Exam 2 Week 2 Flashcards

1
Q

T cells express membrane T cell receptor (TCR) that recognize peptides displayed by MHC molecules. What is the TCR on each T cell clone is specific for?

A

A distinct antigen

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2
Q

What is bubble disease?

A

Pt that lack RAG enzyme that make TCR and BCR

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3
Q

Describe the structure of TCR?

A

Membrane-bound heterodimeric protein composed of alpha and beta chains

Has a variable region (recognize antigen) and constant region

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4
Q

What is the binding site for TCR on MHC class I?

A

MHC Class I – variable domain of alpha chain

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5
Q

What is the binding site for TCR on MHC class II?

A

MHC Class II – variable domains of alpha and beta

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6
Q

How is enormous diversity of TCR generate?

A

Recombination of V, D, and J gene segments (10^16)

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7
Q

What accounts for the diversity of TCR gene?

A

somatic recombination of gene segments

*note this is RANDOM selection of segments

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8
Q

Recombination of TCR gene segments is mediated by what?

A

Lymphocyte-specific VDJ recombinase (RAG) which will bring two segments close together

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9
Q

Put the steps of recombination in order

  1. recombination of D and J segments
  2. recombination of C segment with fused V-D-J elements
  3. recombination of V segments with fused D-J elements
A

1,3,2

recombination of D and J segments
recombination of V segments with fused D-J elements
recombination of C segment with fused V-D-J elements

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10
Q

Which one has more diversity (unlimited diversity)?

A. combinatorial diversity
B. Junction diversity

A

Junctional diversity

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11
Q

Double negative

a. Positive selection for ability to recognize antigen
b. Negative selection
c. Positive selection based on MHC reactivity

A

a. Positive selective for ability to recognize antigen

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12
Q

Double positive for CD4+ and CD8+

a. Positive selection for ability to recognize antigen
b. Negative selection
c. Positive selection based on MHC reactivity

A

b. Negative Selection

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13
Q

Single positive CD4+ or CD8+

a. Positive selection for ability to recognize antigen
b. Negative selection
c. Positive selection based on MHC reactivity

A

c. Positive selection based on MHC reactivity

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14
Q

Do Pre-T cells express TCR alpha or beta?

A

Beta

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15
Q

Pre-TCR promotes ______ ________.

A

Cell survival

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16
Q

Cell that do not express a functional receptor die (T/F)

A

True

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17
Q

Immature T cells express an incomplete TCR. (T/F)

A

False they express a complete TCR that promotes cells survival

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18
Q

Immature T cell express CD_ and CD_.

A

CD4 and CD8

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19
Q

Both strong recognition of MHC peptide or NO recognition of peptide lead to death (T/F)

A

True

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20
Q

Weak recognition of MHC peptide lead to selection of T cells that are ______ _________.

A

single positive

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21
Q

Strength or recognition = weak

Would this mean positive or negative selection?

A

Positive selection that would allow T cells to be selected and migrate to the periphery

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22
Q

What results in clonal expansion?

A

Antigen recognition
Costimulation

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23
Q

Induction/Effector phase of Cell-mediated immunity:

Describe naive T cells role?

A

Circulate from LN to LN in search of antigens

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24
Q

Induction/Effector phase of Cell-mediated immunity:

Antigen recognition leads to proliferation and ________.

A

differentiation

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25
Q

Migration of effector T cells to antigen sites in tissues where they get ______ and carry their _______.

A

Migration of effector T cells to antigen sites in tissues where they get reactivated and carry their function.

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26
Q

Role of Costimulation in T Cell Activation:

Antigen recognition by T cells (signal 1) without costimulation induces _______.

A

Unresponsiveness

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27
Q

Role of Costimulation in T Cell Activation:

Engagement of ____ on APC by CD___ in T cells provides signal _ and induce proliferation.

A

Engagement of B7 on APC by CD28 in T cells provides signal 2 and induce proliferation.

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28
Q

What IL is produced by T cells helps clone and proliferate?

A

IL-2

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29
Q

What is critical for limiting/terminating immune response?

A

Inhibitory receptors

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30
Q

What provides help to activation of CD8 T cells?

A

Concomitant activation of CD4 T cells

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31
Q

Describe expansion and contraction of T cells

A

Antigen specific T cell clones expand in response to antigen to provide large pool of effector cell to fight infection

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32
Q

What T cells proliferate and differentiate?

A

Naive T cells

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33
Q

Most effector T cells leave LN except for ____ which function is to help ___ cells.

