Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

WEEK 10 SEM 4 > CLINICAL WORKSHOP- MYELOMA immunology > Flashcards

CLINICAL WORKSHOP- MYELOMA immunology Flashcards

1
Q

What is the epidemiology of myeloma?

A

uncommon and accounts for 2% of all cases of cancer
It is the 2nd most common haematological cancer
It is about 10% of all haematological malignancies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

In the UK, how many new cases of myeloma are there per year?

A

about 5500 new cases of myeloma per year

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Who are most affected by myeloma?

A

age over 40
The peak average age at diagnosis is 65-70 years old
higher in men and African ethnicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Why is myeloma often called multiple myeloma?

A

involves many lesions in the bone marrow

differentiates from a solitary tumour (plasmacytoma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where does myeloma originate?

A

mature B cell malignancy

in plasma cells of the BONE MARROW

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Where do B cells normally get activated?

A

germinal centres of the secondary lymphoid organs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where do the mutated B cells accumulate?

A

in the bone marrow

proliferate there

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What does monoclonal mean?

A

B cell can produce only one type of antibody

all mutated B cells create same antibody (MONOCLONAL B CELLS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are M proteins?

A

Antibodies secreted by the malignant B cells are called M proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What can M proteins be?

A

full immunoglobulins
OR
immunoglobulin fragments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What do normal plasma cells look like?

A 
terminally differentiated B cell
bigger than B cell
big nucleus
lots of cytoplasm
light area around the nucleus
eccentric nucleus (not in the middle)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does a B cell look like?

A

smaller than plasma cell
small nucleus
little cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is in the light area around the nucleus of the plasma cell?

A

ER

large golgi apparatus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What do plasma cells in multiple myeloma look like?

A 
excess plasma cells
plasma cells= multiple nuclei
Mott cells (in cytoplasm)= contain Ig
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the normal immunoglobin structure?

A

2 identical light chains

2 identical heavy chains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What can the light chains of an Ig be?

A

kappa

lambda

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What can the heavy chains of an Ig be?

A 
Gamma, IgG
Mu, IgM
Alpha, IgA
Delta, IgD
Epsilon, IgE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Which Ig has the highest serum level?

A

IgG (5-16g/L)
IgA (0.8-4g/L)
IgM (0.5-2g/L)
IgD and IgE= very low in healthy individuals except if allergy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the types of secretory myeloma?

A

−IgG secretory myeloma (55-60% cases)
−IgA secretory myeloma (20-25% cases)
−free light chain only secretory myeloma (20% cases)−IgD, IgE secretory myeloma is rare
−IgM secretory myeloma is very rare because most of the IgM lies on B cells before they are activated, and so it is usually secreted in low levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the immunological tests for myeloma detection?

A

serum protein electrophoresis

immunofixation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does serum protein electrophoresis allow us to identify?

A

monoclonal immunoglobin- CANT TELL WHAT CLASS AND WHAT LIGHT CHAINS PRESENT

22
Q

What is the process of electrophoresis?

A
  1. load serum onto gel (on negative side)
  2. electrical fields is passed through gel
  3. negative proteins migrate to positive side
    DEPEND ON SIZE AND CHARGE
23
Q

What do proteins move depending on in electrophoresis?

A

CHARGE: strongly negative proteins migrate faster to the positive side of the electrical field
SIZE: smaller proteins also migrate faster to the positive side of the electrical field

24
Q

What is the order of things seen in serum protein electrophoresis?

A
  1. albumin band (THICKEST)- migrated furthest
  2. globulin alpha 1
    globulin alpha 2
    globulin beta 1
    globulin beta 2
  3. GAMMA GLOBULINS- NO BAND= FUZZY
25
Q

What are gamma globulins?

A 
circulating Igs (all classes of Ig)
this area has no band= fuzzy area BC Igs are of different sizes, glycosylation etc.
26
Q

What is densitometry scanning?

A

the bands are quantified onto a graph using computer software

27
Q

How is the electrophoresis results different in a myeloma patient?

A

gamma band= ACC IS A BAND bc only 1 ANTIBODY is made

28
Q

What does immunofixation allow us to see?

A

what type of Ig it is and what light chain

29
Q

What is the process of immunofixation?

A
  1. put serum on gel
  2. gel has rabbit Ig anti-human Ig (antibodies against human IgG)
  3. rabbit antibody binds to all Human IgG
  4. Human IgG precipitates
  5. gel is washed
  6. when gel is washed all Ig except human IgG will wash out
  7. run precipitate through electrophoresis
  8. normal case: see fuzzy smear
    in IgG myeloma= will have dark band present
  9. repeated with anti-human IgM, anti-human IgA, anti-human IgE, anti-human kappa light chain, and anti-human lambda light chain to determine the heavy and light chain
30
Q

What are paraproteins/M proteins?

