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Immunology > Chapter Five > Flashcards

Chapter Five Flashcards

1
Q

What do activated lymphocytes make?

A

clones of antigen-specific effector cells that mediate adaptive immunity

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2
Q

What does the clonal expression on antigen receptors mean?

A

each lymphocyte is unique among the billions of lymphocytes that each person posses. variation in AA seq at antigen binding site

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3
Q

What determines the receptor’s antigen binding site and allows for seemingly limitless diversity in specificity?

A

Ig domains contain 3 loops made of 3 hypervariable regions, or complementarity determining regions (CDRs)

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4
Q

What is the correlation between # of genes & diversity of lymphocytes?

A

limited size of genome: entire genome is just Ab genes.

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5
Q

What is gene rearrangement?

A

during development of each lymphocytes gene segments (2-3) are rearranged by somatic DNA recombination to form complete and unique variable region coding seq

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6
Q

What does the mechanism of gene rearrangement tell us about evolution of the vert adaptive immune system?

A

common to both B cells and T cells and was probably critical to the evolution of the vert adaptive immune system

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7
Q

What is the primary Ig gene rearrangement for light chains?

A

VL + JL = V

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8
Q

What is the primary Ig gene rearrangement for heavy chains?

A

VH + DH + JH = V

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9
Q

Where are Ig gene rearranged?

A

progenitors of antibody-producing cells

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10
Q

What is the germline theory?

A

there is a separate gene for each different Ig chain and that the antibody repertoire is largely inherited. correct about multiple germline genes

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11
Q

What is the somatic diversification theory?

A

the observed repertoire is generated from a limited number of inherited V region sequences that undergo alteration within B cells during the ind’s lifetime. essentially correct

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12
Q

What is true about the germline theory and the somatic diversification theory?

A

both are correct bc DNA seq encoding each variable region is generated by rearrangement of relatively small group of inherited gene segments

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13
Q

What is somatic hypermutation?

A

occurs in mature activated B cells -> enhances diversity

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14
Q

What is in a single V region exon?

A

3 hypervariable regions or CDR

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15
Q

What 3 things on Ig are related?

A
  1. light chain variable region’s antigen-binding site 2. its domain structure 3. gene that encodes it
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16
Q

Where is the DNA seq of the variable-region exon present?

A

NOT in germline but is originally encoded by 2 separate DNA segments

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17
Q

What originates from the V gene segment?

A

first 95-101 AAs of variable region encoding beta sheets A-F and first 2 complete HV regions

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18
Q

What originates from J (joining) gene segment?

A

other parts of 3rd HV region and remainder of V region including beta sheet G (up to 13 AAs)

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19
Q

Somatic recombination of separate gene segments =

A

complete genes that encode variable region

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20
Q

What is true about V gene segments present at each immunoglobulin locus?

A

multiple V gene segments but not all are functional. some have mutations that prevent them from encoding a functional protein (pseudogenes)

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21
Q

3 cluster of Ig gene segments the encode chains?

A

κ, λ, and heavy-chain loci

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22
Q

How is the heavy chain locus different?

A

instead of single C region, it contains a series of C regions arrayed one after the other each of which corresponds to different Ig “isotype”

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23
Q

What do recombination signal sequences (RSSs) do?

A

guide rearrangement of V, D, and J gene segments. conserved heptamer and nonamer seqs that flank the gene segments encoding V, D, and J regions of Igs

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24
Q

V region gene segments are joined by

A

recombination. joining of V and J segments creates function V region exon

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25
Q

What is V(D)J recombinase?

A

complex of enzymes that act to carry out somatic V(D)J recombination

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26
Q

What are the lymphoid specific components of V(D)J recombinase?

A

RAG-1 and RAG-2. other members of DSBR

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27
Q

Why is the imprecise nature of DSBR important?

A

critical for junctional diversity and adaptive immunity

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28
Q

4 main process that generate extraordinary diversity of Ig repertoire.

A
  1. combinatorial diversity 2. junctional diversity 3. light and heavy combo 4. somatic hypermutation
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29
Q

What is combinatorial diversity?

A

multiple different copies of each type of gene segment and different combos of gene segments can be sued in different rearrangement events. combinatorial diversity is responsible for substantial part of the diversity of V regions

30
Q

Where does junctional diveristy occur?

A

at joints between different gene segments as a result of the addition and subtraction of NTs by recombo process

31
Q

What is the light and heavy combo process?

A

source of diversity: many possible combos of heavy and light chain V regions that pair to form the antigen binding site in the Ig molecule

32
Q

What is somatic hypermutation?

A

only in B cells after initiation of immune response and introduces point mutations into rearranged V-region genes

33
Q

What contributes to diversity of the 3rd HV region?

A

variable addition and subtraction of NTs at junctions between gene segments. added NTs are P-NTs and N-NTs

34
Q

What are P-nucleotides?

A

make up palindromic seqs added to the ends of the gene segments

35
Q

What are N-nucleotides?

