White Blood Cells

Question 1

How are granulocytes and monocytes created?

Answer 1

The multipotent haemopoietic stem cell gives rise to a myeloblast, which in turn can give rise to granulocytes and monocytes.

Question 2

What are granulocytes?

Answer 2

Granulocytes refer to neutrophils, basophils and eosinophils, which have granules present in the cytoplasm that contain agents essential for their microbicidal function.

Question 3

What growth factors influence granulocytes?

Answer 3

Signalling through myeloid growth factors such as as G-CSF, M-CSF, GM-CSF is essential for the proliferation and survival of myeloid cells.
G-CSF granulocyte colony-stimulating factor;
M-CSF, macrophage colony-stimulating factor;
GM-CSF, granulocyte-macrophage colony stimulating factor

Question 4

Whta are the features of normal granulocyte maturation?

Answer 4

Maturation of granulocytes associated with reduction in size and development of granules that contain agents essential for cell function. Cell division occurs in myeloblasts, promyelocytes and myelocytes but does not occur in metamyelocytes or band forms. Precursors not found in bloodstream.

Question 5

What is the earliest recognisable form of a granulocyte?

Answer 5

Myeloblast earliest recognisable granulocytic cell in bone marrow - these cells are recognisable by their large size, open chromatin pattern of their nuclei and their prominent nucleoli.

Question 6

What are 3 features of the neutrophil?

Answer 6

1. The neutrophil granulocyte survives 7–10 hours in the circulation before migrating to tissues.
2. The nucleus of the mature neutrophil is segmented (sometimes referred to as lobulated).
3. Its main function is defence against infection; it phagocytoses and then kills micro-organisms.

Question 7

How does the neutrophil act?

Answer 7

The first step in neutrophil migration to tissues is chemotaxis. Neutrophils become marginated in the vessel lumen, adhere to the endothelium and migrate into tissues. Adhesion occurs via selectins, integrins and other adhesion molecules. Phagocytosis of micro-organisms occurs following cytokine priming. Neutrophils phagocytose microorganisms by the release of the neutrophil’s toxic intracellular contents via 2 mechanisms:

1. Superoxide dep mech – release of ROS known as respiratory burst and this provides substrate for enzyme MPO (Myeloperoxidase) leading to prod of toxic acidic substances
2. Oxygen indep – variety of antimicrobials released

Question 8

What is the purpose of the eosinophil?

Answer 8

A myeloblast can also give rise to eosinophil granulocytes. The eosinophil spends less time in the circulation than does the neutrophil. Its main function is defence against parasitic infection.

Question 9

What is the purpose of the basophil?

Answer 9

A myeloblast can also give rise to basophil granulocytes. Its granules contains stores of histamine and heparin, as well as proteolytic enzymes. Basophils are involved in a a variety of immune and inflammatory responses:

1. Mediation of the immediate-type hypersensitivity reaction in which IgE-coated basophils release histamine and leukotrienes.
2. Modulation of inflammatory responses by releasing heparin and proteases.

Question 10

What is the structure and purpose of a monocyte?

Answer 10

Monocytes spend several days in the circulation.
Monocytes play several key roles that include phagocytosis and antigen presentation to lymphoid cells. Monocytes migrate to tissues where they develop into macrophages (also known as histiocytes) and other specialised cells that have a phagocytic and scavenging function. Macrophages also store and release iron.

Question 11

What is the origin of the lymphocyte?

Answer 11

The multipotent haemopoietic stem cell also gives rise to a lymphoid stem cell. The 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 blood stream. Intravascular life span is very variable.

Question 12

What is the purpose of B-lymphocytes and how do they develop?

Answer 12

B lymphocytes mature into plasma cells, which produce antibodies. Progenitor B cells develop sequentially into pre-B cells and mature B cells during which there is gene rearrangement of the immunoglobulin heavy and light chains leading to the production of surface immunoglobulins against many different antigens. This is known as humoral immunity.

Question 13

What is the purpose of T-lymphocytes and NK cells?

