week 11 Flashcards
what are all the leukocytes
macrophages,monocytes and dendritic cells
granulocytes
B+T lymphocytes
ontogeny
maturation of t and be cells where they develop unique cell receptors
if cell receptors recognise self cells they are eliminated
morphology of neutrophils, eosinophils and basophils
neutrophils = trilobed
basophils and eosinphils = biolbed
life span of neutrophils, eosinophils and basophils
neutrophils = shortest life span 5days max
eosinphils = 12 days max
basophils = 15days max
function of neutrophils 3 + 2 more facts
neutrophils = phagocytosis degranuloation and netosis
rapidly deployed from bone marrow when needed
most common leukocyte
function of eosinophils 2
allergic reaction
parasitic infection
function of basophils 3 + 1 additional
inflammation
paristic infection
allergic reactions
contain granules which include immune mediators
chemotaxis
biological process whereby cells respond to chemical signals
morphology of t cells vs b cells
t cells: limited cytoplasm and irregular shape
b cells: large cytoplasm and round shape
primary lymphoid organs
where lymphocytes undergo development and otogeny
secondary lymphoid organs
where mature lymphocytes encounter antigens and differentiate
chemokines
bind to endothelial cells triggering strong homing receptor production which binds to circulating neutrophils
cytokines
signalling proteins which mediate immune responses
colony stimulating factors
subset of cytokines which stimulate differentiation and production of leukocytes
natural killer cell function
circulates in blood acting as early defence against viruses, infected cells and tumour cells
netosis
nuclear material forms neutrophil extracellular traps (NETs) which immobilise and kill pathogens
opsinins
tag microbes for phagocytosis
process of pathogen recognition (use PRRs and PAMPs) 5
PAMP binds to PRR
Activates molecule and transcription of cytokines allowing immune response
phagocytosis of substance
antigen presentation
t cell recognition
further cytokine release
b cell activation
antibodies
effects of complement activation 3
opsonisation
inflammatory response
membrane attack complex formation
3 pathways through which complement can be activated
classical
alternative
lectin
three substances are associated with each complement activation pathway
classical = C1
alternative C3 and C3b
lectin = mannose binding lectin
classical complement activation pathway
complement C1 recognises immune complexes formed by binding antibodies
alternative complement activation pathway
complement C3 breaks down C3b depositing it on microbes
lectin complement pathway
mannose binding lectin attaches to mannose sugars on bacteria surfaces
the direct and indirect way of triggering phagocytsosis
direct way: recognise microbes via PRRs
indirect way: recognises microbes via opsonins
what do mhc calss 1 proteins display and what do they react w
endogenous antigens
present on all cells and viral,tumour cells
react w CD8
what do mhc calss 2 proteins display and what do they react w
display exogenous antigens from an endosome or phagosome
present in antigen presenting cells
react with CD4 cells
what is the human leukocyte antigen
the molecules which corresponds with either a MHC1 or MHC2 receptor
two ways a b cell can get activated
T dependent antigen pathway
T independent antigen pathway
t dependent antigen pathway for b cell activation 4
B cell binds to pathogen
Antigens internalised and presented to T follicular cell
T follicular cell binds and releases cytokines which activate b cell
B cell can produce both igG and igM
t independent antigen pathway for b cell activation 3
b cell binds to antigen
activates b cell
only igM cells can be produced
isotype switching in b cells
a process by whcih b cells can change the type of antibody produced
requires t follicular cells to cause this change
idiotype of an immunoglobulin
the variable region
epitote
the region where the antigen and antibody bind
role of igM (function+structure)
produced upon initial response
pentameric structure
igG 2
provides long term protection
most abundant antibody
Ignore
igD
found in mucosal seretions protecting the mucosa from pathogens
igE 2
induce allergic reactions and hypersensnitivity
triggers mast cell degranulation
igA
found on b cells and act as a receptor to initate cell activation and maturation
key functions of antibodies 4
neutralisation
agglutination
opsonisation
complement activation
multiple myeloma
malignancy in the final stage of b lymphocyte development whereby plasma cells become malignant and produce monoclonal immunoglobulins
