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Immunology > Chapter 4 sections 7-16 > Flashcards

Chapter 4 sections 7-16 Flashcards

chapter 4 parts 2 and 3

1
Q

flow cytometry

A

use of fluorescent labeled monoclonal antibodies to ID cells

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2
Q

Immunoglobulin diversity before B cells encounter Antigen

A

Germline configuration of gene segments encoding for Igs are inherited via egg and sperm
and encoded in gene segments on regions of chromosome 22,2,14
but only expressed in B cells following successful gene rearrangement

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3
Q

Occurs on chromosome 22,2 14

A

gene segments that code for Ig diversity that was inharerited via egg and sperm

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4
Q

Light chain formation via somatic recombination

2 options for Light chain gene formation

A

from the germline DNA lamda variable segments is selected
which is joined to
J segment and one of the constant segments
or
from the germline DNA kappa variable segments is joined to j segments and a constant kappa segment

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5
Q

Heavy chain formation via somatic recombination

2 options for Heavy chain gene formation

A

from the germline DNA 1 H variable segments is selected
1D segments
which is joined to 1J segments
and one of the Mu constant segments + the gene for the transmembrane component finally V and DJ segments are join

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6
Q

all the components of heavy chain gene

A

1 H variable segment +((1D segment+1J segment)+one Mu constant segment + transmembrane component)

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7
Q

all the components of light chain gene

A

1 lambda variable segment + 1 j segment + 1 constant segment
or
1 Kappa variable segment + 1 J segment + 1 constant Kappa segment

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8
Q

mu version of H chain results in

A

IgM production

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9
Q

somatic recombination

A

the process of choosing of one of many gene segments to form an exon that can be transcribed

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10
Q 
how to find # possibility of type of chain
kappa light chain
lambda light chain
heavy chain
these are only present in B cells
A

(# of possibilities for Variable region) X (#of possibilities of J segments)

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11
Q

how many variations of diversity result from somatic recombination and combinatorial association

A

1,628,400 posiblities in the variable region alone aka tons of diversity
this impacts the hypervariable regions 1& 2

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12
Q

combinatorial association

A

when light and heavy chain bind together their impact on antigen binding

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13
Q

HV

A

hyper variablility

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14
Q

Recombination signal sequences (RSS)

A

directs somatic recombination, RSS that flanks the V and D and J segments there are 2 types
these provide a point for enzymes to cut and rejoin the gene segments

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15
Q

2 Types of RSS

A

hepatamer
and nonamer
these are separated by a 12 base pair segment or a 23 base pair segment

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16
Q

length of bp segment that separated the 2 types of RSS

A

12 or 23 bp length segments

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17
Q

V(D)J recominase

A

enzyme that clips out RSS segment and rejoins gene segments
this enzyme is only made in lymphocytes
enzymes associate with RAG1-2 gene to for RAG complex that forms DNA into a hairpin and then cleaves and rejoins it bringing V and j segments together

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18
Q

RAG-1 and 2

A

recombination -activating genes, these gene products and other enzymes associate to for RAG complex that forms DNA into a hairpin and then cleaves and rejoins it bringing V and j segments together

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19
Q

Junctional diversity

A

occurs when enzymes of RAG complex join the gene segments VD and J

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20
Q

palindromic nucleotides (P nucleotides)

A

nucleotides that are read the same forward and backward the RAG complex adds these P nucleotides by nicking one strand of DNA at the terminus

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21
Q

at Junction

A

enzyme can remove gremlin encoded nucleotides or TdT enzyme can add nucleotides that are not encoded in the Germline

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22
Q

N nucleotides

A

nucleotides that are not encoded in gemline

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23
Q

RAG forms

A

the hairpins and ceaved one strand of DNA

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24
Q

TdT

A

terminal deoxynucleotidyl transferase,

acts as addition of N nucleotides which were never germline

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25
Q

N=

A

nontemplated

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26
Q

Generation of junctional diversity

A

where mutations form, P nucleotides clipped and add nucleotides to J segment and now it have gained 2 more amino acids

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27
Q

Exonuclease’s

A

remove unpaired nucleotides, leaving gaps taht are later filled by actions of other enzymes involved in DNA editing.

