White Blood Cells Flashcards
Which white blood cells are produced from the common myeloid progenitor?
Granulocytes - neutrophils, basophils and eosinophils
monocytes
What is the difference between monocytes and macrophages?
Monocytes are in the blood whilst macrophages are in tissue
What are granulocytes?
multi-lobed, have granules, mature WBC
refers to neutrophils, basophils, eosinophils
the granules contain agents essential for their microbicidal function
What is the growth factor for granulocytes, macrophages and granulocyte-macrophages?
G-CSF granulocyte colony-stimulating factor;
M-CSF, macrophage colony-stimulating factor;
GM-CSF, granulocyte-macrophage colony stimulating factor
What does normal granulocyte maturation look like?
Myeloblast–> promyelocyte–> myelocyte–> metamyelocyte–> band form–> neutrophil (only the neutrophil is not in the bone marrow)
When does cell division occur/ not occur in the formation of a neutrophil?
occurs in myeloblast, promyelocyte and myelocyte
does not occur in metamyelocyte or band forms
How long do neutrophils survive in circulation?
7-10 hours
What is another word for segmented (nucleus)?
lobulated
What are the main functions of neutrophil granulocytes?
Chemotaxis, phagocytosis and killing of phagocytosed bacteria following cytokine priming
What are the main functions of basophils granulocytes?
Chemotaxis, phagocytosis, killing of phagocytosed bacteria, medication of immediate type hypersensitivity, modulates inflammation responses by releasing heparin
What do the granules of basophils contain?
histamine and heparin, as well as proteolytic enzymes
What type of responses are basophils involved with?
Basophils are involved 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
- Mast cells are similar to basophils, but reside in tissues rather than the circulation
What is the main functions of eosinophils?
Chemotaxis, phagocytosis, killing of phagocytosed bacteria, defense against parasitic infection
What do eosinophils play an important role in regulating of?
type I (immediate) hypersensitivity reactions: inactivate the histamine and leukotrienes released by basophils and mast cells
What is left shift?
there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood
How many lobes is normal for a neutrophil?
3-5
What is it called when there are more than 5 lobes in a neutrophil
Hyper segmented neutrophil
What are the steps of chemotaxis?
MARDi MP
Migration Adhesion Rolling Diapediesis Migration Phagocytosis
What is diapedesis?
When white blood cells migrate across the blood vessel wall
How many lobes do eosinophils contains?
2
How do you identify basophils?
They have many granules in their cytoplasm
How are myeloid stem cells related to monocytes?
they give rise to monocyte precursors and thence monocytes
What do monocytes do?
- phagocytosis of micro-organisms covered with antibody and complement
- phagocytosis of bacteria/fungi
- antigen presentation to lymphoid and other
immune cells
How are macrophages formed?
when monocytes migrate to tissues, they then develop into macrophages (aka histiocytes)
How are macrophages related to iron?
They store and release iron
What white blood cells derive from the common lymphoid progenitor?
T cell, B cells and NK cells
What is the lifespan and lymphocytes and what is their path around the body?
Lymphocytes re-circulate to lymph nodes and other tissues and then back to the blood stream
Intravascular life span is very variable
Where do B lymphcytes originate from?
foetal liver and bone marrow
How do B lymphocytes develop/ mature?
Involves Ig heavy and light chain gene rearragement
This 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
This results in recognition of non-self antigens by mature B cell and production of specific Igs and antibodies
Maturation into plasma cells which produce antibodies
What do B plasma lymphocytes produce?
Antibodies
How are T lymphocytes formed?
Lymphocyte progenitors migrate from foetal liver to the thymus leading to development of T lymphocytes
What type of immunity are T lymphocytes involved in?
cell-mediated immunity
What do NK Cells do?
Part of innate immunity - kill tumour and virus infected cells
What are these WBCs?
What is leukocytosis?
To many white blood cells of any type
What does transient leukocytosis suggest?
a reactive (I.e., secondary) cause
when does transient leukocytosis occur?
when a normal or healthy bone marrow responds to an external stimulus such as infection, inflammation or infarction
What does neutrophilia/ monocytosis suggest?
bacterial infection
What does lymphocytosis suggest?
viral infection
What does eosinophilia suggest?
parasitic infection
What is meant by neutrophilia, basophilia and eosinophilia?
Too many of each type of white blood cell
What does persistent leukocytosis suggest?
a primary blood cell disorder
What is a primary blood cell disorder?
