antibody structure and generation of B cell diversity Flashcards

1
Q

the 2 components of an antibody

A

fragment antigen binding (Fab)
fragment crystallization (Fc)

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2
Q

Antibody classes (heavy chain, light chain)

A

heavy: G, M, D, A, E
light: kappa and lambda (kappa is first choice during selection)

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3
Q

Are immunoglobulin chains folded into compact and stable protein domains?

A

Yes

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4
Q

what makes up the V domain (antigen binding domain)

A

heavy and light chain together

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5
Q

Do C domains have sequence variation?

A

No

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6
Q

what is the 3D structure of the Ig C and V domains

A

sammich

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7
Q

what are hypervariable regions?

A

loops

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8
Q

what are framework regions made of?

A

beta strands

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9
Q

what do VL and VH make

A

a composite site
which is a antigen binding site
complementarity determining regions (CDR)
and hypervariable regions (HV)

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10
Q

what is the epitope/antigenic determinant made up of?

A

protein or carbohydrate:
- glycoproteins
- polysaccharides
- glycolipids
- peptidoglycans

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11
Q

what are the destructive antigen binding sites?

A

autoimmune (lupus/DNA)
allergy (antibiotics)

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12
Q

what are multivalent antigens

A

antigen containing more than one epitope or multiple copies of the same epitope

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13
Q

which multivalent antigen would have stronger binding strength?
same or different epitopes

A

same epitopes because it would be more sticky and have stronger binding strength

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14
Q

what can epitopes bind to on an antibody antigen binding site

A

pockets, grooves, extended surfaces, or knobs

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15
Q

types of forces behind antigen-antibody interactions

A

non-covalent:
electrostatic
van der waals
hydrogen bonds
hydrophobic interactions

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16
Q

what is the affinity of antigen-antibodies interactions based on?

A

the strength of the interactions

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17
Q

where are monoclonal antibodies produced from

A

a clone of antibody-producing cells

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18
Q

what 2 things are antibodies useful tools for

A

specificity and affinity strength

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19
Q

4 types of therapeutic monoclonal antibodies

A
  1. mouse
  2. chimeric
  3. humanized
  4. human
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20
Q

specific example of chimeric and humanized Monoclonal antibody names and what it treats

A

chimeric: rituximab, b-cell non-hodkins lymphoma
humanized: trastuzumab, metastatic breast cancer

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21
Q

how is nearly limitless antibody variety achieved

A

a unique genetic organization from gene segments: that are families of alternative versions arrayed sequentially in DNA AND germline form/config.: which is inherited form of immunoglobulin genes

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22
Q

the variable region is comprised of what in both light and heavy chains

A

light chain: 1 variable and 1 joining segment
heavy chain: 1 variable, diversity and joining segments

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23
Q

does random recombination of gene segments produce diversity in antigen binding sites?

A

yes

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24
Q

what is the order of regions being joined together during recombination

A

diversity and joining regions first and then variable region after

25
Q

which segment has the most variation

A

variable region in heavy chain, then kappa light chain and then gamma light chain

26
Q

do light chains have any diversity region?

A

no

27
Q

which segment has the highest amount of constant regions

A

heavy chain

28
Q

are the amount of joining regions pretty similar between both chains?

A

yes

29
Q

where are RAG genes made

A

in lymphocytes

30
Q

are RAG genes active in any other cell type than lymphocytes?

A

no

31
Q

are RAG genes important for functional adaptive immunity?

A

yes they are critical

32
Q

is P nucleotide insertion palindromic?

A

yes

33
Q

how is N nucleotides inserted

A

it is non templated and inserted by terminal deoxynucleotidyl transferase (TdT)

34
Q

how is the antibody isotype determined

A

by the heavy chain

35
Q

which immunoglobulin chains do all naive B cells start with

A

with mew and delta which are able to be expressed simultaneously

36
Q

what determines expression of either IgM or IgD and at what level

A

differential splicing, RNA level

37
Q

how many allele/copy is expressed in each B cell, and what is the result

A

only 1 and each B cell has a single antigen specificity

38
Q

what makes the specificity of antibody response a central principal of adaptive immunity

A

the fact that each antibody has a single antigen specificity

39
Q

what location is immunoglobulin first made on

A

membrane bound form that is present on B cell surface

40
Q

which Ig is produced in large numbers: IgM or IgD

A

IgM is produce in large numbers

41
Q

how are secreted antibodies produced and is rearrangement required

A

an alternative pattern of heavy chain RNA processing, no rearrangement necessary

42
Q

how are rearranged V region sequences further diversified

A

somatic hypermutations by AID

43
Q

what is affinity maturation

A

selection of mutated immunoglobulins with improved antigen-binding

44
Q

what does affinity maturation do

A

allows the human immune system to keep up with the pathogen evolution

45
Q

do the initially made IgM have limitations

A

yes, binds well to repetitive sequences, but has limited ability to clear

46
Q

when does isotype switching occur

A

during an active immune response

47
Q

what is isotype switching dependent on

A

during an active immune response done by cytokines.

(antigen-activated T-cell cytokine secretion)

48
Q

what mechanism initiates antibody secretion?

A

RNA processing/splicing

49
Q

what are the 2 ways antibodies aid in pathogen clearance

A
  1. neutralization
  2. opsonizing
50
Q

does somatic hypermutation enhance affinity or avidity

A

affinity (single site)

51
Q

when would IgG replace IgM

A

when there are 2 sites being of sufficient avidity

52
Q

what Ig is responsible for the synthetization of mast cells

A

IgE

53
Q

what Ig is responsible for transport across the epithelium

A

IgA

54
Q

what Ig i most responsible for transport across the placenta

A

IgG1 (and IgG3,4)

55
Q

where is dimeric IgA made

A

in the lymphoid tissues underlying the mucosal surfaces and is then secreted across them

56
Q

is flexibility crucial for Ig molecules

A

yes, because it binds simultaneously to pathogens and to effector molecules and receptors of the immune system

57
Q

types of movement on Fab arms

A

wave, rotate, wag, bend

58
Q

which IgG subclass has high susceptibility of hinge to proteolytic cleavage

A

IgG3

59
Q

which is the subclass of IgG that has different half life in serum

A

IgG3 (7 days) the rest have 21 days