ICL 2.2: B-Cell and Ig Flashcards
what is innate immunity?
non-specific, first line defense
cell mediated, some general small molecules
responsible for stimulating adaptive immunity
they’re cells and proteins that you just inherently have in your body
what is adaptive immunity?
very specific, creates long term memory for a pathogen
it will adapt to everything you may come into contact with
humoral & cellular mediated
which cells are antigen presenting cells?
macrophage
dendritic cells
epithelial cells
B cells
what are the regions of an antibody?
if you cut an antibody with a papain enzyme you get 2 Fab regions and 1 Fc region
Fab region = the arms of the Y
Fc region = stem of the Y
what is Fab?
fragment antigen binding
what is Fc?
the fragment that’s constant
it also binds the complement
what’s the difference between the types of Ig?
the amount of glycosylation varies between IgG, IgM, IgD, IgA, IgE
which immunoglobulins are monomers, pentamers and dimers
IgG, D and e are monomers
IgM = pentamer
IgA = dimer
what is x-linked agammaglobulinemia?
they don’t produce any antibodies!!
they have no IgG, IgM, IgD, IgA, IgE
don’t live longer than a year or two…
what is affinity maturation?
you’re mutating the CDR regions of the antigen binding site of an antibody so that it increases the affinity towards the antigen
what 3 signals are required for B cell activation?
- first signal is from from antigen binding/internalization to the B cell receptor
- second signal from TH2 helper cell which deliver CD40/CD40L to the B cell
- third signal from cytokines stimulate proliferation and isotype switching
these three signals are going to induce the B cell to become fully mature and allow for somatic hypermutation to increase affinity to antigen
which enzyme is responsible for somatic hypermutation?
AID
without it, the B cells can’t become fully activated
what are germinal centers?
where long-lasting B cell-T cell interaction happens
induce hyper somatic mutation and isotype switching
this is where you develop a good antigen specific response!
what does a swollen lymph node indicate?
the germinal center is growing because you’re doing induce hyper somatic mutation and isotype switching so that you can have a specific targeted response to whatever antigen is making you sick`
what happens in the germinal center?
in the light zone are follicular dendritic cells which are specialized dendritic cells that capture pathogens but doesn’t pagocytose it using complement
the follicular dendritic cells are waiting for B cells to come bind to them = signal number 1 for B cell
then once T cell comes along to help = signal 2
is somatic hypermutation always good?
no!
sometimes the hypermutation produces B cells with a lower affinity for the pathogen
then the B cell can’t present antigens to T cells and the cell dies via apoptosis
what happens to antigen-bound B cells that are under the influence of an IL-10 secreting helper T cell?
BCR cross-linking with helper T cell which releases IL-10 causes B cells to differentiate into plasma cells
plasma cells then make antibodies until nutrients run out and then they die
what happens to antigen-bound B cells that are under the influence of an IL-4 secreting helper T cell?
BCR cross-linking with helper T cell which releases IL-4 causes B cells to differentiate into memory B cells
they stick around for 60 years
they already have rearranged into a certain isotype and have undergone somatic hypermutation so the next time they’re exposed to a pathogen they recognize, you’ll have an immediate response!
what organelle do plasma cells have a lot of?
tons of ER to make proteins for Abs
what is a thymus independent response?
some B cells don’t need T cells do be activated! there are bacterial products that can activate the B1 cell instead
Tl-1 causes proliferation of all B cells
Tl-2 causes proliferation via cross linking thus only mature B cells respond
you are doing this totally independent of the B cell receptor so it doesn’t matter what the antigen specificity is, it’s going to become activated anyways
so if you’re a bacteria, you want to have Tl-1 and Tl-2 structures because you’re gonna activate a million B cells and the odds of one specific to that bacteria finding that bacteria is super low
what is Tl-1?
LPS is a Tl-1 antigen that activates LPS-specific B cells
LPS also activates B cels specific for other bacterial surface antigens in a T-independent manner
bacterial DNA is a Tl-1 antigen that can help activate B cells specific for bacterial surface antigen
the B cell becomes activated but it doesn’t change isotopes or hypermutate so there’s an IgM molecule produced that’s not specific….
what is T1-2?
if you have a bacteria with a very repetitive structure, it can ligate a ton of B cell receptors and if you get enough signal coming off of those, you can activate the B cell
so the good news is the B cell is responding to something but you’re still only getting IgM that is not hyper mutated
what type of immunoglobulin would you expect from a TI-1 response?