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28
Q

Over all BCR diversity is generated as a product of

A

(somatic recombination + combinatorial association)X(Junctional diversity)= overall diversity =(4.8x10^13)

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29
Q

Junctional diversity increases the overall diversity by_______

A

3x10^7

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30
Q

Junction diversity impacts the ________ region

A

Hyper variable

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31
Q

A process similar to junctional diversicty occurs in _________ this is called ____________

A

T cells

functional TCR

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32
Q

SCID (sever combine immune defficency)

A

due to lack of RAG enzymes to form hair pin loos and cleave thus resulting in no functional T or B cells(have no receptors) this is a genetically aquired disorder

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33
Q

AIDS virus causes

A

due to lack of functional T cells(no receptors)

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34
Q

Alternative mRNA splicing

A

Joining of VDJ and transcription of them

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35
Q

results form translation of Transcribed VDJ

A

Surface expression of IgD and IgM of same specificity (same V region but different Constant regions)

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36
Q

the difference and similarity of IgD and IgM structure

A

both have differing constant regions but the same V region
only 2 antibodies expressed simultaneously on B cell surface
only two classes that are express on naive circulating B cells

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37
Q

only Classes that are expressed on circulating niave B cells (not yet encountered antigen)

A

IgD and IgM

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38
Q

Only antibodies expressed simultaneously on B cell surface

A

IgD and IgM both are membrane bound

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39
Q

Allelic exclusion

A

both light and heavy chains occurs so that a developing B cell only expresses an Ig of one specificity.
allowing for clonal selection to occur creating an antibody specific for pathogen

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40
Q

clonal selection

A

finding of specific antigen by B cell = affinity and causes B cell to mature to plasma cell which then releases cytokines to stimulate other B cell maturation

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41
Q

when B cell only expresses an Ig of one specificity

A

Allelic exclusion

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42
Q

B cell Ig receptors

A

are made in the ER and then associated with Ig Alpha and Ig Beta which assist in transport to surface.
the transmembrane portion is hydrophobic and can be imbedded in membrane
When antigen interacts with Fab region of Ig the transmembrane segments of the Ig are too short to send signals so it requires help to send intracellular signals by utilizing IgBeta and Ig Alpha which have longer cytoplasmic tails

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43
Q

IgAlpha and IgBeta

A

have longer cytoplasmic tails then B cell receptor so assist in intracellular signal tansduction
always paired with B cell receptor when receptor present

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44
Q

Diversification of Antibody occurs _____

A

after B cells encounter Antigen

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45
Q

Following B cell encounter with antigen

A

B cell starts changing into plasma cell and starts secreting large amounts of IgM and small amounts of IgD due to alternative splicing and processing of RNA (no change in DNA)

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46
Q

Difference between membrane bound Ig and secreted Antibody

A

membrane bound Ig has hydrophobic C terminus end

antibodies hydrophilic C terminus

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47
Q

Somatic hypermutation

A

the process that increases diversity in Ig after a B cell encounters its Antigen

48
Q

Rate of random pint mutation is

A

1 per cell division, this is 1 million times more frequent than normal

49
Q

When random point mutations occur in variable region of H and L genes(within a single nucleotide substation) it leads to

A

somatic hypermutation

50
Q

CDRs

A

compliment Detemning Regions

where Random point mutations occur

51
Q

somatic hypermutation targets

A

the rearranged gene segments encoding the variable region (aka occurs most frequently in variable region)

52
Q

Immunization IgM and IgG levels

A

low levels of IgM are present within the first week of primary immunization
the second week there is a large increase in the amount of IgM and IgG appearas and is abundant
due to huge changes in receptors due to mutation to encounter and fight antigen/pathogen(from vaccine) this leads to a super high affinity antibody

53
Q

Activation-induced cytidine deaminase (AID)

