Lymph nodes Flashcards
What are lymph nodes?
Lymph nodes are secondary/peripheral lymphoid structures
They are ovoid, encapsulated collections of lymphoid tissue
What are the main primary lymphoid structures?
Bone marrow
Thymus
What are the main secondary lymphoid structures?
Lymph nodes
Tonsils
Spleen
Peyer’s patches
What are the 2 classes of node group location?
- Superficial
- Internal
Lymph drainage of the neck and lower face (Image)
Lymph drainage of the axilla (Image)
Lymph drainage of the inguinal region (Image)
Lymph drainage of the abdominal aorta and pelvic organs (Image)
What structure surrounds the lymph node?
Connective tissue capsule
Describe the movement of lymph through the lymph node
Afferent lymphatics ->
Sub-capsular sinus ->
Trabecular sinus ->
Medullary cords and sinuses ->
Hilum ->
Efferent lymphatics
What is the advantage of cell traffic within lymph nodes?
Cell traffic provides interactions for immune responses, allowing antigenic material to interact with fixed lymphoid tissue
What are the 3 main regions of the lymph node?
Cortex
Paracortex
Medulla
Describe the structure of the lymph node cortex
Nodules of B lymphocytes arranged in follicles
Describe the structure of the lymph node paracortex
Mainly contains T lymphocytes, forming inter-follicular tissue which surrounds follicles and extends out and merges with the medulla
Describe the structure of the lymph node medulla
Cords and sinuses draining into hilum
The medulla contains:
- Blood vessels
- Sinuses
- Medullary cords
- Medullary sinuses
What are the 2 classes of follicles within the lymph nodes?
Primary
Secondary
Describe the structure and function of pimrary follicles
Primary follicles have no germinal centre, and contain small quiescent lymphocytes which are yet to be stimulated
Describe the structure and function of secondary follicles
Secondary follicles contain a germinal centre in which B cells form their final form
These are active follicles, reacting to a stimulus
What is contained in medullary cords?
Plasma cells
B cells
Macrophages
What is contained in medullary sinuses?
Histiocytes
Reticular cells
What types of cells are present in lymph nodes?
Lymphocytes
Macrophages
APCs
Dendritic cells
Endothelial cells
What are some B cells present in the follicles of lymph nodes?
- Follicle centre cells
- Mantle cells
- Marginal cells
- Plasma cells
What are some B cells found between follicles in the lymph nodes?
- Post-germinal centre B cells
- Plasma cells
What is lymphadenopathy?
Lymphadenopathy is lymph node enlargement
What are some descriptions of location of lymphadenopathy?
Localised/Generalised
Peripheral/Central
What are some causes of lymphadenopathy?
Local inflammation
Systemic inflammation
Malignancy
Genetic or systemic disease
What are some possible causes of local inflammation in lymphadenopathy?
- Infection
- Vaccination
- Dermatopathic
What are some forms of infection that have distinct lymphadenopathies patterns?
TB
Toxoplasma
Cat scratch disease (Bartonella henselae)
What are some possible causes of systemic inflammation in lymphadenopathy?
Infection (E.g. viral)
Autoimmune/CT disorders
What are some possible causes of malignancy in lymphadenopathy?
Lymphoma
Leukaemia
Metastatic nodal spread
What are some genetic or systemic diseases that can lead to lymphadenopathy?
- Sarcoidosis
- Kikuchi’s lymphadenitis
- Castleman’s disease
- IgG4 related disease
What is meant by regional lymphadenopathy?
Regional lymphadenopathy is lymph node inflammation found only in one region of the body
What presentation may occur in regional, superficial lymph node infection?
Lymphangitis - red lines extending from an inflamed lymph node group
What is meant by sentinel node?
This is the first node to which a cancer will metastasise, which can be identified using dye or radioactive isotopes
What is meant by generalised lymphadenopathy?
Generalised lymphadenopathy is wide-spread around the body, in a number of locations
This suggests a systemic inflammatory, immunological process or widespread malignancy
What are the 4 main differentials in lymphadenopathy in order of likelihood?
- Bacterial infection (Regional)
- Viral infection (Generalised) - e.g. Glandular fever (EBV)
- Metastatic malignancy
- Lymphoma
What lymph nodes will breast cancer usually metastasise to?
Axillary lymph nodes
What lymph nodes will lung cancer usually metastasise to?
Neck and Virchow’s node (Supra-clavicular)
How will a lymph node feel in viral infection?
Tender
Hard
Smooth
Non-inflamed
Untethered
How will a lymph node feel in bacterial infection?
