11 - Humoral (Antibody) Immunity - Partridge Flashcards
BRIEFLY describe B cell antigen independent differentiation (where initially it takes place and where they move to)
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.
BRIEFLY describe B cell antigen dependent differentiation
B cells activated by antigen divide and differentiate -> plasma cells. may undergo class switching and somatic hypermutation. requires T cell help and AID
Soluble Abs mediate the ____ ____
humoral response
Write the corresponding greek letter for ALL heavy chain Ab classes
IgG -> gamma IgM -> u IgA -> a IgD -> delta IgE -> e/epsilon
Draw the strucutre of IgG including all the domain nomenclatures
DONT FORGET GLYCOSYLATED SITES
311 - 11 word
What is the mw of IgG and what does this mean for where it is located?
around 150,000 kDa (relatively small)
means that it is the main Ab in tissues
What are the 4 subclasses of IgG and state which ones are more biologically active and why? Describe some of the functions of IgG
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
What is FcRn?
neonatal receptor for IgG
What is are the functions of FcRn?
allows placental transfer of IgG (on trophoblast) to protect foetus and newborn. also present on neonatal gut so can acquire IgG from breast milk
which subclasses of IgG have the highest affinity for FcRn
IgG1>3>2>4
Where is FcRn also located and what does this allow?
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)
Draw a diagram illustrating how IgG is transferred to maternal blood to fetal blood
311 - 11 word
Draw the structure of IgM that is mainly found in serum, state any bonds etc that hold it together
held together with disulphide bonds that link the Fc receptors
J chain is also present
no defined hinge region
What is the mw of IgM and explain how this contributes to where it is located
around 970,000 kDa
remains in serum because too large to enter tissues
Why is IgM important in primary responses?
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.
Draw a graph that shows the 1ry/2ndry responses of Ab.
plot [Ab] in serum against time
explain the graph
311 -11 word
Draw a diagram of IgA in its polymeric state and list its components - giving their functions where necessary
311 - 11 word
IgA dimer
J chain
secretory component - thought to protect it from digestion when it is wrapped around the Fc regions
Where is IgA present
secreted and is present at mucosal surfaces
State 5 facts about IgA
- 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
Why is it important that the mucosal lymphoid tissue makes lots of IgA? How much IgA is produced per day?
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
Draw a diagram of the specialised transport system that exists to transport dimeric IgA into the lumen (add labels)
word
Draw a diagram of the layers underneath the mucosal surface and label it
word
What is different about the IgA dimer after it leaves the epithelial cells and enters the lumen?
the secretory component is now attached and is wrapped around the Fc regions
Describe the poly-Ig receptor
binds both IgA and IgM
member of the immunoglobulin supergene family
What are the 2 results of this specialised transport system?
secretory IgA can pass into the lumen
- bacteria that penetrate the mucosal layer can be transported back into the lumen
Why does IgA only play a passive role in infection?
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
Describe IgD in terms of its heavy chain, mon/polymeric?, mw and its % composition in serum
around 184,000D - monomer
delta chain
<1% in serum
What are the functions of IgD?
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
Draw a diagram of IgD and suggest how this may be an advantage
extended hinge regions may mean that the Fab region can reach antigen further away than IgM
Draw a diagram of IgE, state its mw and its composition in serum.
And briefly describe its structure
mw 190,000D
trace in serum
no defined hinge region - loosely folded domains provide a functional hinge region
What are the functions of IgE?
- 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
