3.5 & 3.7 - White Blood Cells Flashcards
1
Q
Origin of white blood cells (leukocytes)
A
- multipotent HSC gives rise to a myeloblast, which in turn can give rise to granulocytes and monocytes
- granulocytes refer to neutrophils, basophils and eosinophils, which have granules present in the cytoplasm that contain agents (proteolytic enzymes) essential for their microbicidal function
- signalling through myeloid growth factors e.g. G-CSF, M-CSF, GM-CSF is essential for the proliferation and survival of myeloid cells
- cell division occurs in myeloblasts, promyelocytes and myelocytes (does not occur in metamyelocytes or band forms)
2
Q
Neutrophil
A
- the neutrophil granulocyte survives 7-10 hours in the circulation before migrating to tissues
- the nucleus of the mature neutrophil is segmented / lobulated
- main function is defence against infection; it phagocytoses and kills microorganisms by two mechanisms:
1. superoxide dependent: the release of reactive oxygen species known as the ‘respiratory burst’ provides a substrate for the enzyme myeloperoxidase –> production of toxic acidic substances
2. oxygen-independent: a variety of antimicrobial agents are released e.g. defensins, gelatinases - neutrophils released from bone marrow –> peripheral blood –> tissues
- first step in neutrophil migration to tissues is chemotaxis
- neutrophils become marginated in the vessel lumen, adhere to the endothelium and migrate into tissues
- phagocytosis of microorganisms occurs following cytokine priming
3
Q
Eosinophil
A
- a myeloblast can also give rise to eosinophil granulocytes
- the eosinophil spends less time in the circulation than the neutrophil
- main function is defence against parasitic infection
- important in regulation of Type 1 (immediate) hypersensitivity reactions - inactivate the histamine and leukotrienes released by basophils and mast cells
- bilobed nuclei (not multilobed)
4
Q
Basophil
A
- a myeloblast can also give rise to basophil granulocytes
- its granules contain stores of histamine and heparin, as well as proteolytic enzymes
- lobulated nucleus harder to see, larger granules and dark stained
Basophils involved in a variety of immune and inflammatory responses e.g: - 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
- mast cells are similar to basophils, but reside in tissues rather than the circulation
5
Q
Monocyte
A
- myeloid stem cell gives rise to monocyte precursors and thence monocytes
- spend several days in circulation
- migrate to tissues where they develop into macrophages and other specialised cells that have a phagocytic and scavenging function
- macrophages also store and release iron
- nucleus looks like a kidney bean
Main functions: - phagocytosis of microorganisms covered with antibody and complement
- phagocytosis of bacteria / fungi
- antigen presentation to lymphoid and other immune cells
6
Q
Origin of white cells: lymphocytes
A
- multipotent HSC also gives rise to a lymphoid stem cell
- lymphoid stem cell gives rise to T cells, B cells and natural killer (NK) cells
- lymphocytes recirculate to lymph nodes and other tissues and then back to the bloodstream
- intravascular lifespan very variable
- nucleus fills most of the space and is single lobed
7
Q
B lymphocytes
A
- originate in foetal liver and bone marrow
- development involves Ig heavy and light chain gene rearrangement - allows specific antibodies to be released
- leads to production of surface Igs against many different antigens - humoral immunity
- subsequent maturation requires exposure to antigens in lymphoid tissue e.g. lymph nodes
- results in recognition of self and non-self antigens by mature B cells and production of specific Igs and antibodies
8
Q
T lymphocytes and NK cells
A
- lymphocyte progenitors migrate from foetal liver to the thymus leading to development of T lymphocytes
- involved in cell-mediated immunity
- NK cells are part of the innate immune system - they can kill tumour cells and virus-infected cells
- cannot differentiate between T and B cells - in order to do this, must stain with antibody
9
Q
White cell abnormalities
A
- changes can be numerical, morphological (type/function) or both
- transient (not permanent) leucocytosis suggests a reactive (secondary) cause, and occurs when a normal bone marrow responds to an external stimulus e.g. infection, inflammation, infarction
- persistent leucocytosis suggests a primary blood cell disorder - leucocyte count is abnormal due to acquired somatic DNA damage affecting a haematopoietic precursor cell giving rise to blood cancers e.g. leukaemia, lymphoma or myeloma
10
Q
Causes of white cell abnormalities
A
Leucocytosis - too many white cells - but which type of white cell is increased?
