T and B cell development Flashcards
When is the thymus the biggest?
age 11-15
Does the thymus have afferent or efferent lymphatics.
Efferent lymphatics
(blank) contains very few B cells, granulocytes, or red cells in thymic tissues.
thymus
Bone marrow has the (blank) stem cells
pluripotent
B cells are made in the (blank)
bone marrow
What happens to self-reactive B cells?
they are eliminated
T cell precursors are made in the (blank) and migrate to the (blank)
bone marrow
thymus
In the thymus, pre-T cells divide and become T cells. T cells that bind to self MHC (Blank), those that dont are killed
live
What is positive selection
• T cells that bind to self MHC live, those that don’t are killed
o You only want T cells that can recognize self MHC, otherwise they’ll never bind to anything
• At this point T cells are double positive, they all have CD4 and CD8
What is negative selection?
• T cells that bind strongly to MHC with self peptide are killed, those that don’t respond to self peptide live
What is central tolerance?
only about 1% of all T cells made, make it through the selection and get out into the blood
Where do NK lymphocytes develop?
bone marrow
B, T, and NK cells originate from pluripotent hematopoietic stem cells in the (blank)
bone marrow
What three mutations could make you have SCID?
RAG-1
RAG-2
TdT
Pre T stem cells come from bone marrow via blood, and lack (blank) (blank) and (blank)
CD3, CD4, CD8
Where does central tolerance occur?
in the primary lymphoid organs (bone marrow and thymus)
Which selection comes first positive or negative?
positive
Explain how T cells develop
Pre T stem cell come from bone marrow and lack CD3, CD4, CD8. In the thymus T cells have CD25 which attracts IL-2 for growth and replication. When T cells leave they drop the CD25 (except for T regulatory cells) and then T cells gain CD3 and then both CD4 and CD8 together.
How do you select your perfect T cells
T cells are positively selected for weak binding to self MHC proteins
T cells are negatively selected for too strong binding to MHC plus self peptides.
T or F
TCRs of T cells bind to the MHC I and II proteins, regardless of the peptide inside.
T
Recognition of antigenic peptide to a T cell adds (blank) strength
binding
Recognition of MHC alone to a T cell is (blank) when the peptide fails to add binding strength
weak
Why is it important that we have positive selection?
So that our TCRs will bind an MHC and add some binding strength so that the foreign peptide doesnt have to provide all the strength to the TCR
What happens to T cells with TCRs that fail to bind to self MHCs?
they die
Why is it important to have negative selection?
Kill T cells with TCRs that bind too well to self MHCs alone or to MHCs combined with self peptides that give strong ligand (we dont want our T cells over reacting and freaking out to our own antigens) We want the foreign peptides to add strong binding strength not anything else
How do TCRs that bind too tightly to MHC die?
through apoptosi
What is AIRE?
AIRE (autoimmune regulator) that induces expression of organ-specific proteins in the thyust to support deletion of “self” reacting T cells
Where do you find AIRE and how does it work?
in the thymic medullary epithelial cells, It interacts with multiple transcription factors to induces organ-specific proteins to be secreted so that CD4 and CD8 cells that react to them can be destroyed.
What do you call deletion of anti-self T cells in the thymus?
central tolerance
The thymus involutes greatly at (blank) but persists for life despite aging losses
puberty
(blank) lymphoid organs generate lymphocytes for life, but the thymus ages remarkably
primary
The (blank) is important for clearance of encapsulated bacteria such as streptococcus pneumoniae
spleen
Where does central tolerance occur?
What does it do?
in primary lymphoid organs
gets rid of anti self T and B cells
Where does peripheral tolerance occur? How does it work
in circulation
If a T or B cell detects a self antigen and doesnt get a second signal they will die or become anergic.
How can a self detecting B or T cell survive in the peripheral blood?
If it never gets stimulated OR if it has a very low affinity and low reactivity with self
What happens when you have an autoimmune response?
self-reactive cells break tolerance and respond
Which cell tolerance is easier to break, T or B cell tolerance?
