortex

Question 15

in positive selection, __ (CD4+/CD8+) T cells that bind (via TCR) to self ___ molecules (on thymic epithelial cells) are selected for __. this binding “rescues” T cells from death by __.

Answer 15

immature, MHC, survival, apoptosis

Question 16

in positive selection, surviving T cells are those that recognize __ __ molecules (give two examples) and then migrate into __ __ for negative selection.

Answer 16

self MHC, thymic medulla
- CD4+ cells recognize MHC-II
- CD8+ cells recognize MHC-I

Question 17

where does negative selection occur

Answer 17

thymic medulla

Question 18

in negative selection, specialized __ in thymic medulla express all self __ and present __ in MHC. T cells that bind strongly to ____ on MHC are selected for death by __. Surviving cells escape into periphery as __ T cells.

Answer 18

APC, proteins, peptides, self-peptides, apoptosis, mature

Question 19

stages in development of T cells

Answer 19

• random expression of alphabeta TCR repertoire (low alphabeta)
• positive selection: exposure to MHC molecules (low alphabeta)
• negative selection: exposure to self antigen (high alphabeta)
• mature T cell pool (high alphabeta)

Question 20

which cells in positive selection continue onto negative selection

Answer 20

cells that engage with MHC class I or II; otherwise there is programmed cell death

Question 21

which cells in negative selection continue onto mature T cell pool

Answer 21

cells that have no interaction with MHC class I/II + self peptide; otherwise there is TCR-induced cell death

Question 22

a few mature T cells that recognize self antigens may escape into the periphery. these can be suppressed by other post-thymic mechanisms like

Answer 22

peripheral tolerance mechanisms

Question 23

in peripheral tolerance mechanisms, if self-reactive T cells interact with __ presenting self-peptides but without ___ molecules, it leads to __

Answer 23

APC, costimulatory, apoptosis

Question 24

in peripheral tolerance mechanisms, regulatory T cells (nTregs) are also generated in the __ to regulate (suppress) self-reactive T cells in the __

Answer 24

thymus, periphery

Question 25

breakdown of self-tolerance can lead to

Answer 25

autoimmune disease

Question 26

what happens if APC present cross-reactive peptides derived from microbes to mature self-reactive T cells, and also have up-regulated costimulatory molecules (driven by PRR)

Answer 26

autoimmune disease

Question 27

in B cell tolerance, B cells require “help” from __ Th cells to generate high-affinity, class-switched __, including IgG. therefore, prevention of B cell auto-antibody production depends partly on __ of self-reactive T cells

Answer 27

CD4+, Ab, removal

Question 28

3 points of B-cell tolerance

Answer 28

1. lack of T cell help
2. clonal detection
3. clonal anergy

Question 29

in B cell tolerance, auto-reactive B cells are __ during their development in __ __. Immature B cells (sIgM+) that bind to antigens on other cell surfaces are __ (“negative selection”). surviving B cells mature, express __ and __, and escape into ___.

Answer 29

eliminated, bone marrow, removed, sIgD, sIgM, periphery

Question 30

in B cell tolerance, surviving mature auto-reactive B cells that encounter soluble, monomeric, self-antigens are not activated because (2 reasons)

Answer 30

• sIg receptors not cross-linked
• B cells rendered anergic

Question 31

tolerance to foreign antigens: some pathogens have evolved mechanisms that __ or __ their hosts’ immune responses

Answer 31

tolerize, suppress

Question 32

tolerance to foreign antigens: neonatal injection of __ cells

Answer 32

allogeneic
- maintenance of tolerance requires chimerism
- best achieved if inoculum contains self-renewing cells (e.g. bone marrow)

Question 33

tolerance to foreign antigens: non-identical twins that share a placenta can develop ___ to each other

Answer 33

tolerance

Question 34

tolerance to foreign antigens: tolerance to foreign antigens can be induced ___, but this must be done in ___ animals

Answer 34

artificially
- by injecting small doses of soluble monomeric proteins
- by injecting very large doses of soluble antigens –> immune paralysis
- by feeding soluble antigens –> oral tolerance

naive
- difficult to tolerize an adult animal that has already been sensitized to an antigen (i.e. in one that has already developed immune responses and has memory cells)