IgM
what is a key change that happens when the B cell is activated?
it changes the expression of the B cell receptor from a membrane bound to soluble form
now it can secrete things!
you start secreting antibodies like IgA, IgG, etc.
where is IgE?
it lines basically every exposed area of the body
skin, respiratory, reproductive tract, etc.
where is IgA found?
all the mucosa
respiratory and digestive primarily
also milk glands
where is IgG found?
it’s everywhere except the brain
it’s the only subclass that can be transferred to an embryo!
what happens when you’re exposed to the flu?
IgA antibodies bind to the virus so it can’t even bind to an epithelial cell in your respiratory system
now the virus can’t infect cells!
what happens if you eat salmonella?
dimeric IgA can neutralize the pathogen!
what is Ab:Ag valence?
valence is the capacity to interact with something
an antigen can interact with 4 antibodies so the valence of that antigen is 4, it has 4 epitopes
how is the IgM pentamer made?
5 IgM are joined by J chains and disulfide bonds
what is IgM good at?
fixing complement
if you can’t make an IgM pentamer, you can’t fix complement
which pathway is IgM best at fixing complement by?
classical pathway
what does IgD do?
you can’t detect it really in the blood and we haven’t identified a receptor for it
we literally don’t know what IgD does…
what does IgA do?
it’s in mucous and really important for neutralizing stuff in GI and respiratory tract
they associate with a secretory component and are associated with secretory surfaces like saliva, tears, milk, mucosa
IgA dimer binds to basolateral surface of epithelial cell via poly-Ig receptor which allows IgA to enter the epithelial cell and go to the apical face of the epithelial cell
IgA is secreted and part of the poly-Ig receptor goes with it which increases the half life of IgA in the mucosa (it’s not hospitable)
how is the IgA dimer made?
two IgA are joined by J chains
what does monomeric IgA do?
monomeric IgA floats through the blood and is recognized by Fc-alpha receptor found on leukocytes
monomeric IgA binding trigger phagocytosis and respiratory burst in response to binding IgA opsonized pathogens
what does IgE do?
allergies!!
it’s found as a monomer in the blood but in low levels
most IgE produced is found bound to a mast cell in tissue
IgE is associated with every external facing part of your body
how does IgE mast cell interaction work?
IgE binds to mast cells and just sit there until you’re exposed to something that can cross-link some of the IgE molecules which causes the mast cell to release it’s granules
the granules have histamine in them!! it causes your throat to close up, swollen, red
it also shuts down blood flow too and allows it to escape into the tissue which is why your skin gets hot; its your blood pooling in the area
what does histamine do?
smooth muscle contraction
vascular leakage
what does IgG do?
most abundant immunoglobulin
binds to Fcγ receptors and activates phagocytosis/respiratory burst after binding IgG coated antigens
Fcγ receptors are found on macrophages, neutrophils, dendritic cells and platelets
what are inhibitory Fcγ receptors?
they produce negative signal upon binding IgG coated antigen which may shut B cell down from producing antibody
this may keep macrophages/neutrophils from destroying tissue due to too robust of a response
found on B cells, macrophages, neutrophils
what is IV Ig used to treat?
lupus, ITP, immunodeficiencies, MS, MG
we don’t really know what it does but we think it may provide Ab not present in the patient or inhibitory Fcγ receptors
hella expensive
which immunoglobulin can be transfered to the embryo from the mother?
IgG
neonatal Fc receptor is responsible for transfer of IgG from mother to the baby
why is it so crucial to have an adaptive immune response?
- Specificity for a particular pathogen
- More effective at clearing pathogen
- Immune memory (vaccines)
what is a polyclonal antibody?
recognizes multiple antigenic sites (epitopes) on an antigen
what is a monoclonal antibody?
recognizes only one antigenic site (epitope) on an antigen
much more specific; it’ll be harder to fight the antigen
