11 - Humoral (Antibody) Immunity - Partridge

Question 1

BRIEFLY describe B cell antigen independent differentiation (where initially it takes place and where they move to)

Answer 1

B cell differentiation in primary lymphoid tissue (bone marrow) and acquire their receptors.
naive/virgin B cells expressing membrane IgM move into 2ndry lymphoid tissue (spleen, lymph nodes etc) and some may express IgD.

Question 2

BRIEFLY describe B cell antigen dependent differentiation

Answer 2

B cells activated by antigen divide and differentiate -> plasma cells. may undergo class switching and somatic hypermutation. requires T cell help and AID

Question 3

Soluble Abs mediate the ____ ____

Answer 3

humoral response

Question 4

Write the corresponding greek letter for ALL heavy chain Ab classes

Answer 4

IgG -> gamma 
IgM -> u 
IgA -> a 
IgD -> delta
IgE -> e/epsilon

Question 5

Draw the strucutre of IgG including all the domain nomenclatures

Answer 5

DONT FORGET GLYCOSYLATED SITES

311 - 11 word

Question 6

What is the mw of IgG and what does this mean for where it is located?

Answer 6

around 150,000 kDa (relatively small)

means that it is the main Ab in tissues

Question 7

What are the 4 subclasses of IgG and state which ones are more biologically active and why? Describe some of the functions of IgG

Answer 7

IgG1/2/3/4
IgG1/3 = > biologically active. They have longer hinge regions meaning less steric hindrance between Fab regions and Fc regions.
- bind and activate complement
- bind Fc receptors on phagocytes and NK cells. important activators of innate immune system
- can cross placenta and bind FcRn on trophoblast therefore important in foetal and newborn immunity
- important in 2ndry responses

Question 8

What is FcRn?

Answer 8

neonatal receptor for IgG

Question 9

What is are the functions of FcRn?

Answer 9

allows placental transfer of IgG (on trophoblast) to protect foetus and newborn. also present on neonatal gut so can acquire IgG from breast milk

Question 10

which subclasses of IgG have the highest affinity for FcRn

Answer 10

IgG1>3>2>4

Question 11

Where is FcRn also located and what does this allow?

Answer 11

on adult guts, endothelial cells and liver
IgG can bind, taken up by cells (internalised) and avoids excretion. IgG is recycled which contributes to its long half life (IgG RECYCLING)

Question 12

Draw a diagram illustrating how IgG is transferred to maternal blood to fetal blood

Answer 12

311 - 11 word

Question 13

Draw the structure of IgM that is mainly found in serum, state any bonds etc that hold it together

Answer 13

held together with disulphide bonds that link the Fc receptors
J chain is also present
no defined hinge region

Question 14

What is the mw of IgM and explain how this contributes to where it is located

Answer 14

around 970,000 kDa

remains in serum because too large to enter tissues

Question 15

Why is IgM important in primary responses?

Answer 15

pentament therefore pentavalent so good agglutination of antigen. activates complement v efficiently (more so than IgG) which is ideal in 1ry responses when needing to respond to antigen quickly.

Question 16

Draw a graph that shows the 1ry/2ndry responses of Ab.
plot [Ab] in serum against time
explain the graph

Answer 16

311 -11 word

Question 17

Draw a diagram of IgA in its polymeric state and list its components - giving their functions where necessary

Answer 17

311 - 11 word
IgA dimer
J chain
secretory component - thought to protect it from digestion when it is wrapped around the Fc regions

Question 18

Where is IgA present

Answer 18

secreted and is present at mucosal surfaces

Question 19

State 5 facts about IgA

Answer 19

• present in milk
• does not activate complement (this could be good because don’t want lots of inflammation @ mucosal surfaces because exposed to high levels of antigen)
• high levels of catabolism
• high valency - good agglutinator of antigen (like IgM)
• secretory IgA does not bind Fc regions on phagocytes but monomeric IgA does

Question 20

Why is it important that the mucosal lymphoid tissue makes lots of IgA? How much IgA is produced per day?

Answer 20

IgA is rapidly catabolised by enzymes @ mucosal surfaces, there are many of them here
- 5g of IgA produced per day by the mucosal lymphoid tissue

Question 21

Draw a diagram of the specialised transport system that exists to transport dimeric IgA into the lumen (add labels)

Answer 21

word

Question 22

Draw a diagram of the layers underneath the mucosal surface and label it

Answer 22

word

Question 23

What is different about the IgA dimer after it leaves the epithelial cells and enters the lumen?

Answer 23

the secretory component is now attached and is wrapped around the Fc regions

Question 24

Describe the poly-Ig receptor

Answer 24

binds both IgA and IgM

member of the immunoglobulin supergene family

Question 25

What are the 2 results of this specialised transport system?

Answer 25

secretory IgA can pass into the lumen

- bacteria that penetrate the mucosal layer can be transported back into the lumen

Question 26

Why does IgA only play a passive role in infection?

Answer 26

because of its location the mucosal layer comes into contact with many external bacteria etc eg antigens from food. dont want an immune response EVERYTIME so IgA binds to these antigens, stops them interacting with host cells and allows them to pass through the body naturally

Question 27

Describe IgD in terms of its heavy chain, mon/polymeric?, mw and its % composition in serum

Answer 27

around 184,000D - monomer
delta chain
<1% in serum

Question 28

What are the functions of IgD?

Answer 28

still largely unknown;

• exists as a B cell surface antigen receptor that is expressed alongside IgM
• can also be secreted by B cells/plasma cells in UPPER RESPIRATORY TRACT. can bind to Fc regions on basophils and induce production of B cell stimulatory factors, inflammation and antimicrobial factors

Question 29

Draw a diagram of IgD and suggest how this may be an advantage

Answer 29

extended hinge regions may mean that the Fab region can reach antigen further away than IgM

Question 30

Draw a diagram of IgE, state its mw and its composition in serum.
And briefly describe its structure

Answer 30

mw 190,000D
trace in serum
no defined hinge region - loosely folded domains provide a functional hinge region

Question 31

What are the functions of IgE?

Answer 31

• assist against extracellular parasitic infections eg helminths
• in the west, plays a role in allergy. binds with high affinity to FcR on mast cells and basophils