Lecture 36

Question 1

What does tolerance ensure

Answer 1

That the immune system avoids destroying host tissue
Helps keep self-reactive recognition molecules/cells (BCRs and TCRs) from circulating in the blood stream

Question 2

Where do T cells develop

Answer 2

Initially in bone marrow (early stages) but then migrate to thymus (reach maturity)

Question 3

Name of developing T cells

Answer 3

Thymocytes

Question 4

Parts of the Thymus

Answer 4

Cortex–>top/superficial
Medulla–>bottom/deep

Question 5

Which cells are in the cortex of the thymus

Answer 5

Cortical epithelial cells and thymocytes

Question 6

Which cells are in the medulla of the Thymus

Answer 6

Medullary epithelial cells, macrophages, and conventional dendritic cells

Question 7

How do T cell precursors enter the thymus from bone marrow

Answer 7

As double negative (DN) cells
Don’t express CD4 OR CD8

Question 8

Pathway of receptor expression during T cell development

Answer 8

Double negative (DN), no expression of CD4 OR CD8–>Double positive (DP), expresses BOTH CD4 AND CD8–> Single positive (SP), expresses EITHER CD4 OR CD8

Question 9

Outcome of Positive selection in T cells

Answer 9

MHC restriction
Selecting thymocytes with receptors capable of binding self-MHC molecules

Question 10

Outcome of Negative selection in T cells

Answer 10

Self-tolerance
Selecting AGAINST thymocytes with high affinity receptors for self/MHC/self peptide complexes

Question 11

What do cortical epithelial cells express high levels of

Answer 11

MHC 1 and 2

Question 12

Outcome of TCR not binding to self-MHC molecules (positive selection)

Answer 12

Death by neglect

Question 13

Outcome of TCR binding too strongly to self-MHC molecules

Answer 13

Cell death/apoptosis

Question 13

Outcome of TCR binding with low affinity-just right to self-MHC molecules

Answer 13

Positive selection occurs, proceed to single-positive stage

Question 13

Outcome of positive selection to MHC II

Answer 13

T cell becomes a SP CD4+ T cell

Question 14

Outcome of Positive selection to MHC 1

Answer 14

T cell becomes a SP CD8+ T cell

Question 15

Which cells express Autoimmune regulator (AIRE, transcription factor) (negative selection)

Answer 15

Medullary epithelial cells

Question 16

Main action of AIRE (autoimmune regulator) (negative selection)

Answer 16

Induce expression of many tissue-specific proteins in thymic epithelial cells (allows many peptides in to then be presented on MHC 1 and 2)

Question 17

What does AIRE permit (negative selection)

Answer 17

Allows T cells to be screened against self-antigens safely in thymus

Question 18

Outcome of TCR NOT binding to self-MHC molecules (negative selection)

Answer 18

Cells survive

Question 19

Outcomes of TCR binding to pMHC (negative selection)

Answer 19

1) Clonal deletion leading to death of self-reactive T cells
2) Clonal anergy (inactivation of autoreactive T cells)
3) Clonal editing (second or third chances at rearranging a non-self-reactive TCR gene)

Question 20

Where does Peripheral tolerance take place

Answer 20

In periphery
Circulation and secondary lymphoid organs

Question 21

Main action of Peripheral tolerance

Answer 21

Helps protect against autoreactive thymocytes that have escapes negative selection in thymus (induce anergy)

Question 22

Which cells help maintain peripheral tolerance

Answer 22

Regulatory T cells (Tregs)

Question 23

Where does B cell development occur

Answer 23

Starts and majority is in bone marrow, but completed in periphery (including spleen)

Question 24

Type of selection required for B cells

Answer 24

Negative selection (self-tolerance), no need for MHC restriction/positive selection

Question 25

Outcomes of Negative selection in B cells (binding to pMHC)

Answer 25

1) Clonal deletion of strongly autoreactive cells (apoptosis) 2) Receptor editing (reactivation of recombination machinery) 3) Anergy (induction of nonresponsiveness to further stimuli)

Question 26

How are self-antigens presented

Answer 26

Present on stromal cells and other cells or just soluble proteins in circulation

Question 27

Where do B cells migrate for further maturation

Answer 27

The Spleen

Question 28

Characteristics of Mature B cells

Answer 28

1) Express high levels of IgM/IgD on their surfaces 2) Negative selection (peripheral tolerance) 3) Recirculate between blood and lymphoid organs 4) Half life ~4.5 months in periphery

Question 29

Where does receptor editing of potential autoreactive receptors happen

Answer 29

In light chains

Question 30

What is central tolerance (negative selection)

Answer 30

Induction of immune tolerance IN primary lymphoid organs (bone marrow, thymus) through; Clonal deletion Receptor editing Clonal anergy

Question 31

What is Peripheral tolerance

Answer 31

Induction of tolerance OUTSIDE primary lymphoid organs through; Anergy Deletion Immune regulation (Tregs)

Question 32

Mechanisms of Central tolerance

Answer 32

1) Clonal deletion 2) Receptor editing 3) Clonal anergy

Question 33

Mechanisms of Peripheral tolerance

Answer 33

1) Anergy 2) Deletion 3) Immune regulation (Tregs)

Question 34

What is autoimmunity

Answer 34

A defect in tolerance

Question 35

What is organ-specific autoimmunity

Answer 35

Predominant injury of AN (singular) organ or tissue

Question 36

What is systemic autoimmunity

Answer 36

Injury of MANY (plural) different tissues

Question 37

Types of mechanism of autoimmunity

Answer 37

1) Cell-mediated autoimmunity (T cells) 2) Antibody-mediated autoimmunity (antibodies)

Question 38

Malfunction of Cell-mediated autoimmunity results in

Answer 38

Multiple sclerosis, Type 1 diabetes, etc

Question 39

Malfunction of antibody-mediated autoimmunity results in

Answer 39

Lupus

Question 40

How are the mechanisms of autoimmunity transferred

Answer 40

Cell-mediated autoimmunity--> T cell transfer Antibody-mediated autoimmunity-->Serum transfer