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57 Cards in this Set

  • Front
  • Back
when are your t cells formed
all of your T cells are formed by the time you are born
where do B cells mature
in primary lymphoid tissue (bone marrow) before they encounter antigen
how does B cell formation differ from T cell formation
T cells are all formed by the time you are born

B cells are constantly shuffling Ig and forming new combinations throughout your life
what are the stages of B cell development
antigen independent
antigen dependent
what occurs in B cell antigen independent development
rearrangment of immunoglobins in primary lymphoid tissue
what occurs in B cell antigen dependent development
occurs in 2ndary lymphoid tissue when the B cell encounters antigen, T cells are present in the 2ndary lymphoid tissue ready to help B cells
when do T cells help B cells in development
antigen dependent step
why is there no antigen dependent step for T cells
because all your T cells are formed by the time you are born or shortly after birth
what are the properties of hematopoietic stem cells
unlimited ability to proliferate
multipotent - they can form any cell in the blood depending on cytokine environment except liver and brain cells
why aren't hematopoietic stem cells totipotent
they are not able to form ANY TYPE OF CELL such as liver/brain cells
what is required for stem cells to renew
SCF
what is the 1st thing that stem cells do
differentiate into myeloid and lymphoid cells
what do lymphoid cells make
lymphocytes ( B and T cells)
what is required for lymphoid development
IL-7 (Interleuken 7)
what is required to make erythrocytes
EPO
what is needed for the formation of macrophages/dendritic cells
GM-CSF ( Granulocyte Macrophage colony stimulating factor)
where does T cell development occur
in the thymus
what are the major regions of the Thymus
cortex and medulla
how is the thymus a perculator
thymocytes (immature T cells) perculate through the thymus making contact with different cell types in the thymus in order to select for certain TCR
how is the thymus a nurturing environment
it secretes peptides that promote T cell differentiation
where do developing thymocytes enter the thymus
cortex (top)
what are some of the different cells contained in the thymus
dendritic cells
nurse cells
macrophages
cortical epithelial cells
medullary epithelial cells
where are cortical epithelial cells located
cortex
where are dendritic cells and macrophages located
medulla
where are nurse cells located
cortex
what do nurse cells do
secrete hormones which promote thymocytes to undergo T cell differentiation
how is T cell differentiation accomplished
by changes in surface markers
what surface markers do T cells have when they first enter the thymus
they are double negative CD4- and CD8- meaning they don't have either marker

they then become double positive CD4+ CD8+

then in later stage become either CD4+ or CD8+
what is the first step in the development of TCR sequence
in cells that are double negative CD4- and CD8- the variable segments of TCR beta chain undergo rearrangement

Beta chain associates w/ pre alpha chain + CD3

if Beta chain that is being tested out is active the beta-alpha CD3 comples will start to send signals
what does a pre alpha chain do
used to try out the newly rearranged beta chain

pre alpha is always working and will associate with the new beta chain and CD3 forming a signaling complex on the cell surface which starts to send signals
if the new beta chain being tested out works and sends signals what happens to the cell
Qthe cell will survive

it will become double positive CD4+ and CD8+ will be expressed on the surface

rearrangment of additional Beta cells will be suppressed

rearrangment of variable alpha chain genes

if rearrangement of alpha chain is successful a mature TCR is formed

if beta chain or alpha chain rearrangment is unsuccessful the T cell dies
why is rearrangment of further beta chains suppressed after an active beta chain has been found
this is allelic exclusion and done because the T cell wants to express only one Beta chain so once it has made a successful one the rest are inhibited
when does the T cell send signals
when the Beta-pre alpha complex is formed and after alpha gene rearrangment

if alpha chain rerrangment works the alpha chain combines with the beta chain and continues to send signals
what is the purpose of positive selection for self MHC restriction
you want to only have TCR that recognize/bind to our MHC b/c TCR/MHC interaction is limited only to our MHC of our own genotype
what performs the positive selection for MHC restriction and how
cortical epithelial cells they have both MHC1 and MHC2
MHC1 binds what
CD8
MHC2 binds what
CD4
what occurs in positive selection for self MHC restriction
dbl positive cells are subjected to positive selection

