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Immunology > Acquired Immmunity-antigen Receptors > Flashcards

Acquired Immmunity-antigen Receptors Flashcards

1
Q

Characteristics of the acquired immune system

A

Specificity, memory, variable intensity

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2
Q

What elements of the immune system bind and recognize antigens

A

Antibodies
T cell receptors
MHC molecules

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3
Q

The part of the antigen with which the antibody interacts is the ___

A

Epitope

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4
Q

Why is the epitope the antigeni determinant

A

Determines which antibody will bind

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5
Q

What are antibodies

A

Large glycoproteins

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6
Q

What is the T cell receptor

A

Large glycoproteins

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7
Q

Unlike an antibody that interacts with the whole intact antige, what do T cell receptors interact with

A

Short segment of aa, the peptide epitope, derived from the intact antigen proteolysis

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8
Q

Can T cells interact with soluble peptide epitope directly?

A

No peptide must be held and presented by other glycoprotein molecules, MHC

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9
Q

What are MHC

A

Glycoprotein

Hold the peptide antigen enclosed within a groove

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10
Q

So what is recognized by a T cell receptors

A

MHC and peptide epitope

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11
Q

What forces do antigens renter act with antibodies, TCR, and MHC

A

Non covalent

H bond and electrostatic attraction and van deer waals

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12
Q

Dissociation constant

A

Strength or affinity of antigen interaction

Concentration allowing half the antibodies to be completed and half to remain in solution

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13
Q

The smaller the Kd the ___ the affinity

A

Higher

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14
Q

Rank affinity for antigens of antibodies, MHD and T cell

A

Antibodies greater than MHC greater than T cell

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15
Q

How many sites does IgM have to bind

A

10, it has five arms

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16
Q

How many sites does igG have to bind

A

2, it has 1 arm

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17
Q

Avidity

A

Strength of attachment

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18
Q

If blood is clotted and removed from he plasma, what is left

A

Serum

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19
Q

Antigen binding site of antibody

A

Regions that are highly variable in their aa content in different molecules

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20
Q

Heavy chains

A

Antibodies have relatively constant parts, hold different functional properties such as ability to activate complement

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21
Q

Describe the basic immunoglobulin

A

Two heavy chains and two light chains connected by inter chain disulphide bonds…within the chains, distinctive motifs are formed by intra chain disulphide bonds

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22
Q

Immunoglobulin. Superego need family

A

Many immunological molecules have similar domain structures

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23
Q

Different heavy chains give rise to different classes. What are they

A

IgA, IgD, igE, iGG, IgM

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24
Q

Formula of an immunoglobulin

A

Heavy2Light2

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25
Q

There are two alternative types of light chain. What are they

A

Kappa and lambda

Either have two kappa(more common) or two lambda

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26
Q

What are the five heavy chain types

A

Alpha, beta, delta, epsilon, gamma, and mu

The 2 will be identical

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27
Q

Each heavy chain and light chain have a stable segment and a zone that varies a lot . What are they called

A

C region-constant (effector function such as complement activation
V regions-variable (antigen binding site

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28
Q

How may hypervariable of complementarity-determining regions(CDR) are in each heavy and light chain

A

3

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29
Q

To form the full antibody molecule, the two heavy chains are linked together by what

A

Two interchain disulphide bonds

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30
Q

Each heavy chain is attached to a light chain by what

A

Interchain disulphide bond

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31
Q

All immunoglobulin domains contain two layers of B pleated sheet with 3 or 4 strange of anti parallel polypeptide chain

A

Ok

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32
Q

Immunoglobulin supergene family

A

MHC, T and adhesion molecules have similar domain structure

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33
Q

V underscore H

A

Variable region heavy

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34
Q

C underscore L

A

Constant region light chain

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35
Q

Hinge region

A

Middle of molecule allows freedom to the two arms bearing the antigen binding sites …flexible

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36
Q

Papain

A

Enzyme cleaves at the hinge region , breaking the two interchain disuphide bonds between the heavy chains in the process, to produce three fragments

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37
Q

When cleaved by papain, describe the 3 fragments

A

2 Identical and retain antigen binding ability
Called Fab fragments (fragment antigen binding)
45kDa each
1 is larger (55kda) and cant bind antigen but retains effector function
It is crystal likable and termed the Fc fragment (bc can bind Fc receptor )