A

is the enzyme important in the process of somatic hypermutation and only is expressed in proliferating B cells

54
Q

AID function

A

converts Cytosine to Uracil (uracil is only found in RNA so DNA repair enzymes replace the Uracil with 1/4 other DNA nucleotides)this leads to mutation due to this some of the newly expressed mutant Ig has a higher affinity which are then selection and become plasma cells

55
Q

High affinity for antigen Mutant Ig on B cells leads to

A

selection and then maturation of these B cells to become plasma cells

56
Q

Affinity maturation

A

antibody of progressively higher affinity for the antigen are then produced as the adaptive Immune response proceeds
a process of evolution that results in an improved product and can be achieved in a few days instead of a few years
allos the slow evolving human to keep up with fast evolving pathogens

57
Q

Isotype

A

aka class switching

58
Q

class swithcing

A

is dependent on AID and occurs only in B cells that are proliferating in response to the encounter of their antigen

59
Q

Class switching consists of

A

DNA recombination of heavy cain constant region
but does not change the specificity of the V region but does result in excision of the perviously expressed heavy chain and insertion of new heavy chain

60
Q

The heavy chain determines the _______ of the antigen

A

Class

61
Q

does class switching change specificity of V region

A

no

62
Q

what does Isotype switching change

A 
swaps heavy chain in consent region for another thus changing the class 
so IgM switch to IgD
63
Q

Paitents who lack AID

A

results in hyper IgM immunodeficiency
the Ig on B cells of patients who lack AId cannot under go somatic hypermutation or isotype switching
only have IgM in body no other antibodies to help fight

64
Q

low affinity of IgM results in

A

high levels of IgM present to compensate for low affinity

65
Q

Increased susceptibility to infection by pyogenic (pus producing) bacteria due to

A

AID low levels of IgM

also there is No IgA to protect MM

66
Q

bond that holds IgM monomers together forming ______

A

a disulfid bonds and a J chain work together to hold 5 IgM monomers together to form a pentameric IgM creating potentially 10 binding sites

67
Q

monomeric IgM contains

A

4 constant regions

68
Q

Joining chain (J chain)

A

helps hold pentameric IgM together and Dimeric IgA

69
Q

IgM affinity

A

low affinity binding site so more sites (petameric molecule) helps counter low affinity by increased # of sites

70
Q

IgG affinity

A

High affinity bindind due to ionic switching thus IgG is less is abundents is nessicary then IgM

71
Q

Different C regions on antibodies results in

A

different effector functions of Antibody classes

72
Q

IgD, IgE, IgM are each a separate

A

class

73
Q

IgA and IgG each have

A

sub classes with varrying affinity

74
Q

IgA sub classes

A

IgA1 and IgA2

75
Q

IgG sub classes and varying affinities *

A

IgG1>IgG2>IgG3>IgG4 these are numbered in terms of abundance in plasma i.e. igG1 is most abundant

76
Q

IgG1

A

is the most abundant in serum

77
Q

IgM function and property

A

neutralization
activation of complement system (best at this)
some is transported across epithelium
a little diffusion into extravascular sites

78
Q

IgD function and property

A

no function or properties

79
Q

IgG1 function and property

A 
great to
Neutralization
Opsonization
Sensitization for killing by NK cells
a little sensitization of mast cells
Activation of Complement system
80
Q

IgG2 function and property

A

Neutralization
Activation of complement system
Transports across placenta
and major at Diffusion into extravascular sites

81
Q

diffusion into extravascular sites facilitated by antigen

A

IgG1, IgG2, IgG3, IgG4

82
Q

IgG3 function and property

A 
neutralization
opsonization
sensitization for killing by NK cells
sensitization of mast cells
Activation of complement system
Transport across placenta
Difusion into extravascular sites
83
Q

neutralization stimulated by this antigen

A

IgG (1,2,3,4)

84
Q

IgG4 function and property

A

Neutralization
Opsonization
Transported across placenta
Diffusion into extravascular sites

