16. Lymphoid Malignancies Flashcards
Major underlying principles of malignant lymphocytes (1)
- Malignant lymphoid cells arise from normal cells and so they share most of their characteristics with normal lymphocytes
- Since normal lymphocytes pass through a range of developmental stages the malignant cells tend to resemble cells at a particular stages of normal developmental stage
- However the cells are “malignant” so while resembling a normal lymphoid cells they also behave a little differently – generally simply because there are too many of them!
Major underlying principles of malignant lymphocytes (2)
There are basically four stages of normal lymphocyte development that malignant cells can resemble:
Phase 1: initial formation – proliferative cells committed to forming many more lymphocytes. occurs in bone marrow as all lymphocytes made in bone marrow. controlled process - make as many as we need then stop
Phase 2: responding to antigen – meeting antigen then proliferating before making maturing into effector cells. after wondering round the body they encounter an antigen and react to it, undergoing a secondary proliferative phase. Occurs in lymph nodes
Phase 3: cells that have met antigen and are performing an action e.g. cytotoxic T cells or antibody producing plasma cells. mature into a cell that reacts to the antigen eg antibody or toxic t cell or helper cell. Ie effector cells, these are not very proliferative, they do things. When antigens disappear from the body so do these as no longer required
Phase 4: memory – after an antigen is successfully eliminated memory cells persist to allow the body to respond rapidly in future. immunological memory
stages in picture form see slide 5
stage 1 is production in bone marrow
stage 2 is response to antigen (lymph node)
stage 3 destroying antigen eg antibody production
stage 4 is memory cells, migrate widely
phase 1 of normal development
Normal lymphocytes undergo an initial wave of proliferation
These cells develop in bone marrow
- Because large numbers are needed, the cells are highly proliferative, growing in bone marrow until they mature and are released into blood.
- In normal cells this process is highly controlled – there should not be too many or too few cells formed
cell has no fatures of maturation , consists of only a nucleus and nucleolus
appearance of phase 1 cells
have features of rapidly growing cells
The nucleus has chromatin that is unwound from histones protein so it can be transcribed into mRNA to make proteins. It therefore looks “unravelled” and “lace-like”.
There are pale round nucleoli present to support the processing and export of RNA to transcribe protein
The cytoplasm is blue because it is packed with ribosomes transcribing mRNA into protein
malignant cells tha develop from phase 1
acute lymphoblastic leukaemias
“acute” reflects their rapid appearance and development
“lympho” refers to their lymphocyte origin
“blastic” is an old term that refers to their capability to make rapid divisions
“leukaemia” another old term “white blood” reflects their tendency to spill over from bone marrow into blood in large numbers
initial behaviour of malignant cells from phase I
The cells resemble normal lymphocytes proliferating in bone marrow
Lymphocytes develop on the edge of bone marrow next to the bony support. At early stages they resemble normal cells. get all nutrition
bony skeleton of bone marrow provides support whilst fat filled spaces provide energy
later behaviour of malignant cells of phase 1
The difference is that they grow rapidly and do not mature
As they increase their number the malignant lymphocytes begin to fill the bone marrow
They supress normal cells
Eventually they fill marrow entirely and move out to other areas, appear in blood
The bone marrow is packed and entirely replaced by abnormal cells
normal cells wiped out so don’t make rbc or platelets
eventual behaviour of malignant cells of phase I
The acute lymphoblastic leukaemia are eventually seen in blood – this is usually the point where people become ill
Acute lymphoblastic leukaemia symptoms
bleeding
infection
lack of rbc
pain
ALL bleeding
The lack of normal platelets means that very small vessel trauma cannot be plugged so patients experience tiny points of bleeding (petechei). These may be simply unsightly on leg, but can be fatal (brain)
haemorrhages eg when standing due to hydrostatic pressure
ALL infection
The lack of normal white cells makes responding to infection very difficult. Initially this is simply an overgrowth of normal organisms that cause no problems in healthy people. E.g. yeast in mouth. Later infection is the major cause of death
ALL lack of rbc
People become pale, lack energy, become short of breath. This can be reversed by transfusion.
ALL other symptoms
The infiltration of bone marrow is sometimes felt as pain as the number of cells restricts oxygen availability and tine areas of cell death occur!
Microthrombosis – death of bits of bone
ALL clinical features
The main symptoms are caused through suppression of normal cells by the rapidly growing malignant cells: patients with acute leukaemia have low red cells, low white cells and low platelets
Other symptoms relate to the effects of this the rapid growth in bone marrow – causing bone pain; and by an excess number of cells accumulating in blood or other sites
phase 2 of normal development
Normal cells go to lymph node where they recognise and respond to antigen
Normal cells go to lymph node where they recognise and respond to antigen
After they meet antigen normal lymphocytes begin to proliferate
the proliferating population matures into cells with particular features.
phase 2 lymph node phase normal
Small resting cells, solid look to nucleus as DNA tightly bound to histones
But later unravel their chromosome for transcribing and synthesising protein
The cells of this phase are also very variable in appearance
Cells that have not yet met antigen tend to be small mature and proliferate slowly and resemble normal lymphocytes
to Later cells are very proliferative and resemble bone marrow cells (but in lymph node)