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PBD > Adaptive Immunity > Flashcards

Adaptive Immunity Flashcards

1
Q

Dendritic Cells share lineage with _________ and _________, and may have their own specific precursor cels.

A

Monocytes, Lymphocytes

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2
Q

What is CMP?

A

Common myeloid progenitor, precursor to dendritic cells shared by monocytes

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3
Q

What is CLP?

A

Common lymphoid progenitor, precursor to dendritic cells shared by lymphocytes

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4
Q

What sites in the body are immature dendritic cells found?

A

Skin, lymph nodes, blood, lining of airway and intestine, and interstitial spaces of most organs

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5
Q

What are Langerhan cells?

A

Dendritic cells of the SKIN and MUCOSA

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6
Q

What are dendritic cells?

A

Antigen presenting cells

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7
Q

What are macrophages?

A

Antigen presenting cells

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8
Q

What are T lymphocytes?

A

Antigen recognition cells

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9
Q

What are B lymphocytes?

A

Antibody production cells

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10
Q

What cells share a CLP (common lymphoid progenitor)?

A

NK cell precursor, B cell precursor, and T cell precursor

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11
Q

What are pluripotent stem cells?

A

Stem cells from which T and B lymphocytes are derived

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12
Q

The B in B lymphocytes stands for…

A

Bursa-derived cells

They mature in bone

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13
Q

Most B cells populate…

A

Lymphoid and related tissues including lymph nodes, spleen, mucosal tissues, and blood

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14
Q

Progenitor T lymphocytes differentiate into mature T cells in the…

A

Thymus

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15
Q

Most T cells populate…

A

Lymphoid and related tissues including lymph nodes, spleen, mucosal tissues, and blood

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16
Q

What cells are used in antigen presentation?

A

Macrophages and dendritic cells

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17
Q

Macrophages and dendritic cells use their _____ such as _____ to recognize ____ on microbes

A

PRRs, TLRs ; PAMPs

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18
Q

When dendritic cells and macrophages recognize a microbe, what do they do?

A

Phagocytose them, migrate to lymph nodes

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19
Q

How many amino acids must something have to initiate an immune response?

A

6

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20
Q

What is an epitope?

A

antigenic determinant; the part of an antigen that is recognized by the immune system

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21
Q

Antigen processing cells usually cut up microorganisms into how many amino acids?

A

10-20 (small fragments)

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22
Q

What does MHC stand for?

A

Major histocompatibility complex

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23
Q

Describe the MHC-1 pathway for antigen processing

A

Cytosolic (endogenous) pathway

Viral proteins in the cytosol are tagged with ubiquitin, processed to small peptides in PROTEASOMES, peptides are bound to TAP and transported to the ER

TAP exchanges peptides with MHC-1 molecules in the GOLGI

MHC-1 with loaded peptides are moved to the cell surface

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24
Q

Describe the MHC-2 pathway for antigen processing

A

Endocytic (exogenous) pathway

Microbial proteins are ingested by the host cell, the endosome fuses with a lysosome to form PHAGOLYSOSOME

They are cut up into small fragments in the phagolysosome

MHC-2 and CD74 combine in the golgi, and enter the phagolysosome

Cathepsin S trims CD74 to CLIP

HLA-DM facilitates exchange of microbial peptides with CLIP

MHC-2 with peptides moves to cell surface

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25
Q

MHC cells are used in…

A

Cell-cell recognition, tissue rejection, and antigen presentation

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26
Q

MHC-1 molecules are made up of…

A

alpha chain (with 3 domains) and beta-2 microglobulin bolecule (b2M)

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27
Q

What are the classical MHC-1 molecules? What does that mean?

A

HLA-A, HLA-B, HLA-C

They are expressed in ALL cells

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28
Q

What are non-classical MHC-1 molecules?

A

HLA-E, HLA-G, HLA-F, MICA, MICB, and HFE (restricted expression)

ABC in all, EGF not

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29
Q

What are the most polymorphic proteins known?

A

The alpha chain of classical MHC-1 molecules

Hundreds of possible MHC alleles compared to 2-3 for most other proteins

10-40 alleles for non-classical MHC-1s

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30
Q

True or False: The B2M chain of classical MHC-1 molecules are not polymorphic

A

True

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31
Q

HLA-A has ____ possible alleles in the human population

A

1800

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32
Q

HLA-B has ____ possible alleles in the human population

A

2400

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33
Q

HLA-C has ____ possible alleles in the human population

A

1300

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34
Q

The genes for MHC proteins are found on which chromosome?

