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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
Q

What happens during the “selection step” of the germinal center reaction? (4)

A

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

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26
Q

What is present in the primary lymphoid organs perivascular space?

A

 Contains mature naïve T-lymphocytes, CD4+ or CD8+ that travel to lymph nodes

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27
Q

Immunochemistry of lymphadenopathy: CD5, CD20 indicate what?

A

Malignancy

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28
Q

Immunochemistry of lymphadenopathy: CD45+?

A

Lymphoma

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29
Q

Possible sources of non-hodgkin lymphomas? (4)

A

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

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30
Q

What is Plasma cell neoplasms/myeloma? What does it include? (3)

A

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
Q

What are the three structures of the lymph nodes?

A

Cortex
Paracortex
Medulla

32
Q

Immunochemistry for Classical Hodgkin lymphomas? (4)

A
  • Positive: CD15, CD30

* Negative: CD20 CD45

33
Q

Whare are T cells made? What are their two functions?

A

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
Q

What are the secondary (peripheral) lymphoid organs? (3)

A

Lymph nodes
Spleen
Mucosa-associated lymphoid tissue (MALT) in the Waldeyer ring and peyer patches

35
Q

What are the different grades of non-hodgkin lymphomas? (4, avec les lymphomas associés)

A

 Low grade: CLL, FL, MZL
 “Bogus” low grade: mantle cell
 Fairly high grade: Diffuse Large B-Cell Lymphoma (DLBCL)
 Very high grade: Burkitt

36
Q

Immunochemistry of lymphadenopathy: CD3+

A

T cell marker

37
Q

Immunochemistry of lymphadenopathy: CD10+?

A

B cell submarker CD10: indicative of germinal center marker + lymphoblastic

38
Q

What happens during the “proliferation step” of the germinal center reaction? (3)

A
  • 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
Q

Where are B cells made?

A

Bone marrow

40
Q

Where in the lymph nodes is the metastases are most commonly found?

A

 Metastases are mostly found in the subcapsular sinus

41
Q

Immunochemistry of lymphadenopathy: CD19, CD20?

A

B cell markers

42
Q

Spleen parenchyma is composed of what? (2)

A

 White pulp: lymphoid nodules and periarteriolar lymphoid sheaths
 Rep pulp: blood filled sinusoids and splenic cords

43
Q

Immunochemistry of lymphadenopathy: BCL2

A

Anti-apoptotic protein; follicular lymphomas

44
Q

What is contained in central lymphoid cortex? (3)

A
  • Cortical epithelial cells that form the cortico-medullary barrier, function as APCs (secrete cytokines)
  • Macrophages
  • T-lymphoblasts = thymocytes = precursor T-cells
45
Q

Where do the B- and T-cells enter the lymph nodes?

A

 Naïve B- and T-cells enter the node via high endothelial venules (HEVs). They are an important source of IgG and IgM

46
Q

Immunochemistry of Mature T- and NK-cell lymphoma? (4)

A

 CD2, CD3, CD5

 CD4:CD8 irregular ratio

47
Q

What is Follicular lymphoma?

A

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
Q

What is the etiology of chronic non-specific lymphadenitis: Sinus histiocytosis?

A

Etiology is not specific, often near cancers

49
Q

What is the early primary immune response? Where does it happens and what are the steps? (2)

A

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
Q

Lymph nodes medulla contains what? (2)

A

o Medullary cords: B- and T-lymphocytes and plasma cells

o Medullary sinuses

51
Q

 L&H cells (popcorn), Hodgkin, Reed-Sternberg cells
 Background cells: B-cells
 Mostly males 30-50yrs old
Dx?

A

Hodgkin lymphomas: Nodular lymphocyte predominant

52
Q

Within the reactive lymphadenopathies, what are the five histological patterns of Chronic non-specific lymphadenitis?

A 
o	Follicular hyperplasia (B-cells)
o	Paracortical hyperplasia (T-cells)/diffuse patterns
o	Sinus histiocytosis
o	Granulomatous
o	Granulomatous with abscesses
53
Q

At the end of the secondary immune response, mature T-cells become what? (4)

A

o Mature T-cell then becomes T-immunoblast and become:
 Effector CD4+ helper cells
 Effector CD8+ cytotoxic cells
 Memory T-cells

54
Q

Pathology/clinical aspects of Plasma cell neoplasms/myeloma with respect to neoplastic plasma cells? (2patho, 3 clinical)

A

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
Q

Etiologies of Mature T- and NK-cell lymphoma?

A

Etiology: EBV, HTLV-1

56
Q

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

A

 Etiology: mycobacteria or sarcoidosis

57
Q

Biomarkers for Follicular lymphoma? (3)

A

 CD10, CD20, BCL2

58
Q

Immunochemistry of lymphadenopathy: BCL6+?

A

B cell submarker BCL6: indicative of germinal center marker

59
Q

What are the primary (central) lymphoid organs? (2)

A

Bone marrow and thymus

60
Q

What do plasma cells do? What are the three subtypes?

A

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
Q

Treatment for Non-Hodgkin Lymphomas?

A

Anti-CD20 Ab (rituximab)

62
Q

Cell characteristics of Mature T- and NK-cell lymphoma

A

Heterogenous population of cells: atypical large, medium, small…

63
Q

Immunochemistry of lymphadenopathy: CD4+

A

T cell submarker: helper T-cell

64
Q

 Monomorphic small round B-lymphocytes in the blood, marrow, spleen, lymph nodes
 Larger prolymphocytes
 Positive for CD20, CD23, CD5
Dx?

A

Leukemia

65
Q

Biomarker of Non-Hodgkin Lymphomas?

A

CD20

66
Q

Pathology/clinical aspects of Plasma cell neoplasms/myeloma with respect to bone? (1patho, 3 clinical)

A

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
Q

Immunochemistry of lymphadenopathy: CD138

A

Kappa & lambda light chains; plasma cells

68
Q

Clinical features of Mature T- and NK-cell lymphoma?

A

Clinical features: adenopathy, variable mixture of lymphoma and leukemia

69
Q

Characteristics of Non-Hodgkin lymphomas? (4)

A

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
Q

Secondary immune response requires what? What are the steps before a change in the mature T-cells occur?

A
  • 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
Q

What is lymphadenopathy?

A

Disease of lymph nodes characterised by their enlargement

72
Q

Translocation t(14; 18) is indicative of what?

A

Follicular lymphomas (IhG on 14 to BCL2 on 18)

73
Q

Immunochemistry of lymphadenopathy: CD8

A

T cell submarker: cytotoxic T-cells

74
Q

What are Hodgkin lymphomas? What are the two types?

A 
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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