Antibodies Flashcards
(72 cards)
1
Q
What see in electrophoresis of lymphoma
A
too much antibody - gamma band
2
Q
Antibody structure
A
3 fragments:
2 identical Fab
1 Fc
Two identical light chains
Two identical heavy chains
3
Q
Each chain consists of _______ held together by ______
A
domains
s—s bonds
4
Q
Light chain has ____ variable/constant
Heavy chain “”””
A
Light - 1 variable (VL), 1 constant (CL)
Heavy - 1 variable (VH), 3-4 constant (CH1, CH2, CH3, CH4)
5
Q
Which domain pushes out
A
CH2 - interact more easily with complement – how ab initiate inflammation (C1q)
6
Q
IgM structure
A
pentamer held together by J chain
4 CH
7
Q
IgG structure
A
3 CH
different kinds
8
Q
IgA structure
A
dimer - j chian
3 CH
9
Q
IgD structure
A
primary function is membrane bound in naive B cells to mediate B cell receptor signaling
3 CH
tailpieces (bound)
10
Q
IgE structure
A
4 CH
secreted as a monomer
11
Q
What define class of antibody
A
5 kinds of H chains (gamma, alpha, mu, epsilon, delta)
12
Q
L chain types
A
kappa, lambda (only 1 kind in each antibody)
13
Q
What happens to chains in class switching
A
heavy chain changes (ie mu –> alpha) but L chain (k or L) stays the same during the switch
14
Q
constant region made up of
A
of 1 (in L chains) to 4 (in epsilon and mu) compact, structurally-similar domains called C domains.
15
Q
variable domain
A
V domains of both the H and L chain (VH and VL) - where antigen binds
16
Q
Valence
A
number of antigenic determinants (epitopes) an antibody molecule can theoretically bind.
17
Q
Valence IgG
A
2
18
Q
Val IgM
A
10
19
Q
Val IgA
A
4
20
Q
Val IgD
A
2
21
Q
Val VL or VH
A
None (need both)
22
Q
Val Fab
A
1
23
Q
Isotypes
A
IgG1, IgG2, IgG3, IgG4 IgA1, IgA2 IgM1, IgM2 IgD IgE
subclasses
slight differences in amino acid sequences of H chain C regions
24
Q
Allotypes
A
Minor allelic differences in sequence of Immunoglobulins between individuals
from parents - useful in genetics
25
Idiotypes
Each antibody will have its unique combining region, made up of the CDR amino acids of its L and H chains
26
Antibodies in human serum (numbers)
```
IgG: 1000 mg/deciliter (dL =100 mL) (MOST)
IgA: 200 mg/dL
IgM: 100 mg/dL
IgD: 5 mg/dL (usually bound)
IgE: 0.02 mg/dL (LEAST)
```
27
IgG
the main antibody in blood and tissue fluids. It neutralizes toxins and blood-borne viruses, binds bacteria and facilitates their destruction by activating complement and by binding them to phagocytic cells.
28
the main antibody in blood and tissue fluids. It neutralizes toxins and blood-borne viruses, binds bacteria and facilitates their destruction by activating complement and by binding them to phagocytic cells.
IgG
29
similar things in the blood as IgG, but its real role is as the dimer form in secretions, where secretory component protects it from proteolysis.
IgA
30
IgA
similar things in the blood as IgG, but its real role is as the dimer form in secretions, where secretory component protects it from proteolysis.
31
much the same as IgG. It is the first antibody to appear in the serum after
immunization, and it is very efficient at activating complement. It does not get into tissue fluids very efficiently, nor is it bound efficiently by phagocytic cells.
IgM
32
IgM
much the same as IgG. It is the first antibody to appear in the serum after
immunization, and it is very efficient at activating complement. It does not get into tissue fluids very efficiently, nor is it bound efficiently by phagocytic cells.
33
role in blood, if any, is uncertain; it seems to function mainly as a receptor on naïve B
cells.
IgD
34
IgD
role in blood, if any, is uncertain; it seems to function mainly as a receptor on naïve B
cells.
35
antibody which causes Type I immunopathology, also called immediate
hypersensitivity or allergy. Its true importance is in resistance to worms and other parasites.
IgE
36
IgE
antibody which causes Type I immunopathology, also called immediate
hypersensitivity or allergy. Its true importance is in resistance to worms and other parasites.
