Antibody functions Flashcards

1
Q

Describe isotype switching

A

All B cells begin making IgM, class switching means memory cells produce IgG, IgA, IgE with the same variable region/specificity.

Retain same V-D-J but change the constant region following after J region via non-homologous DNA recombination where AID enzyme acts on switch region to open dsDNA.

Two switch regions that are acted on come together and inbetween DNA is looped out.

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2
Q

Describe isotype switching

A

All B cells begin making IgM, class switching means memory cells produce IgG, IgA, IgE with the same variable region/specificity.

Retain same V-D-J but change the constant region following after J region via non-homologous DNA recombination

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3
Q

Describe isotype switching

A

All B cells begin making IgM, class swiching means memory cells produce IgG, IgA, IgE with the same variable region

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4
Q

What are switch regions?

A

They are stretches of repetitive DNA upstream of the constant heavy gene segments

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5
Q

What are switch regions?

A

They are stretches of repetitive DNA upstream of the constant heavy gene segments.

AID acts on switch regions

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6
Q

Where in the body can you find each Ig be found?

A

Brain has no Ig: they are too large to cross the blood/brain barrier.

IgM/IgA/IgG in blood

IgA in secretions: dimeric

IgG/IgA in extracellular fluid/in tissues (where IgM is too large to diffuse)

IgE in connective tissue under skin, GI/respiratory tracts

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7
Q

Which Ig protect the internal tissues of the body?

A

IgM, IgG and monomeric IgA

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8
Q

Which Ig protect the mucosal surfaces of the body?

A

dimeric IgA

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9
Q

Which Ig protect the Body from pathogens?

A

IgE

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10
Q

Which Ig are important in pregancy and after birth?

A

IgG is delivered directly to foetal circuation

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11
Q

Which Ig are important in pregancy and after birth?

A

IgG is delivered directly to foetal circuation so baby is born with high level of IgG until it can make its own.

IgM produced soon after birth, but IgG is produced until 6 months

dimeric IgA protects baby GI tract via breast milk passive transfer which helps when IgG is low.

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12
Q

What is colostrum?

A

First breast-feeding milk which high concentrations of IgA

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13
Q

What are high affinity neutralizing antibodies?

A

Where pathogen is neutralised simply by Ab binding and pathogen (virus and bacteria) cannot cause disease.

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14
Q

What are high affinity neutralizing antibodies?

A

Where pathogen is neutralised simply by Ab binding and pathogen (virus and bacteria or pathogen produced toxins) cannot cause disease.

Example Abs coast bacteria at mucosal surface to prevent their attachment to fibronectin in extracellular matrix.

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15
Q

Which antibodies are efficient at binding to soluble toxins

A

IgG, and IgA; prebents binding, internalisation, intracellular dissociation of poisonous toxin which disrupt cell function

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16
Q

Which antibodies are efficient at binding to soluble toxins/exotoxins

A

IgG, and IgA; prebents binding, internalisation, intracellular dissociation of poisonous toxin which disrupt cell function

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17
Q

What are high affinity neutralizing antibodies?

A

Where pathogen is neutralised simply by Ab binding to FAB recognition arms and so pathogen (virus and bacteria or pathogen produced toxins) cannot cause disease.

Example Abs coast bacteria at mucosal surface to prevent their attachment to fibronectin in extracellular matrix.

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18
Q

Which antibodies are efficient at binding to soluble toxins/exotoxins

A

IgG, and IgA; prebents binding, internalisation, intracellular dissociation of poisonous toxin which disrupt cell function

For example Tetanus, Cholera.

19
Q

What is the general effector function

A

Clearance mechanisms mediated by interaction of Fc region with effector molecules

20
Q

Describe IgG

A

It is the most abundant
-Four genes/subclasses: G1-G4 which differ in the structure of the hinge region involving alterations in the disulphide bridges and differences throughout the constant regions.

21
Q

Describe IgG

A

It is the most abundant

  • Four genes/subclasses: G1-G4 which differ in the structure of the hinge region involving alterations in the disulphide bridges and differences throughout the constant regions.
  • It is the only Ig able to cross placenta via Fc receptors
22
Q

What is unique about IgG4?

A

They can undergo Fab arm exchange where the whole half of Ig can spit; no disulphide brige means one heavy chain and one light chain half can dissociate from the other half.

One half can bind with a different half (H and L chains) to make a new combinations; 2 different antigens can be recognised via the different halves variable domains.

23
Q

What are the terms used to describe the flexible movements of IgG molecule? Why is this important for the function?

A
  • waves arms
  • rotates Fab arms
  • wags Fc tail
  • bends Fab elbow (in the middle of arms)

They bind to adjacent antigens a various spacings and simultaneously Fc region engage with an effector molecule likr Fc receptor/complement.

24
Q

What are the terms used to describe the flexible movements of IgG molecule? Why is this important for the function?

