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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

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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

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3
Q

How does the stem cell hierarchy split from the small lymphocyte?

A

small lymphocyte -> T lymphocyte & B lymphocyte

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4
Q

How does the stem cell hierarchy split from the B lymphocyte?

A

B lymphocyte -> plasma cell

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5
Q

How does the stem cell hierarchy split from the common myeloid progenitor?

A

common myeloid progenitor -> megakaryocyte & erythrocyte & mast cell & myeloblast

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6
Q

How does the stem cell hierarchy split from the myeloblast?

A

myeloblast -> basophil & neutrophil & eosinophil & monocyte

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7
Q

Which cells are classified as granulocytes?

A

basophil, neutrophil, eosinophil

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8
Q

How does the stem cell hierarchy continue from monocyte?

A

monocyte -> macrophage

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9
Q

How does the stem cell hierarchy continue from megakaryocyte?

A

megakaryocyte -> thrombocyte

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10
Q

What does the multipotent haemopoietic stem cell give rise to?

A

myeloblast -> granulocytes & monocytes

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11
Q

What are granulocytes?

A

neutrophils, basophils, eosinophils which have granules in the cytoplasm that contain agents essential for their microbicidal function

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12
Q

What does G-CSF stand for?

A

granulocyte colony-stimulating factor

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13
Q

What does M-CSF stand for?

A

macrophage colony-stimulating factor

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14
Q

What does GM-CSF stand for?

A

granulocyte-macrophage colony stimulating factor

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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
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16
Q

How long does neutrophil granulocyte survive for before migrating to tissues?

A

7-10 hours in circulation before migrating to tissues

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17
Q

What does the nucleus of a mature neutrophil look like?

A

segmented (sometimes referred to as lobulated)

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18
Q

What is the main function of a neutrophil?

A

defence against infection - it phagocytoses and then kills micro-organisms

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19
Q

What is the first step in neutrophil migration to tissues?

A

chemotaxis

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20
Q

What happens in chemotaxis of neutrophils?

A
  • become marginated in the vessel lumen
  • adhere to the endothelium
  • migrate into tissues
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21
Q

What happens after cytokine priming (neutrophils)?

A

phagocytosis of micro-organisms

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22
Q

What gives rise to eosinophil granulocytes?

A

myeloblast

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23
Q

How much time does the eosinophil spend in circulation compared to the neutrophil?

A

less time

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24
Q

What is the main function of eosinophils?

A

defence against parasitic infection

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25
Q

What are eosinophils important in the regulation of?

A

regulation of Type I (immediate) hypersensitivity reactions

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26
Q

How are eosinophils important in the regulation if Type I (immediate) hypersensitivity reactions?

A

inactivate the histamine and leukotrienes released by basophils and mast cells

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27
Q

What gives rise to basophil granulocytes?

A

myeloblast

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28
Q

What do the granules of basophils contain?

A

stores of histamine and heparin
as well as proteolytic enzymes

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29
Q

What are basophils involved in?

A

a variety of immune and inflammatory responses

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30
Q

What are two examples of basophil involvement in a variety of immune and inflammatory responses?

A
  • 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
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31
Q

Mast cells vs basophils?

A

mast cells are similar to basophils, but reside in tissues rather than the circulation

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32
Q

What gives rise to monocytes?

A

myeloid stem cell -> monocyte precursors -> monocytes

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33
Q

How long do monocytes spend in the circulation?

A

several days

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34
Q

What are three key roles that monocytes play?

A
  • phagocytosis of micro-organisms covered with antibody and complement
  • phagocytosis of bacteria/fungi (cf antibody)
  • antigen presentation to lymphoid and other immune cells
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35
Q

Where do monocytes migrate to?

A

tissues where they develop into macrophages (aka histiocytes) and other specialised cells that have phagocytic and scavenging function

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36
Q

What is an additional function of macrophages?

A

store and release iron

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37
Q

Describe the lymphoid differentiation which leads to mature B cells.

A

pluripotent HSC -> common lymphoid progenitor -> B cell progenitors in bone marrow -> mature B cells

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38
Q

Describe the lymphoid differentiation which leads to mature T cells.

A

pluripotent HSC -> common lymphoid progenitor -> T cell progenitors (thymus->bone marrow) -> mature T cells

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39
Q

Describe the lymphoid differentiation which leads to myeloid cells.

A

pluripotent HSC -> myeloid cells

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40
Q

What gives rise to lymphoid stem cells?

A

multipotent haemopoietic stem cell

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41
Q

What do lymphoid stem cells give rise to (3)?

A

T cells, B cells and natural killer (NK) cells

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42
Q

Where do lymphocytes recirculate to?

A

lymphocytes recirculate to lymph nodes and other tissues and then back to the blood stream

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43
Q

What is the intravascular life span of lymphocytes?

A

very variable

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44
Q

Where do B lymphocytes originate?

A

in fetal liver and bone marrow

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45
Q

What does the development of B lymphocytes involve?