Answer 13

T lymphocytes are involved in cell-mediated immunity. NK cells are part of the innate immune system ‒ they can kill tumour cells and virus-infected cells.

Question 14

What is leukocytosis and leukopenia?

Answer 14

Leukocytosis - too many WBCs in circulation

Leukopenia - too few WBCs in circulation

Question 15

When is transient leukocytosis seen?

Answer 15

Usually associated with infection.
Bacterial: Neutrophila/Monocytosis
Viral: Lymphocytosis
Parasitic: Eosinophilia

Question 16

When is persistent leukocytosis seen?

Answer 16

Persistent leukocytosis may be caused by leukaemia.
Chronic myeloid leukaemia, CML (neutrophilia, basophilia, eosinophilia)
Acute lymphoblastic leukaemia, ALL (blast cells – lymphoblasts - are found in the blood)
Chronic lymphocytic leukaemia, CLL (lymphocytosis)

Question 17

Name forms of leukocytosis and leukopenia

Answer 17

Leukocytosis:
neutrophilia, eosinophilia, basophilia, lymphocytosis, monocytosis
Leukopenia:
neutropenia, lymphopenia

Question 18

What is often the cause of leukocytosis and leukopenia?

Answer 18

leukocytosis and leukopenia usually result from changes in the neutrophil count since this is usually the most abundant leucocyte in the circulation.

Question 19

What are causes of neutrophilia?

Answer 19

infection (particularly bacterial infection), inflammation, infarction or other tissue damage, myeloproliferative disorders (chronic myeloid leukaemia)

Question 20

When is an increase in neutrophils usually seen?

Answer 20

Neutrophilia is also a normal feature in pregnancy and may be seen following exercise (caused by a rapid shift of neutrophils from the marginated pool to the circulating pool) and after administration of corticosteroids. Toxic granulation is heavy coarse granulation of neutrophils (it can be a feature of pregnancy).

Question 21

What can neutrophilia be accompanied by?

Answer 21

Neutrophilia may be accompanied by toxic changes and ‘left shift’ i.e. the presence of early myeloid cells such as metamyelocytes. Left shift means that there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood.

Question 22

What characterises CML and what is it caused by?

Answer 22

There is an increase in all granulocytes —neutrophils, eosinophils and basophils—and their precursors in both the blood and the bone marrow. CML results from a translocation (exchange of material) between chromosomes 9 and 22, occurring in a single haemopoietic stem cell. The gene product gives the cell a growth and survival advantage and gives rise to a leukaemic clone.

Question 23

Describe genetics of CML

Answer 23

Chr9 contains the ABL1 gene which codes for tyrosine kinase, an enzyme whose activity is tightly regulated. Chr22 contains the BCR gene. During a translocation, part of the ABL1 gene is transferred to Chr22 while a reciprocal change takes place on Chr9. Hence, BCR-ABL1 gene on Chr22 (Philadelphia Chr) encodes a protein with uncontrolled tyrosine kinase activity, which gives rise to leukaemic clone.

Question 24

What is a feature of CML and how is it treated?

Answer 24

There is an enlarged spleen (splenomegaly).
The BCR-ABL1 protein signals between the cell surface and the nucleus, enabling division but it can be inhibited by specific tyrosine kinase inhibitors leading to remission, and potentially cure, of the disease.

Question 25

What can cause neutropenia?

Answer 25

Neutropenia can occur in a large number of conditions. This includes following chemotherapy and radiotherapy. Neutropenia can also result from autoimmune disorders, severe bacterial infections, certain viral infections and drugs, e.g. some anticonvulsant and antipsychotic drugs and some antimalarials. Sometimes, neutropenia has a physiological basis e.g. benign ethnic neutropenia in people of African or Afro-Caribbean ancestry.

Question 26

When does neutropenia require urgent treatment?

Answer 26

Patients with very low neutrophil counts (< 0.5 × 109/l) are at a high risk of serious infection and the need urgent treatment with intravenous antibiotics.