85
Q

IgA function and property

A 
neutralization
Opsonization
activation of complement system
transport across epithelium (dimer)
Diffusion into extravascular sites (monomer)
86
Q

IgE

A

Sensitization of mast cells

Diffusion into extravascular site

87
Q

Transport across epithelium=

A

transport on MM

88
Q

which is trasphers to baby via breast milk

A

IgG

89
Q

Best neutralizing Antibodies belong to class

A

IgG(1-4) and IgA

90
Q

Best Opsonizing antibodies belong to class

A

IgG1, IgG3, igG4 & IgA (

91
Q

Sensitization for NK killing

A

igG1 and IgG3

92
Q

Sensitization of mast cells

A

IgE, IgG1 and IgG3

93
Q

Complment activation

A

IgM, IgG(1,2,3) and IgA

94
Q

transports across epithelium

A

dimeric IgA and some IgM

95
Q

Transports across placenta

A

IgG 1,2,3,,4

96
Q

diffusion into extravascular spaces

A

all IgGs
Monomeric igA
IgE and very little IgM

97
Q

least abundant in serum

A

IgE and IgD

98
Q

IgM

A

First antibody produced during a primary IR and begin with low affinity so have multiple binding sites (10) which increase avidity
a good complement activator not a great opsonin
doesn’t cross easily into extravascular spaces
cannot cross placenta

99
Q

avidity

A

overall strength of binding of entire andtibody and antigen

100
Q

affinity

A

is the strength of binding at one site

101
Q

if a newborn has IgM

A

this indicates and intrauterine infection (this IgM was produced by baby and is its own)

102
Q

IgG

A

most abundant form in blood and lymph
small and flexible can cross extravascular spaces
only class to cross placenta
many effector functions
Higher affinity than IgM
IgG1 and IgG3 are opsonins for phagocytic cells and can activate complement

103
Q

IgA

A

Monomeric Igas in serum (some dimeric)
Dimeric igAs
most abundantly made antibody
monomers of IgA

104
Q

Dimeric igAs

A

form are secreted on all MM, breast milk, sweat and tears

most abundantly made antibody

105
Q

monomers of IgA

A

are joined by a j chain like the one used for joining IgM. also there is secretory component present on thos which are secreted this helps stabilize IgAs so they last longer on MM than other protiens

106
Q

IgE

A

First exposure to Antigen (pollen or parasite ) causes IgE production
Mast cells (tissues),
eosinophil’s (MM)
basophils (blood)
all carry a receptor (Fc and R)this binds to Fc end of IgE even when not bound to antigen thus sensitization of these cells
during re-exposure to antigen which bridges the IgEs on these cells-> release of histamine and proinflammator mediatiors causing allergy or acts to fight parasite

107
Q

basophils

A

blood

108
Q

eosinophil

A

mm

109
Q

mast cells

A

tissues

110
Q

Change in immunoglobulin genes during a B cells life

1.V- region assembly from gene fragments

A

somatic recombination of genomic DNA this is irreversible

111
Q

Change in immunoglobulin genes during a B cells life

2. generation of junctional diversity

A

imprecision in joining rearranged DNA segments adds nongermline nucleotides (P and N) and deletes gemline ducleotides
this is irreversible

112
Q

Change in immunoglobulin genes during a B cells life

3. Assembly of transcriptional controlling elements

A

promoter and enhancer are brought closer together by V region assembly

113
Q

Change in immunoglobulin genes during a B cells life

4.Transcription activated with coexpression of surface IgM and IgD

A

two patterns of splicing and processing RNA are used

reversible and regulated

114
Q

Change in immunoglobulin genes during a B cells life

5. Synthesis changes from membrane Ig to secreted antibody

A

Two Patterns of splicing and processing RNA are used

reversible and regulated

115
Q

Change in immunoglobulin genes during a B cells life

6. somatic hypermutation

A

point mutation of genomic DNA

Irreversible

116
Q

Change in immunoglobulin genes during a B cells life

7. isotype switch

A

somatic recombination of genomic DNA

irreversible

Immunology (4 decks)

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