A

Ig heavy & light chain gene rearrangement

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46
Q

What does development of B lymphocytes lead to?

A

production of surface Igs against many different antigens: humoral immunity

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47
Q

What does subsequent maturation of B lymphocytes require?

A

exposure to antigens in lymphoid tissue e.g., lymph nodes

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48
Q

What does the maturation of B lymphocytes result in?

A
  • recognition of non-self antigens
  • production of specific Igs and antibodies
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49
Q

What do B lymphocytes mature into?

A

plasma cells, which produce antibodies

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50
Q

What leads to the development of T lymphocytes?

A

lymphocyte progenitors migrate from fetal liver to the thymus leading to T lymphocyte development

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51
Q

What are T lymphocytes involved in?

A

cell-mediated immunity

52
Q

What are NK cells part of?

A

the innate immune system

53
Q

What can NK cells do?

A

kill tumour cells and virus-infected cells

54
Q

What abnormalities can occur in white cells (leukocytes)?

A

changes can be numerical, morphological or both

55
Q

What does transient leukocytosis suggest?

A

a Reactive (i.e., secondary) cause

56
Q

What does persistent leukocytosis suggest?

A

a Primary blood cell disorder

57
Q

When does transient leukocytosis occur?

A

when a normal or healthy bone marrow responds to an external stimulus such as infection, inflammation or infarction

58
Q

What response does bacterial infection lead to?

A

neutrophilia / monocytosis

59
Q

What response does viral infection lead to?

A

lymphocytosis

60
Q

What response does parasitic infection lead to?

A

eosinophilia

61
Q

Why is the leukocyte count abnormal in persistent leukocytosis?

A

due to acquired somatic DNA damage affecting a haematopoietic precursor cell giving rise to blood cancers such as leukaemia, lymphoma or myeloma

62
Q

What two groups can the abnormalities of leukocytes be divided into?

A

leukocytosis & leukopenia

63
Q

What is leukocytosis?

A

two many white cells

64
Q

????? Which type of white cell is increased in leukocytosis?

A
  • neutrophilia
  • eosinophilia
  • basophilia
  • lymphocytosis
  • monocytosis
65
Q

What is leukopenia?

A

reduction in total number of white cells

66
Q

What is neutropenia?

A

reduction in neutrophil count

67
Q

What is lymphopenia?

A

reduction in lymphocyte count

68
Q

What do leukocytosis and leukopenia usually result from?

A

changes in the neutrophil count since this is usually the most abundant leukocyte in the circulation

69
Q

What causes neutrophilia?

A
  • infection (particularly bacterial infection)
  • inflammation
  • infarction
  • or other tissue damage
70
Q

What does neutrophilia normally feature in (3)?

A
  • 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
Q

What may neutrophilia be accompanied by?

A

toxic changes and ‘left shift’
i.e., the presence if early myeloid cells such as metamyelocytes

72
Q

What is toxic granulation?

A

heavy course granulation of neutrophils

73
Q

What is chronic myeloid/granulocytic leukaemia (CML) an example of?

A

a myeloproliferative disorde

74
Q

What is chronic myeloid/granulocytic leukaemia (CML)?

A

a primary blood cancer associated with neutrophilia, basophilia and ‘left shift’

75
Q

What does left shift mean?

A

that there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood

76
Q

What are increased non-segmented neutrophils known as?

A

band forms

77
Q

What can neutropenia occur in?

A

a large number of conditions including chemotheraoy and radiotherapy

78
Q

What can neutropenia also result from?

A
  • autoimmune disorders
  • severe nacterial infections
  • certain viral infections and drugs e.g., some anticonvulsant, antipsychotic drugs and some antimalarials
79
Q

Does neutropenia have a physiological basic?

A

sometimes - e.g., benign ethnic neutropenia in people of African or Afro-Caribbean ancestry

80
Q

What are patients with very low neutrophil counts at high risk of?

A

serious infection and need urgent treatment with itnravenous antibiotics

81
Q

What is considered a very low neutrophil count?

A

< 0.5 x 10^9/l

82
Q

How many segments or lobes should a normal neutrophil have?

A

3-5

83
Q

What does neutrophil hypersegmentation mean?

A

that there is an increase in the average number of neutrophil lobes or segments (‘right shift’)

84
Q

What does neutrophil hypersegmentation usually result from?

A

a lack of vitamin B12 or folic acid (megaloblastic anaemia)

85
Q

What is eosinophilia usually due to?

A

allergy or parasitic infection
asthma, eczeme, drugs

86
Q

When can eosinophilia also occur in?

A

in some forms of leukaemia e.g., CML

87
Q

strongyloidiasis blood film….?

A
88
Q

What is basophilia (an uncommon finding) usually due to?

A

leukaemia or a related condition

89
Q

CML blood film….?

A
90
Q

What are the causes of monocytosis?

A

infection (particularly chronic i.e., long bacterial infection) or chronic inflammation

91
Q

What do the terms ‘acute’ and ‘chronic’ refer to?