lymphoma
malignancy that occurs in the lymph nodes predominantly involving b cells
there are two classifications: hodgikins and non hodkins lymphoma
hodgkins lymphoma
presence of Reed sternberg cells
what key gene mutation is chronic myeloid leakaemia associated with
the Philadelphia chromosome
differences between acute and chronic leakaemia
acute: invlves immature lymphocytes
chronic: involves dysfunctional mature cells
difference between lymphoma and leukaemia
lymphoma localised to lymph nodes
leukaemia in blood
common complications of haematological malignancies 6
organomegaly
bleeding
infection
anaemia
renal failure
bone pain
why does organomegaly occur
uncontrolled growth and accumulation of cancerous cells
disrupts structure and function
bleeding
malignant cells invade blood vessels impairing their integrity and disrupting normal clotting processes
infection
underproduction of immune cells due to bone marrow failure
renal failure
due to accumulation of abnormal proteins produced by the cancerous cells which clog and damage the renal tubules
anaemia
due to a dysruption in erythroppoeiss as a result of bone marrow failure and crowding
bone pain
results from the infiltration of abnormal cells into the bone marrow disrupting normal bone structure
what is the most common paedeatric luekaemia
acute lymphoblastic leukaemia
blood findings in acute myeloid leukaemia
excessive immature WBCs
blood findings in chronicmyeloid leukaemia
excessive mature WBCs with features of granulocytes
blood findings in chronic lymphocytic leukeamia 2
excessive mature lymphocytes
smudge cells
blood findings in multiple myeloma
excess clonal plasma cells
flow cytometry
uses antibodies which are fluorescently labelled which bind to cell surface markers
the presence/absence of surface markers indicates the level of cell maturation
in leukaemias, there will be an absence of the correct surface marker
binet staging system in CLL
extent of leukocyte involvement
presence of anemia or thrombocytopenia
stage a of binnet system
less than 3 enlarged lymph node groups and no anaemia/thrombocytopenia
stage b of binnet system
greater than 3 enlarged lymph node groups with no anaemia or thrombocytopenia
stage c of binnet staging system
patients have anaemia and thrombocytopenia
three phases of treatment in haematological malignancy management
induction
consolidation
Maintenance
induction (haematological malignancies treatment)
upon diagnosis of acute leukaemia it is intense chemotherapy
consolidation (haematological malignancies treatment)
when patient is in remission
continual high level of chemotherapy
maintenance (haematological malignancies treatment)
decreased rate of chemotherapy
mechanism of monoclonal antibodies in the treatment of haematological malignacies
they bind to surface antigens on cancer cells
exert therapeutic effects including:
- inteference of cell signalling pathways
-direct cytotoxiicty
how is the philadelphia chromosome
translocation of chromosome 9 to 22 resulting in translocation of ABL1 gene to BCR forming a BCR-ABL1
what is the result of this translocation
causes increased proliferation, increased survival and increased adherance
targeted treatment method in chronic myeloid leaukaemia
use of a tyrosine kinase inhibitor
what does a tyrosine kinase inhibitor do 2
binds to the ATP site of the BCR-ABL1 preventing ATP to bind
prevents substrate from forming as this requires ATP
prevents downstream effects
what is aplastic anaemia
bone marrow failure resulting in a lack of all blood cell production
it is characterised by bone marrow hypoplaisia
what are myeloproliferative neoplasms
these are a group of chronic blood cancers that result in excessive production of near-mature blood cells
examples of myeloproliferative neoplasms
chronic myeloid leukaemia
polycythemia vera
essential thrombocytosis
primary myelofibrosis
polycythemia vera 3
most comon MPN
malignant increased RBC levels independent of EPO levels
caused by JAK 2 mutation
essential thrombocytosis
malignant excess in platelets
high risk of thrombotic complications
JAK 2 mutation
JAK 2 mutations 4
encodes for tyrosine kinase resulting in the increased proliferation as seen in CML
also induces EPO indepedent erythrocytosis
hypersensitivity to cytokines and growth factors
(this is why in CML treatment we use a tyrosine kinase inhibitor)
myelodysplastic snydromes
group of syndromes whereby the bone marrow fails to produce healthy cells
whats a key characteristic of myeloproliferatiove neoplasmic disorders
JAK mutations