you want low affinity to MHC (cell will survive)

don't want too high of an affinity for TCR to MHC because it may lead to autoimmunity

if no affinity btwn TCR and MHC the T cell dies

Progression to single positive
TCR binds MHC1 = CD8
TCR binds MHC2 = CD4
what stage of T cell ontogeny does a T cell progress to being single positive
positive selection for MHC restriction
what occurs in negative selection of T cell
it removes any self reactive T cells, you want to remove any T cells that react to self antigens

conventional dendritic cells and macrophages present ubiquitous self antigens

medullary thymic epithelial cells present tissue specific antigens (albumin made by liver)

if TCR reacts w/ ubiquitos antigen or tissue specefic antigen the T cell dies
where does negative selection for T cells occur
medulla
what cells participate in negative T cell selections
convetional dendritic cells
macrophages
medullary epithelial cells
what are ubiquitos self antigens
proteins present in every cell in your body
what are the stages T cell tolerance
central tolerance
peripheral tolerance
what is central tolerance
removes self reactive T cells
occurs in thymus
what is peripheral tolerance
occurs in lymph nodes and places T cells go (2ndary lymphoid tissue)

this is done because central tolerance isn't 100% effective and a few self reactive T cells leak out and peripheral tolerance removes them
what are the peripheral tolerance mechanisms
activation of induced cell death
CTLA4 expression
regulatory T cells
lack of co stimulation by nonimmune system cells
what is meant by lack of costimulation by nonimmune system cells
every cell in the body has MHC1 and is presenting its own self peptide and when they come in contact w/ cells of the immune system they're not expressing any costimulators (no B7)

these non immune cells aren't capable of stimulating our immune system b/c no costimulatior B7

no costimulation causes: anergy and death of the T cell
what is involved in T cell tolerance
dendritic cells will not make B7 if there is no danger and T cell anergy results if DC tries to present antigen w/o B7
what occurs in the 1st 3 stages of B cell speceficity
stage 1
rearange D and J segments of Ig heavy chain (D-J joins)

stage 2
V-DJ join on one chromosome
if 1st rearrangement is non productive the other chromosome rearranges
if 2nd chromosome is non productive then cell dies

stage 3
V-DJ combimes with MU heavy chain (to test it out) which joins with pseudo light chain (temporary light chain) to form SURRUGATE IgM (sIgM)

sIgM goes to the surface and forms a signaling complex with IgALPHA and IgBETA and begins to send signals

step 4
signals from sIgM provide allelic exclusion of any heavy chain rearrangment of any more V-DJ segments ALLELIC EXCLUSION

stage 5
sIgM signal light chain genes to undergo rearrangement since we already have a successful heavy chain gene so want light chain to pair it up
*if rearrangement doesn't work cell dies IF REARRANGEMENT WORKS LIGHT AND HEAVY CHAINS FORM SURFACE IgM

stage 6
sIgM signals all other light chains to stop rearrangement (allelic exclusion)
virgin mature naive B cells go to 2ndary lymphoid tissue ready for antigen contact
what is a marker for stage 6 of B cell development
IgD expression
what is the mechanism for B cell tolerance
B cells that get activated by self antigen in the marrow undergo apoptosis (clonal deletion)

some B cells have surface Ig that recognize self antigen but don't get activated and anergy occurs and they die

Ignorance may occur - B cell recognizing self antigen never encounters the antigen in the periphery
what is needed for NK cell development
IL-2 (IL2 and IL2 receptor are both expressed by NK cells)
IL-15
what do NK cells produce
IFN GAMMA
what surface proteins does NK cells have
CD56 FcGAMMARIII
what antibodies do neonate have
maternal IgG
HL = 30 days
when do neonates get vaccinated
depending on the [IgG]