Antibodies

Question 1

What are the receptors that recognise pathogens?

Answer 1

PRRs - pathogen recognition receptors
MHC
TCR
BCR

Question 2

What do PRRs recognise?

Answer 2

PAMP - pathogen associated molecular patterns

DAMP - damage associated molecular patterns

Question 3

How many genes encode for PRRs?

Answer 3

100+

Not very polymorphic since there is little variation in PAMPs and DAMPs between individuals

Question 4

What do MHC recognise?

Answer 4

Peptides on classical alpha beta T cells

Question 5

How many genes encode for MHC?

Answer 5

12

Inherit 3 MHC I and 3 MHC II genes from mother and father respectively

Question 6

What do TCRs recognise?

Answer 6

Peptides linked to MHC

Question 7

How many genes encode for TCRs?

Answer 7

Millions

Very polymorphic

Same with BCRs

Question 8

What do BCRs recognise?

Answer 8

Antigens

Question 9

How many genes encode for BCRs?

Answer 9

Millions

Very polymorphic

Question 10

Where are PRRs found?

Answer 10

On surface, intracellularly and secreted

Question 11

What brings about polymorphism in MHC?

Answer 11

Each protein is encoded for individually, so there is increased polymorphism

Question 12

How does the large genetic variation in TCRs and BCRs arise?

Answer 12

Genetic recombination

Question 13

Describe an antibody molecule

Answer 13

Tetramer

Consists of two heavy chains bound together via disulphide bonds

Consists of two light chains bound to the heavy chains via disulphide bonds

Can be split into variable and constant region

Question 14

Where is the constant region?

Answer 14

The constant region is the larger part of the antibody molecule

Determined mostly by the genetic sequence of heavy chain

The light chain can also have variability in the constant chain however, and classify into Kappa and Lambda

Question 15

How heavy are the heavy chains?

Answer 15

50 kD

Question 16

How heavy are the light chains?

Answer 16

25 kD

Question 17

What is the role of the constant region?

Answer 17

Determines the class of antibody

IgM, IgG, IgA, IgD

Question 18

What is the role of the variable region?

Answer 18

Binds to specific epitopes on antigens

Question 19

What is the hypervariable region?

Answer 19

Area on the variable region that has increased variability. Binds to the epitopes of antigens

Also known as conplementarity determining regions

Question 20

What is another name for the hypervariable region?

Answer 20

Complementarity determining region

Question 21

How does variability arise?

Answer 21

Via genetic recombination

Question 22

What are the 3 gene segments on antibodies that give rise to variability?

Answer 22

V, D and J segments

Question 23

How many genes form the J, V and D segments in the heavy chain?

Answer 23

V= 40 
D= 27 
J= 6

Question 24

What does J, V and D stand for?

Answer 24

Variable, diversity and joining

Question 25

How many genes form J and V regions of the Kappa light chain?

Answer 25

``` V = 40 J= 5 ```

Question 26

How does an antibody look like in terms of the V, D and J regions? `

Answer 26

Constant region - J - D - V

Question 27

What controls genetic recombination?

Answer 27

A series of enzymes encoded by RAG-1 and RAG-2

Question 28

What does RAG stand for?

Answer 28

Recombination-activating genes

Question 29

How do RAGs recognise where to recombine?

Answer 29

Via recombination signalling sequences RSSs

Question 30

What are RSSs?

Answer 30

Recombination signalling sequences Sequences of nucelotides found at the end of V, D and J sequences that signal the RAGs to start recombination

Question 31

What is an example of an enzyme encoded by RAG?

Answer 31

Recombinase enzyme is involved with V, D, J recombination

Question 32

Additional mechanisms that increase variability of antibody molecules?

Answer 32

``` Recombinational inaccuracies DIfferent splicing in D J regions Make soluble or transmembrane form Class switching Additional nucleotides added via N-region diversity ```

Question 33

What processes happen in antibody diversification but not TCR diversification?

Answer 33

Class switching Only make transmembrane version Somatic hypermutation

Question 34

What two types of recombination events happen in the maturation of antibodies?

Answer 34

VDG recombination Class switching

Question 35

What is class switching?

Answer 35

Process by which antibody switches its class whilst remaining equally antigen-specific

Question 36

What determines the class of an antibody?

Answer 36

Its constant region

Question 37

How do antibodies switch class?

Answer 37

With the help of T helper cells Switch depending on the type of antibody required to combat the pathogen

Question 38

How is class switching different from VDJ recombination?

Answer 38

Uses different enzymes Uses class switching signals instead of recombination signal sequences

Question 39

What classes do the antibodies switch to?

Answer 39

From IgM and IgD To IgA, IgG and IgE

Question 40

What is the consequence of recombination?

Answer 40

From less than 200 genes (V (40) D (27) and J (6)) we can make millions of possible combinations In the heavy chain, the possibility of different variations is 40*27*6 = 6480 Since some antibodies can have the exact same heavy region but different light chain Kappa regions, the variabiliy increases Possibility of different variations in Kappa light chain is 40*5 = 200 Therefore the possibility of different variations is 200*6480 = over 1 million Increases if add possibility of Delta light chain combinations

Question 41

What are the properties of IgG?

Answer 41

Only antigen that can pass through the placenta phagocytosis and complement activation

Question 42

What are the functions of IgM?

Answer 42

Together with IgD, make up BCR of naive B cells One of the first antibodies found in the site of infection Complement activation and agglutination

Question 43

WHat two antibodies make up the BCR of naive B cells?

Answer 43

IgM and IgD

Question 44

What is the function of IgE?

Answer 44

Triggers inflammatory mediators from mast cells/ basophils

Question 45

What two antibodies form polymers?

Answer 45

IgM and IgA

Question 46

How is IgA found in the circulation?

Answer 46

When IgA dimerises Is bound to secretory components that transport secretory IgA to mucosal surfaces Link together in the ring via J-chains

Question 47

How do the IgA antibodies link together?

Answer 47

Via J-chains

Question 48

How is IgM found in the circulation?

Answer 48

As a monomer

Question 49

What shape does a IgM polymer make when it dimerises?

Answer 49

A pentameric ring

Question 50

How big is the pentameric ring of IgM polymers?

Answer 50

1 million Da Can't escape circulation in polymeric form

Question 51

Where does genetic recombination of antigen happen?

Answer 51

In the variable region