Tolerance Induction/MHC Restriction Flashcards Preview

Immunology Exam Two > Tolerance Induction/MHC Restriction > Flashcards

Flashcards in Tolerance Induction/MHC Restriction Deck (87)
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1
Q

Are HEVs present in the thymus?

A

No

2
Q

What two organs lack afferent lymphatics?

A

Spleen and thymus

3
Q

What hormones are produced by the thymus?

A

Thymulin, thymosin alpha-1, thymopoietin

4
Q

Thymulin produced by the thymus is dependent on what mineral?

A

Zinc

5
Q

What happened when the thymus was removed from neonatal mice?

A

Degeneration of the anterior pituitary within 30 days

6
Q

What is the function of thymulin that is produced by the thymus?

A

Involved with T cell maturation and differentiation (can also affect the neuroendocrine system

7
Q

In what organ do T cells mature?

A

Thymus

8
Q

What does it mean when T cells become mature?

A

Learn tolerance of self aka “central tolerance induction”

9
Q

What does it mean when a T cell is “nude”?

A

Doesn’t express CD4, CD8, or TCR

10
Q

Nude T cells enter the thymus from what location?

A

Bone marrow

11
Q

Where in the thymus do nude T cells proliferate?

A

Cortex

12
Q

Nude T cells are resistant to what process?

A

Apoptosis

13
Q

Why are nude T cells resistant to apoptosis?

A

They express little or no Fas protein

14
Q

What is expressed heavily on nude T cells that help protect them against apoptosis?

A

Bcl-2

15
Q

What does it mean when a T cell becomes a double positive (DP) cell?

A

Possesses both CD4 and CD8 co-receptor molecules, lots of Fas protein on surface, and very little Bcl-2

16
Q

What is the most common lymphocyte in the thymus (80%)?

A

Double positive (DP) cells

17
Q

What two tests must a DP cell pass to avoid death?

A

MHC restriction

Tolerance to self

18
Q

What is CD44?

A

Receptor for hyaluronic acid
Associated with thymocyte migration events
Considered a marker for T-cell activation

19
Q

What is CD25?

A

Alpha chain of IL-2 receptor

Favors IL-2 thymocyte proliferation

20
Q

Which DP test is considered “positive selection”?

A

MHC restriction

21
Q

Which DP test is considered “negative selection”?

A

Tolerance to self

22
Q

What occurs in the positive selection DP test?

A

T cell must only recognize peptides presented on MHCs

23
Q

What occurs in the negative selection DP test?

A

T cell must not recognize self peptides

24
Q

During which DP test does 95% of the maturing T cell deaths occur?

A

Positive selection (MHC restriction)

25
Q

What cells check to see that T cells have receptors (TCR) that recognize one of the “self MHC” molecules (both I and II) during positive selection?

A

Cortical epithelial cells (CEC)

26
Q

Where does the MHC restriction (positive selection) DP test occur?

A

Cortex of thymus

27
Q

What happens to a T cell that recognizes peptides not presented by MHC molecules during positive selection?

A

Eliminated by apoptosis

28
Q

When is a T cell referred to as a single positive cell (SP)?

A

After positive selection when it chooses either CD4 or CD8

29
Q

What cells give the negative selection test?

A

Thymic dendritic cells and medullary thymic epithelial cells

30
Q

After becoming single positive cells, where do the T cells migrate?

A

Medulla (to begin negative selection)

31
Q

From where are thymic dendritic cells derived?

A

Bone marrow

32
Q

Medullary thymic epithelial cells are related to what kind of cells (but have a different function)?

A

Cortical thymic epithelial cells

33
Q

What is the negative selection DP test?

A

Thymic dendritic cells check to see if T cells recognize any of the self peptides displayed by MHC molecules on the cell’s surface

34
Q

What is the goal of the negative selection DP test?

A

Eliminate T cells that recognize self peptides

35
Q

Thymic dendritic cells only live about how long in the thymus?

A

1 week

36
Q

Which test, positive or negative selection, prevents against auto immune disease?

A

Negative selection

37
Q

Which cells express tissue specific proteins (antigens) that are unique to different tissues/organs in the body?

A

Medullary thymic epithelial cells

38
Q

Which cells are responsible for cross presentation?

A

Medullary thymic epithelial cells

39
Q

What cells are responsible for displaying self peptides on MHC molecules?

A

Thymic dendritic cells

40
Q

Are intracellular proteins found on MHC I or MHC II?

A

MHC I (endogenous)

41
Q

Do thymic dendritic cells sample the surrounding environment and present exogenous proteins on MHC I or MHC II?

A

MHC II

42
Q

Medullary thymic epithelial cells engage in what process where they regularly enclose portions of their cytoplasm within a membrane?