A

TfMost effector T cells leave LN except for Tfh which function is to help B cells.

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34
Q

Effector function of CD4 helper T cells:

  • Activate phagocytosis via _______ production and _________
  • Activate ____ cells to produce ___ via cytokine production and __________
A
  • Activate phagocytosis via IFN gamma production and CD40 - CD40L
  • Activate B cells to produce Ig via cytokine production and CD40 - CD40L
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35
Q

What allows for T cell movement?

A

A combination of adhesion molecules and chemokine receptor

  • L-selectin, LFA-1 and CCR7-CCL19/21 for naïve T cells
  • E/P-selectin ligand, LFA-1/VLA-4 and CXCR3-CXCL10 for
    effector/memory T cells
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36
Q

What cells produce cytokines and activate and recruit other cells?

A

CD4 helper T cells

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37
Q

What cells kill infected cells?

A

CD8 cytotoxic T cells

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38
Q

T cell clones express TCR that recognize multiple peptide/MHC complex. (T/F)

A

False T cell clones express TCR that only recognize one peptide/MHC complex

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39
Q

Several peptides can be presented by different MHC I and MHC II molecules on the surface of the same dendritic cell. (T/F)

A

True

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40
Q

What cells patrol LN in search of antigens with the perfect fit?

A

T cells

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41
Q

Development of Thlep effector cells: Different cytokines are produced by dendritic cells or other innate cells that have recognized different types of microbe. Those cytokine determine the fate of?

A

Naive T cells

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42
Q

What does activation of macrophage by Th1 cell involve?

A

CD40L - CD40
IFN gamma -IFN gamma R

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43
Q

Function of Th2 cells:

IL-4 Induces B Cells to produce Ig _
IL-5 induces __________ activation

A

IL-4 Induces B Cells to produce IgE
IL-5 induces eosinophil activation (mediates worm elimination)

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44
Q

What is the function of M1 (alternative macrophage activation)?

A

killing and inflammation

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45
Q

What is the function of M2 (alternative macrophage activation)?

A

Tissue repair and inhibit inflammation

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46
Q

Th17 produce IL___ and IL___

A

IL 17 and IL 22

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47
Q

What do IL-17 and IL-22 induce?

A

antimicrobial peptide production by epithelial cells

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48
Q

What mediates recruitment of neutrophils via induction of cytokine and chemokine from other cells?

A

IL-17

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49
Q

What mediate production of Ig by B cells?

A

IL-21

*From Tfh cells

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50
Q

How dow CD8 CTL kill?

A

Kill via perforin and granzyme released from granules

  1. antigen recognition
  2. CTL activation and granules enter
  3. apoptosis of the cell
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51
Q

What cell activate macrophage to lyse intravesicular microbes?

A

Th1

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52
Q

How to kill intracellular bacteria?

A

CD8 kill infected cells with help from Th1 cells

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53
Q

What produces IgA in salviary glands?

A

Plasma cells

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54
Q

How are B cells receptors expressed on B cells formed?

A

Formed by membrane bound antibodies (Ig) in association with invariant membrane proteins Ig alpha and Ig beta

recognize via membrane Ig
transmit via Ig alpha and beta

55
Q

How many Ig isotypes are there?

A

5

IgE, IgD, IgG (all have 2 binding types)
IgM (10 binding sites)
IgA (4 binding sites)

*Function of isotypes is conferred by heavy chain

56
Q

What is the structure of a immunoglobulin?

A

2 heavy and 2 light chains

57
Q

How many variable and constant regions do light chains have?

A

Light = 1 variable and 1 constant

58
Q

How many variable and constant regions do heavy chains?

A

Heavy = 1 variable and 3-4 constant domains

59
Q

What two forms to Ig exist in?

A

membrane bound or secreted

60
Q

What region of the Ig contains the antigen binding site?

A

Variable region

61
Q

What region mediates effector function? variable or constant region?

A

constant regions of Fc region

*heavy chain

62
Q

What three things does the constant region play in Ig?

A

determines the isotype - determines the function
bind complement
bind Fc receptors

63
Q

The binding site is found in variable domain of just heavy chain (T/F)

A

False: The binding site is found in variable domain of light and heavy chains.

64
Q

The bindings site binds a wide variety of antigens such as:

A

proetins
lipids
Nucleic acids
polysacharides

65
Q

The process antigen is always recognized. (T/F)

A

False Native NOT processed

66
Q

Germline orgnaization of heavy and light chain

A

Heavy chain has VDJC
Light chain has only VJC

67
Q

C gene organization lead to production of which Ig?

