Antibodies: structure and function Flashcards

1
Q

what are antibodies?

A

Antibodies are immunoglobulin (Ig) proteins, produced by plasma cells (differentiated B lymphocytes; aka B cells)

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2
Q

antibodies are part of which immune response?

A

Adaptive ‘humoral’ immune response – specific

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3
Q

Ig structure incorporates features that are…

A

… essential for participation in
the adaptive immune response

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4
Q

Immunoglobulin functions?

A

Specificity where each B cell is programmed to clonally produce an
Ig with specificity for a particular antigen (Ag) and / or epitope

  • Attributed to a defined region (FAB) of the Ig
  • Restricts the Ig to combine with complementary epitopes
  • LARGE variation = large Ig diversity that can react many
    different epitopes
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5
Q

what is specificity attributed to?

A

Attributed to a defined region (FAB) of the Ig

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6
Q

Biological activity is attributed by the…

A

… class of Ig, as well as Ag & epitope specificity defined by the (FC) region

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7
Q

what is biological activity responsible for?

A
  • Complement fixation & activation
  • Passive immunity e.g. crossing placenta
  • Activation of mast cells / basophils (hypersensitivity)
  • Toxin neutralisation (agglutination)
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8
Q

Immunoglobulins (Ig) function as…

A

… antibodies

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9
Q

the antigen (Ag) binding receptors in the B cell surface are secreted by

A

… plasma cells

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10
Q

H chains consist of …

A

… one variable domain
and three constant domains

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11
Q

L chains consist of…

A

one variable domain
and one constant domain

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12
Q

V-domains =

A

specificity

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13
Q

C domains =

A

biological activity

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14
Q

Higher vertebrates produce antibodies and show homology; however …

A

… an immunoglobulin in one species (mouse) is immunogenic in another (rabbit)

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15
Q

Rabbits immunised with mouse Ig will…

A

… produce anti-mouse Ig’s

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16
Q

Subsequent biochemical & serological
have helped distinguish the following
Ab structural characteristics: ???

A
  • Two major L-chain classes, κ and λ
  • κ and λ ratio in humans is 60% κ
  • L-chains are either κ or λ and never one of each
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17
Q
A
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18
Q

how many H-chain classes are there?

A

5

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19
Q

Similarities and differences in the five H-chain classes (isotypes)?

A
  • Differ in peptide sequence, length and CHO (carbohydrate) content
  • Different biological function between types and determine Ig isotype
  • Both H-chain isotypes are identical in any given Ab
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20
Q

what are the five Ig isotypes?

A

IgG
IgA
IgM
Ige
IgD

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21
Q

The five heavy chains?

A

y (gamma)
a (alpha)
u (mu)
e (epsilon)
delta

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22
Q

14

A
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23
Q

Fc (constant) regions provide…

A

… biological activity

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24
Q

Fc (constant) regions provide biological activity while Fab (variable)
regions provide…