37
Ag-Ab interaction change in shape
When ab bind ag - change in angle between two Fab parts to more Y or T shaped --> bulging of Fc
38
Ab-Ag interaction results
binding of phagocytic cells (bind to Fc altered of IgG - not IgM)
C1q binds 2 adjacent Fcs and activated -- IgM better at complement
39
IgG does what better than IgM and vice versa
IgG - binding to phagocytic cells
| IgM - activating complement
40
steps in heavy chain recombination
```
DJ recombination
VDJ recombination
transcription
splicing
translation
```
41
immunoglobulin domains
two or more β-pleated sheets arranged in opposite directions that are stabilized by one or more disulfide bonds.
42
Which ab isotypes fix complement
IgM (and IgG)
43
Which ab isotypes degranulate mast cell/basophil
IgE
44
Which ab isotypes lyse bacteria
IgM > IgG, IgA
45
Which ab isotypes have antiviral
IgM, IgG, IgA (most)
46
which ab isotypes neutralize toxins
IgG, IgA
47
Elevated levels IgM indicate
recent infection or other exposure to antigen
48
Which ab binds macrophage Fc receptors
IgG (not IgM, IgA)
49
Which ab mediates hemolytic disease of newborn
IgG (blue baby, Rh mismatch)
50
Where is antibody diversity from
Genetic rearrangement of various gene sections for heavy and light chains (VDJ and constant regions)
Variation incorporated at joining sites for various segments of heavy and light chains
Hypermutation in variable regions of heavy/light chains during proliferation of B cells
Mixing/matching heavy/light chains in combinatorial manner (genes are separate)
51
primary RNA transcripts of heavy chains
VDJ - combined with constant regions up to end of delta
| can make VDJ-m and VDJ-d
52
light chain recombination
only have VJ (no D)
Kappa, if not, then lambda
53
The enzymes that do the recombination of antibody and T cell receptor DNA (VDJ recombination)
RAG recombinases
54
Syndrome where RAGs are knocked out -
Omenn syndrome
| Cannot make B or T cells
55
RAG-1/2
Catalyze DNA strand breakage and rejoin to form signal and coding joints
56
Tdt
add N region nucleotides to the joints between gene segments in the Ig heavy chains and all joints between TCR gene segments
57
HMG
Stabilize binding of RAG1/2 to recombination signal sequences, stabilize bend introduced into the 23-bp spacer DNA by the RAG 1/2 proteins
58
Ku proteins
Binds DNA coding and signal ends and holds them in protein-DNA complex
59
ARtemis
Opens the coding end hairpins
60
Heavy chain VD and DJ points
loss of coding nucleotides at joint -- TdT adds in non-templated nucleotides = source of variation (and potential cause of non-productive Ab)
Somatic mutation
61
Mature (but not activated) B cells initially express
both IgD and IgM (these are B cell receptors)
62
As mature B cells are activated to divide and differentiate by their cognate antigen, they switch from membrane-bound IgD and IgM to
secretory IgM
Level of processing mRNA transcripts
63
Class switching to IgG, IgE or IgA happens at what level
rearrangements of DNA
64
Variation through somatic hypermutation
Recombined V(D)J is hypermutable, each time a B cell divides after antigenic stimulation - there is a good chance of one daughters iwll make a slightly different antibody = affinity maturation
65
How somatic hypermutation works
Activation-Induced (Cytidine) Deaminase (AID) converts random cytosines in the CDR gene regions to uracil. So a C:G pair becomes a uracil: guanine mismatch. The uracil bases are excised by the repair enzyme uracil-DNA glycosylase. Error-prone DNA polymerases then fill
in the gap, creating mostly single-base substitution mutations, so at the end of cell division one daughter may be making a different (worse? better?) antibody.
66
What changes/stays same in class switching
In all cases, the L chain and the VH domain stays the same but the C region of the H chain changes.
67
How class swtiching happens
cell which has put its particular H-chain VDJ combination together with its mu and delta genes goes back to its DNA, does a loop-out of mu and delta, and puts VDJ next to the C region gene of gamma or epsilon or alpha, while excising and discarding intervening DNA.
require T cell help, AID
68
if a cell makes IgM, what can it make> What about igG
IgM --> anything else (still have DNA)
| IgG cannot go back to make IgM since mu info is gone (from the DNA)
69
IL2, IL4, IL5
B cell proliferation
70
B cell proliferation
IL2, IL4, IL5
71
IL4 + IL5
B cell class switch to IgE
72
IFN gamma
block class switch to IgE induced by IL-4