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38
Q

Pepsin

A

Enzyme that leaves the heavy heavy disulphide bond in tact cuts into two fragments

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39
Q

Describe the two fragments from pepsin digestion of antibody

A

F(ab’)2- 2 Fab fragments linked with antigen binding site, but no effector function remaining

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40
Q

How do we achieve variation of effector region

A

H chain

5 subtypes but gamma is further gone intoy1-4 and alpha a1-2

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41
Q

IgG and igA subclasses

A

IgG1-4

IgA1-2

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42
Q

What is the most abundant immunoglobulin

A

IgG

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43
Q

IgG2

A

Capsulitis bacteria

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44
Q

IgG1-3

A

Activators of the classical complement pathway

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45
Q

How can we increase the binding of C1q to igG

A

Bind igG to antigen

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46
Q

What domain does C1q interact with

A

CH2

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47
Q

The igG has three constant domains on the heavy chain. What are these called

A

CH1-3

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48
Q

IgG is a monomer and has how many classes

A

4

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49
Q

Half life of igG

A

23 days

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50
Q

Proportion of IgG in circulation

A

50

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51
Q

IgA structural form

A

Monomer (circulating )

Diner (secretory)

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52
Q

IgA accessory chain

A

J chain polyimmunoglobulin receptor (secretory chain)

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53
Q

IgA subclasses

A

IgA1, igA2

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54
Q

IgA heavy chain

A

A

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55
Q

IgA number of domains in heavy chain

A

3

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56
Q

IgA half life

A

6 days

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57
Q

IgA proportion in circulation

A

50

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58
Q

IgM structure

A

Pentamer

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59
Q

IgM accessory chain

A

J chain

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60
Q

IgM heavy chain

A

Mu

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61
Q

IgM number of domains in heavy chain

A

4

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62
Q

Half life igM

A

5 days

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63
Q

IgM proportion found in circulation

A

80%

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64
Q

IgD structure

A

Monomer

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65
Q

IgD heavy chain

A

Delta

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66
Q

IgD number of domains in heavy chain

A

3

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67
Q

IgD half life

A

3 days

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68
Q

IgD proportion in circulation

A

75%

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69
Q

IgE structure

A

Monomer

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70
Q

IgE heavy chain

A

Epsilon

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71
Q

IgE number of domains in heavy chain

A

4

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72
Q

IgE half life

A

2.5 days

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73
Q

IgE proportion found in circulation

A

5o

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74
Q

IgG adult serum concentration

A

6-12 g/l

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75
Q

IgA adult serum concentration

A

1-4g/l

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76
Q

IgM adult serum concentration

A

.5-2 g/l

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77
Q

IgD adult serum concentration

A

.04 g/l

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78
Q

IgE adult serum concentration

A

.003 g/l

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79
Q

Rank IgG based on proportion

A

IgG1 more than igG2 more than IgG3 more than IgG4

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80
Q

What are the three cellular receptors for the Fc portion of IgG

A

FcyRI, FcyRII, FcyRIII

81
Q

Strongest igG to tetanus

82
Q

IgG Highest it reaction to bacterial polysaccharides

83
Q

FcyRI receptor

84
Q

FcyRII igG

85
Q

FcRIII igG

86
Q

IgG activation of complement

A

1 mainly. Also 2 and 3

87
Q

Which igG cross placenta

88
Q

The Fcy receptors are important for placental transfer

A

IgG protect newborn

89
Q

FcyRI

A

CD64 high affinity

On monocytes, macrophages and activated neutrophils

90
Q

FcRyII

A

CD32 low affinity on monocytes, neutrophils, eosinophils, and B cells

91
Q

FcyRIII

A

CD 16 low affinity

On monocytes, neutrophils, and NK cells

92
Q

Why is IgA distinct

A

Can be monomer or dimer.

