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Block F: Immunnology > Lymphoid system > Flashcards

Lymphoid system Flashcards

1
Q

What is a lymphoma?

A

Solid malignancy of lymphoid cells with the primary site in lymphoid organs (lymph nodes, GI tract, skin, CNS) with a common leukemic counterpart

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2
Q

What are germinal centers?

A

Germinal centers are sites within secondary lymphoid organs – lymph nodes and the spleen – where mature B cells proliferate, differentiate, and mutate their antibody genes

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3
Q

Immunochemistry for Hodgkin lymphomas: Nodular lymphocyte predominant? (5)

A
  • Positive: CD20, CD45, BCL6

* Negative: CD15, CD30

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4
Q

Grades and treatments for Follicular lymphoma? (2)

A

 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

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5
Q

What is found in the lymph nodes paracortex? (3)

A

• Paracortex: mostly T-cells and interdigitating dendritic cells (IDCs). This is the site of high endothelial venules (HEVs)

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6
Q

Where does the secondary immune response occur? (3)

A

o The paracortex of the lymph nodes
o Periarteriolar sheath of spleen
o Extranodal sites

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7
Q

What are the etiologies of chronic non-specific lymphadenitis: follicular hyperplasia (B-cells)? (3)

A

 Etiology can be rheumatoid arthritis, toxoplasmosis, early HIV infection

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8
Q

What are the etiologies of chronic non-specific lymphadenitis: Paracortical hyperplasia (T-cells)/diffuse patterns? (2)

A

 Etiology: Epstein-Barr Virus, dermatopathic lymphadenopathy

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9
Q

In what phase of the germinal center reaction can we see an increase of affinity of antibodies for antigens?

A
  • Somatic hypermutation of Ig V region genes: this increase affinity of Ab for Ag
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10
Q

What are the two central lymphoid space? What do they do?

A 
	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
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11
Q

What happens in the lymph nodes cortex? (4)

A

• 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)

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12
Q

What is contained in central lymphoid medulla? (2)

A
  • Lymphocytes with mature T-cell immunophenotype (TdT, CD3+, CD4+, CD8+)
  • Hassall’s corpuscles (small spindle-shaped epithelial cells)
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13
Q

 Hodgkin, Reed-Sternberg cells, lacunar cells
 Male or females, 15-35yrs old
 Background cells: mostly CD4+ T-cells
Dx?

A

Classical Hodgkin lymphomas

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14
Q

Immunochemistry of lymphadenopathy: CD45-

A

Carcinomas

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15
Q

What are the functions of o Mucosa-associated lymphoid tissue (MALT) in the Waldeyer ring and peyer patches?

A
  • Defense of internal passages against foreign invaders

* Harbors 70% of body’s immune cells

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16
Q

Treatment for Diffuse Large B-Cell Lymphoma (DLBCL)?

A

 Chemo and adriamycin and rituximab, possible radiotherapy

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17
Q

Translocation t(8; 14) is indicative of what?

A

Burkitt lymphoma (MYC gene on 8)

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18
Q

Immunochemistry of lymphadenopathy: CD34

A

Mostly stem cells

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19
Q

Immunochemistry of lymphadenopathy: CD15, CD30

A

positive in Hodgkin lymphomas

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20
Q

Biomarkers of Diffuse Large B-Cell Lymphoma (DLBCL)? (2)

A

 CD20+, High Ki67 proliferation rate

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21
Q

Immunochemistry of lymphadenopathy: CD5

A

Mostly T-cells lymphomas, but also for some B-cells lymphomas

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22
Q

What are the etiologies of chronic non-specific lymphadenitis: Granulomatous with abscesses? (2)

A

 Etiology is cat scratch or tularemia

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23
Q

What happens during the “differentiation step” of the germinal center reaction?

