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Immunology Block 1 > Ppt 4 Antigen recognition in the adaptive immune syst > Flashcards

Ppt 4 Antigen recognition in the adaptive immune syst Flashcards

1
Q

How do B cells recognize antibodies?(in other words, what kind ofreceptor do they use?)

A

they use membrane bound or secreted antibody receptors

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2
Q

What receptor do T lymphocytes use to recognize antigen?

A

T cell receptor on its membrane (MEMBRANE BOUND)

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3
Q

What is the principal function of antigen receptors in the immunesystem?

A

to detect and trigger a response against it

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4
Q

How are antigenreceptors distributed?(are they clonal or non-clonal?)What does this mean?

A

they are clonalwhich means that the clones are all different for a specific antigen

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5
Q

Antigen receptors are differentfor different antigens, yet, what is still the same among their functionality?

A

theantigen receptors transmit biochemical signals fundamentallythe same which are unrelated to specificity.

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6
Q

What 2 things makeup the structure of a antigen receptor in a lymphocyte? (generally speaking)

A

1) Varibale region2) Constant region

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7
Q

What is the variable region?

A

this is the part that recognizes antigen

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8
Q

What is the constant region?

A

give structural integrity and effectorfunctions

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9
Q

What structure remains unchanged in a antigen receptor clones?

A

Constant region

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10
Q

What gives the variable region the ability to detect different antigens?

A

genes thatvary the polypeptides that detect antigenin the variable region

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11
Q

T cell receptors will recognize what kind of microbes?

A

cell-associated microbes bound to the MHC molecule of APC’s and must bepeptides

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12
Q

Inside the variable region, what specifically binds to antigens and contains the actual variability?

A

the hypervariable region or CDR (complementarity-determining region)

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13
Q

what forms the entire structure of the B cell receptor and the T cell receptor?

A

the antigen receptor (constant and variable region) and the signaling proteins found in the inside of the cell

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14
Q

What is the T cell receptor complex?

A

when you have the:T cell receptor (variable and constant regions found outside) + the internal signaling molecules for t cells (CD3 andζ chains)

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15
Q

what are the internal signaling molecules for T cells?

A

CD3 andζ chain

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16
Q

How do you activate the signaling proteins in both T/B cell receptor complex?

A

you need to cross link 2 or more receptors in order to bring the singaling proteins together- that way they will cause phosphorylation of other proteins inside the lymphocyte and activate transcription

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17
Q

what are the effector molecules of the humoral immunity?

A

antibodies

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18
Q

where do you find antibodies secreted?

A

blood and mucosa

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19
Q

what do membrane bound and secreted immunoglobins use to recognize antigen?

A

they use variable domains

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20
Q

What other 2 cells use receptors thatrecognizesecreted antibody constant regions in order to eliminate microbes?

A

1) Fc receptor in phagocytes2) C1 proteins of complement

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21
Q

what part of the secreted antibody’s structure can be used by other cells to eliminate microbes?

A

the constant region on secreted antibodies

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22
Q

What is the function of membrane bound antibodies on B cells?

A

to bind antigen and initiate a response

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23
Q

what is the function of secreted antibodies?

A

to neutralize microbes before they colonize

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24
Q

What is the structure of an antibody?

A

2 heavy chains2 light chains

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25
Q

each Heavy chain and ligh chain contains individual what?

A

variable and constant regions

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26
Q

to what is the light chain attached?

A

to the heavy chain

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27
Q

to what is the heavy chain attached?

A

to the other heavy chain using disulfide bond

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28
Q

How many V domains does the light chain have?

A

1 V domain

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29
Q

How many V domains does a Heavy chain have?

A

1 V domain

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30
Q

How many C domains does the light chain have?

A

1 C domain

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31
Q

How many C domains does a heavy chain have?

A

3 or 4 C domains

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32
Q

how many hypervariable regions does each Heavy and Light chain have?

A

3 CDR or hypervariable regions

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33
Q

which hypervariable region contains the most variability? (which CDR is highly polymorphic?)

