(12) T-cell III

Question 1

(Immunological Tolerance)

1. What is the absence of an immune response to antigens? This involves regulations of what types of cells?

Answer 1

1. Tolerance; B and T cells

Question 2

(Tolerance)

1. Which type of tolerance is mediated primarily by removing T cell and B cell clones that might recognize self antigens? What is another name for this? When does this happen? where? to what?
2. If something binds can it try to save itself?
3. What type of tolerance is used when a self-reactive t or b cell gets out into the periphery? another name?

Answer 2

1. Central tolerance; deletional tolerance; when b and t cells are differentiating; in bone marrow and thymus; to those cells with receptors that recognize self
2. yes, by altering DNA of light chain (only a limited amount of times though)
3. peripheral tolerance; regulatory tolerance

Question 3

look at this a little

Question 4

1. The positive/negative selection of T cells in the thymus is a form of what kind of tolerance?

(T cell interaction with thymic cortical epithelium)

2. weak or no signal (peptide is irrelevant)?
3. partial signal (peptide is antagonist)
4. signal for apoptosis - too much signal (peptide is agonist)

Answer 4

1. central tolerance
2. cell fails to be positively selected (dies by apoptosis)
3. cell rescued from programmed cell death, survives and matures
4. cell induced to undergo apoptosis

Question 5

1. What kind of tolerance is mediated primarily by inactivating T and B cell clones that might recognize self antigens in peripheral tissues?
2. What happens to these cells?

Answer 5

1. peripheral tolerance
2. apoptosis or anergy (go to sleep)

Question 6

(Anergy)

1. For self-reactive T cells in the periphery, tolerance is induced by what?
2. Without co-stimulation, the T cell is induced to what?
3. How long is this state?

So….

4. co-stimulatory signal alone?
5. specific signal alone?
6. both?

Answer 6

1. lack of co-stimulation
2. anergy (lack of responsiveness)
3. state of anergy is long lasting
4. no effect on t cell
5. inactivates t cell (anergy)
6. proliferation and differentiation of t cells

Question 7

1. B cells can be rendered anergic in the periphery as well if they don’t receive enough what? including help from what?

Answer 7

1. positive signal; T cell help

Question 8

1. What is the fact that certain tissues are capable or restricting the extent of an immune response or the activation of immune cells called? Typically, antigens from these sites can be what if exposed to teh adaptive immune system in the proper contex? What do these tissues have that block the access of pathogens?
2. Immune-privileged sites are operationally defined as what? example?
3. immune-priviledged tissues are operationally defined as what? example?
4. What are 5 immunologically privileged sites?

Answer 8

1. immune privilege; immunogens; tight blood barriers
2. sites where foreign tissue grafts survive for a long period of time; skin from animal A transplanted to brain of animal B
3. organs that experience extended survival when transplanted to conventional sites on a mismatched recipient; cornea from animal A transplanted to skin of animal B
4. brain, eye, testis, uterus, hamster cheek pouch

Question 9

(Immune privilege)

(1-3). Immunge privilege is induced and maintained by 3 things.. .what are they? *also one more he mentioned in next slide

4. What is the bad side of immune privilege?

* I have included the slide from which this info was drawn - I’m a little confused as to where these distinctions were drawn so it might be a good idea to get that cleared up a little

Answer 9

1. expression of ligands on target cells that block access/effector function of Tc cells, or induce apoptosis (ie Fas-FasL)
2. Reduced expression of class 1 MHC molecules (ie in the eye, brain)
3. expression of anti-inflammatory cytokines and immunosuppressive factors in the tissue (THF-beta-2 is a big one here)

*exclusion of inflammatory/cytolytic cells from the tissue

4. these cells not asking for help allows the growth of tumours

Question 10

(T cell tolerance)

1. Occurs in the thymus by deleting self-reactive T cells and by creating what?
2. Thymic stromal lymphopoietin (TSLP) -derived dendritic cells in the thymus (near Hassall’s corpuscle) interact with some self-reactive T cells to make them Treg cells capable of what?
3. What makes TSLP?
4. What happens to with the dendritic cells that haven’t been modified by TSLP?
5. The graph shows the difference between TSLP dendritic cells and others… don’t express some of the cytokines that others do

Answer 10

1. T reg cells
2. muting response to those self antigens in the peripheral tissues such as lymph nodes
3. Hassal’s corpuscle
4. their corresponding cells just die

Question 11

(Regulatory t cels)

1. Treg cells produce what kinds of cytokines such that they inhibit the activity of other cells, including what type?
2. Can the gut be a source of TSLP and TGF-b as well?

Answer 11

1. anti-inflammatory cytokines (IL-10 an TGF-b); activated T cells
2. yes, in peyer’s patches

Question 12

(1-4). Treg cells mediate peripheral tolerance by doing what four things?

Answer 12

1. inhibiting APC activation

2. secreting cytokines that suppress T cell function in the peripheral tissues

3. binding cytokines needed by normal T cells for survival
4. kill autoreactive T cells directly (maybe)

(he says to only know the first two)

Question 13

(Peripheral T cell tolerance)

1. Are some T cells inactivated in the peripheral tissues as well under normal conditions?
2. In the absence of infection, what drives differentiation of Treg cells (sometimes called Tr1 cells)?
3. When inflammation stars, many Th0 cells are pushed initially down what pathway?
4. In the intestine, many treg-like cells exist and are somtimes called what? they make alot of what?

Answer 13

1. yes
2. TGF-beta production by dendritic cells in draining lymph nodes
3. the Th17 pathway (in one specific example anwya)
4. Th3 cells; TGF-beta

Question 14

(Tolerance)

learn this - on ipad

Question 15

(Additional Mechanisms to Induce Tolerance)

1. does tolerance depend on how and when the antigen is intoduced? ex - if a neonate is exposed to antigen, the system does what? T receptor repertoire is malleable until shortly before when?
2. Tolerance can be induced by high doses of antigens - what is this called?
3. What can be induced by feeding antigens? is this well understood?
4. tolerance to fetal antigens is maintained by what three things? (

Answer 15

1. yes; develops tolerance to it; immune maturation
2. clonal exhaustion
3. oral tolerance - no
4. hiding the placenta, blcoking maternal Abs from reaching the fetus, or the presence of Tregs - (they also express an enzyme (IDO) that depletes tryptophan from the site to “starve” autoreactive cells. The fetus also expresses a complement inhibitor, Crry)