A

o Maturing B cells become memory cells and plasma cells

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24
Q

Immunochemistry of lymphadenopathy: Ki67

A

Proliferation marker

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25
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
26
What is present in the primary lymphoid organs perivascular space?
 Contains mature naïve T-lymphocytes, CD4+ or CD8+ that travel to lymph nodes
27
Immunochemistry of lymphadenopathy: CD5, CD20 indicate what?
Malignancy
28
Immunochemistry of lymphadenopathy: CD45+?
Lymphoma
29
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
30
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
31
What are the three structures of the lymph nodes?
Cortex Paracortex Medulla
32
Immunochemistry for Classical Hodgkin lymphomas? (4)
* Positive: CD15, CD30 | * Negative: CD20 CD45
33
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
34
What are the secondary (peripheral) lymphoid organs? (3)
Lymph nodes Spleen Mucosa-associated lymphoid tissue (MALT) in the Waldeyer ring and peyer patches
35
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
36
Immunochemistry of lymphadenopathy: CD3+
T cell marker
37
Immunochemistry of lymphadenopathy: CD10+?
B cell submarker CD10: indicative of germinal center marker + lymphoblastic
38
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
39
Where are B cells made?
Bone marrow
40
Where in the lymph nodes is the metastases are most commonly found?
 Metastases are mostly found in the subcapsular sinus
41
Immunochemistry of lymphadenopathy: CD19, CD20?
B cell markers
42
Spleen parenchyma is composed of what? (2)
 White pulp: lymphoid nodules and periarteriolar lymphoid sheaths  Rep pulp: blood filled sinusoids and splenic cords
43
Immunochemistry of lymphadenopathy: BCL2
Anti-apoptotic protein; follicular lymphomas
44
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
45
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
46
Immunochemistry of Mature T- and NK-cell lymphoma? (4)
 CD2, CD3, CD5 |  CD4:CD8 irregular ratio
47
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
48
What is the etiology of chronic non-specific lymphadenitis: Sinus histiocytosis?
Etiology is not specific, often near cancers
49
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
50
Lymph nodes medulla contains what? (2)
o Medullary cords: B- and T-lymphocytes and plasma cells | o Medullary sinuses
51
 L&H cells (popcorn), Hodgkin, Reed-Sternberg cells  Background cells: B-cells  Mostly males 30-50yrs old Dx?
Hodgkin lymphomas: Nodular lymphocyte predominant
52
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 ```
53
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
54
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
55
Etiologies of Mature T- and NK-cell lymphoma?
Etiology: EBV, HTLV-1
56
What are the etiologies of chronic non-specific lymphadenitis: Granulomatous (2)
 Etiology: mycobacteria or sarcoidosis
57
Biomarkers for Follicular lymphoma? (3)
 CD10, CD20, BCL2
58
Immunochemistry of lymphadenopathy: BCL6+?
B cell submarker BCL6: indicative of germinal center marker
59
What are the primary (central) lymphoid organs? (2)
Bone marrow and thymus
60
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)
61
Treatment for Non-Hodgkin Lymphomas?
Anti-CD20 Ab (rituximab)
62
Cell characteristics of Mature T- and NK-cell lymphoma
Heterogenous population of cells: atypical large, medium, small…
63
Immunochemistry of lymphadenopathy: CD4+
T cell submarker: helper T-cell
64
 Monomorphic small round B-lymphocytes in the blood, marrow, spleen, lymph nodes  Larger prolymphocytes  Positive for CD20, CD23, CD5 Dx?
Leukemia
65
Biomarker of Non-Hodgkin Lymphomas?
CD20
66
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
67
Immunochemistry of lymphadenopathy: CD138
Kappa & lambda light chains; plasma cells
68
Clinical features of Mature T- and NK-cell lymphoma?
Clinical features: adenopathy, variable mixture of lymphoma and leukemia
69
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
70
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
71
What is lymphadenopathy?
Disease of lymph nodes characterised by their enlargement
72
Translocation t(14; 18) is indicative of what?
Follicular lymphomas (IhG on 14 to BCL2 on 18)
73
Immunochemistry of lymphadenopathy: CD8
T cell submarker: cytotoxic T-cells
74
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 ```

Block F: Immunnology (9 decks)

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