L8 T and B cell development - Hudig Flashcards
Where are the pluripotent cells?
bone marrow
Where are the B cells made?
bone marrow
Are all self-reactive B cells destroyed in the bone marrow?
no, but MOST of them
T cell made in the (blank) and mature in the (blank)
bone marrow, thymus
In the thymus, T cells are selected positively for (blank) then negatively for (blank)
positive for weak MHC binding, then negative for strong self MHC binding
Where do NK cells develop?
bone marrow
What three enzyme mutations are involved in SCID?
RAG1
RAG2
TdT
What is central tolerance?
deletion of anti-self T cells in the thymus
SCID mutations effect (t/b) cell dev?
both of them!
preT stem cells from bone marrow lack what markers?
Cd3,/4/8
preT’s in the thymus express CD25 to divide which allows them to bind what?
IL2
Where do T cells get their tCRS
in the thymus
Can the tCR still bind the MHC without it holding a peptide
yes, it is just a weak bind
Why is the first positive selection for T cells for those that can bind to self-MHC?
so all the binding strength during recognition doesnt have to come from the peptide alone
Why is the second negative selection for T cells those that bind self-MHC strongly?
Want the TCR to be able to bind the MHC, but not trigger activation if it is not holding a protein
what percent of thymocytes survive selection?
1%
By what method are the rejected T cells killed?
apoptosis
(blank)Induces Expression of Organ-Specific Proteins in the Thymus to Support Deletion of “Self”-Reacting T Cells
AIRE (Autoimmune Regulator)
AIRE is found in the (blank)
thymic medullary epithelial cells
AIRE protein interacts with multiple (blanks)
transcription factors
T/F: AIRE induced organ specific proteins can be secreted or remain in the cytoplasm, allowing both CD4 and CD8 recogntion
true
at what age does the thymus begin to regress?
puberty
bone marrow contains stem cells for what cell lines?
preT, B, NK, and RBCs, granulocytes, macrophages and platelets
What are the primary lymphoid organs?
thymus and bone marrow
what are the peripheral lymphoid organs?
lymph nodes
spleen
GALT, MALT
does the thymus completely disappear with age?
no, just atrophies
the spleen clears blood infections of (blanked) bacteria, such as strep pneumoniae
encapsulated
Where does central tolerance occur?
central lymphoid organs: bone marrow and thymus
Where does peripheral tolerance occur?
in circulation
What happens if a t or b cell sees a self antigen without signal 2?
they will die or become anergic
Is T cell or B cell self-tolerance easier to break?
b cell
why do b cells break self tolerance?
affinity maturation which reacts with self
B cells will express MHC II if triggered by (blank)
IFNg
Why are B cells more likely to break tolerance?
NO AIRE in the bone!
How do B cells commonly break tolerance?
a true antigen gets stuck to something self; the whole complex is internalized and is all recognized as Ag
Does the thymus contain germinal centers?
no
Does the thymus contain B cells?
only a few
Where in the thymus is T cell proliferation?
cortex
What is the effect of glucocorticoid hormones on thymocyte proliferation?
depresses cortical proliferation
Do glucocorticoid hormones deplete T cell levels in the thymic medulla?
no
Where are Ab generating plasma cells originally formed?
in lymph nodes, peyer’s patches, and the spleen
Do plasma cells travel?
to the bone marrow
T/F: the thymus has only Efferent lymphatics
true
where does the lymph from the thymus drain?
thoracic duct
Do T and B cell interactions occur in the blood?
NO, almost exclusively in lymphoid organs
Lymph fluid lacks what two cell types?
RBCs and granulocytes
T/F: lymph contains the same proteins as plasma
true
T/F: there is lower IgM and C1q in lymph than plasma
true
Soluble antigens, macrophages, and other APCs will enter lymph nodes via (blank)
afferent lymphatics into the subcaspuslar sinusoids
What cells are in the lymph node cortex?
B cells
What cells are in the lymph node paracortex?
T cells
Are B cells dividing in primary follicles?
no
What follicles are B cells dividing in?
secondary/germinal follicles
Are there T cells in the primary follicles of lymph node?
no
Are there T cells in the germinal centers>?
only a select few
Where are dendritic cells found in the lymph node?
Cortex and paracortex
Where are the plasma cells in the lymph node?
in the medullary cords; NOT IN THE B FOLLICLES
Is there cellular movement within the lymph node?
yes
What does it take to activate a b cell in the lymph node?
Ag presentation by DC and signal 2
What do b cells in the lymph node do when they are activated?
become APCs and show the antigen to Thelper cells, and brings it back to a germinal follicle
The spleen clears (blank) infections
intravascular
T/F: the spleen has both types of lymphatics
false, IT LACKS AFFERENT AND EFFERENT; served entirely by blood stream
Where are plasma cells in the spleen?
marginal zone between the white pulp and red pulp
where are the T cells in the spleen?
periarteriolar sheath
Where are the B cells in the spleen?
primary and germinal follicles
After trauma, should you save even a part of the spleen?
yes, save as much as you can
What is the primary product of GALT?