A

IgM

68
Q

____ is the first C region cluster and Ig__ is the first antibody produced.

A

Cu is the first C region cluster and IgM is the first antibody produced.

69
Q

Recombination of Ig gene encompasses ______ selection of segment.

A

random

70
Q

Generation of Ig diversity:
Which has more diversity combinatoria or junctional?

A

Junctional because diversity is unlimited

71
Q

What happens to immature lymphocytes that do NOT rearrange functional receptors?

A

cells die by apoptosis

72
Q

What cells undergo negative or positive selection?

A

mature cells

73
Q

Where does selection of immature B cells occur?

A

In the bone marrow in an antigen-independent manner

74
Q

What are the two checkpoints for maturation of B cells?

A

Checkpoint 1: expression of pre-BCR
Checkpoint 2: signals from IgM

*both promote survival

75
Q

What selection is this: Eliminate immature B cells that can bind with high affinity ubiquitous self antigens?

A

Negative selection

76
Q

Where does recombination occur for receptor editing for B cells?

A

in the light chain

77
Q

What happens in B cell receptor editing?

A

Light chain recombination and results in change of the Ig specificity

78
Q

What are the phases of Humoral Immune Responses with B cell?

A

Plasma cells produce high affinity Ig which migrate to the BM or mucosal tissue to survive for years

Memory B cells last a lifetime in mucosal tissue and blood, Memory B cells DO NOT secrete Ig

79
Q

Secondary response (4 things to know)

A

quicker
peak response is larger
IgG is more abundant
high affinity

80
Q

What is signal 2 of the innate immune system in humoral immunity?

A

Engagement of CR2 or TLR

81
Q

What does signal 2 of innate immune system enhance?

A

B cell activation

82
Q

Protein antigen, isotype switching, high affinity Ig

Does this describe T dependent or independent antibody response?

A

T dependent antibody response

83
Q

Non protein antigen, IgM, low affinity Ig

Does this describe T dependent or independent antibody response?

A

T independent antibody response

84
Q

Definition: Small molecules that cannot elicit an immune response by themselves (poison, nickel, penicillin) but do so after binding to larger proteins.

A

Haptens

85
Q

Antigen presentation by B cells to T helpers cells:

What epitope of the protein does the B cell recognize?

A

Native conformational epitope

86
Q

Antigen presentation by B cells to T helpers cells:

What epitope of the protein does the T cell recognize?

A

Peptide fragment

87
Q

What cells process the antigen?

A

B cells

88
Q

Recognition of peptide presented by B cells induces ______ upregulation in ___ cells and production of ________.

A

Recognition of peptide presented by B cells induces CD40L upregulation in T cells and production of cytokines.

89
Q

What leads to B cell proliferation and differentiation in plasma cells?

A

Engagement of CD40 and cytokine receptor

90
Q

What happens in germinal center?

A

isotype switching
affinity maturation
selection of high affinity B cells

91
Q

What does Ig isotype switching require?

A

CD40L signal from Tfh

92
Q

What region is changed in Ig Isotype switching?

A

constant region of the heavy chain

93
Q

Type of heavy chain isotype is determined by cytokine produced by ____ cells (IgG and IgE) or tissues (IgA).

A

Type of heavy chain isotype is determined by cytokine produced by Tfh cells (IgG and IgE) or tissues (IgA).

94
Q

Switch recombination involves moving the VDJ exon to where?

A

A different C gene

95
Q

In switch recombination specificity of the Ig changes. (T/F)

A

False specificity of the ig does NOT change (same V region)

96
Q

In switch recombination the C region is different and reflects the _________ ____ _____ ____.

A

function of the Ig

97
Q

Affinity maturation:

What is the result of somatic mutation in Ig V genes?

A

Results in the selection of B cells with high-affinity antigen receptors

98
Q

B cells with high affinity interact with what type of cells? What cells promote their survival?

A

follicular dendritic cells
Tfh promote survival via CD40-CD40L

99
Q

How are FDC are different from classical dendritic cells?

A

different progenitor
no processing of antigen
no binding of antigen to MHC molecules

100
Q

What cells produce IgA in salivary glands?

