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Immunity > Major Histocompatibility Complex (MHC) and T Cell Development > Flashcards

Major Histocompatibility Complex (MHC) and T Cell Development Flashcards

1
Q

Discovered in the early 1900s by tumor biologists who noticed that tumors arising in a particular inbred strain of mice could be transplanted into mice of the same inbred strain but not to mice of other inbred strains

A

MHC Locus

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2
Q

Further genetic studies revealed that the rejection of transplanted tumors as well as normal tissues is governed mostly by one set of cell surface antigens which were termed

A

Major histocompatibility antigens

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3
Q

The MHC complex in humans is called

A

Human Leukocyte Antigen (HLA)

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4
Q

The MHC in the mouse is called

A

H-2

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5
Q

MHC antigens are divided into which two types?

A

Class I and Class II

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6
Q

Both classes of MHC antigens are

A

Heterodimers

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7
Q

The most polymorphic genes of the human MHC. The ones that are routinely matched in pre-transplantation testing

A

Genes A, B, and DR

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8
Q

Made of a polymorphic alpha chain and a non-polymorphic beta chain called B2-microglobulin

A

Class I antigens

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9
Q

Made of polymorphic alpha and beta chains

A

Class II antigens

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10
Q

These proteins belong to the immunoglobulin superfamily and have similar domain structures

A

Class I and II antigens

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11
Q

Remember that MHC nomenclature is

A

Case sensitive

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12
Q

The mouse MHC locus (H-2) contains three polymorphic class-I genes encoding three class I alpha chain genes called

A

K, D, and L

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13
Q

The mouse MHC locus (H-2) contains 4 genes encoding two a and two B class two chains, which make the

A

A and E class II antigens

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14
Q

The murine MHC locus is located on chromosome

A

17

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15
Q

The human MHC (HLA) is similar in structure to the murine H-2 and encodes three class I antigens called

A

A, B, and C

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16
Q

The human MHC (HLA) encodes three class II antigens called

A

DP, DQ, and DR

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17
Q

The class II region also contains which 4 non-polymorphic class II genes

A

DM, DO, LMP, and TAP genes

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18
Q

The human MHC is located on chromosome

A

6

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19
Q

Not part of the MHC and is located on chromosome 15 in humans and 2 in mice

A

B2-microglobulin

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20
Q

The MHC locus in all species contains other genes some of which are related to antigen processing and MHC-peptide complex formation and some are totally unrelated to the function of MHC. These unrelated genes, as a group, are called

A

MHC Class III genes

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21
Q

The particular combination of MHC alleles on a chromosome is called an

A

MHC Haplotype

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22
Q

In mice all members of an inbred stain would, by definition, have the same haplotype which is designated by a small letter such as

A

b, d, k, or q (remember, casesensitive!)

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23
Q

Strains in which the endogenous MHC is replaced by an entire MHC locus from another strain

A

Congenic strains

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24
Q

A congenic strain in which the H-2d from the DBA/2 strain was introduced into the a B10 mouse

A

B10.D2

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25
Q

Strains in which only a portion of the endogenous MHC complex has been replaced by MHC of another haplotype, by breeding from one strain into another

A

Recombinant strains

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26
Q

Expressed on all cells in the body

A

MHC class I antigens

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27
Q

Normally expressed only on antigen presenting cells (APC)

A

MHC Class II antigens

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28
Q

Which three types of cells express the most class II antigens?

A

B cells, Dendritic Cells, and thymic epithelium

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29
Q

Do not express Class II, brain microglia, of the monocyte/macrophage lineage, do

A

Neurons

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30
Q

Recognize viral antigens in virus-infected cells only as a complex with MHC antigens

A

T Cells

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31
Q

In an experiment, T cells ‘primed’ by exposure to a virus in a particular mouse strain could only recognize and kill virus-infected cells of the same

A

MHC haplotype

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32
Q

The ability of T cells to recognize a particular MHC as self depends on the MHC haplotype(s) present in the