Major immunoglobulin excreted on external surfaces

93
Q

What is a j chain

A

Short peptide joins 2 igA

94
Q

The IgA in circulation is ___ the IgA in secretion is ___(saliva, bronchial fluid, gut secretions, gut secretions, tears)

A

Monomer

Dimer

95
Q

How is IgA secreted

A

Attachment of dimeric IgA to a molecule, poly-IgR, which is synthesized by epithelial cells lining mucosal surfaces

96
Q

What happens to the IgA-poly-IgR complex

A

Endocytosed, transported through the epithelial cell and secreted into the lumen …then it is cleaved , releasing IgA and a remnant of poly-IgR, termed the secretory chain

97
Q

Selective IgA defiency

A

Severe, intractable infections of the major mucosal surfaces (GI, upper and lower respiratory tracts) are common

98
Q

As the major secretory immunoglobulin, what does IgA protect against

A

Bacterial, viral, protozoan infections of mucosa and can activate complement through the alternative pathway as well as having specific receptors FcaR on monocytes and neutrophils

99
Q

IgA receptor

A

FacR on monocytes and neutrophils

100
Q

How is IgM distinctive

A

A oentamer of five monomers joined by J chain

101
Q

IgM is the __ antibody synthesized in an antibody response (primary response)

102
Q

Does igM activate compllement

A

Yes very well

103
Q

How many binding sites does IgM have

104
Q

IgM can become ____ so that when reacting with repeating epitopes on a cell or bacterial surface

105
Q

Why is flexing of igM important

A

Helpful bc they dont have high affinity like later produced ones..use more binding sites

106
Q

IgD

A

Low serum concentration
Surface expression of IgD is evident at a relatively immature stage of B cell cycle, and the signaling provided by this receptor on interaction with antigen in a lymphoid follicle is critical part of B lymphocyte activation

107
Q

IgE is the ___ immunoglobulin monomer

108
Q

How many CH domains does IgE have

109
Q

When do IgE levels rise

A

Allergic reactions and immune responses to parasitic both involving activation of mast cells, which is the main effector of IgE

110
Q

__ cells bear 10^4-10^6 high affinity FcERI receptors for IgE

A

Mast cells

111
Q

What happens when IgE activates mast cells

A

Itchy, hypervascular responses

112
Q

What has low affinity FceRII(CD23) receptors for IgE

A

B cells and eosinophils

113
Q

What happens when FceRII on B cells bind

A

Regulation of IgE production

114
Q

Isotype

A

Structural features of a particular immunoglobulin class or heavy or light chain type in a species

115
Q

Allotropes

A

Other parts of immunoglobulins have genetically determined differences between individuals

116
Q

What do immunoglobulins on B cells do

A

Bind antigen, internalize, break down, and a portion os presented to T cells to activate their response to the antigen

117
Q

Isotypes

A

Epiptopes that are present on all molecules of a class or chain type in a species

118
Q

Allotypes

A

Vary between individuals,

119
Q

Idiotypes

A

Reflect variation in the antigen binding sites of immunoglobulins

120
Q

Primary immune response

121
Q

Repeat exposure

A

More rapid IgG, higher peak and baseline

122
Q

Each plasma cell produces a __ antibody

123
Q

How do B cells insert into B cell

A

Short extension of immunoglobulin molecules at the carboxy-terminus during synthesis

124
Q

What antibodies are on B cells

125
Q

What happens when B cells bind antigen through antibody

A

Internalization and antigen processing and presentation for T cells

126
Q

Primary immune response

A

Inject
Antibody response 5-10days later IgM
Rises 10-20 days
Declines

127
Q

Secondary antibody response (same antigen again)

A 
More rapid
Higher peak level and declines to a higher base level 
IgG
Antigen specific response 
Displays memory
128
Q

Does IgM or IgG have higher affinity

A

IgG

Darwin..highest affinity compete and win

129
Q

Hapten

A

Small molecules too small to elicit immune response. If bind to a larger protein carrier can elicit production of antibodies
DRUGS

130
Q

Monoclonal antibody

A

Clone of plasma cells, unvarying aa sequence

131
Q

Polyclonal

A

Many different clones of plasma cells and many different antibody types in a typical antibody response

132
Q

Dominant epitopes

A

Antibody responses to large macromolecular antigen are not evenly distributed throughout the antigen, some areas are targeted more frequently than others and are termed the dominant

133
Q

What are the two situations where monoclonal antibodies are identifiable in any quantity

A
  1. Tumor of plasma cell origin leads to expansion of a single clone of cells, like myeloma
  2. Tumor is fused with a B cell to give an immortalized, antibody producing clone of B lymphocytes
134
Q