A

abnormal proteins

result from proliferation of one clone of plasma

31
Q

What can paraproteins be?

A

full immunoglobins (light and heavy chains assembled together)
full immunoglobin + free light chain
just free light chains
just heavy chains= VERY RARE

32
Q

What are bence jones proteins?

A

paraproteins can be just free light chains
low molecular weight
can pass in urine

33
Q

What shows multiple myeloma?

A

more than 30g/L immunoglobulin in serum
or more than 60g/L immunoglobulin in urine

fragmentation of immunoglobulins bc normal= fully assembled

suppression of normal immunoglobulins will also indicate multiple myeloma

34
Q

What malignant things can M proteins be in?

A

multiple myeloma
waldenstrom’s macroglobulinemia
lymphoma
chronic lymphocytic leukemia

35
Q

What benign conditions can M proteins be present in?

A

MGUS (monoclonal gammopathy of undetermined significance)

36
Q

What is the diagnostic criteria for myeloma?

A

any 2 of:
−M protein/paraprotein in serum and/or urine
−abnormal number of plasma cell, and increased number of plasma cells in the bone marrow
−osteolytic lesions in bones

37
Q

What are clinical symptoms of myeloma?

A 
anaemia
less wbc
amyloid deposits in organs
viscous blood
high infection risk
renal failure
38
Q

How does a myeloma patient get anaemia?

A 
malignant cells degrade bone
more Ca2+ released
more Ca2+ in serum
malignant plasma cells compete with other cells developing in bone marrow so bone marrow is suppressed
so you get anaemia and low WBC
39
Q

Why does the blood become viscous?

A

lots or proteins in blood (M proteins)

40
Q

How is renal failure caused?

A

small light chains pass in kidney, go to urine- block renal tubes= cause renal failure

41
Q

Why do plasma cells in myeloma go malignant?

A

plasma cell DNA mutation

  • mutations in the proto-oncogenes that control the cell -cycle like cyclins
  • deletion of tumour suppressing genes eg TP53
42
Q

What happens if there is rearrangement between the heavy Ig locus and proto-oncogenes at places in DNA?

A
  • if there is a proto-oncogene which translocates into the immunoglobulin heavy chain locus, it may activate the immunoglobulin locus
  • if this proto-oncogene becomes a full oncogene, then it means the cell does not follow the usual rules of proliferation and the cell will become immortal and will refuse to die
43
Q

What can mutations in the NF-Kappa-B transcription factor promote?

A

B cell survival

44
Q

When is IL6 released?

A

produced by plasma cells
produced by stromal cells in the bone marrow
released when bone is destroyed

IT PROMOTES THE GROWTH OF A MALIGNANT CELL

45
Q

How does myeloma cause bones to break?

A

mutated myeloma cells produce growth factors (MIP- 1ALPHA)
they interact with molecules present on stromal cell of bone marrow
increase RANK ligand expression on stromal cells
stromal cells ligate RANK on osteoclasts
osteoclasts activated
inhibit bone formation
IL6 released= supports proliferation and survival of BAD plasma cell

46
Q

What are the different reasons of kidney failure with myeloma?

A 
hypercalcaemia
excess production of light chains- toxic to renal tubular epithelial cells
amyloid deposits in kidney
infections
hyperuricemia
47
Q

What are the treatments of myeloma?

A 
chemotherapy- control myeloma progression
radiotherapy-localised bone pain
bone marrow/stem cell transplantation
IL6  inhibitor
anti-angiogenic
proteasome inhibitor- BORTEZOMIB
bisphosphonate
48
Q

What are examples of IL6?

A

thalidomide, lenalidomide

49
Q

What do proteasomes do?

A

proteasome is an organelle inside cells= degrades unwanted and misfolded proteins

it recognizes misfolded/bad proteins because these unwanted proteins are labelled with ubiquitin, and this is what the proteasome recognizes

after breakdown, the cell reuses the amino acids to make new proteins

50
Q

What do proteasome inhibitors do?

A

proteasome inhibitors act as a plug on the proteasome and block entry into the proteasome

so now unwanted proteins cannot enter the proteasome

because of this, unwanted proteins will begin to accumulate inside the cell and the cell will become apoptotic

multiple myeloma produces a lot of proteins, and some of these molecules need to be degraded in the proteasome

using these drugs blocks the proteasome, which makes them more sensitive to apoptosis, radiotherapy, and chemotherapy

proteasome inhibitors also reduce the expression of RANK ligands on the stromal cells which inhibit activation of osteoclasts and thus reduce bone lysis−bisph

51
Q

What do bisphosphonates do?

A

inhibit bone resorption, reduce fractures, and limit hypercalcemia, and stop destruction of bone mediated by malignant plasma cells

WEEK 10 SEM 4 (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions