Chp 4—Antibodies & B-Cells Flashcards
1
Q
antibody repertoire
A
from 10^9 to 10^16 - highly specific
2
Q
Agammaglobulinemia
A
inability to make antibodies
3
Q
4 parts of an antibody
A
2 identical heavy chains
2 identical light chains
4
Q
glycosylation occurs on…
A
heavy chain
5
Q
C termini
A
stalk of the Y
6
Q
N termini
A
“ends” of the Y which bind antigen
7
Q
N termini domain bound to C termini domain by…
A
disulfide bonds
8
Q
disulfide bonds also called…
A
hinge region
9
Q
Fc
A
fragment that crystallizes - stalk of Y - only constant regions are present
10
Q
Fab
A
“arms” - contain all 4 variable regions - remain soluble
11
Q
Antibody isotypes
A
G
M
D
A
E
12
Q
extra fifth domain
A
IgE
IgM
13
Q
predominant circulating antibody
A
IgG
14
Q
predominant secretory antibody
A
IgA
15
Q
least important Ig
A
IgD
16
Q
types of heavy chains
A
𝛄, μ, δ, 𝛼
17
Q
types of light chains
A
ƛ or 𝝹
18
Q
____% light chains are kappa
____% light chains are lambda
A
67
33
19
Q
epitope also called…
A
antigenic determinant
20
Q
2 types of antigen geometry
A
linear
discontinuous
21
Q
denatured _______ antigen impedes action of antibody
A
linear
22
Q
multivalent
A
antigen with multiple epitopes
23
Q
types of forces contributing to affinity
A
H bonds
VDW forces
electrostatic
hydrophobic interactions
24
Q
catalytic antibodies…
A
bind and inactivate target molecules
25
variable regions divided into...
framework regions
hypervariable regions
26
hypervariable regions divided into...
CDR1
CDR2
CDR3
27
intravenous antibody
from 10k - 60k people
28
Mab
preparation of a single useful antibody (monoclonal)
29
hybridoma
canceous myeloma cell is fused to all B-cells from immunized animal - Myeloma and B cells are killed off - hybridoma produces Mab
30
original use of Mab
bind all CD3 antigens on human T-cells, preventing kidney transplant rejection
31
4 types of therapeutic Mab
mouse
chimera
humanized
human
32
mouse Mab use
only used once for one person
33
chimera Mab structure & use
human constant region, mouse variable region
Rituximab - treats non-Hodgkin B-cell lymphoma
34
humanized Mab structure & use
all human except CDRs
Omalizumab - treats severe allergic asthma
35
human Mab use
Adalimumab - binds TNF-𝛼 to treat rheumatoid arthritis
36
L =
V =
J =
D =
C =
MC =
SC =
L = leader
V = variable
J = joiner
D = diversity
C = constant
MC = membrane component
SC = soluble component
37
somatic recombination
fragments of genes recombine when lymphoid precursor differentiates into a naive B-cell
38
Somatic recombinations of regions on light and heavy chains give ______ antibody genotypes
1.6 million
39
Allelic exclusion
once gene rearrangement for effective light and heavy chains are complete, the cell stops rearrangement processes
40
lambda chromosome
22
41
kappa chromosome
2
42
Variable regions of light chain formed from recombination of...
V & J
43
heavy chain chromosome
14
44
Variable regions of heavy chain formed from recombination of....
V, D, J
45
junctional diversity occurs with...
CDR3
46
During junctional diversity, an extra __ bases after ___, and before ___ line up
7 bases (heptamer)
after D
before J
47
randomly adds N (new) nucleotides during junctional diversity
terminal deoxynucleotidyl transferase (TdT)
48
removes unpaired bases from the end during junctional diversity
gaps are filled to complete novel joining regions
exonuclease
49
In B-cells, mRNA splicing leads only to...
in naive B cells
IgM or IgD
50
MC connected to ...
poly-A tails
51
function of dimer Ig𝛼 + Igβ
help guide antibody to membrane from golgi apparatus
help send transduction signals to nucleus in case of binding between antibody and antigen
52
selection
meeting of antigen with specific B cell
53
selection causes...
mRNA splicing to be modified, so MC is replaced with SC
54
explain affinity maturation
- name of mutation type
- enzyme involved & function
- type of mutation resulting
- allows for...
During clonal expansion after selection, additional variability is induced by somatic hypermutation
activation-induced cytidine deaminase (AID) changes cytosines to uracils, which are randomly replaced with nucelotide bases over time
results in point mutations, which leads to better and better antibodies
Allows competition between nearly identical B cell clones - CDRs improve - Cells with best variable regions expand fastest
55
AID-deficient patients...
make lots of IgM
56
IgM pentamer forms with Fc portions joining at...
J chain
57
avidity
overall strength of antibody
58
explain IgM avidity
low affinity, but lots of binding sites leads to greater avidity
59
isotypes made by gene rearrangement upon reexposure to antigen
IgA, IgG, IgE
60
Explain IgG synthesis as modified from IgM/D
Switch (S) region added before and after C regions
AID modifies them, allowing them to splice out Cμ and Cδ regions, and replace them with C𝛄 regions
61
isotype switching only occurs when...
Only occurs when B cell is activated by cytokines from T cells, which must be activated by that same antigen
62
2 general modes of action for antibodies
opsonization
neutralization
63
Gold standard
neutralization
64
explain antibody opsonization
Fc region binds of C1q
activates classical pathway of complement
leads to phagocytosis by cells with Fc receptor
65
IgM +++ function
activation of complement system (MAC)
66
IgD +++ function
sensitization of basophils
67
IgG1 and IgG3 +++ functions
neutralization
opsonization
NK sensitization
activation of complement (MAC)
placenta transport
extravascular diffusion
68
IgG2 +++ functions
neutralization
extravascular diffusion
69
IgG3 +++ functions
neutralization
opsonization
NK sensitization
70
IgG4 +++ functions
neutralization
placenta transport
extravascular diffusion
71
IgA +++ functions
neutralization
epithelial transport
extravascular diffusion
72
IgE+++ functions
mast cell sensitization
basophil sensitization
(also eosinophils)
73
IgA (monomer/dimer) present in blood
monomer
74
IgE binds to inflamatory cells (with/without) antigen
without - waits for antigen to come along
75
Respiratory antibody
IgE
76
IgG subclasses differ in...
hinge region
77
stretched hinge region
IgG3
78
can swap variable chains in the blood
IgG4
79
prevents IgE binding, dampening allergic response
IgG4
