Myeloma Flashcards
(52 cards)
Which immune system are the B-cells a part of?
What are their roles?
- part of the adaptive immune system
2. Roles: Ab prodn/ Antigen presenting cells
What are immunoglobulins?
- Abs made by B-cells and plasma cells
Where do B-cells develop?
in the Bone marrow
How is the Ig variable element genrated from?
- from the V-D-J region recombination found at Ag binding site
- early in development
What do the naive B cells do in the periphery?
- travel to the FOLLICLE germinal centre of the lymph node
- identify the Ag and improve the fit by somatic mutation or be deleted.
- may return to marrow as a plasma cell or as a memory B-cell
What does a b-cell appear on histology?
- clock-face nucleus
- open chromatin (synthesizes mRNA)
- -plentiful BLUE cytoplasm (laden with protein)
- –pale perinuclear area (gogli apparatus)
What is polyclonal incr. in immunoglobulins?
Why may it occur?
- produced by MANY diff. plasma cell CLONES
- reactive to INFECTION/ AUTOIMMUNE/ MALIGNANCY/ LIVER DISEASE
What is monoclonal rise in immunoglobulins?
- Ig all derived from clonal expansion of a SINGLE B-cell —-IDENTICAL Ab specificity and structure
monoclonal Ig= paraprotein
What may monoclonal rise in Ig indicate?
marker of UNERLYING clonal B-cell disorder.
How are Ig detected?
- by serum electrophoresis
- —serate serum proteins appear as dstinct bands
- –proteins move at differing rates determined by their SIZE and CHARGE
Where willl albumin be seen on electrophoresis?
- given it’s the MOST NEGATIVELY charged molecule
- —it will be seen close to ANODE
Why is there a rise in the amount of free light chains in the plasma and in the urine?
- when Ig is produced in the plasma cells, MORE LIGHT chains are made than heavy chains
- –the free light chains are secreted into the plasma along with intact Ig
IN what conditions may free light chains INCREASE in the plasma?
- polyclonal INCREASE (d.t INFECTION)
- MONOCLONAL incr. in plasma cells (d.t multiple myeloma)
both of which will result in INCR. of free light chains in the plasma
Name causes of paraproteinaemia.
- Myeloma
- MGUS (56%)
- Amyloidosis (10%)
- Lymphoma
- aymptomatic myeloma
- solitary/ extramedullary plasmocytoma
- Chronic lymphocytic leukaemia
- Waldenstrom Macroglobulinaemia
What is Bence Jones protein?
- immunoglobulin light chains
- detected by urine electrophoresis
How does myeloma develop?
normal plasma cells hit with genetic mutations> MGUS clone (benign) > few more genetic hits> ASYMPTOMATIC MYELOMA (MALIGNANT but no organ damage)
> more hits= MYELOMA
How does myeloma affect the body?
- clonal PLASMA cells
How does myeloma bring about organ damage?
- Direct tumor cell effects
2. Paraprotein mediated effects
What are exs. of DIRECT tumor cell defect?
- bone lesions
- incr. CALCIUM
- bone pain
- replaced normal bone marrow–> MARROW failure
What are some paraprotein mediated efx?
- renal failure
- immune supression
- hyperviscocity
- amyloid
What kind of bony lesions are seen with multiple myeloma?
lesions arise from medullary cavity> erosion of cancellous bone> cortical bone destruction»FRACTURES (usually in vertebral column and femur) – compression fractures
- punched out defects
- diffuse SKELETAL demineralization (rise in Ca)
How can myeloma be classified?
- by the type of Ab produced (seen in serum/ urine)
- –60% produce IgG
- Bence Jones myeloma (15%)
- —some don’t produce monoclonal proteins at all (Non-secretory myeloma)
Why do myelomas cause lytic bone disease?
- flourish of myeloma cells> RISE in IL-6> further rise in IL-6 and TGF-beta
- the rise in these chemokines> OSTEOCLAST ACTIVATION (and suppression of osteoblasts)
—-BONE RESORPTION! in bone matrix
–RISE in Ca2+
What is the risk of hypercalcemia?
- renal stones
- bone pain (spinal cord impingement is possible on vertebral #)
- abdominal groans
- neuro: confusion and lethargy
- thirst and dehydration
- renal impairment