A

it is CDR 3 or Hypervariable region 3

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34
Q

where is the CDR 3 located?

A

in the junction of the V and C region

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35
Q

which hypervariable region contributes the most to antigen binding?

A

CDR 3 because its the most polymorphic

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36
Q

what is found between the Fab region and the Fc region?

A

the flexible hinge region

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37
Q

What is the top box?

A

the Fab regions (there are 2)

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38
Q

what is the bottom box?

A

the Fc region, only 1

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39
Q

who generates 1F(ab)2 region capable of binding antigen and bridging?

A

Pepsin

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40
Q

What does Papain generate?

A

2 Fab fragments and 1 Fc fragment

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41
Q

what is the differene in the production of Fab regions by papain and pepsin?

A

papain generates Fab regions that are monovalentpepsin generates Fab regions that are divalent

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42
Q

what is the Fab region?

A

fragment of antigen binding- its a light chain attached to the V and C domain of a constant region

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43
Q

how many Fab regions are in an immunoglobulin?

A

2 identical one’s

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44
Q

What are the 5isotypes of antibodies?

A

Ig G/M/E/A/D

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45
Q

what is the heavy chain for IgE

A

epsilon (e)

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46
Q

what is the heavy chain for IgA?and for IgG?and for IgM?and for IgD?

A

IgA = alphaIgG = gamma (y)IgM = mew (µ)IgD = delta

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47
Q

what does IgA do?

A

mucosal immunity

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48
Q

what does IgM do?

A

its a naive B cell antigen receptor

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49
Q

what does IgE do?

A

its used for Mast cell degranulation and defends against parasites

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50
Q

what does IgG do?

A

its coats microbe for opsonization and also serves for ADCC

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51
Q

what 2 antibodies are found always as monomers?

A

IgG and IgE

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52
Q

What antibody is always found as a pentamer?

A

IgM

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53
Q

what antibody is not secreted?

A

IgD

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54
Q

what antibody do we find as a dimer, monomer or trimer?

A

IgA

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55
Q

what antibodies lasts a long time after it is secreted?

A

IgG

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56
Q

what antibody is removed fast after it has done its function?

A

IgE

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57
Q

what antibodies have 2 antigen binding sites?

A

IgG, IgE, IgD

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58
Q

how many antigens can IgA bind?

A

4

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59
Q

how many antigens can IgM bind?

A

10

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60
Q

what is avidity?

A

the total strenght which an antibody binds an antigen

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61
Q

what is cross reaction?

A

when an antibody binds another antigen that looks similar to the one it was initially going to bind

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62
Q

what are the 2 types of light chains?

A

kappa and lambda

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63
Q

How does the kappa and lambda light chains differ?

A

they have different C regions

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64
Q

how are kappa and lamda light chains similar?

A

they have the same function

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65
Q

can B cells express both kappa and lambda chains?

A

no

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66
Q

what is different about the heavy chains of each antibody?

A

they all have different C regions

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67
Q

Can light chains join or complex with any type of heavy chain?

A

yes

68
Q

naive B cells have what 2 antibody isotypes in their membrane?

A

IgM, IgD

69
Q

what other cell helps B cells differentiate?

A

helper T cells

70
Q

what antibody do naive B cells secrete?

A

IgM

71
Q

what process or mechanism allows B cells to produce other heavy chains different than IgM or IgD?

A

heavy chain class switching

72
Q

in isotype switching or heavy chain switching, do B cells chainge their specificity or their V chains?

A

No, they remain specific for an antigen and their V region does not change

73
Q

What makes up the signaling proteins in the B cell receptor?

A

Ig (alpha) and Ig (beta)

74
Q

What are Ig alpha and Ig beta involved with when antigen is recognized?

A

B cell activation

75
Q

what are the parts of antigens recognized by antibodies?

A

the epitopes

76
Q

what is another name for the antigen epitopes?

