Lymphoid Organs and Lymphoid Ontogeny Flashcards
This is where lymphocytes are generated from stem cells
primary lymphoid organs
This is where mature cells reside in resting states and/or divide in response to immunogens.
secondary lymphoid organs
Two primary lymphoid organs in adult humans
bone marrow
thymus
What types of cells mature in the thymus?
T cells only!
Does the thymus have afferent lymphatics? Efferent lymphatics?
only efferent!!
T cells divide and mature in the (blank) without exposure to foreign antigens, and, if exposed to high affinity self antigens during development in the thymus, (blank).
thymus; die
List the secondary lymph organs.
lymph nodes
spleen
GALT (gut-associated)
MALT (mucosal-associated)
In healthy people, where do T cell and B cell interactions and proliferation occur?
in lymphoid organs *not in blood or extraneous sites
Lymph fluid is found in the lymphatic vessels that interconnect the lymph nodes and is released into the blood at the (blank). Lymph fluid lacks (blank) and (blank). Lymph contains the same proteins as plasma but in lower concentrations and with a size bias that favors the smaller proteins
thoracic duct; RBC; granulocytes
Different lymphocytes reside in different regions of the lymph node. The cortex is a predominantly (blank) region, whereas the paracortex located just under the cortex is the predominantly (blank) region.
B cell; T cell
The B lymphocytes of the cortex have (blank) where B cells are not dividing and (blank) where B cells are dividing in germinal centers.
primary follicles; secondary or germinal follicles
The plasma (B) cells that secrete antibodies are found in the (blank). Plasma cells are found almost exclusively within the medullary cords, NOT in the B cell follicles.
medulla
There is a lot of cellular movement in the lymph node, particularly of T cells. After B cells encounter native antigen bound on the outside of DCs or bind free antigenic proteins, the B cells (if they get ‘second signals’) become (blank). Then, B cells themselves can become (blank), presenting ingested antigens in their induced (blank) to Thelper cells.
activated; APCs; MHCII
Where are B cells primarily located? Where are T cells primarily located? Where do they meet?
cortex; paracortex; at the boundary of the two areas
When a B cell bearing MHCII-peptide antigen binds a cognate T cell that recognizes one of the particular peptides being displayed, the antigen-reactive pair of B cell (to naïve antigen) and T cell (recognizing a peptide presented by the B cell) becomes a firmly attached and mobile pair. Also, the (blank) of the B cell (a co-stimulatory receptor, for the ‘second signal’ in addition to antigen) binds to (blank)) costimulatory protein on the activated T cell. The B cell drags the helper T cell back into a germinal follicle, where the rare T cell gives its help on site.
CD40; CD40L
What are the functions of the spleen?
- clear intravascular antigens from the blood
- make antibodies
- remove aged RBCs from circulation
Does the spleen have afferent or efferent lymphatics?
neither; it is served entirely by the blood stream
The spleen is a major site for clearance of (blank) by phagocytic cells, just as the liver is, by the (blank) cells of the liver.
bacteria; Kuppfer
What are people without spleens at risk for?
serious bacterial infections, particularly with encapsulated bacteria like Streptococcus pneumoniae **must be treated rapidly with antibiotics if this is the case
The gut-associated lymphoid tissue (GALT) contains enormous numbers of (blank).
lymphocytes
What is the primary product of the GALT?
IgA
What type of cells carry antigens from the lumen of the gut to lymphocytes in the Peyer’s patches?
M cells *specialized epithelial cells
a receptor used to shuttle the IgA across their epithelial cell body to allow the IgA to enter the lumen of the gut
secretory component
Found in tears, milk, saliva, nasal mucus, vaginal secretions and the gut to protect the body against invasion by viruses and by bacteria
IgA
What are the 3 major areas of the GALT?
tonsillar ring
Peyer’s patches
appendix
Specialized thin epithelial regions of the gut with germinal centers of IgA B lymphocytes
Peyer’s patches
M cells are so named because they have many microfolds on the gut side of the mucosa and are inductive sites for (blank) production, carrying antigen to macrophages and DCs that are sequestered in the pockets of the M cells. M cells have (blank) proteins. They acquire (blank) from the gut, digest them and present them as immunogenic peptides
IgA; MHC II; antigens
(blank) antibodies block bacterial attachment to gut epithelial cells and may even affect bacterial growth rates
IgA
The GALT immune system, with Peyer’s patches and mesenteric lymph nodes, controls the (blank) of the gut
microbiota
The GALT is part of the (blank) that also includes the bronchus-associated lymphoid tissue (BALT) and the lymphocytes in the mucosal lamina propria, which include (blank), (blank) and (blank)
mucosal associated immune system (MALT); Ab secreting B cells; helper T cells; cytotoxic T cells
New T cells differentiate and mature in the thymus throughout life. The thymus is continually populated with (blank) from the bone marrow.
pre-T cells
What are the two regions of the thymus? Which region has great T cell proliferation? Where do maturing, non-dividing cells move?
cortex and medulla; cortex; medulla
Does the thymus contain B cells? Does it have germinal centers?
hardly any B cells are found in the thymus; no germinal centers
What can kill the dividing T cells in the thymic cortex?
glucocorticoids, like dexamethasone
These are distinguishing features of the thymus, and a source of thymic growth factors like thymopoietin and thymosin.
