Introduction and Overview of Lymphoid Neoplasms Flashcards
What cells make up the
innate immune system ?
- NK cells
- NK-like cells (CD3 and CD56 +)
- Gamma delta T cells
They are important in mucosal and cutaneous defences
They do not encounter antigens and the MHC molecules so do not need APC cells.
What is the definition of
naive B cells ?
- often CD5 positive
- small resting lymphocytes that circulate in the PB and also occupy primary lymphoid follicles and follicle mantle zones
What neoplasm arises from bone marrow
precursor B cells ?
- B lymphoblastic leukemia/lymphoma
- the precursors seen in the BM include:
- Progenitor B cells
- Pre-B cell
- Immature B cell
What neoplasms arise from
cells in the interfollicular area of
peripheral lymphoid tissue ?
- Mantle cell lymphoma
- pre-GC lymphoma
- Cells included in normal interfollicular areas:
- Naive B cells
- Extrafollicular B blast
- short-lived plasma cell
What lymphomas arise from the germinal
center cells ?
- Follicular lymphoma
- Burkitt lymphoma
- DLBCL (some)
- Hodgkin Lymphoma
What neoplasms arise from the post
GC cells?
- Marginal zone, MALT lymphomas
- LPL
- CLL/SLL
- DLBCL (some)
- Plasma cell myeloma
- Post GC cells include:
- long lived plasma cells
- memory B cells (marginal zone)
What cells normally express
IRF4/MUM1?
- late centrocytes and plasma cells
- centrocytes after interaction with FDCs and antigens turn of BCL6 and differentiate into memory B cells and plasma cells
- expression of BCL6 and MUM1 are opposite
What is the normal role of MYC
in B cell maturation ?
- MYC is upregulated upon interaction of naive B cells with antigen and T cells by the action of BCL6
- MYC is essential for germinal center formation
- In normal reactive lymph nodes MYC highlights a population of centrocytes in the light zone of the germinal center.
- it is repressed in the dark zone
Note: BCL6 gets switched off by centrocytes when they differentiate into memory B cells or plasma cells
Where can post-germinal center B
cells be found in the body ?
- these are memory B cells
- they circulate in the:
- PB
- some are found in marginal zones of lymph nodes, spleen, and mucosa-associated lymphoid tissue (MALT)
- Marginal zone B cells usually express pan B cell antigens with IgM (only low levels of IgD)
- they are negative for CD5 and CD10
Note: plasma cells home to the bone marrow
What are the markers typically seen on
post-germinal center plasma cells ?
- IgG or IgA cytoplasmic immunoglobulins
- lack surface Ig and CD20
- positive for IRF4, CD79a, CD38 and CD138
IMP: both memory B cells and plasma cells have mutated IGV genes but no do not continue to undergo mutation
What is the immunoprofile of cortical thymocytes ?
- immature T cell phenotype
- (+) TdT, CD1a, CD3, CD5, and CD7
- CD3 is first expressed in the cytoplasm prior to complete T cell gene rearrangement and export to the cell membrane
- double negative for CD4 and CD8
Note: T lymphocytes develop in the bone marrow and then move to the thymus to undergo maturation
What is known about medullary thymocytes ?
- similar immunophenotype to mature T cells
- there are 2 classes of T cells
- alpha beta
- gamma delta
- distinction is based no structure of the T cell receptor
- both are associated with the CD3 complex, which contains gamma, delta and epsilon chains
How are NK cells different ?
- they do not have a complete T cell receptor complex
- only express the epsilon and zeta chains of CD3 in their cytoplasm
- positive for:
- CD2, CD7 and sometimes CD8 but surface CD3 is negative
- CD16 and CD56 with variable expression of CD57
- they have cytoplasmic cytotoxic granules
How do NK cells kill their targets ?
- they kill them through an antibody-mediated cell toxicity mechanism
- OR
- mechanism that involves the killer cell immunoglobulin like receptors (KIRS)
What neoplasms arise from the innate
lymphoid cells ?
- aggressive NK cell leukemia
- systemic EBV positive T cell lymphoma of childhood
- hepatosplenic gamma delta T cell lymphoma
- gamma delta T cell lymphoma arising in mucosal sites
What is the immunophenotype of gamma delta cells ?
- lack expression of CD4, CD8 and CD5
- account for <5% of all normal T cells
- they have a restricted distribution
- found mainly in splenic red pulp, intestinal epithelium, and other epithelial sites
- first line of defense against bacterial peptides and major component against immunity against mycobacteria and mucosal infections
What are the T cells of the adaptive immune system ?
- heterogeneous and very complex system
- Naive T cells
- Effector T cells
- regulatory and cytotoxic
- Memory T cells
Note: T cell lymphomas of the adaptive immune system primarily occur in adults and are mainly nodal. Innate lymphomas tend to be in younger people and extranodal.
What do we know about CD4+ T cells?
- these are primarily regulatory and act via cytokine production
- they are divided into 2 groups
- T helper 1
- secrete IL2 and interferon gamma but not IL4, IL5 or IL6
- provide help mainly to other T cells and macrophages
- T helper 2
- secrete IL4, IL5, IL6, and IL10
- help B cells and are key to antibody production
- T helper 1
IMP: CD4 + T cells can act both to help and to suppress immune responses and consist of multiple subpopulations
What is the purpose of T regulatory cells?
- they have many functions including suppressing the immune response to cancer and limiting inflammatory responses in tissues
- thought to prevent autoimmunity
- CD4+ T cells
- Immunophenotype expression:
- CD25
- FOXP3
- CD4
- ATLL has been linked to T regulatory cells
- has associated with marked immunosuppression
What are the T helper 17 cells?
- they are a recently identified subset of CD4+ effector T cells
- they express IL17
- important role in immune-mediated inflammtory diseases and in other conditions
What are T follicular helper cells?
- they are a CD4+ subset of T cells
- they are found in normal germinal centers
- they provide assistance to B cells in the germinal center reactions
- Unique immunophenotype:
- BCL6 and CD10
- CD4, CD57, PD1 and CXCL13
- Note: CXCL13
- causes induction and proliferation of follicular dendritic cells
- facilitates migration of B and T cells expressing CXCR5 in the germinal centers
What is the role of CXCL13 ?
- causes induction and proliferation of follicular dendritic cells
- also facilitates the migration of B cells and T cells expressing CXCR5 into the germinal center
What are two neoplasms with a T follicular helper cell immunophenotype ?
- AITL
- Primary cutaneous CD4+ small/medium T cell lymphoproliferative disorder
What T cells are antigen independent ?
- prothymocyte
- subcapsular thymocyte
- cortical thymocytes
- medullary thymocytes
What are the antigen dependent T cells ?
- Peripheral T cell
- Follicular T helper cell
- T-regulatory cell
- TH1
- TH2
- TH17
