Exam III and IV Flashcards

1
Q

Pro B cell stages

A

Heavy Chain rearrangement

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2
Q

Pre B cell

A

First checkpoint –> light chain rearrangement –> Second checkpoint

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3
Q

Immature B cell

A

Makes functional IgM

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4
Q

Survival of pro-B cell depends first on the productive rearrangement of the

A

heavy chain

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5
Q

Immature B cell can either be

A

u:k or u:l

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6
Q

how many successive attempts can be made of the kappa chain

A

5 successive attempts can be made of the kappa chain.

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7
Q

Immature B cell first undergoes

A

negative selection in the BM

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8
Q

receptor editing allows

A

the immature B cell more chances to make a nonreactive BCR (only editing in light chain)

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9
Q

B cell undergoes receptor editing

A

to make IgM with different specificities and not till the receptor is NOT self reactive, the B cell leaves the BM.

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10
Q

Maturation of B cells

A

immature B cells leave BM and enter circulation and secondary lymphoid organs.

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11
Q

Interaction with _ provides the required maturation and survival signals _

A

FDC; Positive selection

(competition with other B cell is the limiting factor for space in folice

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12
Q

enigmatic follicular dendritic cell

A

storage vessel for antigens ready for B cell stimulation.

CR1 and CR2 bind to intact virus particles and retain them at the cell surface

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13
Q

capture and display of intact antigens by CR2 expressed on

A

FDC and macrophages

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14
Q

How do B cells become activated?

A

When their receptors are cross linked by antigens

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15
Q

Much like T cell activation, B cell activation requires

A

Cross linking (clustering) and association with signaling adapters

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16
Q

B cell signaling cascade initiated from

A

ITAM domains in IgA and IgB

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17
Q

BCR triggering is greatly ENHANCED by

A

B cell coreceptor:
CD19/CR2/CD81

increase BCR signal intensity by 10,000 fold.

Work best with complement labeled antigens

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18
Q

CR2

A

binds to the antigen/microbe and initiates B cell activation

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19
Q

Binding of CR1 to C3b

A

bound to a pathogen facilitates its cleavage by Factor I to iC3b and C3d.

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20
Q

The CR2 component binds to

A

C3d

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21
Q

Two types of antigens activate B cells

A

T dependent: Require T cell help for production of antibodies (protein antigens)

T independent:

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22
Q

T dependent B cell activation

A

CD40/CD40Ligand interaction with T cells

Essential for T cell help

Required for isotype switching, affinity maturation

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23
Q

CD40:CD40L

A

B cells need two signals for activation by T cell dependent antigens.

To obtains T cell help, B cell must take up antigen through BCR, process and present peptide via MHC class II

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24
Q

T independent antigens

A

T1 and T2

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25
Q

TI1 (T independent antigens)

A

combination of BCR and TLR signals activate B cell

Require contribution from TLR signaling.

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26
Q

TI2

A

repetitive carbohydrate antigens present at high density on a pathogen surface, leads to extensive BCR cross linking

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27
Q

TI1

A

TLR

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28
Q

TI2

A

crosslinking

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29
Q

plasma cells

A

migrate to medullary cords or BM

  • have no cell surface immunoglobulin or MHC class II, no further division, specialized for antibody secretion
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30
Q

primary expansion of antigen activated B cells

A

medullary cords –> primary follicle –> creates the germinal center

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31
Q

cell entire devoted to antibody production

A

plasma cell

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32
Q

germinal centers

A

sites where somatic hyper mutation, affinity maturation and isotype switching occurs

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33
Q

memory B cells

A

maintained and circulate through body ready to rapidly respond upon pre-exposure to pathogen.

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34
Q

somatic hypermutation

A

Changes affinity for antibody

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35
Q

Resting B cell

A

Surface Ig: Yes
MHC class II: yes
High rate Ig Secretion: no
Growth : yes
Somatic hyper M.: yes
Isotype switch: yes

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36
Q

plasma cell properties

A

Surface Ig: no
MHC class II; no
High rate Ig Secretion ; yes
Growth ; no
Somatic hyper M.; no
Isotype switch: ; no