A

Thymus when they mature

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33
Q

Most cytotoxic cells express the T cell marker

A

CD8

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34
Q

Helper T cells always express the T cell marker

A

CD4

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35
Q

Cells expressing CD4 antigen always recognize antigens in the context of

A

MHC Class II antigens

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36
Q

Always recognize antigen in the context of MHC class I antigens

A

CD8 T cells

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37
Q

Can only recognize a mutation on self MHC class I antigens

A

CD8 T cells

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38
Q

Can only recognize a mutation on self MHC class II antigens

A

CD4 T cells

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39
Q

Restricted by Class I molecules of the MHC

A

Hapten-specific CTL’s

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40
Q

A congenic strain in which the normal MHC haplotype d of strain B10 has been replaced with haplotype k

A

B10.DR

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41
Q

A recombinant strain whose MHC is derived from haplotypes s, k, and d

A

AT.L

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42
Q

Engraftment experiments showed that T cell restriction occurred in vivo and was imposed by the MHC haplotype present in the thymus in which the

A

T cell was produced

43
Q

A x B TH that mature in a strain B thymus will only recognize antigen when it is presented by

A

APC of strain B

44
Q

A x B CTL that mature in a Strain A thymus will kill virus-infected cells of

A

Strain A but not Strain B

45
Q

T cells will only ‘help’ B cells of the same

A

MHC type

46
Q

Specifically bind to MHC class II and MHC class I molecules respectively

A

CD4 and CD8 molecules

47
Q

Binding determines the Class of MHC recognized by a T cell

A

T cell

48
Q

Although CD4+ cells can sometimes function as CTL, they will always be restricted by (= recognize antigen bound to)

A

MHC class II

49
Q

Antigens originating outside of the cell (like bacterial and other extracellular pathogens) are presented as a complex with

-only expressed on antigen presenting cells

A

MHC class II

50
Q

Antigens originating within the cell (like viral and tumor antigens) are presented as a complex with

A

MHC class I

51
Q

Some antigens can “cross” between the two pathways and will be then presented on both

A

Class I and Class II molecules

52
Q

For example, viral antigens which are mostly presented by MHC class I molecules can also end up in endosomes and be processed for

A

MHC class II presentation

53
Q

The physiological importance of having two antigen presenting pathways, which lead to two different types of immune responses, is to ensure proper immune reactions to different types of

A

Pathogens

54
Q

Most bacteria are extracellular and T cell help will be required for antibody production and will therefore be processed for

A

MHC class II

55
Q

Viruses on the other hand reside inside cells, where antibody cannot reach them. To kill the infected cell, they require

A

Cytotoxic T Lymphocytes (CTL’s)

56
Q

TH recognize exogenous antigen which is phagocytosed and presented by Class II. CTL recognize antigen synthesized inside cells, which is presented by

A

Class I

57
Q

Cleaves antigens into fragments

A

Proteosome

58
Q

Transports the fragments to the lumen of the rough ER, where they bind to newly made Class I

A

Transport of Antigenic Peptides (TAP) system

59
Q

Obviously, the immune system has to be able to get rid of all virus infected cells and therefore all cells in the body must express

A

MHC class I antigens

60
Q

No MHC means no

A

Immune recognition

61
Q

All other immune responses are tightly regulated such that the initiation of antigen specific reactions is controlled by specialized cells called the

A

APC

62
Q

The APC expresses

A

Class II antigens

63
Q

Obviously, a certain MHC haplotype will not bind all possible peptides processed for

A

Presentation

64
Q

However, it is highly unlikely that NONE of the peptides processed from a particular viral or bacterial proteins will bind to a particular MHC haplotype therefore ensuring an immune response to practically all

A

Pathogens

65
Q

Successful T cell activation requires, in addition to the recognition of antigen/MHC, the presence of co-stimulatory molecules on

A

APC

66
Q

These molecules on APC bind to specific ligands expressed on

A

T cells

67
Q

The main molecules of this type of the APC are

A

B7-1 and B7-2

68
Q

Engagement of the T cell receptor (TCR) in the absence of costimulatory molecules leads to a state of antigen-specific unresponsiveness often referred to as

A

Anergy

69
Q

CD4+ cells can be further divided into which two subtypes based on their cytokine secretion profile and on their immune functions?