A

Chromosome 6

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35
Q

Which MHC is a heterodimer?

A

MHC-2, with an alpha and beta chain, each with 2 domains

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36
Q

What are the classical MHC-2 molecules?

A

HLA-DP, HLA-DQ, HLA-DR (APCs)

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37
Q

What are the non-classical MHC-2 molecules?

A

HLA-DM, HLA-DN, HLA-DO, TAP, TAPBP

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38
Q

What is the order of MHC genes on chromosome 6?

A

MHC2 - MHC3 - MHC1

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39
Q

True or False: MHC-2 B chains are far more polymorphic than MHC-2 alpha chains

A

True

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40
Q

True or False: MHC-2 DR Beta chains are encoded by 4 different genes

A

True

B1, B3, B4, B5

41
Q

How many possible alpha chain alleles are present in HLA-DP?

A

30

42
Q

How many possible beta chain alleles are present in HLA-DP?

A

150

43
Q

How many possible alpha chain alleles are present in HLA-DQ?

A

40

44
Q

How many possible beta chain alleles are present in HLA-DQ?

A

150

45
Q

How many possible alpha chain alleles are present in HLA-DR?

A

<10

46
Q

How many possible beta-1 chain alleles are present in HLA-DR?

A

1000

47
Q

How many possible beta-3,4,5 chain alleles are present in HLA-DR?

A

90

48
Q

How many possible combinations of MHC-1 molecules are there in the human population?

A

5.6 billion

49
Q

How many possible combinations of MHC-2 molecules are there in the human population?

A

342.9 billion

50
Q

What are MHC-III molecules?

A

Member of the complement system and cytokine tumor necrosis factor (TMF)

51
Q

What is a haplotype?

A

A haplotype is a collection of specific alleles (particular DNA sequences) in a cluster of tightly-linked genes

Important bc chromosome 6 genes for MHC are inherited this way. This is why it is hard to find a tissue match for donation.

52
Q

The expression of haplotypes is…

A

co-dominant

53
Q

Why is polymorphism/polygenecity in MHC-1 and 2 complexes important?

A

Ensures maximum diversity in recognizing a vast number of pathogens

54
Q

Polymosphism in MHC is centered on the…

A

antigen binding grooves

55
Q

Can T cells recognize free antigens?

A

No, they must be picked up by MHC

56
Q

What is TCR?

A

T-Cell Receptor, expressed on T-cell surface to recognize APCs

57
Q

TCRs are made up of…

A

two heterodimers of two peptides (30-40 KDa) linked by a disulfide bond

58
Q

90% of T cells express _______. 10% express ______.

A

Alpha and beta heterodimer; gamma and delta

59
Q

What is V(D)J recombination?

A

Somatic recombination; causes each chain of T cells to have a constant region and a variable region that is different from T cell to T cell

60
Q

The genes for alpha and beta chains of TCR are located on which chromosomes?

A

Alpha - 14

Beta - 7

61
Q

TCR needs to form a complex with ____ and ______ (all called _______) for signal transduction after antigen recognition.

A

CD3, CD247, TCR Zeta chain

62
Q

MHC-II presented antigen is recognized by ____ expressing _______. These bind to the ___ site on MHC-II, and leads to the induction of what?

A

CD4-expressing Helper T Cells; beta2 site; antibody generation

63
Q

MHC-I presented antigens are recognized by ____ expressing ______. This binds to the ___ domain of MHC-I. This interaction leads to what?

A

CD8-expressing cytotoxic T cells; alpha 3; Leads to the killing of the antigen-presenting cell.

64
Q

The association of the _______ complex on cytotoxic T cells with MHC-I recruits ______.

A

TCR-CD3-CD8+, tyrosine kinase

65
Q

What happens when tyrosine kinases are recruited in cytotoxic t cells?

A

Cytotoxic T cells phosphorylate tyrosine residues in ITAM (immunoreceptor tyrosine-based activation motifs) domains of CD3 and CD247.

66
Q

What does ITAM do?

