Haem: Lymphoma MDT Pt.1 Flashcards
Outline the difference in prevalence of Hodgkin’s lymphoma and Non-Hodgkin lymphoma.
- NHL = 80%
- Hodgkin = 20%
Outline the processes by which immunoglobulins and T cell receptors become capable of identifying a wide variety of antigens.
- The germline VDJ genes undergo recombination in the bone marrow to generate a wide repertoire of specificities.
- In germinal centres, a second stage of DNA alteration involving isotype switching and somatic hypermutation (point mutations) generates even more diversity.
Which proteins carry out VDJ recombination and somatic hypermutation
VDJ recombination: RAG1 and RAG2 combine to form RAG complex
SHM: activation induced cytidine deaminase
What is the main downside of the processes that generate variety in immunoglobulins and TCR during the adaptive immune response?
Recombination errors and new point mutations can occur
Lymphocytes are reliant on apoptosis to keep their massive proliferation under control (90% of lymphocytes die in the germinal centre)
- If a mutation turns off apoptosis, it can lead to malignancy or autoimmunity
Rapid proliferation within germinal centres - increased risk of DNA replication errors
Outline how chromosomal translocations in B cells can lead to malignancy.
- Immunoglobulin gene promoters in B cells are highly active because they are designed to produce loads of immunoglobulin
- If an error occurs and an oncogene is translocated downstream of the promoter, malignant genes can be expressed
List some oncogenes that are implicated in lymphoma/leukaemia.
- Bcl2
- Bcl6
- Cyclin D1
- c-Myc
List some risk factors that contribute to the aetiology of NHL.
- Constant antigenic stimulation
- Viral infection
- Loss of T cell function (immunosuppression)
List some examples of how constant antigenic stimulation can lead to lymphoma.
- H. pylori → gastric MALT - marginal zone NHL of the stomach
- Sjogren syndrome → marginal zone NHL of the parotid
- Coeliac disease → small bowel T cell lymphoma, enteropathy-associated T cell NHL
Give an example of how viral infections that can lead to lymphoma.
Direct viral integration: HTLV1
- HTLV1 infects T cells by vertical transmission
- Viral genome integrates into T cell genome and drives proliferation
- May cause adult T cell leukaemia/lymphoma (very aggressive)
Give an example of how loss of T cell function can lead to lymphoma
EBV infection and immunosuppression
- EBV established latent infection in B cells which is kept in check by cytotoxic T cell (kill EBV antigen-expressing B cells)
- Loss of T cell function (e.g. HIV, post-transplant immunosuppression) can lead to EBV-driven lymphoma
List some different types of tissues of the lymphoreticular system.
- Generative tissue: bone marrow and thymus (generates or matures lymphoid cells)
- Reactive tissue: lymph nodes and spleen (development of immune reaction)
- Acquired tissue: extra-nodal lymphoid tissue (e.g. skin, stomach, lung - responsible for developing a local immune response)
List the different cell types of the lymphoreticular system.
Lymphocytes
- B cells
- T cells
Accessory cells
- Antigen-presenting cells
- Macrophages
- Connective tissue cells
Describe the normal histological appearance of a lymph node.
Round areas full of B cells (B cell follicles)
- Mantle zone - a crescent-shaped region where naïve unstimulated B cells are found
- Germinal centre - where naïve B cells will eventually migrate, and mature B cells will end up in the medulla.
- Antigen presenting cells present antigens to B cells in germinal centre to activate them
Paracortical T cell zone - surrounds the B cell follicles
Describe the composition of T cell areas in lymph nodes.
- Consists of lots of T cells, antigen-presenting cells and high-endothelial venules
- This is the site where T cells bind to antigens and are selected/activated
What is the main technique used to identify different types of lymphocyte within a lymph node biopsy?
Immunohistochemistry