A

determinants

77
Q

how are different different antigens recognized? (based on their epitopes)

A

because epitopes may be sequential or conformational(AKA: they are linear or with a shape)

78
Q

what is the term used for the strenght of the antigen binding surface to the epitope?What is the symbol used for this term?

A

affinity; Kd

79
Q

what does a low Kd mean?

A

there is a high affinity for that antigen epitope

80
Q

what is affinity maturation?

A

when antibodies become adapt to binding to a specific antigens epitopes. Usually by repeated expossure

81
Q

what is a monoclonal antibody?

A

its a antibody that has been fused with a myeloma cell causing it to last very long and secrete a specific antibody

82
Q

what is a myeloma cell?

A

a tumor cell of plasma cells

83
Q

what is a hybridoma?

A

the cell that forms when a B cell is fused with a myeloma cell

84
Q

how do you make monoclonal antibodies?

A

1) immunise a mouse2) he now makes antibodies3) fuse those plasma cells with myeloma cells4) select the hybridomas of choice

85
Q

can monoclonal antibodies be repeatedly injected into humans? why?

A

NO, because our immune system will see the mouse Immunoglobulin as foreign and will attack it

86
Q

how can you inject monoclonal antibodies repeatedly into humans?

A

by replacing the Ig part of the antibodies with human Ig

87
Q

besides replacing the Ig part of antibodies, how else can you make monoclonal antibodies suitable for injection into humans?

A

through DNA recombination

88
Q

the t cell receptor for antigen is a membrane bound receptor, is it made a heterodimer or homodimer?

A

it is a heterodimer

89
Q

What chainsmakes up the T cell recpetor dimers?

A

the alpha and beta chains

90
Q

how many Variable and Constant regions to T cell alpha and beta chains have?

A

1 variable and 1 constant

91
Q

how many hypervariable regions does each variable chain have?

A

3 CDR

92
Q

which CDR in the T cell variable chain is the most…variable or polymorphic?

A

CDR 3

93
Q

do t cell receptors undergo affinity maturation or isotype switching?

A

No!!

94
Q

how to t cells differentiate between complex microbes?

A

detecting amino acid sequences in the immuno-dominant epitopes

95
Q

are gamma delta T cell receptors structurally the same as alpha beta receptors?

A

yes

96
Q

how to Alpha Beta TCR differ from Gamma Delta TCR?

A

Gamma Delta TCR will recognize protein and non-protein antigens and theydon’thave to be displayed by MHC molecules

97
Q

where are gamma delta TCR found in the body?

A

in the epithelium

98
Q

what subunits in the TCR variable region make up the antigen binding part?

A

Va (alpha) and Vb (beta)

99
Q

What subunits compose the TCR constant regions?

A

Ca (alpha) and Cb (beta)

100
Q

When transmiting signals to the inside of the cell, besides CD3 andζ, what else is needed to fully activate a T cell response?

A

engagement of the co-receptor molecules CD4 and CD8

101
Q

what do CD8 and CD4 molecules recognize in the MHC molecules?

A

the nonpolymorphic portions of the MHC

102
Q

maturation of lymphocytes in the bone marrow consists of 3 processes:

A

1) proliferation of immature cells2) expression of the antigen receptor genes3) selecting the lymphocytes that express the full antigen receptor

103
Q

how are lymphocytes selected during the maturation process?

A

those that express the antigen receptor and are able to recognize only the antigen (not self cells)

104
Q

what happens to lymphocytes that do not express the full antigen receptor?

A

they die through apoptosis

105
Q

how is diversity of B/T receptors achieved?

A

recombining the receptor genes during the maturation process

106
Q

what is the main goal in the maturation process?

A

to express diverse amounts of antigen receptors

107
Q

what process do B/T cells after the end of the maturation process?

A

they undergo Positive and Negative selection

108
Q

Is the generation of useful antigenreceptors aefficient or inefficient process? Why?

A

A highly inefficient process, because it involves random genetic recombination events that fail more often than not

109
Q

What does IL-7 do?