A

Th1 (inflammatory) and Th2 (helper)

70
Q

The thymus is essential for the development of

A

T cells

71
Q

Very few T cells migrate out of the

A

Thymus

72
Q

Development of monoclonal antibodies specific for particular TCR families supplied the first clue for what happens during

A

Thymic selection

73
Q

T cells that recognize self antigens are not allowed to exit the thymus and are eliminated by a process termed

A

Negative selection

74
Q

The thymic selection process was elegantly demonstrated in experiments using

A

TCR transgenic mice

75
Q

For teaching purposes, we will accept the “theoretical truth” that a rearranged TCR will prevent any further rearrangements of other

A

TCR genes (= “allelic exclusion”)

76
Q

In both experiments summarized below, the TCR was molecularly cloned from a CD8+ CTL clone originating from an H-2b mouse, which means that the TCR recognizes antigen in the context of

A

MHC class I of the b haplotype

77
Q

In the Herald von Boehmer experiment, all T cells recognize H-Y peptides bound to H-2b Class I MHC. T-cells which carry receptors of this specificity are

A

CD8+

78
Q

In male mice, H-Y peptides are present. Immature cells in the thymus which recognize H-Y/H-2b Class I MHC are dangerous because they recognize

A

Self

79
Q

They are thus eliminated by

A

Negative selection

80
Q

In the HvB experiment, in female mice H-Y peptides are not present, so these cells are not dangerous and are allowed to survive and leave the

A

Thymus

81
Q

The lack of CD4+ in both males and female in the HvB experiment showed that there is another form of selection in the thymus called

A

Positive selection

82
Q

Only cells with TCR that match self MHC, at least with some affinity, are allowed to mature further

A

Positive selection

83
Q

The reason for positive selection is that in a mouse antigens are presented only by

-because there is no other MHC available

A

Self MHC

84
Q

So if a Tcell has a receptor that does not ‘match’ self MHC, that cell is

A

Useless

85
Q

T cells of irrelevant specificity are not only useless, but present a

A

Risk

86
Q

Secondary lymphoid organs will become large, swollen with huge numbers of useless

A

T cells

87
Q

CTL cloned from an H-2b mouse with receptor specificity anti-Ld. The TCR genes were cloned and transgenic mice made carrying different types of MHC

A

Denis Lo experiment

88
Q

In the Denis Lo experiment. What was found in

  1. ) H-2b mice?
  2. ) H-2s mice?
A
  1. ) Only CD8+ and no CD4+

2. ) No CD8+ or CD4+

89
Q

In homozygous H-2b mice positive selection takes place, since the clone that was the source of the TCR transgenes was positivelyselected by

A

H-2b MHC

90
Q

This positive selection will only operate on

A

CD8+ cells

91
Q

No CD4+ cells will form since there is no positive selection for them, because the TCR specificity is for

A

Class I

92
Q

Since the clone came from an H-2b mouse CD8+ cells escape negative selection by

A

H-2b mice

93
Q

In b x s mice the same things happen since a single b haplotype suffices for

A

Positive selection

94
Q

In b x d mice there will also be positive selection but now negative selection will also occur since

A

Ld is present

95
Q

In homozygous H-2s mice there will be no positive selection: the receptor specificity requires the

A

H-2b haplotype for positive selection

96
Q

Two processes, during maturation in the thymus, determine the final T cell repertoire in the adult. This was a conclusion from the

A

Denis Lo experiment

97
Q

Allows only T cells that recognize self MHC to develop further

A

Positive Selection

98
Q

Removes T cells that show a dangerously high reactivity towards self

A

Negative selection

99
Q

The crucial factor is the affinity of the developing thymocyte for

A

Self MHC + Self antigens

100
Q

On one hand, T cells that recognize self antigens with high affinity can become autoreactive and cause

A

Autoimmune disease

101
Q

Only T cells that recognize self MHC in a narrow range of affinity (high enough to be useful, low enough not to be dangerous) are allowed to

A

Mature

102
Q

This is why only a few percent of T cells formed in the thymus are allowed to

A

Leave it

103
Q

The set of foreign antigens encountered determines which immature T cells will make

-the “third-round” of selection

A

Immune responses

Immunity (33 decks)

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