- neutrophilia
- eosinophilia
- basophilia
- lymphocytosis
- monocytosis
Leukopenia - reduction in total number of white cells
- neutropenia - reduction in neutrophil count
- lymphopenia - reduction in lymphocyte count
- leucocytosis and leukopenia usually result from changes in neutrophil count since this is usually the most abundant leucocyte in circulation
11
Q
Neutrophilia
A
- too many neutrophils
- causes: infection (particularly bacterial), inflammation, infarction or other tissue damage
- normal feature in pregnancy and may be seen following exercise (caused by rapid shift of neutrophils from the marginated pool to the circulating pool) and after administration of corticosteroids
- may be accompanied by toxic changes and ‘left shift’ - the presence of early myeloid cells e.g. metamyelocytes
- left shift - increase in non-segmented neutrophils, or that there are neutrophil precursors in the blood
- toxic granulation is heavy coarse granulation of neutrophils - bigger, more prominent granules and vacuolation
- chronic myeloid/granulocyte leukaemia (CML) = myeloproliferative disorder - primary blood cancer associated with neutrophilia, basophilia and left shift
12
Q
Neutropenia
A
- too few neutrophils
- can occur in a large number of conditions and following chemotherapy / radiotherapy
- can also result from autoimmune disorders, severe bacterial infections, certain viral infections and drugs (some anticonvulsants, antipsychotics and antimalarials)
- can have a physiological basis e.g. benign ethnic neutropenia in people of African or Afro-Caribbean ancestry
- very low neutrophil count increases risk of serious infection and the need for urgent treatment with intravenous antibiotics
- look at differential WBC count as well as just total WBC count
13
Q
Hypersegmented neutrophil
A
- normal neutrophil should have between 3 and 5 lobes
- neutrophil hypersegmentation means there is an increase in the average number of neutrophil lobes or segments (‘right shift’)
- usually due to lack of vitamin B12 or folic acid (megaloblastic anaemia)
14
Q
Eosinophilia
A
- too many eosinophils
- usually due to allergy or parasitic infection - asthma, eczema, drugs
- can occur in some forms of leukaemia e.g. CML
15
Q
Basophilia
A
- too many basophils
- uncommon finding - usually due to leukaemia or a related condition
16
Q
Monocytosis
A
- causes: infection (particularly chronic i.e. long bacterial infection) or chronic inflammation
- some types of leukaemia
17
Q
Lymphocytosis
A
- too many lymphocytes
- often a response to viral infection (transient)
- can result from lymphoproliferative disorder e.g. chronic lymphocytic leukaemia (persistent)
18
Q
Lymphopenia
A
- decrease in number of circulating lymphocytes
- defined as a total lymphocyte count < 1 x 10^9/l
- in normal blood, most lymphocytes are CD4+ T cells
- causes include: HIV infection, chemotherapy, radiotherapy, corticosteroids
- patients with severe infection may develop a transient low lymphocyte count
19
Q
Leukaemia
A
- a cancer of the blood - a bone marrow disease
- leukaemias are described as being myeloid or lymphoid according to whether the causative acquired mutation in the bone marrow is in a myeloid or lymphoid progenitor, and acute or chronic
- mutations lead the progeny to show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of the leukemic clone
- the leukemic cells replace normal HSCs in the bone marrow and may overspill into the blood
20
Q
Why does leukaemia occur?
A
- results from a number of somatic mutations occurring in a primitive cell (HSC) that, as a result, has a growth or survival advantage over normal cells
- these mutations may be spontaneous, random or result from exposure to mutagens e.g. chemo/radiotherapy
- the single cell gives rise to a clone that steadily replaces normal cells
- may not require usual growth factors
- disturbance in proliferation and/or maturation
- failure of apoptosis
- mutations concerned are in oncogenes and sometimes in tumour suppressor genes
21
Q
How is leukaemia classified?
