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biosci S1 Pt2 > Lec 23 - antibodies and gene rearrangement > Flashcards

Lec 23 - antibodies and gene rearrangement Flashcards

1
Q

How does the affinity of B cells towards an antigen change?

A

increases with time and persistance of antigen

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2
Q

How was our antibody repitoire created?

A

through a random process of rearrangement of genes coding for antigen receptors.

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3
Q

What was the first species to have adaptive immunity?

A

the Hagfish, a jawless fish ~500 mya

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4
Q

How did adaptive immunity first develop?

A

A transposon was inserted into a primodial receptor gene 500mya. the transposase is the enzyme that operates on the transposon.

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5
Q

Why are they called TRANSposons and TRANSposase

A

Because they operate in trans, they effect other genes without effecting its own position in the genome

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6
Q

What are the ancient tranposons in our genome called?

A

RAG1 and RAG2 (recomination activation genes)

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7
Q

What are recognition sequences (RS)?

A

Base pair sequences found at the ends of any gene segments that rearrange. RS are the substrates for RAG1 and RAG2 directed recombination

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8
Q

True or false: RS and RAG1 and RAG2 are indentical in all species with adaptive immunity

A

True

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9
Q

Antibodies are formed from…?

A

repeating protein units called Ig domains

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10
Q

What is the name for the Ig domain fold?

A

The beta barrel coz it looks like a barrel duh

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11
Q

How many amino acids are there in a beta barrel?

A

~110

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12
Q

What are the two important features of the Ig domain’s beta barrel shape?

A

It is stable
The loops that join the strands together vary a lot, allows different conformational changes. Due to low constraint

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13
Q

What are the bonds in an Ig domain?

A

Disulphide bonds

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14
Q

Describe the basic antibody structure in terms of chains

A

They consist of two identical light chains, which consist of 2 domains (Ig) and two identical heavy chains which consist of 4 domains

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15
Q

Where are the antigen binding sites located?

A

At the tips of the two arms, and is formed from the N terminal domains of the light and heavy chains

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16
Q

Explain the bonding in the structure of an antibody

A

1 Heavy chain is disulphide linked to 1 light chain. The two heavy chains are disulphide linkes

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17
Q

What does Fab stand for?

A

Fragment antigen binding, at it consists of the arms of the Y antibody

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18
Q

In the structure, what does Fc stand for and why is it called that?

A

Fc stands for fragment crystalline, because, if you separate the arms from the Fc part, it crystallises easily

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19
Q

Name the five Ig classes

A

IgM
IgG
IgD
IgE
IgA

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20
Q

Which Ig class is found at mucosal linings and what are some locations?

A

IgA
Surface of the lungs, tears, breast milk
secretory antibody

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21
Q

Which is the antibody that every mature B cell makes?

A

IgM, serum and membrane antibody. default

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22
Q

what is the most common form of antibody?

A

IgG, serum antibody

23
Q

Which antibody do we typically refer to when we make a vaccine?

A

IgG

24
Q

Which antiobody is very important for atopic allergy?

A

IgE
Also works with parasites, cytotoxic granules etc

25
Q

Describe the structure of an IgM molecule

A

Made up of 5 antibody molecules, which would all be made by the same B cell
Joined together by linker proteins called the J chain

26
Q

How many binding sites does IgM have

A

10, all for the same anitgen

27
Q

What is the benefit of having 10 binding sites on the one IgM molecule?

A

that some of them will react with some affinity towards bacteria

28
Q

How does the affinity and avidity compare in an IgM molecule?

A

Even though the affinity of the antigens are very low, since there are 10 of them, the avidity is high

29
Q

What is affinity?

A

The net attractive force between an antibody and the epitope of an antigen

30
Q

How do we measure the affinity of an antibody?

A

We measure the concentration it takes for one half of the antibody to be bound and the other arm to be free (lasts almost the lifetime of the antibody)

31
Q

How many molecule do we need for an antibody to bind and be bound to the antigen for a long period of time?

A

A very small amount, very small concentration

32
Q

Which is more important and why- affinity and avidity

A

Avidity, because the majority of antibodies bind through more than one site.

33
Q

What is the concept of complementarity?

A

describes the attactive forces (similarities) between an antibody and the surface of an antigen

34
Q

How does affinity relate to complementarity?

A

If there is an affinity interaction betwen two surfaces, then there is complementarity

35
Q

How does affinity happen?

A

There is an affinity interaction between two surfaces if the attractive forces outweigh the repulsive forces

36
Q

how easily is it for an anitbody to form complementarity with something?

A

Very easy, due to the diverse range of amino acids at the binding site

37
Q

What does it mean if an anitbody is bivalent?

A

It binds with avidity to the surface, both of the sites bind simultaneously 2 IDENTICAL ANTIGEN BINDING SITES

38
Q

What causes the amino acid variation in antigen binding sites?

A

due to the complementarity determining regions (CDRs)

39
Q

What are the CDRs?

A

The loops that bind the 1st domains on the H and L chains.

40
Q

What shape do the three loops of CDRs form? (CDR1 CDR2 CDR3)

A

they form a roughly rectangular surface

41
Q

What is an H gene locus?

A

The gene that codes for the heavy chain

42
Q

What are the four regions in a germ line locus called?

A

Variable (v segment)
Joining
Diveristy
Constant

43
Q

There is both a light chain and a heavy chain locus. Which one only has three clusters of germ line genes and which one is missing?

A

The light chain gene locus doesn’t have a diversity gene cluster

44
Q

What happens in the bone marrow when a B cell decides to become a B cell?

A

There is rearrangement of the clusters of germ line genes

45
Q

What is the gene that is responsible for rearrangement and is only found in the B and T lymphocytes?

A

recombination activation genes (RAG1 and RAG2)

46
Q

What are the major rearrangements of germ line genes in heavy chain locuses?

A

V to D and D to J. Intervening DNA is lost

47
Q

is the joining of different germ line genes precise and what is the effect?

A

It is imprecise, so base pairs are changed during repair, which leads to HUGE VARIATION in the VDJ join

48
Q

What does the VDJ join region code for?

A

CDR3

49
Q

What is the fundamental feature of adaptive immunity?

A

The variation in the antibody binding sites. The enormous repertoire of different antibodies

50
Q

What is the only part of our genome capable of rearranging?

A

The Ig gene locus

51
Q

What are the benefits of a second booster shot for vaccinations?

A

For things like covid-19, we want HIGH AFFINITY IGG. so going for your second booster drives the B cells to undergo colonal selection and affinity maturation, which is good at finding the spike protein

52
Q

What is colonal selection and affinity maturation of B cells good for?

A

Makes it easier for the B cells to find the spike protein and we end up getting a high IgG affinity occurring

53
Q

What is the role of the lymph nodes in infection in terms of B cells?

A

The lymph nodes stimulate B cells to undergo the process of colonal selection and affinity maturation. (when this happens a lot, our lymph nodes hurt)

54
Q

What is the process of affinity maturation of B cells?

A
  1. B cell encounters antigen in lymph nodes
  2. Antigen expands B cell clones that weakly bind the antigen
  3. the B cells that are replicating underdo somatic hypermutation
  4. resulting in some having higher affinity
  5. after many rounds of this, the mature B cell becomes a plasma cell, secreting soluble Ig. Some B cells will remain as long term memory cells

biosci S1 Pt2 (16 decks)

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