white blood cells Flashcards
1
Q
What is the first part of the stem cell hierarchy?
A
multipotential haematopoietic stem cell (haemocytoblast) -> common myeloid progenitor & common lymphoid progenitor
2
Q
How does the stem cell hierarchy split from the common lymphoid progenitor?
A
common lymphoid progenitor -> natural killer cell (large granular lymphocyte) & small lymphocyte
3
Q
How does the stem cell hierarchy split from the small lymphocyte?
A
small lymphocyte -> T lymphocyte & B lymphocyte
4
Q
How does the stem cell hierarchy split from the B lymphocyte?
A
B lymphocyte -> plasma cell
5
Q
How does the stem cell hierarchy split from the common myeloid progenitor?
A
common myeloid progenitor -> megakaryocyte & erythrocyte & mast cell & myeloblast
6
Q
How does the stem cell hierarchy split from the myeloblast?
A
myeloblast -> basophil & neutrophil & eosinophil & monocyte
7
Q
Which cells are classified as granulocytes?
A
basophil, neutrophil, eosinophil
8
Q
How does the stem cell hierarchy continue from monocyte?
A
monocyte -> macrophage
9
Q
How does the stem cell hierarchy continue from megakaryocyte?
A
megakaryocyte -> thrombocyte
10
Q
What does the multipotent haemopoietic stem cell give rise to?
A
myeloblast -> granulocytes & monocytes
11
Q
What are granulocytes?
A
neutrophils, basophils, eosinophils which have granules in the cytoplasm that contain agents essential for their microbicidal function
12
Q
What does G-CSF stand for?
A
granulocyte colony-stimulating factor
13
Q
What does M-CSF stand for?
A
macrophage colony-stimulating factor
14
Q
What does GM-CSF stand for?
A
granulocyte-macrophage colony stimulating factor
15
Q
Where does cell division occur in normal granulocyte maturation?
A
- occurs in myeloblasts, promyelocytes and myelocytes
- does not occur in metamyelocytes or band forms
16
Q
How long does neutrophil granulocyte survive for before migrating to tissues?
A
7-10 hours in circulation before migrating to tissues
17
Q
What does the nucleus of a mature neutrophil look like?
A
segmented (sometimes referred to as lobulated)
18
Q
What is the main function of a neutrophil?
A
defence against infection - it phagocytoses and then kills micro-organisms
19
Q
What is the first step in neutrophil migration to tissues?
A
chemotaxis
20
Q
What happens in chemotaxis of neutrophils?
A
- become marginated in the vessel lumen
- adhere to the endothelium
- migrate into tissues
21
Q
What happens after cytokine priming (neutrophils)?
A
phagocytosis of micro-organisms
22
Q
What gives rise to eosinophil granulocytes?
A
myeloblast
23
Q
How much time does the eosinophil spend in circulation compared to the neutrophil?
A
less time
24
Q
What is the main function of eosinophils?
A
defence against parasitic infection
25
What are eosinophils important in the regulation of?
regulation of Type I (immediate) hypersensitivity reactions
26
How are eosinophils important in the regulation if Type I (immediate) hypersensitivity reactions?
inactivate the histamine and leukotrienes released by basophils and mast cells
27
What gives rise to basophil granulocytes?
myeloblast
28
What do the granules of basophils contain?
stores of histamine and heparin
as well as proteolytic enzymes
29
What are basophils involved in?
a variety of immune and inflammatory responses
30
What are two examples of basophil involvement in a variety of immune and inflammatory responses?
- mediation of the immediate-type hypersensitivity reaction in which IgE-coated basophils release histamine and leukotrienes
- modulation of inflammatory responses by releasing heparin and proteases
31
Mast cells vs basophils?
mast cells are similar to basophils, but reside in tissues rather than the circulation
32
What gives rise to monocytes?
myeloid stem cell -> monocyte precursors -> monocytes
33
How long do monocytes spend in the circulation?
several days
34
What are three key roles that monocytes play?
- phagocytosis of micro-organisms covered with antibody and complement
- phagocytosis of bacteria/fungi (cf antibody)
- antigen presentation to lymphoid and other immune cells
35
Where do monocytes migrate to?
tissues where they develop into macrophages (aka histiocytes) and other specialised cells that have phagocytic and scavenging function
36
What is an additional function of macrophages?
store and release iron
37
Describe the lymphoid differentiation which leads to mature B cells.
pluripotent HSC -> common lymphoid progenitor -> B cell progenitors in bone marrow -> mature B cells
38
Describe the lymphoid differentiation which leads to mature T cells.
pluripotent HSC -> common lymphoid progenitor -> T cell progenitors (thymus->bone marrow) -> mature T cells
39
Describe the lymphoid differentiation which leads to myeloid cells.
pluripotent HSC -> myeloid cells
40
What gives rise to lymphoid stem cells?
multipotent haemopoietic stem cell
41
What do lymphoid stem cells give rise to (3)?
