Immunological Tolerance

Question 1

What is immuno tolerance?

Answer 1

Unresponsiveness to an Ag

Question 2

Describe central tolerance?

Answer 2

Induced in immature self reactive lymphocytes in PRIMARY organs ensuring only non reactive mature lymphocytes are relased

Question 3

Describe peripheral tolerance?

Answer 3

Induced in mature self reactive lymphocytes in peripheral sites to prevent activation of dangerous lymphocytes in tissues

Question 4

What three actions occur in central tolerance?

Answer 4

Immature lymphocytes for self Ag are deleted, change BCR specificity, or develop into Treg cells.

Question 5

What three actions can occur in peripheral tolerance?

Answer 5

Mature self reactive lymphocytes in peripheral tissues can be inactivated, deleted, or suppressed by Treg cells.

Question 6

What is major mechanism for mediating central tolerance of developing autoreactive B cells?

Answer 6

Clonal deletion and Anergy

Question 7

How are self reactive lymphocytes deleted in central tolerance?

Answer 7

Intrinsic Mitochondrial Pathway. Cell injury due to deficiency of growth factors/survival signals or DNA damage/protein misfolding causes cytochrome C release from mt. and initates caspase 9 which initiates executioner caspase 3.

Question 8

What happens when Self Ags are recognized by immature T cells in the thymus?

Answer 8

Leads to cell death via intrinsic path by negative selection or to development of Treg cells that enter peripheral tissues

Question 9

What are natural Treg cells? What cytokine is necessary for survival?

Answer 9

develop from thymus expressing FoxP3 and CD4 CD25 and CTLA4.
IL-2 critical for survival

Question 10

Describe induced Treg cells?

Answer 10

Differentiate into Treg inside the periphery. FoxP3 is induced in naive CD4 through recognition of TGF-B if IL-6 is NOT present. (if present dev into Th17).
iTreg also needs IL-2 and RA

Question 11

Where are inducible T reg cells specifically produced?

Answer 11

By Ag recognition in the LN’s and GI tract

Question 12

What are the key mediatiors of perhipheral tolerance?

Answer 12

Treg cells- they can inhibit T cell activation by APCs and inhibit differentiation into CTL’s and can prevent T cells from providing help to B cells to produce Ab’s

Question 13

What cytokines do Treg cells produce when they are activated by APC’s?

Answer 13

Produce inhibitory cytokines IL-4, IL-10 and TGF-B to inhibit APC causing a decrease in CD40, CD80/86, and IL-12, but increasing IL-10 causing APC to lose its ability to induce effectors.

Question 14

What are some functions of TGF-B?

Answer 14

Inhibits proliferation and functions of T cells, inhibits TH1 and 2 promotes Th17. Inhibits M1 macrophages, regulates differentiation of induced FoxP3 Treg stimulates IgA production, promotes tissue repair collagen synthesis

Question 15

What causes T cell Anergy and Suppression in peripheral tolerance?

Answer 15

Ag recognition without adequate CD80:CD28 costimulation causes anergy.
T cell receptor CD28 may engage CTLA-4 or PD-1 to cause suppression of T cell response.

Question 16

What two ways can cell death occur in T cell peripheral tolerance?

Answer 16

Cause death by Ag recognition without costimulation OR death by engagement of death receptors (FAS-extrinsic pathway)