Lymphoid system Flashcards
What is a lymphoma?
Solid malignancy of lymphoid cells with the primary site in lymphoid organs (lymph nodes, GI tract, skin, CNS) with a common leukemic counterpart
What are germinal centers?
Germinal centers are sites within secondary lymphoid organs – lymph nodes and the spleen – where mature B cells proliferate, differentiate, and mutate their antibody genes
Immunochemistry for Hodgkin lymphomas: Nodular lymphocyte predominant? (5)
- Positive: CD20, CD45, BCL6
* Negative: CD15, CD30
Grades and treatments for Follicular lymphoma? (2)
Low grade 1 and 2: <15 centroblasts per high power field
• Treatment: watch and wait, or chemo with rituximab
High grade 3A, B: >15 centroblasts per high power field. Bone marrow is involved
• Treatment: chemo and adriamycin and rituximab
What is found in the lymph nodes paracortex? (3)
• Paracortex: mostly T-cells and interdigitating dendritic cells (IDCs). This is the site of high endothelial venules (HEVs)
Where does the secondary immune response occur? (3)
o The paracortex of the lymph nodes
o Periarteriolar sheath of spleen
o Extranodal sites
What are the etiologies of chronic non-specific lymphadenitis: follicular hyperplasia (B-cells)? (3)
Etiology can be rheumatoid arthritis, toxoplasmosis, early HIV infection
What are the etiologies of chronic non-specific lymphadenitis: Paracortical hyperplasia (T-cells)/diffuse patterns? (2)
Etiology: Epstein-Barr Virus, dermatopathic lymphadenopathy
In what phase of the germinal center reaction can we see an increase of affinity of antibodies for antigens?
- Somatic hypermutation of Ig V region genes: this increase affinity of Ab for Ag
What are the two central lymphoid space? What do they do?
Cortex, which makes a positive selection for the survival of T-cells with function T-cell receptors (TCRs) recognizing MHC class I and class II molecules Medulla, which make a negative selection that allows the survival of T-cells that don’t bind tightly to self-antigens
What happens in the lymph nodes cortex? (4)
• Cortex: mostly B-cells, will form in germinal centers with Ag stimulation. Germinal centers is the site where:
o Centrocytes and centroblasts are activated
o Production of helper CD4+ T-cells
o Production of Follicular dendritic cells (APCs)
What is contained in central lymphoid medulla? (2)
- Lymphocytes with mature T-cell immunophenotype (TdT, CD3+, CD4+, CD8+)
- Hassall’s corpuscles (small spindle-shaped epithelial cells)
Hodgkin, Reed-Sternberg cells, lacunar cells
Male or females, 15-35yrs old
Background cells: mostly CD4+ T-cells
Dx?
Classical Hodgkin lymphomas
Immunochemistry of lymphadenopathy: CD45-
Carcinomas
What are the functions of o Mucosa-associated lymphoid tissue (MALT) in the Waldeyer ring and peyer patches?
- Defense of internal passages against foreign invaders
* Harbors 70% of body’s immune cells
Treatment for Diffuse Large B-Cell Lymphoma (DLBCL)?
Chemo and adriamycin and rituximab, possible radiotherapy
Translocation t(8; 14) is indicative of what?
Burkitt lymphoma (MYC gene on 8)
Immunochemistry of lymphadenopathy: CD34
Mostly stem cells
Immunochemistry of lymphadenopathy: CD15, CD30
positive in Hodgkin lymphomas
Biomarkers of Diffuse Large B-Cell Lymphoma (DLBCL)? (2)
CD20+, High Ki67 proliferation rate
Immunochemistry of lymphadenopathy: CD5
Mostly T-cells lymphomas, but also for some B-cells lymphomas
What are the etiologies of chronic non-specific lymphadenitis: Granulomatous with abscesses? (2)
Etiology is cat scratch or tularemia
What happens during the “differentiation step” of the germinal center reaction?
o Maturing B cells become memory cells and plasma cells
Immunochemistry of lymphadenopathy: Ki67
Proliferation marker
What happens during the “selection step” of the germinal center reaction? (4)
o Centroblasts mature centrocytes light zone of germinal center
o Ig heavy chain switch from IgM to IgG or IgA
o Centrocytes with high affinity ot Ag bind to it, interact with T-cells and are rescued from apoptosis
o Centrocytes with low affinity undergo apoptosis
What is present in the primary lymphoid organs perivascular space?
