3: Adaptive Immunity Flashcards
Natural Killer cells
ensure homeostasis!
cells off in any way? NK cells clean up prob by killing cell
initial response to viruses
dealing with most cancerous cell growths
How NK cells work
healthy cells have receptor that activate NK by saying “i’m self!”
Primary way of recognition of problem: Receptor counting
then kill
Receptor Counting
NK counts things like MHC... # of MHCs changes with some viruses, or MHCs are modified by viruse
what can NK take caere of
most diseases/cancers unless things get waaaay out of control
Antibody Stimulation of NK Cells
antibodies sent to cell surface proteins
NK cells bind to clusters of antibodies on surface
granules released, apoptosis
cancer vaccines
molecs are on cancer cell surface only
antibodies to protein stimulated
NK come kill
this is very specific, so expensive and hard
Apoptosis
NOT NECROSIS
not pro-inflmmatory
blobs form dead cells endocytosed and recycled
chop up DNA to destroy virus genome
programmed cell dealth
necrosis
pro-inflammatory cell death
recruit immune system
all cell dealth other than apoptosis is pro-inflammatory
B cells
adaptive immunity
One antigen for one B cell… true love. SPECIFICITY
has antibody on surface, with different shape so it can interact with just its antigen
antigen binding domain is pretty much randomly generated
How are B cells generated
RANDOMLY
in ABSENCE of the antigen (not made in response to it)
When the antigen binds to the B cell
reproduction and maturation eventual development into plasma cell all bind to same antigens all have same binding site all make same antibody
what do plasma cells do?
secrete antibodies
two things activated B cells can produce
eventual plasma cells
memory B cells
Memory B cells
stick around for years
quicker response to an old stimulant
Memory B and vaccines
vaccines don’t last a lifetime, but do last for years
because a lot of things we vaccinate against we aren’t often in contact with, so B cell supply not kept up
antigens don’t interact with B cells since they arent around much
SO why is B cell adaptive?
the SECOND set of B cells (reproduction) is created because of antigen binding
Understand pic on slide 8
Understand pic on slide 8
Antigen Binding site (variation)
lots of variation due to
2 proteins, 2 copies of each protein (heavy and light)
these proteins can be made of a ton of variation in V, D, and J
10^14 possible antigen binding sites
Antigen Binding Site: Stem region (Fc)
Fc region is the same for the same immunoglobulin (all same stem for IgG for ex)
transmits info to immune system
INTERACTS WITH HOST CELL
attached to the heavy chain
Antigen Binding Site: VDJ region
where the antigen attaches
2, bind 2 antigens per binding apparatus
Each LINE of antibody has a different binding site
ability to cross-link and agglutinate
most general job of antibody
transmit info to immune cells about presence of non-innate antigen
transmit through Fc region
we can recognize about 10^14 molec patterns this way
innate receptors
recognize non self molecular patterns
we only recognize about 20 PAMPS this way
what is the difference between the 5 immunoglobulin classes
the FC region
so they can interact with dffernt cell types
IgG
most common in blood recognized by NK cells enhances phagocytosis neutralize toxins and viruses protects fetus/newborn
IgM
agglutinates antigens
first antibodies produced in response to initial infection
IgA
mostly found in mucous
agglutination bc not many immune cells in mucous
has FOUR antigen binding sites
stopping colds
in secretions, a little in blood and lymph
IgD
blood and lymph
serum function unknown
On B cells for initiation of immune response
IgE
allergic reactions
lysis of worms
mast cells and basophils
least common immunoglobulin
STUDY SLIDE 10
STUDY SLIDE 10
B stem cells
in bone marrow of long bones
right cytokines to stem cells leads to B cell production
VDJ
how we make 10^14 different antigen binding sites
VDJ region… lots of ways to have V, D, and J
VDJ chromosome
9 loci on each V, D, and J
random rearrangement of VDJ region occurs during development
how we pick mates
can tell by smell if someone has different VDJs than us
which is good, then our offspring can have variation
Negative Selection
in bone marrow test
see if B cell is stimulated by self
if so, KILL IT (we don’t want self to stimulate B cell response, that would kill us)
Negative selection laymens terms
(B cell) killed if you recognize self
autoimmunity
if something goes wrong with negative selection
If B cell passes negative selection
go to lymph node and spleen
look for antigens here
If B cell activated in lymph node/spleen
Go to periphery
IgA in gut
bc lots of associated lymph cells
Memory cells
stay in lymph nodes
lymph nodes
central controlling region of body
isotype switching
chnage in class of immunoglobin being made occurs in thymus with help from helper T cells
what does isotype class of antibody do?
determines how antibody does its job
What do be cells start with
IgM
transition to other classes later (mostly IgG)
how is it determined what type of isoltype the B cell siwthces to?
by co-stimulatory facotrs like LPS and cytokines presented.
Review slide 15
review slide 15
baby immune system
baby born supplemented with mothers immune system
doesnt really have its own
where do T cells develop
stem cells in long bone marrow (like B)
where do T cells mature?
In thymus
How antibodies protect from infection?
Complement Pathway (classical pathway) antibody mediated can be done by IgGs
Positive Selection
select for T cell receptor that CAN interact with MHC
can T cell recognize the MHC?
tests for growing T cells
positive selection
Negative selection
Negative selection
select for T cell receptors that DONT BIND TO SELF PEPTIDES
(kill those that do)
you only survive if you dont bind to self
Neutralization
preventing something from occuring
of:
toxins: prevention of binding of toxin
bacteria: adhesion to host cell blocked. mostly in gut and mucus
viruses: neutrilze receptors of virus or something
Toxins
Tetnus: 2 parts, A and B
B: binding toxin to human cell
A: kill human cell
antibody mediated activation of Macrophages
aggregated immuonglubulins go to bacterial surface
cross linking of Fc receptors
macrophage activated
kill everything
antibody mediated opsonization
makes it easy for marophage to endocytose
antibody mediated recruitment of NK Cells
antibodies on surface cluster
degranulation happens
apoptosis
Mast Cell Activation (degranulation)
antigen binding to antibodies… degran of mast cells
allergies
do antibodies kill things?
NO! they recuit NK cells, MAC attack, or somethig else to kill
what do antibodies DO? (broadly)
mark things and tell immune system to kill them
VDJ in T cells
similar to B, but different VDJ
how T cells recognize things
through presentation by MHC
where things happen in T cells: Recombination
bone marrow (creating VDJ and whatever)
where things happen in T cells: maturation
(to nieve)
THYMUS (positive and negative selection here)
what is selection?
surviving
selection means surviving in a consequence of death
primary functions of T cells
kill (CD8) or help (CD4)
after maturation in thymus?
T cells go to body
what recognizes floating antigens?
antibodies
what do T cells recognize?
antigens ONLY when in the context of MHC
what are MHCs
molecs present on surface of macrophages
B cells, processional APCs (antigen presenting cells) and cells infected with intracellular pathogen
whats HLA
human version of MHC
we want differences in both in mates
professional APCs
macrophages
B cells
B cells make
antibodies
macrophages…
control immune response
antigen presentation is a
check on improper activation
macrophages check with T cells so they don’t improperly activate and kill everything
MHC class one activate
CD8 T cells
MHC class two activate
CD4 T cells
CD8 T cells
kill cells
CD4 T cells
activate something else to kill