T cells, B cells and natural killer (NK) cells
42
Where do lymphocytes recirculate to?
lymphocytes recirculate to lymph nodes and other tissues and then back to the blood stream
43
What is the intravascular life span of lymphocytes?
very variable
44
Where do B lymphocytes originate?
in fetal liver and bone marrow
45
What does the development of B lymphocytes involve?
Ig heavy & light chain gene rearrangement
46
What does development of B lymphocytes lead to?
production of surface Igs against many different antigens: humoral immunity
47
What does subsequent maturation of B lymphocytes require?
exposure to antigens in lymphoid tissue e.g., lymph nodes
48
What does the maturation of B lymphocytes result in?
- recognition of non-self antigens
- production of specific Igs and antibodies
49
What do B lymphocytes mature into?
plasma cells, which produce antibodies
50
What leads to the development of T lymphocytes?
lymphocyte progenitors migrate from fetal liver to the thymus leading to T lymphocyte development
51
What are T lymphocytes involved in?
cell-mediated immunity
52
What are NK cells part of?
the innate immune system
53
What can NK cells do?
kill tumour cells and virus-infected cells
54
What abnormalities can occur in white cells (leukocytes)?
changes can be numerical, morphological or both
55
What does transient leukocytosis suggest?
a Reactive (i.e., secondary) cause
56
What does persistent leukocytosis suggest?
a Primary blood cell disorder
57
When does transient leukocytosis occur?
when a normal or healthy bone marrow responds to an external stimulus such as infection, inflammation or infarction
58
What response does bacterial infection lead to?
neutrophilia / monocytosis
59
What response does viral infection lead to?
lymphocytosis
60
What response does parasitic infection lead to?
eosinophilia
61
Why is the leukocyte count abnormal in persistent leukocytosis?
due to acquired somatic DNA damage affecting a haematopoietic precursor cell giving rise to blood cancers such as leukaemia, lymphoma or myeloma
62
What two groups can the abnormalities of leukocytes be divided into?
leukocytosis & leukopenia
63
What is leukocytosis?
two many white cells
64
????? Which type of white cell is increased in leukocytosis?
- neutrophilia
- eosinophilia
- basophilia
- lymphocytosis
- monocytosis
65
What is leukopenia?
reduction in total number of white cells
66
What is neutropenia?
reduction in neutrophil count
67
What is lymphopenia?
reduction in lymphocyte count
68
What do leukocytosis and leukopenia usually result from?
changes in the neutrophil count since this is usually the most abundant leukocyte in the circulation
69
What causes neutrophilia?
- infection (particularly bacterial infection)
- inflammation
- infarction
- or other tissue damage
70
What does neutrophilia normally feature in (3)?
- normal feature in pregnancy
- may be seen following exercise (caused by a rapid shift if neutrophils from the marginated pool to the circulating pool)
- after administration of corticosteroids
71
What may neutrophilia be accompanied by?
toxic changes and ‘left shift’
i.e., the presence if early myeloid cells such as metamyelocytes
72
What is toxic granulation?
heavy course granulation of neutrophils
73
What is chronic myeloid/granulocytic leukaemia (CML) an example of?
a myeloproliferative disorde
74
What is chronic myeloid/granulocytic leukaemia (CML)?
a primary blood cancer associated with neutrophilia, basophilia and ‘left shift’
75
What does left shift mean?
that there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood
76
What are increased non-segmented neutrophils known as?
band forms
77
What can neutropenia occur in?
a large number of conditions including chemotheraoy and radiotherapy
78
What can neutropenia also result from?
- autoimmune disorders
- severe nacterial infections
- certain viral infections and drugs e.g., some anticonvulsant, antipsychotic drugs and some antimalarials
79
Does neutropenia have a physiological basic?
sometimes - e.g., benign ethnic neutropenia in people of African or Afro-Caribbean ancestry
80
What are patients with very low neutrophil counts at high risk of?
serious infection and need urgent treatment with itnravenous antibiotics
81
What is considered a very low neutrophil count?
< 0.5 x 10^9/l
82
How many segments or lobes should a normal neutrophil have?
3-5
83
What does neutrophil hypersegmentation mean?
that there is an increase in the average number of neutrophil lobes or segments (‘right shift’)
84
What does neutrophil hypersegmentation usually result from?
a lack of vitamin B12 or folic acid (megaloblastic anaemia)
85
What is eosinophilia usually due to?
allergy or parasitic infection
asthma, eczeme, drugs
86
When can eosinophilia also occur in?
in some forms of leukaemia e.g., CML
87
strongyloidiasis blood film….?
88
What is basophilia (an uncommon finding) usually due to?
leukaemia or a related condition
89
CML blood film….?