Hassall’s corpuscles
In the thymic cortex, anti-self T cells are deleted or killed to prevent autoimmune response. What percentage of dividing T cells actually exit the thymus?
1%
This is a key organ where SELF is distinguished from NON-SELF.
thymus
Positive selection of T cells occurs first. Describe what this entails.
T cells with newly derived TCRs are tested for WEAK binding to MHC I and II molecules. Only T cells that bind to MHCs can live. Living is a positive thing, so cells that are positively selected LIVE.
What happens after positive selection?
surviving T cells are tested for how well they bind to an array of self-peptides in MHC. Those that bind too well are killed.
This is a regulatory factor in the thymus that induces production of self proteins that normally occur in many organs of the body. When these self proteins are processed into peptides and presented on MHC molecules in the thymus, auto-reactive T cells are killed. About 99% die.
AIRE
So, T cells that live must survive both (blank) and (blank) selection
positive; negative
Outline the life history of a T cell from production in the bone marrow to activation by antigen.
- bone marrow stem cells produce pre-T cells which are sent out into the circulation
- they reach the thymus and divide in the cortex where the germline DNA is rearranged to allow for expression of different TCRs. T cells also get CD4 AND CD8, and undergo positive selection.
- T cells that are positively selected move to the medulla to mature and before differentiated as CD4 or CD8. Here they undergo negative selection.
- T cells then leave the thymus via lymphatics and enter the bloodstream where they circulate for days, weaks, or years until they come in contact with the antigen that matches their TCR antigen receptor.
- After encountering its specific antigen, the T cell will divide, and will function as a T helper, T killer, T reg or T memory cell.
How do thymocytes die?
via apoptotic death which can be initiated with glucocorticoids
These proteins are physically associated with T cell receptor for antigen 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 membranes.
CD3
This is a T cell marker protein (and the co-receptor for antigen recognition by T helper cells) which recognizes MHC class II molecules. It is found on helper T cells.
CD4
This 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
This is the alpha chain of the IL-2 receptor that confers high affinity for IL-2. It is found on T cells in lymph nodes and the spleen that are activated immediately after antigen encounter and on dividing thymocytes
CD25
Do mature T cells in the circulation that have yet to encounter antigen have CD25? Do circulating T regs have CD25?
no; yes
What is the difference between a “mature” T cell and a “memory” T cell?
A mature T cell is a circulating T cell that is capable of responding to antigen (and may be a naive or ‘virgin’ T cell or a memory T cell). A memory T cell has encountered its antigen, has already divided in response this antigen, and has become a long-lived resting cell, capable of responding when and if its antigen reappears in the body.
T cell surface developmental markers can be used to diagnose different (blank)
lymphoid tumors
a substance that initiates cell division
mitogen
(blank) will proliferate in response to specific antigens, or T cell-reactive lectins, or antibodies to CD2 or CD3
mature T cells
These are proteins that bind sugars.
lectins
T cells can be stimulated to divide by some monoclonal antibodies to (blank)
CD3
T cell activity can be measured by radioactive thymidine incorporation or by measurement of (blank) production from stimulated T helper cells.
IL-2
In vivo, T cell function can be measured by the ability to respond with a delayed type hypersensitivity (DTH) response to chemicals like dinitrochlorobenzene (DNCB) upon (blank) application of the chemical to the skin
secondary **
B cell ontogeny starts in the (blank) but in adults is only in the (blank).
fetal liver; bone marrow
**Starting at approximately 9 weeks of age, the fetal liver is the site of B cell proliferation. Later in life, the pluripotent stem cells go from the fetal liver to the bone marrow.
One pluripotent stem cell will generate committed stem cells for erythrocytes, lymphocytes, monocytes, granulocytes, and platelets. Does the bone marrow have all these stem cells at birth?
yes
Both B cell formation and later B cell Ig secretion require (blank)
cell division
Describe the life cycle of a B cell.
- stem cells for B cells divide and become pre-B cells
- the dividing cells have mu Ig heavy chains
- mature B cells acquire kappa or lambda light chains and express IgM and IgD
- The cells are released into the blood stream
- In the periphery, they will go to B cell areas of lymph organs or to Peyer’s patches in the gut. When they encounter the appropriate antigen, they will divide in a germinal follicle.
- To become plasma cells that secrete Igs, they need T cells which provide differentiation factors
- Some B cells will stop dividing and become memory B cells
B cell function can be detected in vitro by cell division with radioactive thymidine uptake or by (blank) secretion generated in response to specific antigens.
Ig
What are these?
antibodies to immunoglobulins protein A of Staphylococcus aureus
some lipopolysaccharides of Gram negative bacteria
virions of Epstein Barr Virus (EBV).
B cell POLYCLONAL mitogens
What makes a B cell mitogen polyclonal?
it stimulates ALL B cells to divide, whereas monoclonal mitogens stimulate only specfiic B cells to divide
Keep in mind that lymphocyte trafficking is controlled. Lymphocytes enter tissues in response to infection and inflammation, and respond to changes in (blank) in the tissues
cell surface expression of integrins and selectin adhesion molecules