The leukocyte count is abnormal due to acquired somatic DNA damage affecting a haematopoietic precursor cell giving rise to blood cancers such as leukaemia, lymphoma, or myeloma
What is leukopenia?
reduction in total number of white blood cell
What is the most abundant type of white blood cell?
Neutrophils
What is a reduction in neutrophil and lymphocytes called?
neutropenia and lymphopenia
What cell is leukocytosis and leukopenia most likely affected by and why?
changes in neutrophil count since this is usually the most abundant leukocyte in the circulation
What color of eosinophils appear when stained?
Red granules and two lobes
What can cause too many neutrophils?
NICE PreT
Neoplasm Infection/ Inflammation/ Infarction/ Tissue damage Corticosteroids Exercise Pregnancy Tissue damage
What usually accompanies neutrophilia?
toxic changes, and left shit (I.e., the presence of early myeloid cells such as metamyelocytes)
How does exercise increase the number of neutrophils?
Exercise causes a rapid shift of neutrophils from marginated pool to circulating pool
What is toxic granulation of neutrophils?
Heavy course granulation of neutrophils
What is CML and what is it an example of?
chronic myeloid/ granulocytic leukaemia
- a primary blood cancer associated with neutrophilia, basophilia and left shift
- myeloproliferative disorder
What causes neutropenia?
BRAID
Benign ethnic neutropenia - people of African descent
Radiotherapy
Autoimmune disorders
Infections - severe viral and bacterial infections
Drugs - eg chemotherapy, anticonvulsants and antipsychotics
What are examples of physiological reasons for neutropenia?
benign ethnic neutropenia in people of African or afro-Caribbean ancestry
What is considered a very low neutrophil count?
<0.5 x 10^9/L
What happens with patients with very low neutrophil count?
they are at high risk of serious infection and they need urgent treatment with intravenous antibiotics
What is lymphocytosis?
Too many lymphocytes
What causes lymphocytosis?
Often a response to viral infection (transient)
Can result from a lymphoproliferative disorder e.g., chronic lymphocytic leukaemia (persistent)
How to recognize lymphocytosis from a blood film?
Find atypical lymphocytes eg in Epstein Barr Virus infection
Basophillic cytoplasm
Scalloped margins of WBC
What condition in children causes lymphocytosis?
Whopping cough
What is the most common lymphocyte in normal blood?
CD4+ T cells
What is a cause of lymphopenia?
HIV infection
Also: chemotherapy, radiotherapy, corticosteroid
What causes eosinophilia?
Due to allergy or parasitic infection, asthma, eczema
It can occur in some forms of leukaemia e.g., CML
What causes basophillia?
Leukaemia or related condition e.g., CML
What causes monocytosis?
infection (particularly chronic I.e., long bacterial infection) or chronic inflammation
Some types of leukaemia
How many lobes should a normal neutrophil have?
between 3 and 5 segments or lobes
What does neutrophil segmentation mean?
There is an increase in the average number of neutrophil lobes or segments (‘right shift’)
What causes hyper-segmented neutrophil?
Usually results from a lack of B12 or folic acid (megaloblastic anaemia)
A 6-year old child is diagnosed with acute lymphoblastic leukaemia. The doctor warns the parents that their child is more susceptible to infections. Why is this the case?
The child’s bone marrow cells are not infiltrated with cancer cells
What do B lymphocytes mature into?
Plasma cells which secrete antibodies
What is meant by Reactive or Secondary changes?
Occur when a normal or healthy bone marrow responds to an external stimulus such as Infection, inflammation or infarction
What is a primary blood cell disorder?
The leukocyte count or morphology is abnormal due to acquired somatic DNA damage affecting a haematopoietic precursor cell giving rise to blood cancers such as leukaemia, lymphoma, myeloma or myeloproliferative disorders
What are causes of neutrophillia?
infection (particularly bacterial infection), inflammation, infarction or other tissue damage,
What lifestyle factors could cause neutrophillia?
Pregnancy
Exercise
Corticosteroids
When might toxic granulation be seen?
During pregnancy
What is meant by left shft in terms of neutrophillia?
There is an increase in non-segmented neutrophils in the blood (these are known as band forms)
What is leukaemia?