IgA
what carries Ags from the lumen of the gut to PPs?
M cells–specialized epithelial APCs
Plasma cells in GALT secrete (blank)
dimers of IgA with a J chain
What are the three major areas of GALT?
tonsillar rings, Peyer’s patches, and the appendix
Do tonsils have lypmhatic vessles?
no
Describe B cell architecture in the tonsil?
germinal centers and IgA-secreting plasma cells
What type of epithelium lies of PP’s?
flat (thin), not columnar epithelium without goblet cells or microvilli
What two things are released into the draining lymph from PP’s?
IgA blast cells and Ag
What lymph nodes drain PP’s?
mesenteric nodes
What is the fate of the IgA blast cells released from PPs?
they go to other secretory sites throughout the gut, AND salivary, lacrimal, and lactating mammary glands, become plasma cells and secrete IgA
what type of MHC do M cells have?
MHCII
where is the germinal center in PPs?
central
where are the T cells in PPs?
peripherally ringing the germinal center
Where else are M cells located besides PPs?
respiratory and GU tract
What three things control gut microbiota?
GALT, PPs, and mesenteric lymph nodes
What functions to limit bacterial-epithelial contact in the gut?
mucus layer, epithelial antibacterial proteins, and IgA secreted by lamina propriia plasma cells
Defensins (blank) bacteria
kill
IgA (blanks) bacterial adhesion
blocks
RegIIIg is an antibacterial lectin that secreted by (blank) and limits bacterial peentration of the mucus layer
epithelial cells
Where do Ag loaded DCs from the gut travel to?
PPs or mesenteric lymph nodes, BUT NO FARTHER
IgA secreting plasma cells are found throughout the (blank) of thegut
lamina propria
T/F: the appendix is part of the GALT
true!
Does the appendix have lymphatics?
yes, both
where are the germinal centers located in the appendix?
cortex
what types of lymphocytes are found in the lamina propria of MALT?
plasma cells, T helper cells, and CTLs
The mucosa of the lacrimal glands, vagina, the bladder, mammary glands is (blank)
MALT
what is the first barrier to infection for HIV?
secretory immune system
Dexamethasone and cortisone (blank) dividing T cells in thymic cortex
KILLLLLL
T/F: local and endocrine hormones signal thymic cells to differentiate
true
Thymopoietin and thymosin come from (blank)
Hassal’s corpuscles
T stem cells are found in the ?
bone marrow
Pro-T, pre-T, double pos T, and single positive T are found in the?
thymus
naive mature T cells are found in the?
periphery
At what point in differentiation does the T cells gain a/BTCR?
double positive
Where does T cell germline rearrangement occur?
thymic cortex
where is the second negative selection in T cell screeining?
the medulla
Do T cells die naturally of necrosis or apoptosis
apoptosis if everything goes according to plan
When is CD3 expressed on T cells?
AFTER t cells are presenting TCRs on their membrane
What is the co-receptor for antigen recognition by CTLs?
CD8 itself!
If not in the blood and you’re not a Treg, where would you find CD25 T cells and what are they doing?
lymph nodes and spleen and are dividing post Ag exposure
What will trigger mature T cell division?
specific ags, T cell reactive lectins, or Abs to CD2 or 3
Ag-specific proliferative assays measure the activity of what cell type?
T memory cells
what are lectins?
proteins that bind sugars
what are the two lectins that are T cell mitogens?
Con A and PHA
Do conA and pHA stimulate B cells?
no
Can mAbs to CD3 stim t cell division?
yes
what radioactive method can measure T cell activity?
3H-TdR incorporation
How do you measure T cell activity in VIVO?
ability to respond to a DTH to chemicals like DNCB upon SECONDARY skin application
Where do you find pro and pre b cells?
bone marrow
where do you find immature and mature b cells?
periphery
The committed dividing B cells first only express Ig mu heavy chains and NO LIGHT chains in their (blank)
cytoplasm
Where do B cells divide once they have encountered antigen?
in a germinal follicle in lymphoid tissue
Where do B cells go to become plasma cells?
medullary cords of lymph nodes, marginal areas of the spleen, or PPs
Where do memory B cells hang out?
blood circulation
How do you measure B cell activity in vitro?
radioactive thymidine uptake
What are the B cell polyclonal mitogens? What do they do?
protein A of Staph Aureus (binds Fc of IgG), LPS of gram neg bacteria, and EBV virions; stimulate ALL B cells to divide
What cytokine stimulates B cell IgG1/3 production?
IFNg
What cytokine stimulates B cell IgE production?
IL4
What cytokine stimulates B cell IgA production?
TGF-b