A

duration rather than severity
- acute=recent
- chronic=longstanding

92
Q

What is lymphocytosis often a response to?

A

viral infection (transient)

93
Q

Other than viral infection, what can lymphocytosis result from?

A

lymphoproliferative disorder e.g., chronic lymphocytic leukaemia (persistent)

94
Q

Give an example of a disease which is an important cause of lymphocytosis in children.

A

whooping cough (Bordatella pertussis)

95
Q

What does lymphopenia refer to?

A

a decease in the number of circulating lymphocytes

96
Q

What is lymphopenia defined as (range)?

A

total lymphocyte count < 1 x 10^9/l

97
Q

What are most lymphocytes in normal blood?

A

CD4+ T cells

98
Q

What are some (4) important causes of lymphopenia?

A
  • HIV infection
  • chemotherapy
  • radiotherapy
  • corticosteroids
99
Q

Where does the word leukaemia derive from?

A

Greek words for white and blood

100
Q

What is leukaemia?

A

cancer of the blood

101
Q

How are leukaemias described?

A

myeloid or lymphoid

102
Q

According to what are leukaemias described as being myeloid or lymphoid?

A

whether the causative acquired mutation in the bone marrow is in the myeloid or lymphoid progenitor

103
Q

What do leukaemic cells do?

A

replace normal haemopoietic stem cells in the bond marrow and may overspill into the blood

104
Q

What percentage of cancers are cancers of the blood?

A

5%

105
Q

Why does leukaemia occur?

A

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
Q

Why do the mutations leading to leukaemia occur?

A

may be spontaneous, random, or result from exposure to mutagens

107
Q

Where are the mutations concerning leukaemia?

A

in oncogenes
& sometimes in tumour suppressor genes

108
Q

????? What does the single cell give rise to in leukaemia?

A

a clone that steadily replaces normal cells:
- may not require usual growth factors
- disturbance in proliferation +/- maturation
- failure of apoptosis (normal cell death)

109
Q

How does leukaemia differ from many other cancers?

A

in that the abnormal cells circulate in the blood stream and migrate into various tissues

110
Q

Which concepts/terms do not apply to leukaemia?

A
  • concepts of local invasion and metastasis
  • terms malignant and benign used to describe solid tumours do not apply
111
Q

?.? What characteristics of leukaemia do you have to look at to understand that leukaemia is a type of cancer?

A
  • terms acute and chronic
  • describe the natural history of the leukaemia in the absence of effective treatment
112
Q

What are acute conditions like?

A

severe and sudden in onset

113
Q

What are chronic conditions like?

A

the disease and deterioration go on for a long period of time

114
Q

What determines whether a leukaemia is acute or chronic?

A

nature of the mutation

115
Q

What are the main types of leukaemia?

A
  • acute lymphoblastic leukaemia (ALL, blast because immature cells)
  • acute myeloid leukaemia (AML)
  • chronic lymphocytic leukaemia (CLL)
  • chronic myeloid leukaemia (CML)
116
Q

What do the types of leukaemia differ in?

A
  • aetiology
  • nature of the mutational events
  • age of onset
  • clinical & haematological features and prognosis
117
Q

Describe some details and examples on the main types of leukaemia ALL, CLL, CML.

A
  • 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
Q

???? What are two details of chronic lymphocytic leukaemia?

A
  • steady expansion of clone of cells that are functionally useless
  • this eventually leads to replacement of normal cells by the leukaemic clone
119
Q

??? What are two points on B cell acute lymphoblastic leukaemia?

A
  • 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
Q

Describe what the accumulation of abnormal cells leads to (7)?

A
  • leukocytosis
  • bone pain (if leukaemia is acute)
  • hepatomegaly
  • splenomegaly
  • lymphadenopathy (if lymphoid)
  • thymic enlargement (if T lymphoid)
  • skin infiltration
121
Q

Describe 4 metabolic effects of leukaemic cell proliferation.

A
  • hyperuricaemia and renal failure
  • weight loss
  • low grade fever
  • sweating
122
Q

Describe the clinical features of ‘crowding out’o of normal haemopoiesis (3).

A
  • fatigue, lethargy, pallor, breathlessness (caused by anaemia)
  • fever and other features of infection (caused by neutropenia)
  • bruising, petechiae, bleeding (caused by thrombocytopenia)
123
Q

??? Describe the loss of normal immune function which is a feature of chronic lymphocytic leukaemia.

A

loss of normal T cell and B cell function

124
Q

What four questions should you consider when interpreting white cells on blood count and film?

A
  • 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
Q

What is production of granulocytes and macrophages controlled by?

A

growth factors such as GM-CSF

126
Q

What is maturation of granulocytes characterised by?

A
  • a reduction in cell size
  • the development of granules that contain agents essential for cell function
127
Q

What does leukopenia usually result from?

A

a low neutrophil count since this is usually the most abundant leukocyte in the circulation

POM (5 decks)

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