What does changing heavy chains do

A

Modify effector function without altering antigen binding

135
Q

Potential binding capacity exceeds 10^11

136
Q

Each heavy and light chain is encoded by a gene ___

137
Q

Each gene complex there are ___ that encode variable regions and constant regions

138
Q

J genes

A

Join these two

139
Q

D genes

A

Generate diversity

140
Q

What is IGKV1

A

Immunogloblun kappa variable chain gene number 1

141
Q

What chromosome is kappa on (light chain)

142
Q

What chromosome is lamba light chain on

143
Q

What is the sequence of genes of the light chain from 5’-3’ end

144
Q

Why are there 200 different kappa light chains and 15- different lamda light chains

A

Kappa-4- IGKV gene segments and 5 IGKJ segments and one IGKC segment
Lambda-30 IGLV, 5IGLC, each C gene accompanied by its own IGLJ

145
Q

What chromosome is the heavy chain on

146
Q

What are the differences between light and heavy chain genes

A 
Additional diversity is achieved by D segments 
The constant region gene segments encoding the heavy chain isotypes (IGHG1-4 for the IgG subclass heavy chains; IGHA1-2 for IgA subclasses;IGHM, IGHD and IGHE for IgM, IgD and IgE ) are located together, downstream from the IGHV, IGHD, and IGHJ segments rather than on separate chromosomes
147
Q

How many possibilities are there for heavy chains and how

A

5.67 million …combitorial diversity since relies on combinations of different genes

148
Q

What is junctional diversity and how much does it increase immunoglobulin diversity

A

Deliberate imprecision in the joining together of IGHD and IGHJ, IGHV to the IGHD-IGHJ combination that forms, and also in equalize the V-J segments as they join for the light chain genes

30 million times

149
Q

Combinatorial and junctional diversity focus on changes in ___ regions , which are mainly encoded from the joining regions of the genes ….can make many different shapes in antibody binding region

A

Hypervariable regions (CDRs)

150
Q

Somatic hypermutation

A

Parts of the variable regions of different antibodies differ in single aa which is changed after antigenic stimulation

Substitution, deletion or addition of a single nucleotide occurring after gene arrangement
Class switch between primary and secondary immune response

151
Q

When does somatic hypermutation occur

A

Cell is undertaking the class switch between the primary and secondary responses

152
Q

What does somatic hypermutation do

A

Introduces additional diversity and is focused around CdR

153
Q

Somatic hypermutation is dependent on what enzyme

A

Activation induced cytidine deaminase

154
Q

Genetic effects in activation induced cytidine deaminase

A

Failure of B cells to generate diversity through this process resulting in poor production of high affinity antibodies and a rare immune defiency state called hyper IgM syndrome type 3

155
Q

Heavy chain light chain potential for functional diversity

156
Q

TCRaB potential for diversity

157
Q

TCR ydelta

158
Q

Class switch recombination

A 
Antigen specificity doesn’t change 
IgM class developed.
Then to sIgM to bind antigen 
Then class switch 
Activation induced cytidine deaminase
159
Q

Affinity maturity

A

IgM low affinity igG high
Darwinian
In limited antigen supply, they bind to highest affinity and lymph nodes only select bound antigens for maturation and differentiation

160
Q

The heavy genes on the chromosome are assembled first. Describe this

A

IGHD and IGHJ segment combining before IGHV segment is added.
VDJ is produced through this arrangement (allelic exclusion0other chromosome is inhibited from undergoing same process)
Constant heavy chain added to the rearranged IGH VVDJ
Invariable the IGHM is selected

161
Q

The light chain genes rearranges after heavy. Describe this

A

V and J segments are rearranged and combined with the constant region gene
The IGK gene is selected first(if unsuccessful on both chromosome 2 then IGL is sought note majority are unsuccessful since kappa greater than lambda)

162
Q

Class switching

A

IgM heavy chain replaced by selection of IGHG, IGHA or IGHE genes
By switch region 5’ to IGH genes

163
Q

The only IGH gene not to have a switch region is IGHD. What does this explain

A

Few mature b cellls express sIgD and few IgD is made

164
Q

VJD recombinant

Recombination activation genes (RAG1 and RAG2)

A

The heptamer and nonamer must be separated by a 12-mer on one side and a 23-mer on the other. This is the 12-23 rule. These two enzymes catalyst this process
Critical for developing B cells and T cells.

