21 - antibodies Flashcards

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1
Q

structure of antibody (IgG) molecules

A
  • 2 heavy (H) chains - 50kDa
  • 2 light (L) chains - 25kDa
  • variable (V) regions at N terminal - from antigen binding sites
  • 2 binding sites per IgG
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2
Q

what are the 6 domain names of IgG?

A

C(H)1-3
C(L)
V(H)
V(L)

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3
Q

antigen binding sites

A

hypervariable (HV)
complementary-determining regions (CDR)

3 loops of HV on each H and L chains

6 CDR form the antigen binding sites

an immunoglobulin would have 12 in total

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4
Q

light chain domain structures

A

compact immunoglobulin domains - 100-110 AA

2 sheets of beta strands

form the antigen binding site

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5
Q

why are the domains important?

A

they are of structural and evolutionary significance

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6
Q

where are Ig-like domains found in other molecules?

A
  • T cell receptors
  • MHC molecules
  • various cell adhesion molecules
  • signalling molecules
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7
Q

what are the 2 types of light chains?

A

kappa or lambda

an antibody has either kappa or lama light chains - not one of each

no functional difference

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8
Q

what are the 5 classes of antibodies?

A

Ig: M, A, D, G, E

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9
Q

what are the 5 different heavy chain isotypes?

A
gamma 
mu 
delta 
alpha 
epsilon 

differ in size, structure and function of C region

determine class of antibody

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10
Q

what is antibody valency?

A

the quantity of the antigen binding sites

single antibodies have a valency of 2

IgM pentamer has a valency of 10

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11
Q

IgM structure

A
  • pentamer
  • MW = 900,000
  • covalent bound to J chain
  • mainly found in blood
  • valency of 10
  • no hinge
  • relatively low affinity
  • can have avidity - total binding of the antibody
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12
Q

why is IgM mainly found in blood?

A

cannot cross cells and the placenta as its too larger

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13
Q

what is the first isotope to be produced by neonates and during a primary immune response?

A

IgM

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14
Q

functions of IgM

A
  • complement activation
  • agglutination
  • B cell antigen receptor
  • produced rapidly
  • vital in primary response
  • protects from common pathogens
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15
Q

IgG structure

A
  • 4 domains - H(2)L(2)
  • MW = 150,000
  • most prevalent class in serum but not confined to intravascular compartment
  • production increases in secondary response
  • high affinity - good binder
  • 4 sub-classes
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16
Q

why is IgG not confined to intravascular compartment?

A

can move across membranes and can cross the placenta from mother to neonate - helps to transfer immunity to child

17
Q

what are the 4 subclasses of IgG

A

differences are all due to the hinge regions

IgG1 - 66%
IgG2 - 23%
IgG3 - 7%
IgG4 - 4%

longer hinge regions give the antibodies a longer reach
• doesn’t have much flexibility due to the disulphide bonds

18
Q

functions of IgG

A
  • predominant isotype in serum
  • large increase in secondary response
  • complement activation
  • opsonisation
  • ADCC
  • only Ig to cross placenta
19
Q

what does ADCC stand for?

A

antibody dependent cell cytotoxicity

20
Q

antibody production in response to antigens

A

IgM first produced followed by IgG

if theres a 2nd exposure, memory B cells recognise the antigens and start the IgG response
• much larger IgG response - still a little IgM

21
Q

IgA structure

A
  • monomer in serum
  • dimer in secretions
  • MW = 70,000
  • bound to J chain and secretory component alpha chain - 4 domains
  • 2 sub-classes
22
Q

what are the 2 subclasses of IgA?

A

differ in susceptibility to bacterial proteases

IgA1 - serum
IgA2 - secretions

23
Q

what is the secretory component of IgA?

A

made by epithelial cells

involved in transport of IgA dimers through epithelial cells

if removed it cannot be secreted into the mucosal surface

24
Q

transport of IgA across the epithelia

A

1) B cells secrete IgA
2) epithelial cells have Ig receptors specific to IgA which bind and engulf IgA
3) transported to the lumen where it is secreted
4) has to have binding portion cleaved
5) IgA and secretory component secreted in the lumen

25
Q

what happens to IgA once transported to the gut lumen through epithelial cells?

A

IgA binds to the mucus layer overlying the epithelium

IgA in the gut neutralises pathogens and their toxins

26
Q

functions of IgA

A
  • inhibition of microbial adherence to mucosal surfaces
  • neutralise pathogens and toxins
  • prevent commensal bacteria entering blood stream
  • present in early milk
27
Q

what is commensal bacteria?

A

part of the normal flora in the mouth

28
Q

IgD structure

A
  • MW = 185,000
  • 4 domains - long hinge
  • low conc in serum
  • can be present on B cells with IgM - only Ig’s that can be co-expressed
  • present in upper respiratory tract
29
Q

IgD functions

A

stimulate basophils and mast cells to release antimicrobial peptides - small proteins that kill pathogens

antigen receptor in B lymphocytes

30
Q

IgE structure

A
  • MW = 200,000
  • 5 domains
  • low conc in serum
  • very potent effects
31
Q

IgE functions

A

binds with high affinity to FcR on mast cells and basophils - release vasoactive/inflammatory mediators

role in allergy and asthma

importnat for ADCC

induces eosinophils and basophils to release histamine and proteases

32
Q

what is anaphylaxis?

A

severe allergic reaction
• IgE
• Fc receptors in mast cells and basophils
• increased release of histamine
• increases TNF-alpha - inflammatory mediators
• increases vasodilation

33
Q

what does an epipen do?

A

injects epinephrine
• increases vasoconstriction
• increases blood glucose levels

34
Q

distribution of Ig in the body

A
  • IgG and IgM predominant in blood
  • IgG and monomeric IgA predominant in extracellular fluid
  • dimeric IgA in secretions - breast milk
  • foetus recipes IgG from mother
  • brain has no Ig
35
Q

class switching

A

happens post antigen stimulation

IgM can be switched to other Ig’s

irreversible DNA recombination - cutting and joining of heavy chain

once switched cannot switch back

36
Q

affinity definition

A

strength of interaction between antigen binding site and epitope

37
Q

valency definition

A

all Ig’s have a valency of 2 but some are dimers or pentameric so have a higher number

38
Q

avidity definition

A

measurement of overall strength of the antibody-antigen interactions

it depends on:
• affinity
• valency
• structural parts between the 2 entities interacting