Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
28 Cards in this Set
- Front
- Back
|
Primary and secondary lymphoid tissues
|
Primary
-bone marrow -thymus Secondary: -lymph nodes -spleen -tonsils -clusters in GI and pulmonary tracks |
|
|
Normal B cell development
|
Mature in the bone marrow
Enter the peripheral blood circulation and migrate to secondary lymphoid tissues |
|
|
Lymph node anatomy
|
Cortex:
-Primary follicles (naive B cells) -Secondary follicles (B cells proliferating after encountering an antigen, naive B cells get pushed to periphery) --Germinal center dark zone: centroblasts --Light zone: centrocytes --Tingible body macrophages destry B cells with "wrong" antibodies Paracortex -T cells -Antigen presenting dendritic cells -High endothelial venules Medulla -Plasma cells -Medullary sinuses Sinuses -Macrophages, histiocytes that capture antigen and process it |
|
|
Normal T cell development
|
Lymphoid stem cells migrate to thymus via the peripheral blood circulation
-Occurs even after puberty Cortex -Thymic epithelial cells interact with lymphocytes to help them differentiate --Physical and chemical interactions -Rapid proliferation (look like lymphoblasts) and move in toward medulla Medulla -Final development occurs here -Look like resting lymphocytes -Only 5% of the cells in the cortex make it this far (why?) |
|
|
T cell positive selection
|
Positive selection:
Thymic epithelial cell has an MHC (major histocompatibility complex) molecule on its surface TEC presents a peptide produced from processing an antigen Thymocyte recognizes the MHC protein (self) and the antigenic peptide (nonself) via the T cell receptor Signal for spontaneous apoptosis is turned off |
|
|
T cell negative selection
|
Central tolerance:
-Any thymocyte that has a high affinity for the self MHC molecule and a peptide found on the antigen presenting cells in the thymus gets apoptosis induced Peripheral tolerance: -Many tissue specific antigens are not present in the thymus -Similar mechanism that occurs outside the thymus, except: -Cells do not undergo apoptosis, but anergy (unresponsiveness) Why is this helpful? -Fewer autoimmune problems -Molecular mimicry may play a role |
|
|
T cell receptor genes and migration
|
If T cell receptor is produced from alpha and beta genes, then T cells primarily stay in thymus
If T cell receptor is produced from gamma and delta genes, then T cells primarmily migrate to various places in the body, such as the epithelium of the GI tract (to help with mucosal defenses) |
|
|
Leukemia vs lymphoma
|
Leukemia
-white blood -no matter how much lymph node/spleen involvement, if it is in the blood its still a leukemia Lymphoma -any lymphoma has the ability for the lymphocytes to begin circulating and become a leukemia CLL vs SLL Burkitt's leukemia vs Burkitt's lymphoma ALL vs Acute Lymphoblastic Lymphoma |
|
|
Follicular lymphoma epidemiology
|
Most common low grade non-Hodgkin lymphoma
-22% of all new NHL diagnoses Incidence increases with age -Median age 60-70 years of age |
|
|
Follicular lymphoma cytology
|
“Small cleaved cells”
Mature-appearing Flow cytometry: -CD20+ -CD10+ -bcl-2+ -CD5- B cell lineage |
|
|
Follicular lymphoma grading
|
Follicular lymphoma cells
consist of centrocytes, the small cleaved cells, and centroblasts, larger cells that divide more The larger the number of centroblasts, the more aggressive the follicular lymphoma Grade I: 0-5 centroblasts/hpf Grade II: 6-15 centroblasts/hpf Grade IIIa: centrocytes present Grade IIIb: solid sheets of centroblasts Acts more like intermediate grade lymphomas |
|
|
Follicular lymphoma and lymph node
|
Overall lymph node architecture is recognizable but…
Mantle zone is lost Follicles start to merge together Polarization of germinal center is lost Paracortex is lost |