A
  • waves arms
  • rotates Fab arms
  • wags Fc tail
  • bends Fab elbow (in the middle of arms)

They bind to adjacent antigens a various spacings and simultaneously Fc region engage with an effector molecule like Fc receptor/complement.

25
Q

Are antibodies long lived?

A

Yes, they have a long half life relative to other proteins. IgG1,2,4 can live up to 21 days

26
Q

Describe IgM

A

It is a pentamer; made of 5 subunits and therefoer 10 binding sites so it is good at binding/agglutinating to lots of antigen. They are joined by J chain and disulphide bridges.
This is present only in secretions as it is too large to enter tissues

27
Q

Describe IgM

A

It is a pentamer; made of 5 subunits and therefore 10 binding sites so it is good at binding/agglutinating to lots of antigen. They are joined by J chain and disulphide bridges.

This is present only in secretions as it is too large to enter tissues

28
Q

Which Igs begins the classical pathway of complement?

A

pentamer IgM binds to antigen on pathogen surface from a planar structure to a staple structure on antigen where C1q heads molecules fit with.

monomer IgG also activates as at least 2 heads of C1q binds to 2 IgG molecules.

29
Q

What is Cyro-AFM?

A

A technique called atomic force microscopy where molecules are frozen and imaged.

30
Q

Describe Fc receptors.

A

There are receptors that bind IgG with gamma chains

There are receptors that bind to IgE with beta chains.

31
Q

Describe FcRn

A

This binds IgG: it has 3 alpha domains and a B2 microglobulin

32
Q

Describe FcRn.

A

This binds IgG: it has 3 alpha domains and a B2 microglobulin.

a1 and a2 domains form the binding site for Fc region of IgG.

33
Q

What are the functions/purpose of FcRn?

A

1) it maintains high levels of IgG in fluids
2) Selectiviely protects IgG from degradation
3) This means IgG have a longer half life
4) FcRn means IgG can cross placenta

34
Q

Describe Fc receptors.

A

There are receptors that bind IgG with gamma chains

There are receptors that bind to IgE with beta chains.

There are receptors that bind to IgA with alpha chains.

35
Q

What are the functions/purpose of FcRn?

A

1) it maintains high levels of IgG in fluids by transporting IgG from blood in low pH, through endothelial cells into extracellular space where there is high pH via endocytosis.
2) Selectiviely protects IgG from degradation; it is carried away from lysosomes in endocytic vesicles
3) This means IgG have a longer half life
4) FcRn means IgG can cross placenta

36
Q

Where doe FcRn interact with the IgG

A

The Fc interdomain region

37
Q

Describe Fc receptors.

A

There are receptors that bind IgG with gamma chains

There are receptors that bind to IgE with beta chains.

There are receptors that bind to IgA with alpha chains.

38
Q

What are the three classes of IgG receptors?

A

1) Fc-gamma-R1/CD64 with the highest affinity for IgG
2) Fc-gamma-R2/CD32
3) Fc-gamma-R3/CD16

They are transmembrane, with ITAM (activating) signalling motifs or ITIMs (inhibitory)

39
Q

What are the three classes of IgG receptors?

A

1) Fc-gamma-R1/CD64 with the highest affinity for IgG1 and IgG3
2) Fc-gamma-R2/CD32
3) Fc-gamma-R3/CD16

They are transmembrane, with ITAM (activating) signalling motifs or ITIMs (inhibitory)

They bind to lower hinge region of Ch2 on constant heavy chain.

Different IgG subclasses G1-G4 vary in the binding between each receptor type.

40
Q

What happens when Fc receptor binds to Ig

A

1) Increases efficiency of phagocytosis; coated bacterium allows activation signals that trigger engulfment ect.
2) The receptors can trigger ACC- antibody cell mediated cytotoxicity

41
Q

What is ACC- antibody cell mediated cytotoxicity ?

A

Fc receptors on NK cell recognise the Ab bound to target cells.

This leads to cross-linking of Fc receptors trigger NK to kill target cell via apoptosis.

42
Q

Describe IgD

A
  • Not present in high concentrations in blood; it is mainly found on B cell surface
  • produced in upper respiratory tract, where it can bind bacteria as well as a specific receptor on basophils which caused 1) release of cytokines
    2) release of microbial factors to inhibit bacterial growth.
43
Q

What happens when Fc receptor binds to Ig

A

It mediate elimination of antibody coated targets

1) Increases efficiency of phagocytosis; coated bacterium allows activation signals that trigger engulfment ect.
2) The receptors can trigger ACC- antibody cell mediated cytotoxicity

44
Q

Describe IgD

A
  • Not present in high concentrations in blood; it is mainly found on B cell surface
  • produced/protects in upper respiratory tract, where it can bind bacteria as well as a specific receptor on basophils which caused 1) release of cytokines
    2) release of microbial factors to inhibit bacterial growth.