A

… epitope specificity

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25
The greatest variability is in the...
... N-terminal 110 amino-acids of both the Light (VL1) and Heavy (VH1)
26
15
27
Functioin of Complementary Determining Regions (CDRs)?
Participate in binding to antigen via epitope complementary structures
28
There are 3 CDRs for each...
... Light (VL1) and Heavy (VH1) chain: CDR1, CDR2 and CDR3
29
The CDRs are...
... spatially separate in primary sequence
30
The CDRs are spatially separate in primary sequence (CDR1 ~aa26-33; CDR2 ~aa48-60 and CDR3 ~aa88-98) come together in...
... the secondary β-sheet (Greek key motif), known as the combining site
31
CDRs provide a...
... rich diversity in the shape of the combining site
32
Ab:Ag are...
... weak integrations
33
Ab:Ag are weak integrations so there should...
... be a close fit over a large area where Ab:Ag binding requires both H and L chains
34
Combining sites sometimes ...
... form a cleft
35
On occasion small hydrophobic molecules (e.g. hapten)...
... do not occupy the full combining site yet have sufficient affinity for binding
36
On occasion small hydrophobic molecules (e.g. hapten) do not occupy the full combining site yet have sufficient affinity for binding. Thus these sites may...
... be able to bind diverse epitopes – redundancy
37
Define allotype ?
Allotype refers to the genetic variation between individuals for the same gene at the same loci (alleles)
38
Allotypic differences in immunoglobulins usually involve...
... one or two amino-acid changes in the Fc region and generally doesn’t affect Ab:Ag binding .
39
whats an idiotype?
refers to the uniqueness of an Ab’s combining site
40
Anti-sera raised to this ‘idiotype’ can then...
... block the biological activity of this Ab through competitive interaction at the combining site.
41
What are the functions of an antibody?
Agglutination Activation of other immune components Neutralisation of toxins Immobilisation of microbes Passive immunity
42
What's agglutination?
- Clumping together - Precipitation - Promoting phagocytosis (opsonising)
43
what happens in neutralisation of toxins?
antibodies bind to regions of the toxin responsible for adverse biological effects
44
Immobilisation of microbes alspo has an ...
... opsonising effect.
45
Passive immunity is present in...
- placenta - breast feeding
46
Activation of other immune components...
- Classical complement pathway - Causes cell lysis - Phagocytosis (opsonising) - Activates natural killer cells (ADCC)
47
IgG structure?
two (κ or λ) L-chains and two γ H-chains mol.wt 150 kDa (150 000 Da)
48
Where is IgG located?
Blood (plasma and serum), lymph, cerebrospinal fluid (CSF) and peritoneal fluid.
49
WHat are the subclasses of IgG ?
IgG1, IgG2(a and b), , IgG3 and IgG4
50
Half lives of IgG ?
IgG1, IgG2 and IgG4 – 23 days IgG3 – 7 days
51
what kind of agent is IgG?
IgG is a potent agglutinating agent
52
IgG is a potent agglutinating agent. What does this mean?
readily forms precipitates with multivalent Ag (bacteria etc…) Precipitant à insoluble Ab:Ag à phagocytosis.
53
Passive immunity
All IgG subclasses (except IgG2) pass through placenta
54
What does opsonisation increase the likelihood of?
increases the likelihood of phagocytosis via precipitation/agglutination, and phagocyte cell surface.
55
What does ADCC stand for ?
Antibody Dependent Cell Cytotoxicity
56
What is ADCC ?
where Fab region bind target (virus, bacteria) and protruding Fc region engages with Fcγ-receptor on cytotoxic immune cell e.g. CD16 on a Natural Killer cell.
57
Antibody Dependent Cell Cytotoxicity process ?
1) Antibodies bind antigens on the surface of target cells. 2) NK cell CD16 Fc receptors recognise cell-bound antibodies. 3) Cross-linking of CD16 triggers degranulation into a lytic synapse 4) Tumour cells die by apoptosis.
58
what mediates cell lysis ?
Complement activation
59
To neutralise toxins, where does IgG bind?
Binds to active part of toxin neutralising the biological effects – horse IgG given to humans to counteract snake bite venom
60
to imobilise bacteria, what does IgG interact with?
IgG interacts with epitope sites on Ag (e.g. flagella) preventing movement…. Immobile à agglutination à phagocytosis
61
How does IgG neutralise viruses?
Binds to viral Ag on viral coat preventing viral attachment to host cells and thus penetration into cell.
62
IgA structure?
two (κ or λ) L-chains and two α H-chains mol.wt 160 kDa (160 000 Da) per monomer.
63
What does IgA exist as?
... exists as a dimer (or trimer) linked together with a J chain; mucosal IgA also has a secretory component
64
where is IgA located?
Saliva, sweat, mucus, gastric juice, plasma (low levels) and tears
65
What are the IgA subclasses?
IgA1 (93%) and IgA2, both with half lives of 5.5 days
66
What is Plasma IgA ?
monomers that are released prior to dimerisation
67
When is secretory IgA formed?
formed during transport through mucosa epithelial cells (transcytosis)
68
Dimeric IgA binds to ...
... poly Ig receptor on basolateral membrane of epithelial cell (endocytosis)
69
At apical surface, poly Ig receptor is...
... cleaved enzymatically
70
At apical surface, poly Ig receptor is cleaved enzymatically. What is then released?
releasing IgA, which remains bound to the poly-Ig receptor (secretory component).
71