Where do B cells come from
pluripotent HSC in bone marrow
are B cells part of the innate or adaptive immune system
adaptive (slower, more specific response)
what are immunoglobulins
antibodies produced by B cells and plasma cells
what are immunoglobulins made of
2 heavy chains: IgG/A/M/E/D
2 light chains: k/lambda
each antibody can recognise multiple antigens, true or false
false
each antibody recognises a specific antigen
which Ig antibodies are monomeric
IgG, IgD, IgE
which Ig antibody is dimeric
IgA
which Ig antibody is pentameric
IgM
what allows for variability in Ig
V-D-J region recombination
Where do B cells in the periphery travel to
follicle germinal centres in lymph nodes to identify antigens
what can happen to a B cell after it finishes in the lymph node
may return to the bone marrow as a plasma cell or circulate as a memory B cell
what are plasma cells
factory cells that pump out antibody
what are histological features of plasma cells
eccentric clock face nucleus with H&E staining
open chromatin
plentiful blue cytoplasm
pale perinuclear area
define polyclonal
produced by many different plasma cell clones
what can polyclonal proliferation be indicative of
infection
autoimmune condition
malignancy - as a reaction from the host to a malignant clone
liver disease
define monoclonal
all derived from clonal expansion of a single B cell
characteristics of monoclonal antibodies
identical structure and specificity
what are monoclonal antibodies also known as
paraprotein
what are paraproteins a marker of
underlying clonal B cell disorder
what investigation is used to detect immunoglobulins
serum electrophoresis
in serum electrophoresis, what causes proteins to move the way they do
their shape and charge
what investigation is used to classify abnormal protein bands found in electrophoresis
serum immunofixation
What are Bence Jones Proteins BJPs
free light chains detected by urine electrophoresis
are light chains normally secreted into plasma
yes, in very small amounts 0.5g/l
what can cause raised free light chains
polyclonal (infection) or monoclonal (multiple myeloma) increase in plasma cells
causes of paraproteinaemia
myeloma lymphoma MGUS amyloidosis plasmacytoma CLL
MGUS is benign/malignant
benign/premalignant
asymptomatic myeloma is benign/malignant
malignant - but no organ damage
what are the direct tumour effects of myeloma on the body
bone lesions
bone pain
hypercalcaemia
marrow failure
what are the paraprotein mediated effects of myeloma on the body
renal failure
immunosuppression
hyperviscosity
amyloid
how can multiple myeloma be classified
according to Ig Ab produced
why do you get lytic bone lesions in myeloma
malignant myeloma cells suppress osteoblasts and activate osteoclasts (also the reason for hypercalcaemia)
list consequences of hypercalcaemia
kidney stones psychiatric moans abdominal groans painful bones thirst and dehydration renal impairment
how can multiple myeloma lead to renal failure by cast nephropathy
free light chains can filter through glomerulus
proximal convoluted tubule cannot deal with light chain overload so they pass to ascending limb of loop of Henle
ascending limb produces Tam-Horsfall proteins which bind to light chains and make them insoluble forming casts
this blocks the nephron
what is the prompt management for dealing with cast nephropathy
rehydration
stop nephrotoxic drugs
start chemo/steroids to reduce light chain production
what is the median age for multiple myeloma
65 years old
what is the mainstay of treatment for multiple myeloma
combination chemotherapy
what can be used to monitor response to treatment in multiple myeloma
paraprotein levels
what is AHSCT (autologous haemopoeitic stem cell transplant)
a method of administering very high dose chemotherapy relatively safely
many patients dont tend to relapse in multiple myeloma, true or false
false
relapse in inevitable
how can you control symptoms in multiple myeloma
opiate analgesia (not NSAIDs)
local radiotherapy
bisphsphonates
vertebroplasty
what does MGUS stand for
monoclonal gammopathy of undetermined significance
how can you define MGUS
paraprotein <30g/l
bone marrow plasma cells <10%
no evidence of end organ damage from myeloma
what is AL amyloidosis
rare disorder
slowly progressive multisystem disease
what is the pathophysiology of AL amyloidosis
mutation in light chain causes abnormal structure which precipitates in tissues as insoluble pleated B sheets
what organ damage can occur in AL amyloidosis
kidneys - nephrotic syndrome heart - cardiomyopathy liver - hepatomegaly, deranged LFTs neuropathy - ANS, PNS GI tract - malabsorption
how can you diagnose AL amyloidosis
organ biopsy with congo red stain
(positive result - apple green birefringence under polarised light)
or less invasive rectal/fat biopsy
what is a SAP scan for AL amyloidosis
serum amyloid P scintigraphy scan can localise amyloid deposits rapidly and specifically
what is Waldenstroms macroglobulinaemia
lymphoplasmacytoid neoplasm = clonal disorders of cells which are in between a lymphocyte and a plasma cell
what is characteristic of Waldenstroms macroglobulinaemia
IgM paraprotein
what can IgM paraprotein cause in Waldenstroms macroglobulinaemia
hyperviscosity
neuropathy
what is the treatment of Waldenstroms macroglobulinaemia
chemo
plasmapharesis
what is plasmapharesis
removal of paraprotein from your circulation and replacing with donor plasma