A

Plasma cells

101
Q

Effector functions of antibodies or Ig

  1. _______ of microbes and toxins
  2. _______ and phagocytosis of microbes
  3. Antibody-dependent _______ __________
  4. Complement activation
    a. _______ of microbes
    b. phagocytosis of
    microbes opsonized
    with ________ fragments
    (ex. C3b)
    c. ____________
A

Effector functions of antibodies or Ig

  1. Neutralization of microbes and toxins
  2. Opsonization and phagocytosis of microbes
  3. Antibody-dependent cellular cytotoxicity
  4. Complement activation
    a. Lysis of microbes
    b. phagocytosis of
    microbes opsonized
    with complement fragments
    (ex. C3b)
    c. Inflammation
102
Q

What is the role of antibodies variable region in humoral immunity?

A

Neutralization

103
Q

What is the role of antibodies constant region in humoral immunity?

A

elimination

104
Q

How do Ig Neutralize Microbes and their toxins?

A

Antibody blocks binding of microbe which is require for infecting other cells/tissues, resulting in blocking off colonization

105
Q

Which is the most effective
a. antibodies with low affinity for antigens
b. antibodies with high affinity for antigens

A

b. antibodies with high affinity for antigens

106
Q

FcR bind constant region of Ig. What does clustering of FcR require in order to induce cellular activation?

A

Clustering of FcR requires recognition of multivalent antigen by Ig

107
Q

What promotes phagocytosis of Ig-coated microbes by phagocytes?

A

Fc gamma RI/IIA

108
Q

What induces killing of Ig-coated infected cells by NK cells (ADCC)?

A

Fc gamma RIIIA (CD16)

109
Q

What induces degranulation of mast cells and basophils/eosinophils?

A

Fc epsilon RI

110
Q

What is required for antibody-mediated opsonization and phagocytosis?

A

Multivalent antibody coated microbe and FcR clustering

111
Q

Antibody dependent cell-mediated cytotoxicity (ADCC):

NK cells bind IgG coated cells via ____________

A

Fc gamma RIIIA (CD 16)

112
Q

What is involved in the killing of helminth?

A

IgE and eosinophil

113
Q

Fc epsilon RI binds ___ portion of Ig_ coated-helminth.

Triggers ________ of toxic mediators that ____ helminth.

What is the important thing to note?

A

Fc epsilon RI binds Fc porting of IgE coated-helminth.

Triggers degranulation of toxic mediators that kill helminth.

Does NOT target infected cells

114
Q

What binds Fc portion of IgE coated helminth?

A

Fc epsilon RI

115
Q

Mast cells and basophils are coated with ____ specific for allergens via _________.

A

Mast cells and basophils are coated with IgE specific for allergens via Fc epsilon RI.

116
Q

Clustering of Fc epsilon RI bound to IgE by multivalent allergen trigger _________.

A

degranulation

117
Q

What does activation of the complement involve?

A

sequential proteolysis of those proteins to generate enzymes (zymogens) with proteolytic activity

118
Q

Complement activation:

What are plasma proteins activated by?

A

microbes

119
Q

In the early steps of complement activation what is the most important step?

A

Cleavage of C3 by C3 convertase; net result is the coating of microbes with C3b

120
Q

In the early steps of complement activation what is the opsonin?

A

C3b

121
Q

What is the receptor of C3b?

A

CR1

122
Q

In the early steps of complement activation what is the anaphylatoxin (leukocyte recruitment and activation)?

A

C3a

123
Q

What does the late step of complement activation result in the formation of?

A

membrane attack complex (MAC)

124
Q

What is involved in the membrane attack complex (MAC)?

A

C5b, C6, C7, C8
multiple C9 that form a pore

125
Q

Well most microbes have evolved to be resistant to MAC mediated lysis. What is the one microbe that is susceptible due to its thin wall?

A

Neisseria

126
Q

Name the complement pathway:

Triggered by binding of C3b to microbial surface

A

Alternative pathway

127
Q

Name the complement pathway:

Triggered by binding of C1 to microbe bond antibodies (IgG, IgM)

A

Classical pathway

128
Q

Name the complement pathway:

Triggered by binding of circulating lectins (MBL) to microbial polysaccharides

A

Lectin Pathway

129
Q

Regulation of complement activation prevents complement fixation at the surface of mammalian cells with what protiens?

A

Plasma and membrane proteins

130
Q

Functions of the complement system

A
  1. opsonization
  2. Anaphylatoxins (C5a> C3a>C4a)
    • increase vascular permeability
    • increase extravasation of plasma proteins and monocyte/ neutrophils
    • increase microbial activity
131
Q

Does the complement play a role in periodontitis?

A

Complement is subverted by oral bacteria, leading to chronic inflammation, tissue degradation, and persistent infection

132
Q
A
133
Q

Do memory B cells secrete Ig?

A

No