A

expands the number of T cellprogenitors before they express antigen receptors

110
Q

When does IL-7 stop being the signal to proliferate in maturing precursor lymphocytes?

A

when they acquire the first antigen receptor

111
Q

What receptor is defective in SCID?

A

IL-7

112
Q

Where does positive selection occur?

A

in the thymus

113
Q

What is positive selection?

A

When immature T cells are selected to reacognize self MHC molecules

114
Q

What do mature T cells need find after positive selection in order to get activated?

A

The same MHC molecules they wherepresented during positive selection

115
Q

What 2things are needed to pass positive selection?

A

1) recognition of MHC molecules2) expression of survival and proliferation signal

116
Q

What is Negative selection?What does it prevent?

A

Selectionagainst high-affinity recognition of self antigens in the bone marrow andthymus.It prevents self reactiveantigens

117
Q

How is the expression of B and T lymphocyte antigen receptors is initiated? what is generated during this process?

A

Bysomatic recombination of gene segments that code for the variableregions of the receptors.Somatic recombination generates diversity

118
Q

early lymphoid progenitor cells in the bone marrow contain what genes needed for the maturation process?

A

Immunoglobulin and TCR genes already in the germline

119
Q

Do early lymphoid progenitor cells alreadycontain the Ig heavy chain and light chain?

A

yes

120
Q

Do early lymphoid progenitor cells that have the TCR already have the alpha/beta chain?

A

yes

121
Q

How many variable region genesdo each beta and alpha chains of the early lymphoid progenitor T cell contain?

A

multiple variable region genes

122
Q

How many constant region genesdo each beta and alpha chains of the early lymphoid progenitor T cell contain?

A

few

123
Q

between the V and C region genes in the early lymphoid progenitor cells there are what?

A

J(joining) and D (diversity) gene segments

124
Q

Of the VCJD genes found:which do we find in the antigen receptor gene loci?Which do we find in Immunoglobulin heavy chain?Which do we find in the TCR beta chain?

A

VJCVDJCVDJC

125
Q

How do we know the early lymphoid progenitor cell is commited to becoming a B cell?

A

because there will be recombination of the Varible heavy chain in the Immunoglobulin with the D or J segment

126
Q

What do we find in a developing B cell gene loci for the heavy chain locus?

A

a recombined VDJ gene in the heavy chain locus

127
Q

The VDJ gene in the heavy chain locus gets spliced into the C region and thentranslated, what will it produce?

A

the µ mRNA

128
Q

what will the µ mRNA produce?

A

the µ Heavy chainthe first Ig proteinin B cell maturation

129
Q

what are the 2 recombination events for the production of the immunoglobulins heavy chain?Who will cause the recombination between VDJ?who activates VDJ recombinase?

A

D-J gene segments joining and then joining the V regionVDJ recombinaseRAG-1 and RAG-2

130
Q

what gives the antigen receptor its diversity?

A

1)combinatorial diversity:different combination of the V D J gene segments2) Junctional diversity: inserting nucleotides at the junctions of V D and J

131
Q

combinatorial and junctional diversity will increase diversity in what part of the antigen receptor?

A

the CDR 3 of the variable region

132
Q

what are 3 ways to do junctional diversity?

A
  • exonucleases: removes nuclotides from VDJ when recombining
  • TdT (terminal deoxyribonucleotidyl transferase): it add random nucleotides during recombination of VDJ
  • P-nucleotides: during VDJ recombination, breaks are formed and the p-nucleotides fill the overhangs with nucleotides
133
Q

where do B lymphocytes mature?

A

in the bone marrow

134
Q

how are progenitor cell committed to becoming B cell called?What chains do they have?

A

pro-B cellsIg alpha and Ig beta

135
Q

afer pro-B cells, what are the next committed cells called?what is characteristic of these cells?

A

pre-B cells and they have- cytoplasmic µ (the heavy chain protein)- surrogate light chains

136
Q

what forms the pre-B cell receptor complex?