A

Autophagy

43
Q

When medullary thymic epithelial cells engage in autophagy, do they present protein samples on MHC I or MHC II molecules?

A

MHC II

44
Q

What is the location for negative selection DP test?

A

Medulla

45
Q

Do mature T cells recognize MHC-peptide complexes?

A

Yes

46
Q

Self antigens are presented on which cells of the thymus during the negative selection test?

A

Thymic dendritic cells and medullary thymic epithelial cells

47
Q

How long does the T cell maturation process take?

A

About 2 weeks

48
Q

What is the pass rate of T cell maturation?

A

1/30

49
Q

What happens to T cells that fail the maturation process?

A

Death by apoptosis and eaten up by macrophages

50
Q

About how many double positive T cells begin a DP test each day?

A

60 million

51
Q

What is the riddle of MHC restriction and tolerance induction?

A

How any T cells can possibly pass both the positive and negative selection

52
Q

What is a rogue T cell?

A

One that got out but should have been killed

53
Q

What is the issue with rogue T cells?

A

Likely to be self-reactive

54
Q

How are natural regulatory T cells able to enter into secondary lymphoid organs?

A

Expression of a gene called Foxp3 enabling them to receive adhesion molecules that are used as “passports” for temporary travel

55
Q

What do people who lack the Foxp3 protein end to die young of?

A

Autoimmune disease?

56
Q

What is peripheral tolerance?

A

When a virgin T cell strays into abnormal tissues and encounters a rare self antigen that they weren’t exposed to in the thymus

57
Q

What is a cell called when it recognizes its “cognate antigen” but does not receive the co-stimulatory signal?

A

Anergized

58
Q

What happens to anergized cells?

A

They can’t function and die quickly

59
Q

What is the “two key” activation required of T cells?

A
  1. Enough antigen to cluster receptors

2. Co-stimulatory signals

60
Q

What kind of cells present lots of antigen and co-stimulatory (B7) molecules?

A

Antigen-presenting cells

61
Q

What is the extra level of protection against naive T cells that travel outside their normal traffic pattern?

A

Peripheral tolerance

62
Q

When a T cell passes even through peripheral tolerance, what is the next layer of defense?

A

Tolerance due to activation-induced cell death (AICD)

63
Q

What is tolerance due to activation-induced cell death (AICD)?

A

When stimulated many times by self antigens, T cells then become more sensitive to ligation of their Fas proteins thereby leading them to be killed via apoptosis

64
Q

What is central tolerance?

A

Positive and negative selection tests

65
Q

What is tolerance by ignorance?

A

Restricted traffic patterns preventing self reaction of T cells

66
Q

What is the order of T cell tolerance?

A
Central tolerance
Tolerance by ignorance
Tolerance induction in secondary lymphoid organs
Peripheral tolerance
Tolerance due to AICD
67
Q

Most B cells are tolerized where?

A

Bone marrow

68
Q

After testing, B cells that do not react to self are sent where?

A

To circulate blood and lymph

69
Q

What happens to virgin B cells that venture into tissues that meet their cognant antigen but do not receive T cell help?

A

Either anergized or deleted

70
Q

What is the process by which B cells modify their receptors after they have been activated?

A

Somatic hypermutation

71
Q

Can T cells go through somatic hypermutation?

A

No, only B cells

72
Q

What cells are the source of antigen for B cells in germinal centers?

A

Follicular dendritic cells

73
Q

Are self antigens usually opsonized?

A

No

74
Q

Where does B cell tolerance occur?

A

Bone marrow

75
Q

What is receptor editing of B cells?

A

When B cells that recognize “self” are given a chance to change

76
Q

About what percent of B cells successfully go through receptor editing?

A

25%

77
Q

What happens to B cells that get into tissues and deviate from their usual restricted travel?

A

Either anergized or deleted

78
Q

Where are iTregs developed?

A

MALT

79
Q

What is the function of iTregs?

A

Restrain the immune system to keep it from over-reacting to foreign antigen in tissue

80
Q

How do iTregs work?

A

By producing cytokines that suppress the immune response

81
Q

Where are nTregs developed?

A

Thymus

82
Q

What is the function of nTregs?

A

To provide protection against T cells in lymph nodes with the potential to react against self antigens that escaped negative selection in the thymus

83
Q

What type of “Treg” is thought to require direct cell to cell contact and are antigen specific?

A

nTreg

84
Q

What type of “Treg” is mainly CD4+?

A

nTreg

85
Q

What type of “Treg” can be either CD4+ or CD8+?

A

S.N. Tregs

86
Q

Which is considered a strong interaction: positive or negative selection?

A

Negative selection

87
Q

Which is considered a weak interaction: positive or negative selection?

A

Positive selection