A

(Activated in cytotoxic t cells after antigen recognition)

Recruits protein kinase ZAP-70 to initiate a phosphorylation cascade leading to the release of PERFORIN and GRANZYME to kill the MHC-I through the same mechanism used by NK cells

67
Q

the MHC-II:antigen complex leads to what?

A

Same downstream signaling pathway as MHC-I cytotoxic T cells (ITAM -> ZAP-70). The phosphorylation cascade activated the CD4+ helper T cell to work with B cells to promote antibody generation.

68
Q

What are naive b cells?

A

Newly matured B cells that have not interacted with anigens

69
Q

Naive B cells express what as their BCR? Some also use what?

A

Monomeric IgM as their B cell antigen receptors; IgD

70
Q

B cells enter circulation and migrate to ________ where they interact with _____. They then become activated and turn into ____________.

A

Lymphoid tissues; T helper cells; anti-body producing plasma cells or memory cells

71
Q

What is the concentration of IgG in serum?

A

10 mg/ml

72
Q

Describe the structure of immunoglobulin

A 
Light chain (25 KDa) variable (VL)
Light chain constant (CL)
Heavy chain (50-70 KDa) variable (VH)
Heavy chain constant (CH)
FAB region (fragment antibody binding) (at the top w/ V)
Fc region (crystallizable fragment) binds complement proteins and Fc receptors on NK cells and macrophages
73
Q

How many types of heavy chains are there?

A

5, alpha delta gamma epsilon mu

74
Q

How many types of light chains are there?

A

2, lambda and kappa

75
Q

Which heavy chain types are the smallest?

A

Alpha and Delta (450)

rest are 550

76
Q

IgMs make up __% of total Ig

A

10%

77
Q

Which antibody is first produced as BCR on B cell surface

A

IgM

78
Q

IgMs in free blood are…

A

pentamers

79
Q

IgGs make up __% of total Ig

A

75%

80
Q

What is the half life of IgG?

A

20 days

81
Q

Which Ig is the only one that can get into placenta to provide immunity for the fetus?

A

IgG

82
Q

IgD make up __% of total Ig

A

0.2%

83
Q

IgE make up __% of total Ig

A

0.004%

84
Q

IgE are involved in…

A

hypersensitivity

85
Q

IgA make up __% of total Ig

A

10%

86
Q

IgA are involved in…

A

mucosal immunity

87
Q

Ig_ is the only dimer

A

IgA

88
Q

How do Ig molecules achieve diversity?

A

V(D)J somatic gene rearrangement (10^14 possible Ig molecules in an individual)

Somatic hypermutation (point mutation in the V regions of both heavy and light and occur for each cycle of division, greatly increases diversity)

89
Q

Directly activated B cells can only produce what?

A

IgM

90
Q

T-cell independent B cell activation is an early stage immune response and mainly against _________

A

Blood borne pathogens (before IgG is produced)

91
Q

True or False: T-cell independent naive b cell activations have limited variety and potency

A

True

92
Q

What is meant by the phrase “T-cell dependent B cell activation is a linked recognition”?

A

Binding of microbial antigenic structures causes BCR receptor crosslinking, followed by internalization, degradation, and presentation of antigens on B cell’s MHC-II. The antigen is then presented to a T helper cells whose TCR is capable of recognizing the same antigen.

93
Q

Only a ________ can recognize the same antigen presented by a B cell’s MHC-II

A

armed T helper cell

94
Q

What is an armed T helper cell?

A

CD4+ T cell that has encountered the antigen through prior interaction with an APC

95
Q

What is the consequence of T-helper cell mediated antigen recognition?

A

Upon interaction w/ B cells, armed T helper cells become activated and release cytokines IL-4 and IL-5

These induce “linked” B cell to proliferate into a single clone of large number of plasma cells (clonal expansion) to produce antibodies for the same antigen

B cells shed surface IgM during clonal expansion

B cells also undergo “Ig class switch” from producing IgM to producing IgG and some IgA specific for the same antigen

96
Q

When undergoing class switch from IgM to IgG to IgA, what remains the same?

A

Variable region

97
Q

How are B memory cells produced?

A

Activation of B cells by IL-4 and IL-5 from T helper cells also causes the differentiation of a population of the B cells into B memory cells

98
Q

How are T helper memory cells formed?

A

Activated T helper cells also release IL-2 to cause the expansion of Th cells forming T memory cells, in an autocrine fashion

PBD (7 decks)

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