White Blood Cells Flashcards
Name the granulocytes
Neutrophil, basophil, esoinophil
What do the granules in granulocytes contain?
agents for killing phagocytic material
What growth factors control the synthesis of granulocytes?
G-CSF
M-CSF
GM-CSF
What are the earliest visible precursors of granulocytes?
Myeloblast
What are the precursors of macrophages?
Monocytes
How long does the neutrophil survive for in the circulation?
7-10 hrs
Describe the nucleus of the mature neutrophil
segmented (sometimes referred to as lobulated)
What is the main function neutrophils?
Defence against infection; it phagocytoses and then kills micro-organisms
What is the first step in neutrophil migration?
Chemotaxis
Outline neutrophil migration to tissues
Neutrophils become marginated in the vessel lumen, adhere to the endothelium and migrate into tissues.
Phagocytosis of micro-organisms occurs following cytokine priming
What are eosinophils characterised by on a blood film?
Bright pink with H and E staining
What is the main function of eosinophils?
Defence against parasitic infection
What do basophil granules contain?
Stores of histamine, heparin and proteolytic enzymes
What immune and inflammatory responses are basophils involved in?
Mediation of type 1 hypersensitivity reaction on which IgE-coated basophils release histamine and leukotrienes
Mediation of inflammatory response by releasing heparin and proteases
Precursor of macrophages?
Monocytes
How long are macrophages in circulation?
Several days in circulation
Another name for macrophages?
Histiocytes
What is the role of macrophages?
Play several key roles that include phagocytosis and APCs to lymphoid cells
What do lymphoid stem cells give rise to?
T cells, B cells and NK cells
Where do T cells undergo their final maturation?
Thymus gland
What types of cells can NK cells kill?
Part of the innate immune system - they can kill tumour cells and virus-infected cells
What do leukocytosis and leukopenia usually result from?
Both usually result from changes in the neutrophil count since this is usually the most abundant leukocyte in the circulation
Causes of neutrophilia?
Infection (particularly bacterial), inflammation, infarction or other tissue damage, myeloproliferative disorders (CML)
What is neutrophilia a normal feature of?
Pregnancy
After administration of corticosteroids
May be seen following exercise (caused by a rapid shift of neutrophils from the marginated pool to the circulating pool)
What can neutrophilia be accompanied by?
Left shift
Toxic granulation
What is left-shift?
Increase in non-segmented neutrophils or that there are neutrophil precursors in the blood.
Their presence reflects an increase output from the bone marrow.
What is toxic granulation?
Heavy coarse granulation of neutrophils (it can be a feature of pregnancy)
Which myeloproliferative disorder can cause neutrophilia?
CML -Increase in all granulocytes and their precursors in both blood and the bone marrow.
What is the cause of CML?
Translocation between chromosome 9 and 22, occurring in a single HSC
BCR-ABL1 fusion gene
Formation of 2 fusion genes.
BCR-ABL1 gene encodes a protein with uncontrolled tyrosine kinase activity, which gives rise to leukaemic clone
What feature can be a sign of CML?
Splenomegaly
How can you prevent or inhibit CML?
Tyrosine kinase inhibitors leading to remission, and potentially cure the disease.
Conditions in which neutropenia can occur
Chemotherapy
Radiotherapy
Autoimmune disorders
Severe bacterial infections, certain viral infections and drugs e.g. some anticonvulsant and antipsychotic drugs and some antimalarials
Benign ethnic neutropenia (African or Afro-Caribbean descent)
What value is considered a low neutrophil count?
<0.5x10^9/l
Patients at a high risk of serious infection and they need urgent treatment with IV antibiotics
What is neutrophil hypersegementation?
Means that there is an increase in the average number of neutrophil lobes (right shift)
How many lobes does a normal neutrophil have?
Between 3 and 5 lobes
What causes neutrophil hypersegementation?
Lack of VB12 or folic acid deficiency
Causes of eosinophilia
Allergy or parasitic infection - asthma, eczema, drugs
Can occur in leukaemia e.g. CML
Causes of basophilia
Leukaemia or related condition
Causes of monocytosis
Infection (particularly chronic bacterial infection) or chronic inflammation
Some types of leukaemia
What is transient lymphocytosis often a response to?
Infection
What can be seen on a blood film of a patient with transient lymphocytosis caused by a bacterial, viral and parasitic infection respectively?
Bacterial - Neutrophilia/monocytosis
Viral - Lymphocytosis
Parasitic - Eosinophilia
What can persistent lymphocytosis result from?
Can result from lymphoproliferative and myeloproliferative disorders
What bacterium causes whooping cough?
Bordatella pertussis - Important cause of lymphocytosis in children.
What are often seen when lymphocytosis is due to a viral infection?
Atypical lymphocytes
What infection can infectious mononucleosis (Glandular fever) result from?
Epstein-Barr virus infection
(Blood film: Atypical lymphocyte: Middle lymphocyte has intensely basophilic cytoplasm. Hugging of surrounding RBCs is a characteristic finding in infectious mononucleosis)
What is a leukaemia?
Cancer originating in haemopoietic or lymphoid cells
What is CLL?
Lymphoproliferative disorder
Most common cause of persistent lymphocytosis in elderly.
What is seen on a blood film of a patient with CLL?
4 mature CLL lymphocytes
Squashed CLL lymphocyte (smear/smudge cell → characteristic of CLL
On a blood film of a patient with ALL what is there an increase in?
Very immature cells (lymphoblasts) with a failure of these to develop into mature lymphocytes.
In ALL, what is infiltrated by mature lymphoblasts?
Bone marrow resulting in impaired haemopoiesis. Lymphoblasts circulate in the peripheral blood.
Describe the onset of acute conditions.
Severe and sudden onset.
If acute leukaemias aren’t treated the disease is very aggressive and patients die quickly
List the haematological features of ALL.
Leukocytosis with lymphoblasts in blood → suppression of normal haemopoiesis
Anaemia (normocytic, normochromic)
Neutropenia
Thrombocytopenia (low platelet)
Replacement of normal bone marrow cells by lymphoblasts
What is a good and bad prognosis for ALL?
Good - Hyperdiploidy
Bad - t(4;11) > Translocation 4 to 11.
Why is cytogenetic and molecule genetic analysis useful?
Useful for managing individual patient because it gives info about prognosis
How can you treat ALL?
Supportive - Red cells, platelets, antibiotics
Systemic chemotherapy
Intrathecal chemotherapy
Compare ALL and CLL.
CLL: Leukaemic cells are mature, although abnormal T cells, B cells and NK cells. Chronic therefore disease and deterioration go in for a long period of time.
ALL: Leukaemic cells are immature (lymphoblasts). Acute therefore severe and sudden onset.
Define lymphopenia
Too few lymphocytes in circulation.
Total lymphocyte count - <1x10^9/l
Important causes of lymphopenia?
HIV infection
Radiotherapy
Corticosteroids
Patients with lymphopenia and a severe infection may develop what?
Transient low lymphocyte count