Contains mature naïve T-lymphocytes, CD4+ or CD8+ that travel to lymph nodes
Immunochemistry of lymphadenopathy: CD5, CD20 indicate what?
Malignancy
Immunochemistry of lymphadenopathy: CD45+?
Lymphoma
Possible sources of non-hodgkin lymphomas? (4)
o Derived from precursor B- or T-cells
B-lymphoblastic: develop in bone marrow with leukemia, common in children
T-lymphoblastic: develop in thymus, mostly a mass
o Derived from mature T-cells
o Derived from mature B-cells: most common, and better response to treatment. Often with leukemia
What is Plasma cell neoplasms/myeloma? What does it include? (3)
Plasma cell neoplasms/myeloma: clonal expansion of immunoglobulin (Ig)-secreting plasma cells
This includes:
- Multiple Myeloma (aka, plasma cell neoplasm and end-organ damage)
- Plasmacytoma (solitary lesion)
- Monoclonal gammopathy
What are the three structures of the lymph nodes?
Cortex
Paracortex
Medulla
Immunochemistry for Classical Hodgkin lymphomas? (4)
- Positive: CD15, CD30
* Negative: CD20 CD45
Whare are T cells made? What are their two functions?
Made in thymus. T-lymphoblasts from marrow migrate and proliferate in thymic epithelial space to become naïve T-cells
Functions:
Induction of central tolerance to prevent autoimmunity (regulatory T cells)
Maturation and selection of T-lymphoblasts into mature naïve T-cells
What are the secondary (peripheral) lymphoid organs? (3)
Lymph nodes
Spleen
Mucosa-associated lymphoid tissue (MALT) in the Waldeyer ring and peyer patches
What are the different grades of non-hodgkin lymphomas? (4, avec les lymphomas associés)
Low grade: CLL, FL, MZL
“Bogus” low grade: mantle cell
Fairly high grade: Diffuse Large B-Cell Lymphoma (DLBCL)
Very high grade: Burkitt
Immunochemistry of lymphadenopathy: CD3+
T cell marker
Immunochemistry of lymphadenopathy: CD10+?
B cell submarker CD10: indicative of germinal center marker + lymphoblastic
What happens during the “proliferation step” of the germinal center reaction? (3)
- Proliferation: occur in “dark zone“ of germinal center
o Mature peripheral B cells known as follicular (Fo) B cells acquire antigen from FDCs and in turn present it to cognate CD4+ TFH cells at the border that demarcates the T cell zone and B cell follicles
o Inactivation of BCL2 anti-apoptotic gene (apoptosis is facilitated)
o Macrophages eat apoptotic cells
Where are B cells made?
Bone marrow
Where in the lymph nodes is the metastases are most commonly found?
Metastases are mostly found in the subcapsular sinus
Immunochemistry of lymphadenopathy: CD19, CD20?
B cell markers
Spleen parenchyma is composed of what? (2)
White pulp: lymphoid nodules and periarteriolar lymphoid sheaths
Rep pulp: blood filled sinusoids and splenic cords
Immunochemistry of lymphadenopathy: BCL2
Anti-apoptotic protein; follicular lymphomas
What is contained in central lymphoid cortex? (3)
- Cortical epithelial cells that form the cortico-medullary barrier, function as APCs (secrete cytokines)
- Macrophages
- T-lymphoblasts = thymocytes = precursor T-cells
Where do the B- and T-cells enter the lymph nodes?
Naïve B- and T-cells enter the node via high endothelial venules (HEVs). They are an important source of IgG and IgM
Immunochemistry of Mature T- and NK-cell lymphoma? (4)
CD2, CD3, CD5
CD4:CD8 irregular ratio
What is Follicular lymphoma?
A subtype of Non-Hodgkin caused by constitutive inhibition of apoptosis due to translocation of IGH gene placed on chromosome 14 and BCL2 placed on chromosome 18
What is the etiology of chronic non-specific lymphadenitis: Sinus histiocytosis?
Etiology is not specific, often near cancers
What is the early primary immune response? Where does it happens and what are the steps? (2)
Early primary immune response: first B-cell response
- Occur in paracortex of lymph node
- T-cell independent activation of naïve B-cells to B-immunoblasts. This activates short-lives IgM-secreting plasma cells (no memory cells)
- Come of IgM+ B-blasts migrate to primary B-follicle to initiate the secondary response
Lymph nodes medulla contains what? (2)
o Medullary cords: B- and T-lymphocytes and plasma cells
o Medullary sinuses
L&H cells (popcorn), Hodgkin, Reed-Sternberg cells
Background cells: B-cells
Mostly males 30-50yrs old
Dx?