90
What are the causes of monocytosis?
infection (particularly chronic i.e., long bacterial infection) or chronic inflammation
91
What do the terms ‘acute’ and ‘chronic’ refer to?
duration rather than severity
- acute=recent
- chronic=longstanding
92
What is lymphocytosis often a response to?
viral infection (transient)
93
Other than viral infection, what can lymphocytosis result from?
lymphoproliferative disorder e.g., chronic lymphocytic leukaemia (persistent)
94
Give an example of a disease which is an important cause of lymphocytosis in children.
whooping cough (Bordatella pertussis)
95
What does lymphopenia refer to?
a decease in the number of circulating lymphocytes
96
What is lymphopenia defined as (range)?
total lymphocyte count < 1 x 10^9/l
97
What are most lymphocytes in normal blood?
CD4+ T cells
98
What are some (4) important causes of lymphopenia?
- HIV infection
- chemotherapy
- radiotherapy
- corticosteroids
99
Where does the word leukaemia derive from?
Greek words for white and blood
100
What is leukaemia?
cancer of the blood
101
How are leukaemias described?
myeloid or lymphoid
102
According to what are leukaemias described as being myeloid or lymphoid?
whether the causative acquired mutation in the bone marrow is in the myeloid or lymphoid progenitor
103
What do leukaemic cells do?
replace normal haemopoietic stem cells in the bond marrow and may overspill into the blood
104
What percentage of cancers are cancers of the blood?
5%
105
Why does leukaemia occur?
results from a number of somatic mutations occurring in a primitive cell that, as a result, has a growth or survival advantage over normal cells
106
Why do the mutations leading to leukaemia occur?
may be spontaneous, random, or result from exposure to mutagens
107
Where are the mutations concerning leukaemia?
in oncogenes
& sometimes in tumour suppressor genes
108
????? What does the single cell give rise to in leukaemia?
a clone that steadily replaces normal cells:
- may not require usual growth factors
- disturbance in proliferation +/- maturation
- failure of apoptosis (normal cell death)
109
How does leukaemia differ from many other cancers?
in that the abnormal cells circulate in the blood stream and migrate into various tissues
110
Which concepts/terms do not apply to leukaemia?
- concepts of local invasion and metastasis
- terms malignant and benign used to describe solid tumours do not apply
111
?.? What characteristics of leukaemia do you have to look at to understand that leukaemia is a type of cancer?
- terms acute and chronic
- describe the natural history of the leukaemia in the absence of effective treatment
112
What are acute conditions like?
severe and sudden in onset
113
What are chronic conditions like?
the disease and deterioration go on for a long period of time
114
What determines whether a leukaemia is acute or chronic?
nature of the mutation
115
What are the main types of leukaemia?
- acute lymphoblastic leukaemia (ALL, blast because immature cells)
- acute myeloid leukaemia (AML)
- chronic lymphocytic leukaemia (CLL)
- chronic myeloid leukaemia (CML)
116
What do the types of leukaemia differ in?
- aetiology
- nature of the mutational events
- age of onset
- clinical & haematological features and prognosis
117
Describe some details and examples on the main types of leukaemia ALL, CLL, CML.
- ALL is particularly a disease of childhood - results from somatic mutations in utero
- CLL predominantly affects the elderly
- CML results from the activation of signalling pathways by fusion protein BCR-ABL1
118
???? What are two details of chronic lymphocytic leukaemia?
- steady expansion of clone of cells that are functionally useless
- this eventually leads to replacement of normal cells by the leukaemic clone
119
??? What are two points on B cell acute lymphoblastic leukaemia?
- progenitors acquire mutations, often in genes encoding transcription factors
- this affects the ability of cells to mature, while proliferation continues, leading to the accumulation of Blast cells
120
Describe what the accumulation of abnormal cells leads to (7)?
- leukocytosis
- bone pain (if leukaemia is acute)
- hepatomegaly
- splenomegaly
- lymphadenopathy (if lymphoid)
- thymic enlargement (if T lymphoid)
- skin infiltration
121
Describe 4 metabolic effects of leukaemic cell proliferation.
- hyperuricaemia and renal failure
- weight loss
- low grade fever
- sweating
122
Describe the clinical features of ‘crowding out’o of normal haemopoiesis (3).
- fatigue, lethargy, pallor, breathlessness (caused by anaemia)
- fever and other features of infection (caused by neutropenia)
- bruising, petechiae, bleeding (caused by thrombocytopenia)
123
??? Describe the loss of normal immune function which is a feature of chronic lymphocytic leukaemia.
loss of normal T cell and B cell function
124
What four questions should you consider when interpreting white cells on blood count and film?
- is there an abnormality?
- if so, which cell line is abnormal?
- are there any clues in the clinical history?
- are there any clues in the blood film?
125
What is production of granulocytes and macrophages controlled by?
growth factors such as GM-CSF
126
What is maturation of granulocytes characterised by?
- a reduction in cell size
- the development of granules that contain agents essential for cell function
127
What does leukopenia usually result from?
a low neutrophil count since this is usually the most abundant leukocyte in the circulation