Question 27

What does a hypersegmented neutrophil signify?

Answer 27

A normal neutrophil should have between 3 and 5 segments or lobes. Neutrophil hypersegmentation means that there is an increase in the average number of neutrophil lobes or segments (‘right shift’). It usually results from a lack of vitamin B12 or folic acid (megaloblastic anaemia).

Question 28

When is eosinophilia seen?

Answer 28

Usually due to allergy or parasitic infection e.g. asthma, eczema, drugs. Can occur in leukaemia e.g. CML.

Question 29

When is basophilia or monocytosis seen?

Answer 29

Basophilia is uncommon and usually due to leukaemia or a related condition. Monocytosis usually due to infection (particularly chronic bacterial infection) or chronic inflammation.

Question 30

When is lymphocytosis seen?

Answer 30

Often a response to viral infection (transient). Can result from a lymphoproliferative disorder (persistent). When lymphocytosis is due to a viral infection there are often ‘atypical lymphocytes’.

Question 31

How can infectious mononucleosis be spotted?

Answer 31

Infectious mononucleosis (‘glandular fever’) results from Epstein‒Barr virus infection. Lymphocytes tend to have intensely basophilic cytoplasm and the scalloped margins and ‘hugging’ of the surrounding red blood cells is a characteristic finding in infectious mononucleosis.

Question 32

What are characteristics of chronic lymphocytic leukaemia (CLL)?

Answer 32

Smear/smudge cells can be seen which are squashed CLL lymphocytes. CLL is a lymphoproliferative disorder
and the most common cause of persistent lymphocytosis in the elderly. Characterising the profile of cell surface markers expressed by lymphocytes helps determine the cause of the lymphocytosis.

Question 33

What is the difference between acute and chronic lymphoid leukaemias?

Answer 33

Leukaemia is a cancer originating in haemopoietic or lymphoid cells. In ALL, there is an increase in very immature cells (lymphoblasts) with a failure of these to develop into mature lymphocytes and the bone marrow is infiltrated by immature lymphoblasts, resulting in impaired haemopoiesis: lymphoblasts circulate in the peripheral blood. In CLL, the leukaemic cells are mature, although abnormal, T cells or B cells or natural killer (NK) cells.

Question 34

What is the difference between acute and chronic conditions?

Answer 34

Acute conditions are severe and sudden in onset. If acute leukaemias are not treated, the disease is very aggressive and patients die quickly. Chronic conditions means that the disease and deterioration go on for a long period of time.

Question 35

What are haematological features of ALL?

Answer 35

Leukocytosis with lymphoblasts in the blood
Anaemia (normocytic, normochromic)
Neutropenia
Thrombocytopenia (low platelet count)
Replacement of normal bone marrow cells by lymphoblasts

Question 36

Why is cytogenetic and molecular genetic analysis useful?

Answer 36

Cytogenetic/molecular genetic analysis is useful for managing the individual patient because it gives us information about prognosis. Advanced knowledge of leukaemia because permitted the discovery of leukaemogenic mechanisms and the development of
targeted treatment.

Question 37

What are clinical features of ALL?

Answer 37

Prominent bruising is due to reduced platelets (thrombocytopenia). Paleness due to low Hb (anaemia).
Thrombocytopenia and anaemia result from the
replacement of normal bone marrow cells by
lymphoblasts.

Question 38

What treatment is provided for ALL?

Answer 38

Red cells, Platelets, Antibiotics. Systemic chemotherapy. Intrathecal chemotherapy.

Question 39

What is lymphopenia defined as?

Answer 39

Lymphopenia refers to a decrease in the number of circulating lymphocytes. It is defined as a total lymphocyte count < 1 × 109/l. In normal blood, most lymphocytes are CD4+ T cells.

Question 40

What are common causes of lymphopenia?

Answer 40

HIV infection
Chemotherapy
Radiotherapy
Corticosteroids
Patients with severe infection may develop a transient low lymphocyte count.