165
Q

RAG knockout

A

Can’t rearrange immunoglobulin genes of T cell receptors and are profoundly immune deficient

166
Q

Downstream from V (of VDJ) is what

A

Heptamer (7 nucleotide sequence) followed by a random set of nucleotides (12 or 23) and then a further 9 (a nonamer)

167
Q

What is upstream

A

Nonamer-random 12 or 13-heptamer

Opposite

168
Q

The two heptamer and nonamer are __

A

Palandromic

169
Q

What doe this allow

A

A loop to be made of dsdna

170
Q

TCR is composed of two chains. What are they. Which is more common

A

A/B (90%) gamma/delta(10%)

171
Q

Are the TCR chains part of the immunoglobulin supergene family.

172
Q

How do TCR vary in structure

A

Large pool of gene segments for individual receptor chains; and random imprecision int he joining together of the selected variable, diversity and joining genes

173
Q

Do tCR somaticalaly mutate after gene rearrangement

174
Q

What do TCR bind

A

Antigen and MHC

175
Q

The _TCR appears not he surface of primitive T cell in thymus before _ can be seen

A

Gamma delta

Alpha beta

176
Q

Is ab of gamma delta more common

177
Q

Describe ab TCR

A

Disulphide bonded heterodimer comprising an a chain and a b chain
Va, Vb, Ca C3b for constant and variable regions
Structure of domains in TCR is analogous with immunoglobulin domains and form part of immunoglobulin supergene family
Have hypervariable regions in variable domain , forming CDR1-3

178
Q

What do CDR 1 and 2 interact with

A

Two a helices of the a1 and a2 domain of MHC as run along the sides of the antigen binding groove

179
Q

What does CDR3 interact with

A

Peptide int he groove

180
Q

Gamma delta TCR

A 
Gene reagrrangement is an early thymic arrangement 
Disulfide linked heterodimer 
Or
Non disulfide linked heterodimer
Or
disulfide linked yy homodimer
181
Q

Describe formation of a chain

A

Analogous to heavy and light chain
TRAV, TRAJ, TRAC recombination
Potential diversity is 2500

182
Q

What are the functional segments of b chain

A

TRBV, TRBD, TRBJ, TRBC

Potential diversity is 2600

183
Q

What makes TCR genes different from immunoglobulins

A
  1. TRAC and TRBC genes do not encode segments typical of secreted proteins, indicating that secretion of TCD is not an important functional characteristic
  2. no somatic hypermutation in the genes encoding a complete ab TCR.
184
Q

Human gamma chain

A

TRGV, TRGJ, TRGC

Diversity 120

185
Q

Delta chain

A

In the middle of the a chin
TRDV, TRDD, TRDJ, TRDC
Diversity is 36

186
Q

Diversity of gamma and delta together

187
Q

How do we bring different gene components of the TCR together

A

Nonamer heptamer sequence and 12 23 nucleotide sequence

12-23 rule

188
Q

What other mechanisms create tcr diversity

A

Imprecise joining (frameshift mutatiosn and new nucleotide sequences)

189
Q

Heavy chain, light chain, a chain, b chain, gamma chain, delta chain number of variable segments

A

45, 30-40, 50, 50, 8, 10

190
Q

Heavy chain, light chain, a chain, b , gamma, delta number of D segments

A

30, 0, 0, 2, 0, 2

191
Q

Which chains allow D segments to be read in all three reading frames

A

Beta and delta

Rarely heavy

192
Q

Heavy chain, light chain, alpha chain, beta chain, gamma hair, delta chain hunger of joining J segments

A

12, 4-5, 50, 13, 2, 3,

193
Q

Heavy chain combat oral diversity

194
Q

Heavy chain light chain somatic hypermutation

195
Q

Total potential heavy and light chain

A

10^11-10^12

196
Q

Alpha beta chain combitoral diversity

197
Q

A b chain total potential diversity

198
Q

Gamma delta combitorial diversity

199
Q

Gamma delta total potential diversity

Immunology (14 decks)

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