Myeloma and Plasma Cell Dyscrasias Flashcards
Are B cells part of the adaptive or innate immune system response?
Adaptive
What are the main functions of B cells?
Make antibodies
- can also act as antigen presenting cells
Describe the structure of the Antibodies produced by B cells?
2 heavy chains (denoted by greek letters, but indicate type of Ab => M,G,D,A,E)
2 light chains (kappa or lambda)
What type of antibody can form a dimer?
IgA
What type of antibody can form a pentamer?
IgM
Why do antibodies have variable regions?
To change their structure in order to bind different antigens
- VDJ proteins are rearranged in order to do this
Describe the Precursors of the B cell, starting with a haematopoietic stem cell
Stem cell lymphoid progenitor Pro B cell (can make IgM) Pre B cell (can make IgM and IgD) **then leave bone marrow and enter circulation** B cell can then mature to plasma cell
B cells have to undergo class switching before maturing to a plasma cell. TRUE/FALSE?
TRUE
- as plasma cell can only make one type of Ab
Where do B cells travel to after they leave the bone marrow and what is their role here?
- travel to follicle germinal centre in lymph node
- identify antigen and improve fit
- can return to marrow as plasma cell or circulate as memory B cell
Describe the appearance of a plasma cell on blood film
- “eccentric” clock face nucleus with H+E staining
- open chromatin nucleus
- plentiful blue cytoplasm (lots of protein)
- pale perinuclear area (golgi apparatus)
Describe the difference between a polyclonal and monoclonal expansion
Polyclonal = increase in number of cells, but all are different monoclonal = increase in cells but all are the same
What would cause a polyclonal rise in Ig (i.e. different types of Ab produced?
- infection
- autoimmune
- malignancy (reaction of the host to non-haem malignancy in their body)
- liver disease
What would cause a monoclonal rise in Ig?
clonal expansion of B cells (also called paraprotein)
identical Ab produced
marker of underlying clonal B cell disorder
How are Ig detected?
Serum electrophoresis
- detects abnormal protein bands (i.e. if there is too much of a specific protein)
How are the abnormal Ig in the blood classified and quantifed?
serum immunofixation
What is Bence Jones protein and where is it found?
- light chains are found in the patients urine
- can either be monomer light chain (kappa)
OR can be dimer light chain (lambda)
What are the potential causes of paraproteinaemia?
MGUS - Monoclonal Gammaopathy of Unknown Significance
Myeloma
Amyloidosis
Lymphoma
What is MGUS?
Monoclonal expansion of a B cell creating a high number of certain Ig
- considered a benign/pre-malignant stage of Myeloma
What are the two ways in which myeloma can affect the body?
Direct tumour effects:
- bone lesions and pain
- increased calcium
- marrow failure
Paraprotein effects
- renal failure
- immunosuppression
- hyperviscosity
- amyloid
Describe how myeloma bone lesions normally appear on X-ray?
lytic bone disease
=> punched out lesions are common in the skull
=> wedge fractures in the spine = common
What types of Ig are most commonly produced in myeloma?
IgG
IgA
Why does lytic bone disease occur in myeloma?
myeloma cells increase IL-6 from marrow stromal cells
=> these activate osteoclasts to breakdown bone and release Ca2+
What symptoms do patients often experience if they have hypercalcaemia?
- stones
- bones
- abdominal groans
- psychiatric moans
- thirst
- polyuria
- dehydration
- renal impairment
Why do patients with myeloma get cast nephropathy if the kidneys can usually filter light chains?
- proximal tubules usually reabsorb light chains
- if overwhelmed they pass into loop of henle and combine with Tamm-Horsfall Protein in thick ascending limb
- this compound then can block the nephron