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37
Q

T cells, development and selection

A

Thymus

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38
Q

B cell location and development

A

BM

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39
Q

Function of T cell

A

kill or make cytokines

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40
Q

Function of B cell

A

make antibodies

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41
Q

Like B cells, T cells generate receptors through

A

somatic recombination

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42
Q

T cells are more _ than B cells

A

diverse

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43
Q

two classes of T cell receptors

A

alpha/beta and gamma/delta

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44
Q

majority of conventional T cells

A

alpha beta

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45
Q

T cell receptor class with high degree of receptor diversity

A

alpha beta

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46
Q

alpha/beta recognize

A

MHC/peptides

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47
Q

where are alpha/beta abundant

A

all secondary lymphoid tissues

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48
Q

gamma/delta abundant in

A

gut mucosa

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49
Q

types of alpha/beta T cells

A

CD4 and CD8

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50
Q

CD4+ T helper cells

A

Produce cytokines to help clear infections

recognize MHC II

Antigens tend to be from extracellular sources

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51
Q

CD8 + Cytolytic T cells

A

Killer cell

MHC I though CD8

Cytoplasmic sources

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52
Q

CD4 consists of

A

D1-4

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53
Q

CD8 consists of

A

alpha and beta chain

54
Q

TCR complex needs help from

A

CD3 to transmit signals.

Also required for Cell surface expression

55
Q

preTCR

A

Beta + pTalpha

56
Q

steps in T cell receptor formation

A
  1. beta, gamma and delta chains attempt to rearranged simultaneously
  • if beta is successful, then it’s tested with preTCR
    If gamma and delta are both successful, then rearrangement is complete and cell becomes a gamma/delta
  1. alpha, gamma and delta attempt rearrangement.
57
Q

double positive

A

when CD4 and CD8 are both expressed. after cell has rearranged beta chain successfully

58
Q

Pre TCR purpose

A

tests the ability of a rearranged beta chain to form complex with the preTalpha.

Stops rearrangement at the other beta locus - allelic exclusion

59
Q

which chain in T cell receptors have more attempts at functional rearrangement?

A

alpha

60
Q

implication for AB vs. GD TCR rearrangement

A

Delta gene is situated within alpha gene locus. Rearrangement of the alpha chain results in the deletion of delta loci, so no chance to make a gamma/delta.

61
Q

timing of rearrangement of the beta and alpha chains

A

RAG expression

62
Q

when T cells begin rearrangement, they are

A

double negative.

Neither CD4 or CD8 expressed

63
Q

when PreTCR is tested and proven to be successful,

A

CD4 and CD8 will be unregulated (double positive)

64
Q

after selection is complete,

A

T cells enter the periphery, only CD4 or CD8 will be expressed.

65
Q

thymic involution

A

as we get older, our thymus produces less and less T cells

66
Q

Cortex contains

A

cortical epithelial cells

thymocytes

medullary epithelial cells

67
Q

Medulla contains

A

dendritic cell

macrophage

68
Q

Positive selection of T cells occur in

A

cortex of thymus

69
Q

Positive selection of T cells occur

A

first, then negative

gets rid off poor binders

70
Q

what cells do positive selection in T cells

A

thymic epithelial cells

71
Q

negative selection of T cells occur in

A

Cortico-meduallry region

72
Q

Negative selection cells

A

dendritic cells.

Overly strong binders eliminated

73
Q

Positive selection determines whether a T cell will

A

commit to the CD4 or CD8 phenotype.

74
Q

Positive selection determines whether a T cell will

A

commit to the CD4 or CD8 phenotype.

75
Q

Lack of CD8 Case study

A

Patient had a deficiency in TAP which is needed for MHC class I, and with our CD8, there is no + selection for CD8 T cells in the thymus

76
Q

Pneumocytosis carinii

A

lacking CD4 T cells

77
Q

MHC class II deficiency seems from

A

B cells not expressing HLA-DQ or HLA-DR

78
Q

CD3 chains

A

EY
ED

79
Q

What cells activate T cells?

A

Dendritic cells, in the sites of infection, take up pathogen derived antigens. When triggered by PAMPs and inflammation at sites of infection, DC migrate to draining lymph nodes. They undergo maturation, enhancing their ability to present antigen and activate T cells.

80
Q

Naive T cells

A

Prior to recognition of antigen and activation.

Need several signals (MHC and co-stimulation) to become activated.

81
Q

Effector T cell

A

Activated cell, antigen experienced.

Need ONE signal, short lived

82
Q

Memory T cell

A

antigen experienced, easily activated state indefinitely.

REQUIRE ONE signal

83
Q

Two signals needed for naive T cells

A

MHC peptide

Costimulaiton through B7-1 or B7-2.

84
Q

B7-1 and B7-2 are

A

co-stimulatory molecules that are uniquely expressed by DC, Macrophages, B cells.

85
Q

B7 binds to CD28 on

A

naive T cell

86
Q

What happens when T cells recognize their cognate antigen?