A

added by quite different mechanism before the ends are rejoined. non-template encoded

36
Q

What are non-productive rearrangements?

A

DNA rearrangements readings that disrupt the reading frame of the coding sequence beyond the joint. frameshifts lead to non-functional protein

37
Q

How many rearrangements will be nonproductive?

A

2 in 3. B-cell progenitors don’t become Ig don’t become mature B cells

38
Q

What is the cost of junctional diversity?

A

loss of cells during B cell development due to non-productive rearrangements

39
Q

Compare TCR gene segment arrangement of Ig gene segment arrangement.

A

similar pattern by the same enzymes

40
Q

What is consequence of alternative mRNA splicing?

A

same antibody gene can generate both membrane bound Ig and secrete Ig

41
Q

How are different classes of Ig distinguished?

A

by the structure of their heavy chain constant regions

42
Q

What are the 4 subclass of IgG in decreasing order of their abundance in serum?

A

IgG1, IgG2, IgG3, IgG4

43
Q

What are the 2 subclasses of IgA?

A

IgA1 and IgA2

44
Q

What are the heavy chain isotypes?

A

μ, δ, γ, ε, and α

45
Q

What is the Macroglobulin?

A

IgM because it is 190kDa

46
Q

What is IgE associated with?

A

immediate-type hypersensitivity. when fixed to tissue mast cells has much longer half-life than its half-life in plasma shown here

47
Q

Constant region confers

A

functional specialization on the antibody.

48
Q

3 main effector function of Fc region.

A
  1. Fc receptor binding 2. complement activation 3. regulation of secretion
49
Q

What does the Fc region bind to?

A

specialized Fc receptors expressed by immune effector cells

50
Q

What do Fcγ receptors on macrophages & neutrophils bind to?

A

Fc portions of IgG1 and IgG3 antibodies faciliating phagocytosis of pathogens coated w these antibodies

51
Q

What do Fcε receptors bind to?

A

Fc region of IgE. Fcε receptor on mast cells, basophils, and activated eosinophils then triggers release of inflammatory mediators in response to antigens

52
Q

How does Fc activate complement activation?

A

binds C1q complement protein and initiates “classical” complement cascade which recruits and activates phagocytes to engulf and destroy pathogens

53
Q

How does Fc regulate secretion?

A

can deliver antibodies to places they can’t each w/o active transport: IgA into mucous secretions, tears, and milks, and transfer of IgG from pregnant mother into fetal blood circulation

54
Q

How do microorganisms fight the destructive potential of Fc?

A

evolving proteins that either bind it or cleave it so Fc doesn’t work

55
Q

How are IgM and IgD similar?

A

derived from the same pre-mRNA transcript and both expressed on surface of mature B cells

56
Q

What is unique about IgD?

A

hinge region is more flexible than those in IgM. suggested to be auxiliary receptor that may facilitate binding of antigens by naive B cells

57
Q

What true about the coexpression of IgM and IgD?

A

regulated by RNA processing: long primary mRNA transcript is deferentially spliced to yield either of 2 distinct mRNA molecules -> ZFP318

58
Q

What is ZFP318?

A

RNA-protein complex required for mRNA splicing. expressed in mature and activated B cells that coexpress IgD and IgM

59
Q

What is RNA splicing?

A

process that deletes introns and joins together successive exons to form mature RNA

60
Q

Do bacteria have introns?

A

no only humans do

61
Q

What is longer DNA or RNA seq?

A

DNA

62
Q

What are introns?

A

found in gene’s DNA but not in mature mRNA

63
Q

What are exons?

A

found in both gene’s DNA and mature mRNA

64
Q

What do introns exist?

A

molecular mechanism -> different mRNA can be produced from same primary transcripts via alternative splicing

65
Q

When are introns removed?

A

from pre-mRNAs by RNA splicing

66
Q

What is a spliceosome?

A

complicated intranuclear machine that splices RNA

67
Q

What are spliceosomes made of?

A

4 subunits = small nuclear ribonucleoproteins (snRNPS) = each snRNP has 1 or 2 small nuclear RNAs (snRNAs) 100-300 NT long associated with proteins in discrete particles

68
Q

What is the C-value paradox?

A

alt splicing explains how 27,000 genes in human genome can encode hundreds of thousands of different proteins

69
Q

How are transmembrane and secreted forms of Ig generated?

A

via alternative heavy-chain mRNA transcripts. in actived B cells most transcripts are spliced to make the secreted form of whichever heavy-chain isotype B cell is expressing

70
Q

What can IgM and IgA do?

A

form polymers by interacting with the J chain. C regions of IgM and IgA have cysteine residue needed for polymerization

71
Q

What is true about IgM?

A

recognize repetitive epitopes on bac cell wall polysaccs but individual binding sites are often low of affinity because IgM is made early in immune response before somatic hypermutation and affinity maturation

Immunology (8 decks)

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