B cell
How can B cells express MHC II proteins?
if triggered by IFN gamma
What contains few B cells and no germinal centers?
the thymus
Where in the thymus do you make thymocytes?
cortex
What happens when glucocorticoids are given to a person?
it will depress cortical thymocyte proliferation and will deplete the cortex (will not deplete the T cells in the medulla)
The efferent lymphatic of the thymus drains the thymus into what and why?
the thoracic duct, to enter the blood circulation
What is the secondary lymphoid organs?
lymph node, spleen, GALT, MALT
In healthy people, T and B cell interactions and proliferation occur almost exclusively in (Blank)
lymphoid organs
NOT in blood or extraneous sites
T or F
lymph fluid has red cells and granuocytes
F!!!!!
The B lymphocytes of the cortex of the lymph node have (blank) where B cells are not dividing and (blank) where B cells are dividing in germinal centers
Primary follicles
secondary/germinal follicles
T or F
There are virtually no T cells in the primary follicles of lymph nodes and a few selected T cells in secondary follicles
T
B cells are in the cortex and T cells are in the paracortex. THey meet up at the boundary to induce a response.
T or F
T
Explain how in a lymph node that a B cell can initiate a reaction to stimulate a T cell
A b cell can become activated by an antigen and then become APCs themselves and present the antigen with their MHC II receptor and connect with a T heper cell.The CD40 of the B cell meets with the CD40L. B cell drags T cell into germinal follice :)
In what disease is lymph node architecture lost?
AIDS
The (blank) functions to clear intravascular antigens from the blood, to make antibodies and to remove aged RBCs from circulation
Spleen
T or F
the spleen lacks afferent or efferent lymphatics and is served entirely by blood stream.
T
What does the periarteriolar sheeth in the spleen contain?
T cell!
What does the white pulp of the spleen contain?
B ells
What do you find in the marginal zone between the white pulp and red pulp of the spleen?
plasma cells
What 2 organs are major sites for clearance of bacteria by phagocytic cells?
liver and spleen
Why is the spleen uniquely important?
it is super awesome at killing encapsulted bacteria (such as strep pneumonia) so you should always try to save the spleen!
What is the primary product of GALT?
secretory IgA
(blank) is found in tears, milk, saliva, nasal mucus, vaginal secretions and the gut
IgA
How does IgA get made in the gut?
M cells carry antigen into peyers patches where plasma cell will bind and secrete IgA which will be picked up by the secretory component and transported though the epithelial cell to the lumen of the gut.
Viruses must enter cells to (blank)
replicate
(blank) must adhere to cells of the gut to survive
intestinal bacteria
What are the three major areas of the GALT
tonsillar rings
peyers patches
appendix
The tonsillar ring has (blank) and (blank) secreting plasma cells
Germinal centers
IgA secreting
Do tonsils have afferent and efferent lymphatics?
no
(blank) are specialized regions of gut with germinal centers
Peyers patches
What is found in the thin epithelium above peyers patches?
M cells that let antigens from the gut get through
So M cells let antigen in the gut, peyers patches are exposed to antigen, B cells within it will make plasma cell which will travel through gut mucosa and such to become (Blank)
IgA
Many of the intraepithelial T cells of GALT have (blank) TCRs
gamma-delta
M cells have (MHC class I/ MHC class II) antigens
MHC class II
(blank) antibodies block bacterial attachment to gut epithelial cells and may even affect bacterial growth rate.
IgA
What is reg III?
antibacterial lectin that is secreted by eptihelial cells and limits bacterial penetration of small intestinal mucus layer
What is GALT?
MALT and BALT
Mucosal lymphocytes traffic selectively within (blank), and traffic less to the spleen
GALT
What corpuscles are found within the thymus and what do they do?