A

the µ chain and surrogate light chain associated with the Ig alpha and Ig beta

137
Q

what are the 2surrogate light chains?

A

1) lambda 52) VpreB

138
Q

What is the first checkpoint in B cell formation?

A

the expression of the B cell receptor complex

139
Q

what happens if the µ chain is not produced?

A

the cell is not selected and it dies

140
Q

what areother two processes that theµ chain and BCR complex will signal?

A

1) stops recombination of the Ig heavy chain genes- allows to only express 1 Ig gene from the 2 given by parents2) recombination of the Ig light chain locus

141
Q

when the light chain is produced, it associates with what? What will it produce?

A

the µ chain and produces IgM antigen receptor

142
Q

What does the IgM receptor do?What is special about the IgM receptor expression?

A

provide signal of survival and proliferationIgM receptor expression is the 2nd checkpoint in the B cell maturation

143
Q

what do we call the IgM expressing B cell?

A

immature b cell

144
Q

immature B cells will do what?

A

leave the bone marrow and enter the spleen

145
Q

what is the final step in the maturation of B cells?

A

coexpression of IgM and IgD

146
Q

why does coexpression of IgM and IgD occur?

A

because the recombined VDJ heavy chain RNA is spliced onto CµRNA and CδRNA- you end up with:µRNA orδRNA

147
Q

what do we call a B cell expressing both IgM and IgD?

A

Mature B cell

148
Q

What happens in negative selection of B cells?

A

if B cell binds to antigen strongly in bone marrow it is killed or undergoes receptor editing

149
Q

what is receptor editing?

A

when B cell fails negative selection and the VDJ recombinase is activated to make a new light chain to change the specificity of the antigen receptor

150
Q

what are the progenitor cells that are committed to become T cell called?

A

pro-T cells or double negative T cells

151
Q

why are progenitor cells that will become T cells calleddouble negative T cells?

A

because they dont express CD4 or CD8

152
Q

for double negative progenitor t cells to proliferate and survive, what must be expressed?

A

IL-7

153
Q

some double negative progenitor T cells will undergo what process on their TCR beta gene? What will it result in?

A

TCR beta gene recombination using VDJ recombinasea beta chain will be produced and expressed in the surface in association with pre-Talpha

154
Q

what does the pre-Talpha and the newly made beta chain produce?

A

a pre-TCR complex in pro-T cells

155
Q

what 3 things will the pre-TCR complex provide?

A

the first checkpoint: the pre-TCR now provides1) survival and proliferation signal2) TCR alpha gene recombination3) inhibition of VDJ recombination in the second Beta chain locus

156
Q

cells that survive by expressing the pre-TCR will also express what receptors?

A

CD4 and CD8 co-receptors

157
Q

when the pro-Tcells express the co-receptors for CD4/8 and have the pre-TCR, what are these cell now called?

A

double positive T cells

158
Q

how to double positive t cells pass positive selection?

A

it must recognize the MHC molecule in the thymus

159
Q

what happens to double positive T cells that do not recognize MHC molecules in the thymus?

A

they do not pass positive selection and undergo apoptosis

160
Q

in positive selection, double positive t cells that recognize MHC 1 remain whith what co-receptor?and which is lost?

A

CD8 remainsCD4 is lost

161
Q

in positive selection, double positive t cells that recognize MHC 2remain whith what co-receptor?and which is lost?

A

CD4 remains and CD8 is lost

162
Q

immature t cells that remain with CD8 co-receptor can become what?

A

CTL’s

163
Q

immature t cells that remain with CD4co-receptor can become what?

A

Helper T cells

164
Q

if a double positive T cell recognized MHC too strongly, what happens to it?What is this process called?

A

it is killedthis is negative selection

165
Q

if the double positive cell recognizes the MHC molecule with low avidity, the result is?

A

positive selection

166
Q

if the double positive cell recognizes the MHC molecule with high avidity, the result is?

A

negative selection

Immunology Block 1 (5 decks)

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