A
  • TCR initiates signaling through CD3 and CD4/CD8
  • immune synapse forms at site of T cell-APC interaction
  • T cell and APC remind in sustained interaction for up to 24hrs
  • T cell disengages divides and emigrates from lymph node to seek out infected cell in periphery
87
Q

ITAM

A

immunoreceptor tyrosine based activation motifs

these are not phosphorylated in resting T cell.

Binding of MHC ligand to T cell receptor leads to phosphorylation of ITAMs

88
Q

PLC-y –>

A

CA2+, NFkB, AP1, NFAT

change the pattern of gene expression, cell division, proliferation and differentiation to effector T cells.

89
Q

Immunological synapse

A

structure that forms along the interface of T cell and APC during sustained interaction of T cell activation

90
Q

P-SMAC

A

peripheral,

adhesion molecules

91
Q

C-SMAC

A

TCR, co-stimulatory molecules and lots of signaling molecules

92
Q

MOST important cytokine for T cell proliferation

A

IL2!!!!!!!!!!

93
Q

T cell gets signal 1 and 2

A

activated T cell

94
Q

T cells get signal 1, not 2

A

T cell becomes anergic

95
Q

T cell gets signal 2, not signal 1

A

no effect on T cell

96
Q

cytotoxins

A

perforin
granzymes
granulysin

97
Q

cytokines

A

IFNy
LT

98
Q

Th2 cell

A

IL4, IL13, IL 5

99
Q

Th2 effect

A

barrier immunity on

eosinophils
basophils
mast cells
macrophages

100
Q

Treg cells

A

IL10, TGF-beta

101
Q

Treg effect

A

inhibition of other T cell types

Dendritic cells

102
Q

Th17 cells

A

IL17

Neutrophils

103
Q

Th17 effect

A

acute inflammation - neutrophils

104
Q

Th1 cells secrete

A

IFN-y

105
Q

Th1 effect

A

systemic immunity

macrophages
NK cells
CD8 T cells

106
Q

3 signal hypothesis

A

MHC/peptide
Costimualtion CD80/86
Cytokines IL12

107
Q

Signal 3 (cytokines, IL12)

A

instructs T cell differentiation

108
Q

Th1 driven responses

A

intracellular pathogens and tumors

109
Q

Th1 product

A

IFN-y

110
Q

IFNy effect

A

increased MHC class I and II
Th1 cells development
Isotype switching
Macrophage activation

111
Q

activated macrophage results in

A

Increased expression of costimulators - B7 molecules

Killing of phagocytosed microbes

Secretion of cytokines (TNF, IL1, IL12)

Increased expression of MHC molecules

112
Q

Th2 responses provide protection against

A

multicellular parasites and mediate hypersensitivity responses

113
Q

Th2 provide proliferative signals to

A

B cells, and drive isotype switching between IgG1 and E

Often associated with allergy

114
Q

Th2, signature cytokine product

A

IL4

115
Q

Th2 –> IL4/13

A

activation of eptithelial cells and smooth muscle cells

116
Q

Th2 –> IL5

A

eosinophil and B cells

117
Q

Th2 –> IL3/IL9

A

basophils and mast cells

118
Q

Actions of IL4

A

Iso-type switching to IgE

Inhibition of macrophage activation

Development and expansion of Th2 cells

119
Q

Th17 protects against

A

extracellular bacteria, by recruiting neutrophils.

120
Q

Th17 often associated with

A

immune disorders

121
Q

Major product of Th17

A

IL 17 (IL23 is important for maintenance of Th17 phenotype)

Th17, appear early in infection - before Th1 and Th2

122
Q

how does CD4 become a Th17 cell?

A

must be exposed to TGF beta and IL6

123
Q

Th17 –> IL17 –>

A

activate endothelial cells which recruit neutrophils via IL6

124
Q

IL22

A

induces keratinocytes and epithelial cells to express antimicrobial peptides

125
Q

Treg cells main function

A

suppress immune responses

126
Q

TF for Tregs

A

FoxP3

127
Q

Tregs suppress T cells expressing

A

CD4 and CD25

128
Q

Tregs secrete

A

IL10 and TGF-beta

129
Q

IL 10 function

A

Reduces IL12 and TNFalpha, reduces expression of MHC costimulatory molecules

130
Q

TGF-beta function

A

blocks cytokine production, proliferation of T and B cells and cytolytic activity

131
Q

How Tregs can have a negative effect

A

tumors secrete TGF-beta, which induces Tregs at the tumor site to suppress anti tumor responses

132
Q

Tfh Cells secrete

A

IL21

Provide B cells with help to class switch and high affinity antibody production