Lecture 3 Flashcards
All antibodies start as
IgM
IgM initially has a constant region encoded by
Cu genes
What is the “effector function” of a antibody?
give some examples
what happens after it is bound to the antigen
I.e
compliment activation
placental transfer
sensitising mast cells
Secreted IgM is _____ which helps increase avidity
pentameric
Only IgA antibody are found on ______ surfaces
mucosal
(protection against things you eat
Isotypes have the same ______ region
variable
Only____ chains undergo class switch recombination (CSR)
heavy
____ will cut the DNA and moves the VDJ region upstream, bypassing the unwanted heavy chain genes to make different ______
AID will cut the DNA and moves the VDJ region upstream, bypassing the unwanted heavy chain genes to make different Isotypes
AID recognises a target sequence in DNA, finds _______ in that sequence and removes (deaminates) it and converts it to Uracil.
AID recognises a target sequence in DNA, finds cytosines in that sequence and removes (deaminatese) it and converts it to Uracil.
Uracil is then removed from DNA as per normal DNA repair mechanisms
Uracil is then removed from DNA as per normal DNA repair mechanisms. This can cause __ ___ ___ if the cleavages are close enough together
double-stranded breaks
(If two such breaks occur, one on either strand a staggered double-strand break can be formed (DSB). It is thought that the formation of these DSBs in either the switch regions or the Ig variable region can lead to CSR or GC, respectively.)
This whole system is targeted and specific by signalling from…
T cells
An activated dentifrice (APC) will present to t cells.
The T cell will then produce…
IL4, IL5, IL13 etc
interleukins
The IL’s, will then signal to B cells to under go ____ ___________, with the hope of changing the isotype of the antibodies
CSR differentiation
Mutations are introduced into GC B cell Ig V genes at “random” = somatic
what is meant by this?
Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children.
match the T(helper) cell receptor to its B cell counter part
(which together induct CSR and SHM in germinal centres)
CD40L
TCR
ICOS
CD40L - CD40
TCR - MHCII
ICOS - ICOSL
AID initiates __ ___ ____ and somatic mutation
What are some immune deficiencies realted to this pathway
Class switch recombination
CVID - common variable immune deficiency is the most ______
Common
Live attenuated virus are?
a non-pathogenic sample of viruses
HIV targets ____ _ cells
cd40+ t cells
Recombinant proteins (virus-like antigens) provide opportunities to tailor Vaccine responses because:
Individual antigens can be chosen
Antigens can be modified hrough pritein engineering to change their properties in favourble ways
Antigens can be made as soluble subunit vaccines, as VLPs (virus-like particles)
The GP120 and gp41 antigens have been used as the basis for…
HIV vaccine trials
none of the big 3 trials have worked
With HIV: A very large number of _____ _____ circulate at the same time
genetic variants
Mutations introduced during viral replication change _______ _________ on the virus: rendering existing immune responses irrelevant.
Mutations introduced during viral replication change immune determinants on the virus: rendering existing immune responses irrelevant.
Another way that HIV avoids immune responses is by shedding gp120 to expose ___ ____ ______
irrelevant antibody epitopes
Immune responses do not occue to all antigens eually, some dominate at the expense of others
Increasing the number of irrelevant targets////
increases the likelihood of irrelevant antibodies dominating the response
HIV also shields itself with
Carbohydrates
Each gp120 molecule carries between 20 and 30 N-linked glycans
HIV protection measure 4: The highly conserved co-receptor binding site on _____ is only exposed after binding to _____ , thus this site is not accessible for neutralising antibodies
HIV protection measure 4: The highly conserved co-receptor binding site on gp120 is only exposed after binding to CD4, thus this site is not accessible for neutralising antibodies
The immune system in some individuals can generate _______ antibodies that work ________multiple of HIV isolates
The immune system in some individuals can generate neutraliing antibodies that work against multiple of HIV isolates