Hodgkin lymphomas: Nodular lymphocyte predominant
Within the reactive lymphadenopathies, what are the five histological patterns of Chronic non-specific lymphadenitis?
o Follicular hyperplasia (B-cells) o Paracortical hyperplasia (T-cells)/diffuse patterns o Sinus histiocytosis o Granulomatous o Granulomatous with abscesses
At the end of the secondary immune response, mature T-cells become what? (4)
o Mature T-cell then becomes T-immunoblast and become:
Effector CD4+ helper cells
Effector CD8+ cytotoxic cells
Memory T-cells
Pathology/clinical aspects of Plasma cell neoplasms/myeloma with respect to neoplastic plasma cells? (2patho, 3 clinical)
o Pathology:
Suppress production of normal Ig heavy chains
Stimulate osteoclastic bone resorption via interleukin-6 (IL-6), IL-1b, TNF-alpha
o Clinical:
Lowered humoral immunity; recurrent bacterial infection
Lytic bone lesions
Hypercalcemia with neurologic signs and renal failure
Etiologies of Mature T- and NK-cell lymphoma?
Etiology: EBV, HTLV-1
What are the etiologies of chronic non-specific lymphadenitis: Granulomatous (2)
Etiology: mycobacteria or sarcoidosis
Biomarkers for Follicular lymphoma? (3)
CD10, CD20, BCL2
Immunochemistry of lymphadenopathy: BCL6+?
B cell submarker BCL6: indicative of germinal center marker
What are the primary (central) lymphoid organs? (2)
Bone marrow and thymus
What do plasma cells do? What are the three subtypes?
Plasma cells: travel to medulla of lymph node, or bone marrow to produce the antibodies
- IgM-secreting plasma cells (short lived)
- IgA, IgG-secreting plasma cells (long lived)
Each single plasma cell secretes either kappa of lambda light chain and only one heavy chain (IgG, IgA…)
Plasma cells in a normal lymph node are polyconal (mix of kappa and lambda secreting)
Treatment for Non-Hodgkin Lymphomas?
Anti-CD20 Ab (rituximab)
Cell characteristics of Mature T- and NK-cell lymphoma
Heterogenous population of cells: atypical large, medium, small…
Immunochemistry of lymphadenopathy: CD4+
T cell submarker: helper T-cell
Monomorphic small round B-lymphocytes in the blood, marrow, spleen, lymph nodes
Larger prolymphocytes
Positive for CD20, CD23, CD5
Dx?
Leukemia
Biomarker of Non-Hodgkin Lymphomas?
CD20
Pathology/clinical aspects of Plasma cell neoplasms/myeloma with respect to bone? (1patho, 3 clinical)
o Pathology: infiltration of bone and marrow by neoplastic plasma cells
o Clinical:
Bone pain, of bone lesions
Anemia
Cells secrete M and Bence Jones proteins
Immunochemistry of lymphadenopathy: CD138
Kappa & lambda light chains; plasma cells
Clinical features of Mature T- and NK-cell lymphoma?
Clinical features: adenopathy, variable mixture of lymphoma and leukemia
Characteristics of Non-Hodgkin lymphomas? (4)
o Involve multiple lymph nodes, in a non-contiguous spread
o Mesenteric nodes and Waldeyer ring often involved
o Often with leukemia
o Numerous malignant cells forming sheets, with reactive cells not prominent generally
Secondary immune response requires what? What are the steps before a change in the mature T-cells occur?
- Requires cytokines +BCL6 and CD10 to occur
- Ag is presented to T-cells by APCs CD4 or CD8 on T-cells bind to MHC class II or class I respectively on APCs
What is lymphadenopathy?
Disease of lymph nodes characterised by their enlargement
Translocation t(14; 18) is indicative of what?
Follicular lymphomas (IhG on 14 to BCL2 on 18)
Immunochemistry of lymphadenopathy: CD8
T cell submarker: cytotoxic T-cells
What are Hodgkin lymphomas? What are the two types?
Malignant cells (“Reed-Sternberg” or other “Hodgkin” cells) from germinal center B-cells with numerous reactive cells Subtypes are: Classical and Nodular lymphocyte predominant
