Lecture 18 B3

Question 1

When and what animal are the origins of adaptive immunity

Answer 1

500 mya in the jawless fish, there was an event that allowed gene rearrangement/recombination. Same RS and RAGs in all adaptive immunity species and this gives selective advantage

Question 2

What are jumping genes and how did they occur

Answer 2

A transposon inserted into a primordial receptor gene and then the transposase (that cuts and shifts this gene) moved to another part of the genome, enabling it to operate in trans.

Question 3

What are the ancient transposases in your genome called and what do they rearrange

Answer 3

RAG1 and RAG2 (recombination Activation genes) rearrange Recognition sequences (RS), base pair sequences at the ends of Ig and Tcellrecp gene regions.

Question 4

How many protein chains does an antibody IgG molecule have and how many domains do they have in how many chains

Answer 4

There are 4 protein chains that are all made up of repeating Ig domains. There are 2 domains in the 2 Light chains (25kd) and 4-5 domains in the 2 heavy chains (50-75kd)

Question 5

How are the light and heavy chains linked together in IgG

Answer 5

L-ss- H- ss- H-ss-L

The H chains are joined by disulphide bonds while the L chains are joined to the H chains by disulphide bonds

Question 6

What is the effector region of an IgG antibody

Answer 6

invariant heavy chain section at the bottom of the Y. It is bound by Fc receptors and complement component C1.

Question 7

Where is the antigen binding region on an iGg antibody

Answer 7

The tip of the two arms- the n terminal domains of the L and H chains. The loops of the Ig fold in the domain form the antigen binding site

Question 8

What are Ig protein domain fold general stucture

Answer 8

Made of two anitparallel B pleated sheets stablised in the middle by a disulphide bond. The sheets are rotated 30 degrees to each other to form soluble B - barrel structure

Question 9

what causes extreme amino acid diversity in Ig protein fold

Answer 9

The strands in the middle are connected by loops on the outerside. They are not constrained in the structure thus allowing extreme amino acid diversity without affecting the stability of the fold.

Question 10

In what forms do secretory IgG and IgM exist in

Answer 10

dimer and pentermeric respect.

Question 11

What is the total mW of IgG molecule

Answer 11

150 kD (always multiple of 25)

Question 12

What is IgM, the two forms,

Answer 12

the default antibody produced by all immature B cells. It has membrane bound monomer form called B-cell antigen receptor (BCR) and soluble pentamer form with 10 identical binding sites

Question 13

What is IgM good at

Answer 13

They have high avidity, low affinity binding with microbe surfaces so good primary surveillance. Good at fixing complement with the 5 Fc regions that bind C1.

Question 14

What is avidity

Answer 14

when two or more binding sites contribute. It results from multiple affinity contacts.

Question 15

What is affinity

Answer 15

the quantitive term for the sum of attractive molecular forces at two surfaces exceeding the repulsive forces.

Question 16

The higher the affinity …

Answer 16

the fewer molecules it takes per unit volume to associate and dissociate slowly

Question 17

When there are more than one arm, the binding is governed by af or av ?

Answer 17

avidity and it makes it much stronger than the affinity of each individual arm - up to 7 fold in pentameric IgMq

Question 18

What are the 5 classes of antibodies and what differs on them. Where are they all found

Answer 18

Ig- GEAMD. Different functions depending on H chain gene used. All found in serum with M&D also in membrane and A in mucosa

Question 19

When a naiive B cell enounters an antigen and activates what heavy chain gene does it switch to from u gene in membrane bound IgM

Answer 19

gamma (y) gene to produce the IgG molecule- most abundant

Question 20

Features of IgE

Answer 20

rarest, causes atopic allergy and has high affinity receptors on mast cells.

Question 21

Which Ig antibody gives foetal immunity at placenta transfer/ breast milk

Answer 21

IgG

Question 22

What is the complementarity determining regions of the antibody binding site of Ig and TcR

Answer 22

6 protein loop regions (3 H and 3 L chain loops) that connect b strands in the Ig variable domain. These form a flat surface and contain massive amino acid diversity so can form complementarity to anything because can get affinity

Question 23

What regions are the germline Ig and TcR gene loci segmented into

Answer 23

Variable, Diversity, Joining and Constant regions

Question 24

What is the order of splicing by RAGs in a heavy chain segment

Answer 24

The D segment joins to J, then to a V segment joins to D. intervening DNA is lost. This pre RNA is then spliced to a C region segment.

Question 25

What does the VDJ region code for

Answer 25

CDR3 in protein loop

Question 26

What region differs in the light chain locus and how does this affect genetic recombination

Answer 26

it doesn’t have D segments so V joins to J.

Question 27

What leads to huge diversity in amino acids of the chains- and therefore antibodies

Answer 27

The joining is very imprecise so base pairs are changed during repair, leading to variation at the VDJ/VJ join.

Question 28

What are the principles behind clonal selection

Answer 28

10^11 different B cell antigen specificities are produced as result of the different antigen receptor combinations produced through stochastic gene rearrangement. individual b cell clones are selected to mature when they encounter antigen within germinal centres in lymph nodes

Question 29

Recollect the 4 stages of affinity maturation

Answer 29

Antigen triggers a small number of B cells with low affinity cognate to proliferate. Somatic hypermutation then occurs introducing random mutations into the VDJ genes.
This produces a B cell with high affinity receptor. Then becomes either a plasma cell- secreting high affinity soluble igG or a memory cell that waits in the lymph nodes.

Question 30

Affinity maturation happens over time. What is the only cell that does this

Answer 30

B cells

Question 31

What process is behind vaccination and what features of the adaptive immune response help vaccination

Answer 31

Affinity maturation. Adaptive immunity has memory and changes with both time and persistence of antigen. A secondary response it stronger and more rapid than the naiive response- providing the basis for vaccination.

Question 32

What iG are produced in the primary naiive response and 2ndary response of b cell lymphocytes

Answer 32

First immunisation results in antigen specific low affinity igM in blood peaking for 2 weeks.
Second and third immunisations generate a rapid intense burst of antigen specific high affinity IgG.

Question 33

What are B cells and where are they

Answer 33

They produce anitbodies and form the humoral arm of the adaptive response. Begin in the bone marrow and mature in the secondary lymphatic organs eg spleen and lymph nodes

Question 34

What is the B cell receptor

Answer 34

The antigen receptor is a membrane bound IgM molecule that is associated with the intracellular molecules that transmit an activation signal via phosphorylation

Question 35

What is T cell and where is it found

Answer 35

T lymphocytes provide adaptive cellular immunity. Found in the thymus going from immature to functional

Question 36

What is the T cell receptor

Answer 36

The antigen receptor on T lymphocytes, coded for by a specific gene locus. Immunoglobulin like.

Question 37

What gene do the naive b cells use first and what do they switch to

Answer 37

use u gene for H chain first for IgM B cell antigen receptor. Then after activation use y gene for IgG

Question 38

Which ig gives foetal immunity through placenta transfer

Answer 38

IgG