|
|
Follicular lymphoma cytogenetics
|
Approximately 85% of patients with follicular lymphoma will have t(14;18)
-Up to 30% of DLBCL will have t(14;18) as well -Chromosome 14: IgH locus -Chromosome 18: bcl-2 locus May help in diagnosing but is not specific |
|
|
Follicular lymphoma treatment
|
Not curable
But is very treatable, ie: responsive to chemotherapy “Reset the clock”, “mow the grass” No definite standard of care Treatments may range from watchful waiting to stem cell transplantation |
|
|
FLIPI: Follicular Lymphoma International Prognostic Index
|
5 adverse prognostic factors:
-Age > 60 years -Ann Arbor Stage III-IV -Hb < 12 g/dl -Number of nodal areas >4 -LDH > upper limit of normal Risk group: Low -0-1 factors Intermediate -2 High - greater than or equal to 3 |
|
|
Diffuse Large B Cell Lymphoma: epidemiology
|
Most common of the intermediate grade lymphomas
Comprises ~30% of all new NHL diagnoses |
|
|
Diffuse Large B Cell Lymphoma: cytology
|
CD19+, CD20+
B cell lineage Cells are larger than a normal lymphocyte No standard cytogenetics Normal lymph node architecture is usually effaced Often very responsive to chemotherapy |
|
|
Diffuse Large B Cell Lymphoma treatment
|
R-CHOP
R: rituximab (Rituxan) C: cyclophosphamide (Cytoxan) H: Hydroxy-doxorubicin (doxorubicin) O: Oncovin (vincristine) P: Prednisone |
|
|
Diffuse Large B Cell Lymphoma: Prognostic Index
|
5 adverse prognostic factors:
-Age > 60 yo -ECOG > 2 -LDH > upper limit of normal ->1 extranodal site -Stage III/IV disease As # of factors increase, 4 year OS decreases |
|
|
Burkitt's lymphoma aggressiveness
|
One of the fastest growing tumors that exist
-Doubling time is 24 to 48 hours |
|
|
Burkitt's lymphoma: three types
|
African: affects jaw or facial bone
“American”, or endemic: affects lymph nodes in abdomen, GI tract Immunodeficiency-associated |
|
|
African Burkitt's lymphoma origin
|
High rates of Burkitt’s also had high rates of malaria
Children with sickle cell trait were mostly free of both malaria and Burkitt’s lymphoma Infection with malaria causes excess production of B cells, which are infected with EBV Tumor cells originate from a single EBV infected B cell |
|
|
African Burkitt's lymphoma epidemiology
|
Usually 4-7 years of age
Male : female 2:1 Incidence is 50 times higher than in US Involves bones of the jaw and other facial bones; kidneys, GI tract, other extranodal sites EBV is almost always found |
|
|
Sporadic/endemic/american Burkitt's lymphoma: epidemiology
|
Usually what we see in the US
Occurs worldwide regardless of climate Accounts for 1-2% of lymphomas in adults and up to 40% of lymphomas in children Involves the abdomen, ovaries, kidneys, omentum, Waldeyer’s ring, and other extranodal sites 15-30% of cases will be EBV(+) |
|
|
Immunodeficiency associated Burkitt's lymphoma
|
Primarily occurs in patients affected with HIV
Also seen in allograft recipients, congenital immunodeficiency states Accounts for 30-40% of all of NHL in HIV (+) patients Other AIDS-defining malignancies: -Kaposi’s sarcoma -Systemic NHL, primary effusion lymphoma, CNS lymphoma -Cervical cancer |
|
|
Burkitt's lymphoma cytology
|
Diagnose with tissue
Starry sky pattern ~100% Ki-67 staining (actively dividing) CD20(+), CD10(+), CD5(-) |
|
|
Burkitt's lymphoma cytogenetics
|
All have a cytogenetic abnormality involving chromosome 8: c-myc
-t(8;14): Ig heavy chain gene on chr 14 -t(2;8): Kappa light chain gene on chr 2 -t(8;22): Lambda light chain gene on chr 22 |
|
|
Burkitt's lymphoma treatment
|
Treatment must begin immediately
These patients are at extremely high risk for spontaneous tumor lysis syndrome Need intrathecal prophylaxis -penetrates BBB -CNS is a sanctuary site (so are testicles) |