hassals corpuscles
source of thymic growth factors such as thymopoietin and thymosin
Tell me the life history of a T cell
Bone marrow stem cells produce pre T committed cells-> pre T cell in blood circulation-> pre T cell enter thymus and divides in the cortex-> rearranges T cell receptor genes to form functional genes for T cell antigen receptors. T cells aquired both CD4 and CD8 becoming double positive. Cells with TCR receptors that weakly recognize the MHC class I and class II proteins live, the ones that fai to bind to MHC proteins die. T cells mature in thymic medulla and differentiate to CD4 pos or CD8 pos. In the medulla T cells that strongly recognize MHC proteins holding self peptides are deleted (negative selection to prevent auto-immunity). Leaves via thymic lymphatic and then enters bloodstream-> circulates as a naive T cell in blood for days, week, even years. -> CD4 encounters an APC Class II OR CD8 encounters Class I with viral peptide -> antigen responding cell divides in T cell areas of lymphoid organs-> function in T help, T killing, or T regulation-> some become memory T cell. -> restimulation with antigen-MHC can proliferate agan, re-express proteins needed for T cell functions (IL-2, IL-10, perforin, granzymes) and regain effector functions.
(blank) proteins are physically associated with T cell receptor for antigen (TCR) that is found on mature T cells. It is expressed on thymic lymphocytes after the T cells have started to put the TCR receptors on their membrane.
CD3
(blank) is a T cell marker protein (and the co-receptor for antigen recognition by T helper cells) which recognizes MHC class II molecues. This is found on all helper T cels.
CD4
(blank) is a T cell marker protein which recognizes class I molecules. It is usually on cytotoxic T cells and actually binds to class I molecules (and is the co-receptor for antigen recognition by T killer cells)
CD8
(blank) is the alpha chain of the IL-2 receptor that confers high affinity for IL-2 and is found on T cells in lymph nodes and the spleen that are activated immediately after antigen encounter and on dividing thymocytes. Mature T cells in blood circulation (that have yet to encounter antigens) lack this. HOWEVER this is found on Tregulatory cells in the blood
CD25
(blank) is a circulating T cell that is capable of responding to antigen (and may be naive or ‘virgin’ T cell or a memory T cell)
A mature
A (blank) has encountered its antigen, has already divided in response to this antigen, and has become a long-lived resting cell capable of responding when and if its antigen reappears in the body.
memory T cell
What will mature T cells proliferate in response to?
specific antigens, T cell-reactive lectins, or antibodies to CD2 or CD3
A (blank) is a substance that initiates cell division
mitogen
(blank) is a specific mitogen for the specific T cell that can recognize it.
antigen (in MHC)
(blank) are proteins that bind sugars
lectins
What are the 2 plant lectins that are T cell specific mitogens?
What are they?
Do they stimulated B cells to divide?
concanavalin A and phytohemagglutinin (PHA)
T cell polyclonal activators
NO
T cells can be stimulated to divide by some monoclonal antibodies to (blank)
CD3
How can you measure T cell activity?
with IL-2 production from stimulated T helper cells.
AND
via DTH response
Starting at app. 9 weeks of age, the fetal liver is the site of (blank)
B cell proliferation
Describe the steps of a B cell life
Committed dividing cells express mu Ig heavy chains in their cytoplasm-> cells stop dividing and become smaller lymphocytes-> mature b cells acquire rearranged kappa or lambda light chains and express membrane IgM and IgD. The cells are released into the blood stream where they have IgM. As IgM or IgD they are virgin and immunocompetent. In periphery they go to B cell areas of lymph nodes, spleen or the peyer’s patches of the gut. WHen they encounter the appropriate antigen, they will divide in a germinal follicle-> antigen is signal 1-> Il2 and IL4 provided by T helper cells causes growth and isotype switching
For a B cell to become a plasma cell and secrete Igs where does it have to go?
it will move out to medullary cords of lymph nodes, marginal areas of spleen, or into special regions of peyer’s patches and other mucosal tissue
How can you detect B cell function?
w/ radioactive thymidine uptake or by Ig secretion.
What are some B cell polyclonal mitogens?
Why do we call them polyclonal?
antibodies to immunoglobulins, Protein A of staph aureus (binds to Fc of IgG) some LPS of gram neg bacteria and virions of EBV.
Because they stimulate all B cells to divide, whereas antigens stimulate only “cognate” B cells to divide.
The lectin (blank) stimulates both T cells and B cells to divide and also stimulates B cells to secrete Ig whereas EBV immortalizes the B cells without causing them to secrete Ig.
pokeweed