A
- leukaemia differs from many other cancers in that the abnormal cells circulate in the bloodstream and migrate into various tissues
- concepts of local invasion and metastasis do not apply
- terms malignant and benign do not apply
- the terms chronic (long term) and acute (severe and sudden in onset) are used
- nature of mutation determines whether a leukaemia is acute or chronic
The main types of leukaemia are: - acute lymphoblastic leukaemia (ALL) - progenitors acquire mutations, often in genes encoding transcription factors = affects ability of cells to mature, while proliferation continues = accumulation of blast cells
- acute myeloid leukaemia (AML) - blast cells
- chronic lymphocytic leukaemia (CLL) - steady expansion of clone of cells that are functionally useless = replacement of normal cells by leukemic clone
- chronic myeloid leukaemia (CML) - mature myeloid cells
- different types of leukaemia differ in aetiology, nature of the mutational events, age of onset, clinical and haematological features and prognosis
22
Q
Acute vs chronic leukaemias
A
- acute - increase in immature cells (myeloblasts or lymphoblasts) with a failure of these to develop into mature leukocytes
- chronic - cells are mature but abnormal - granulocytes (CML) or lymphocytes (CLL)
- acute - bone marrow infiltrated by blast cells = impaired haemopoiesis - blast cells also circulate in peripheral blood and can be seen on the blood film
- if acute leukaemias not treated, the disease is aggressive and patients die quickly
- chronic - disease and deterioration go on for a long period of time
- CML - mature end cells still able to function
- CLL - lymphocytes are functionally useless and there is a loss of normal immune function
23
Q
What is infectious mononucleosis (glandular fever)?
A
- when lymphocytosis is due to a viral infection there are often ‘atypical’ lymphocytes
- blood film shows ‘atypical’ lymphocytes with features e.g:
- lymphocyte with intensely basophilic (blue) cytoplasm
- scalloped margins and ‘hugging’ of the surrounding red blood cells is a characteristic finding, resulting from Epstein-Barr virus infection
24
Q
What is chronic lymphocytic leukaemia (CLL)?
A
- blood film contains mature CLL lymphocytes (stained purple) and squashed CLL lymphocytes - known as a ‘smear’ or ‘smudge’ cell
- lymphoproliferative disorder
- most common cause of persistent lymphocytosis in elderly
- characterising the profile of cell surface markers expressed by lymphocytes using flow cytometry helps confirm diagnosis
- CLL is staged according to the degree of lymph node/liver/spleen involvement, and whether Hb and platelet count are reduced
25
Q
Acute lymphoblastic leukaemia - cytogenic and molecular genetic analysis
A
- cytogenic/molecular analysis is useful for managing the individual patient as it gives us information about prognosis
- advances knowledge of leukaemia because it has permitted discovery of leukaemogenic mechanisms and the development of targeted treatment
26
Q
What are some treatment approaches for acute lymphoblastic leukaemia?
A
- supportive - red blood cells, platelets, antibiotics
- systemic chemotherapy
- intrathecal (around spinal cord) chemotherapy
27
Q
What clinical features may be found in leukaemia? Accumulation of abnormal cells leading to:
A
- leukocytosis
- bone pain (if acute)
- hepatomegaly
- splenomegaly
- lymphadenopathy (if lymphoid)
- thymic enlargement (if T lymphoid)
- skin infiltration
28
Q
What clinical features may be found in leukaemia? Metabolic effects of leukaemic cell proliferation
A
- hyperuricaemia and renal failure
- weight loss
- low grade fever
- sweating
29
Q
What clinical features may be found in leukaemia? ‘Crowding out of normal haemopoiesis
A
- fatigue, lethargy, pallor, breathlessness (caused by anaemia)
- fever and other features of infection (caused by neutropenia)
- bruising, petechiae, bleeding (caused by thrombocytopenia)
30
Q
What clinical features may be found in leukaemia? Loss of immune function?
A
- loss of normal T and B cell function
- feature of CLL
