L3 - B cell and antibody

History of adaptive immunity

Ehrlich theory → each cell has differnet recptors (side chains ) that recognise toxins, when toxin entres and binds to side chain , cell makes more of that recleptor and relases it into blood that then goes to attack toxin

Burnetts theory → each cell only expresses 1 recptor type if recpotor binds to correct antigen then get clonal explansion to produces antibody - this is theory we use today

main goal of adaptive immunity

to be able to respond to all types of pathogens

Antibody structure

it is a dimer made up of 2 polypeptides heavy and light chain joined by covalent bond

variable region at top

constant region from mid to bottom - helps anchor Ab to cell when acting like B cell receptor

Ribbon representation of antibody

• Each variable region is made up of 3 folded Beta pleated sheets known as the Immunoglobulin (Ig) domains

• As have 2 variable region have 2 Ig domains and so 6 loops together

• each of the 3 loops are called Complementary determining region; CDR1, CDR2, CDR3 → determine antibody matches antigen

what bonds are between antigen and antibody

non covalent bonds

• VDW, hydrophobic, hydrogen, electrostatic

How do we make so mnay antibodies when only limited genes

• Due to VDJ recombination

• happens in B cell developement in bone marrow causes majority of diversity

• once b cells exposed to pathogen get further diversity through maturation response

Immunoglobulin gene loci

Heavy chain - 1

• V genes = variable regions

• D genes = diversity genes

• J genes = joining genes

Light chain -2 possibilities - can be lamda or kappa

• V genes

• J genes

these genes involved in variable region of antibody

how does this recombination happen in heavy chain

• happens on DNA level in bone marrow

• First pick which D and J genes want and remove any unwanted ones

• then pick which V gene they want

• then form a continouse reading frame

• then picks first constant region to add delta 1

• non reversible process

what happens on light chain recombination

• same thing happnes

• no D genes so V and J regions just come together

enzymes involved in VDJ combination

RAG-1 and RAG-2 recognise recombinat signal sequenses RSS

• RSS are located of either side of each VDJ gene

• when enzyme joins these does it impricisely - not really a strong joing - helps increase diversity

what does the imprecise joining cause:

1- Deletion

• removal of nuclotides by endonucleases during recombination

• could be left with removed a codon (so change AA sequence) or could end up with frame shift - so end up with non functional antibody and then cell will die

2- Addition

• additional amino acids added in by TdT (terminal deoxynucleotidyl tarsferase)

• binds to 3’ OH groups that have been open by by endonucleases and adds back base pairs

These processes happen at random so even if have same VDJ sequnce could still end up with different antibody

what happens if Heavy and light chains dont want to part with each otehr

so usually kappa chain is first to pair with H chian - if dont want to pair up (as dont match up/ non complementary to each other mayeb due to deletion) B cell will try and save Ab by pairing up with lamda chain if this works then have fucntional Ab if not then have non functional Ab then get destroyed/deleted by bone marrow

what is somatic hypermutation

• happens after B cell encounters pathogen NOT IN BONE MARROW

• happens in germinal center in lymph nodes

• this is unique to B cells does not happen in T cells

How does B cells go from binding pathgen to making natibody

• pathogen antigen binds to receptor

• B cell internizes certain proetin from virus/ bacteria

• Constat region is really small on B cell so needs to rectruit other proetins to help to do this - Ig B and Ig A

• once antigen has gone inside B cell it chops it up and presents it for T cell this process alows B cells to then secreate its antibody

What are B cells called when secreate antibodies

Plasma blast or plasma cell

• non reversible cannot go back to being B cell