- “Leukaemia” is a cancer of the blood
- 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
- The leukaemic cells replace normal haemopoietic stem cells in the bone marrow and may overspill into the blood
- 5% of all cancers are cancers of the blood
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
- These mutations may be spontaneous, random or result from exposure to mutagens
- The single cell gives rise to a clone that
steadily replaces normal cells: - May not require usual growth factors
- Disturbance in proliferation +/- maturation
- Failure of apoptosis (normal cell death)
- The mutations concerned are in oncogenes & sometimes in tumour suppressor genes
How is leukaemia classified?
- Leukaemia differs from many other cancers in that the abnormal cells circulate in the blood stream and migrate into various tissues
- Concepts of local invasion and metastasis do not apply
- Terms malignant and benign used to describe solid tumours do not apply
- We therefore have to look at other characteristics of this disease to understand that leukaemia is a type of cancer
- The terms used are acute and chronic
- Describe the natural history of the leukaemia in the absence of effective treatment
- Acute conditions are severe and sudden in onset
- In Chronic conditions the disease and deterioration go on for a long period of time
- Nature of the mutation determines whether a leukaemia is acute or chronic
What are the main types of leukaemia?
Acute Lymphoblastic Leukaemia (ALL, blast because immature cells)
Acute Myeloid Leukaemia (AML) (blast cells)
Chronic Lymphocytic Leukaemia (CLL, cytic because mature lymphoid cells)
Chronic Myeloid Leukaemia (CML) (mature myeloid cells)
How do leukaemias differ?
Differ in aetiology, nature of the mutational events, age of onset, clinical and haemotological features and prognosis
What is special about ALL?
particular disease of childhood, results from somatic mutation in utero
What is special about CLL?
predominantly affects the elderly
What results in CML?
Results from the activation of signalling pathways by fusion protein BCR-ABL1
What causes chronic myeloid leukaemia?
CML results from a translocation (exchange of material) between chromosomes 9 and 22, occurring in a single haemopoietic stem cell, resulting in the formation of a fusion gene, ABL:BCR
What causes the replacement of normal cells by the leukaemic clone?
Steady expansion of clone cells that are functionally useless
This eventually leads to replacement of normal cells by the leukaemic clone
What causes the accumulation of blast cells in 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
Why does the fusion gene BCR:ABL cause CML?
The fusion protein has constitutive tyrosine kinase activity which drives autonomous blood cell proliferation
What happens to the spleen in CML?
Enlarged spleen
What causes too many monocytes?
infection (particularly chronic bacterial infection) or chronic inflammation
What might lymphocytes due to a viral infection look like?
Intensely basophilic cytoplasm, scalloped margins and hugging of the surrounding red blood cells
What cell type is characteristic of chronic myeloid leukaemia?
Smudge cells
What are some haematological features of acute lymphoblastic leukaemia?
Leukocytosis with lymphoblasts in the blood
Anaemia (normocytic, normochromic)
Neutropenia
Thrombocytopenia (low platelet count)
Replacement of normal bone marrow cells by lymphoblasts
Why might a child with acute lymphoblastic leukaemia have bruising and be pale?
Bruising is due to lack of platelets
Pale is due to anaemia
both these occur due to the replacement of normal bone marrow cells with lymphoblasts
What are the treatment options for ALL?
Supportive Red cells Platelets Antibiotics Systemic chemotherapy Intrathecal chemotherapy
What are the causes of lymphopenia?
HIV infection
Chemotherapy
Radiotherapy
Corticosteroids
What clinical features may be found in leukaemia?
Accumulation of abnormal cells leading
Metabolic effects of leukaemia cell proliferation
‘Crowding out’ of normal haemopoiesis
Loss of normal immune function
What does accumulation of abnormal cells lead to?
- Leukocytosis
- Bone pain (if leukaemia is acute)
- Hepatomegaly (enlarged liver)
- Splenomegaly
- Lymphadenopathy (if lymphoid)
- Thymic enlargement (if T lymphoid)
- Skin infiltration
What are examples of metabolic effects of leukaemic cell proliferation?
Hyperuricaemia and renal failure
Weight loss
Low grade fever
Sweating
What is meant by loss of normal immune function and what leukaemia is it a specific feature of?
loss of normal T and B cell function
a feature of Chronic lymphocytic leukaemia
What is meant by ‘crowding out’ of normal haemopoieisis?
Fatigue, lethargy, pallor, breathlessness (caused by anaemia)
Fever and other features of infection (caused by neutropenia)
Bruising, petechiae, bleeding (caused by thrombocytopenia)
What do you look out for when interpreting white cells on a blood count?
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?