Tender
Hard
Smooth
Inflamed
Possibly tethered
How will a lymph node feel in lymphoma?
Non-tender
Rubbery
Smooth
Non-inflamed
Untethered
How will a lymph node feel in metastatic carcinoma?
Non-tender
Hard
Irregular
Un-inflamed
Tethered
What investigation technique is used in lymphadenopathy if suspicious of malignancy?
Whole lymph node biopsy
Why is fine needle aspiration not used in suspicious lymphadenopathy?
This will not provide enough tissue for all samples and for reliable samples
What tests can be performed on lymph node biopsy?
- Histology
- Immunohistochemistry of tissue (Solid sample)
- Immunophenotyping of blood or bone marrow (Liquid sample)
- Genetic analysis
- Molecular analysis
What is an example of a condition that can be diagnosed based on lymph node histology?
Nodular sclerosing Hodgkin’s lymphoma
What is involved in immunohistochemistry?
Immunohistochemistry involves the staining of a solid lymph node section using antibodies against protein patterns and enzyme reactions
CD (Cluster of designation) numbered antibodies are used for varying markers
What colour is seen in positive immunohistochemistry?
Brown
Name the cell type that responds to CD3
T-cells
Name the cell type that responds to CD19 and CD20
B-cells
Name the cell type that responds to CD30
Reed-sternberg cells (Hodgkin’s lymphoma)
Name the cell type that responds to CD23
Follicular dendritic cells
What are the 2 forms of genetic analysis used in lymph node biopsy?
G-Banding
FISH (Fluorescent In Situ Hybridisation)
What does G-banding involve?
G banding involves an aspirate node, grow cells in culture, look at spread of chromosomes
What does FISH involve?
FISH (Fluorescent In Situ Hybridisation) involves looking for specific abnormalities in chromosomes using probes that emit specific light colours
What is the difference between immunohistochemistry and immunophenotyping?
Immunohistochemistry - Solid tissue
Immunophenotyping - Liquid tissue
What is involved in molecular analysis?
Molecular analysis involves looking for patterns of gene expression, with multiple analyses looking at patterns of genes that are switched on and off
Describe the follicular reaction of lymph node activation
In the follicles, quiescent B cells are activated in response to antigenic challenge
Antigen-antibody complexes are captured by follicular dendritic cells (FDCs), which are specialised antigen presenting cells
These are mesenchymal and form mesh-works through the germinal centre
Antigens on the FDCs are presented to naive B cells T helper cells assist
What is the function of follicular dendritic cells?
Follicular dendritic cells, (not dendritic cells) are mesenchymal in origin and provide architectural support to germinal centres
They facilitate debris removal through secretion of bridging factor, causing macrophages to come and phagocytose debris
They also play a role in antigen capture for memory B cells
Describe the dark zone reaction of follicular activation
After the beginning of the follicular reaction, the B cells are triggered to start dividing
Clonal expansion occurs in which cells proliferate, differentiate and undergo somatic hypermutation
Affinity maturation then occurs, in which B cells with the increased antigen affinity go into the light zone, while the rest apoptose
What are the advantages of somatic hypermutation?
Somatic hypermutation is what allows the immune system to adapt quickly to make antibody producing plasma cells and memory B cells
This causes up to a million times greater than the normal rate of mutations in the human genome (Some advantageous, some disadvantageous)
What are centroblasts?
B cells proliferating in the dark zone (Will become centrocytes in the light zone)
Describe the light zone reaction of lymph node activation
In the light zone, positive selection of B cells
Cell division slows down and FDCs present antigens to B cells
B cells bind and internalise the antigen and present it on their MHCII to T cells
This allows T cell to help B cell on its journey
What are centrocytes?
Centrocytes are B cells in the light zone, which will become either memory B cells or plasma cells
What are the 3 B-cell outcomes of follicular activation?
- Reenter dark zone and keep proliferating (and expressing cMyc to regulate GC formation)
- Differentiate into plasma cells
- Differentiate into memory B cells
What can trigger B-cell response in the lymph node?
Autoimmune conditions
Infection
IgG4-Related disease
What can trigger phagocytic responses in the lymph node?
- Draining a tumour site
- Reacting to a tumour
- Dermatopathic disease
- Granulomatous disease
What can trigger a T-cell response in the lymph node?
- Viral infection
- Drugs (e.g. phenytoin)
- Dermatopathic disease
What are some causes of granulomatous lymphadenitis?
- Sarcoidosis (Malignancy may also cause sarcoid)
- Mycobacteria (Caseous necrosis)
- Granulomatous inflammation
