27-09-21 - White Blood Cells - Normal and Malignant

Question 1

What is chemotaxis?

Answer 1

• Chemotaxis is the movement of a cell/organism in a direction that correlates to a gradient of increasing or decreasing concentration of a particular substance

Question 2

What are the 5 common types of white blood cell?

How can they be identified on a microscope?

Answer 2

• Granulocytes – Neutrophils - multilobed nucleus
• Granulocytes – eosinophils - bilobed nucleus (may appear orange and pink)
• Granulocytes – basophils - corse purple granules with bilobed nucleus
• Lymphocytes - dark nucleus with thin rim of cytoplasm
• Monocytes - nuclei with indentation to one side

Question 3

Granulocyte neutrophils:

• What % of WBC in blood are these?
• What is their lifespan?
• What causes them to rise?
• What kind of immunity are they part of?
• What type of cells are neutrophils?
• What do they do with foreign bodies?

Answer 3

• Most common WBC type – make 50-70% of WBC count in blood.
• Short lifespan – 8-10 hours
• Neutrophils rise as an acute response to bacterial infection, inflammation and malignancy (e.g bacteria wall antigens) – this is chemotaxis
• Part of innate immune response.
• Neutrophils are phagocytic cells
• Foreign bodies (e.g bacteria) ingested and killed by enzymes in granules ex lysozyme and peroxidase.

Question 4

Granulocytes – eosinophils

• What % of WBC in blood are these?
• What is their lifespan?
• What is their growth promoted by?
• What causes them to rise?
• How do they kill foreign bodies?
• What kind of immunity are they part of?
• What stains the granules?

Answer 4

• Make up 1-6% of total WBC count in blood.
• Life span in blood is 4-5 hours (longer in tissues).
• Growth promoted by interleukin 5.
• Chemokines (signalling proteins) attract them to specific tissues.
• Their granules contain Major Basic Protein and reactive O2 species, which are toxic to what the eosinophils are trying to kill (parasites)
• Part of innate immunity.
• Eosin stains granules orange and pink.

Question 5

Eosinophils:

• What is their marked rise in numbers?
• Where are they most commonly seen?
• What causes their numbers to rise and fall?

Answer 5

• Marked rise in numbers in blood from 0.4 – 2-6 x 10^9/l
• Commonly seen in atopy – problem with your immune system that makes you more likely to develop allergic diseases e.g., eczema, asthma and hay fever
• Can also be found in Hodgkin’s disease, CML and other malignancy, adverse drug reactions, and helminth infection (intestinal worm)
• The blood levels of eosinophils often correlate with clinical activity e.g., during hay fever season.

Question 6

Granulocytes – Basophils:

• What % of WBC in blood are these?
• What is their lifespan?
• What do their granules consist of?
• What 3 roles do they play?
• What kind of immunity are they part of?

Answer 6

• Make up less than 1% of WBC count in blood.
• Lifespan of 1-2 days
• Dark basophilic granules contain histamine, leukotrienes, proteases and heparin
• Acts as a cell surface receptor for IgE – binding produces degranulation following chemotaxis.
• Role in phagocytosis
• Role in hypersensitivity (allergic) reactions
• Part of the innate immunity

Question 7

What is the specific term given to an allergic reaction?

What can it cause?

Answer 7

• Anaphylaxis – type 1 allergic reaction
• Can results in:
• Swelling of lips, tongue and or throat
• Skin – hives, itching, flushing
• Light-headedness, loss of consciousness, confusion, headache

Question 8

Lymphocytes:

• What % of WBC in blood are these?
• What is their lifespan?
• How are they formed?
• What are the 2 types and where are they found?
• What are they both responsible for?
• What causes them to rise?
• What can they indicate?
• What kind of immunity are they part of?

Answer 8

• Make up 20-40% of total WBC count in blood.
• Lifespan of 1 week to a few months
• Differentiate early from other marrow derived cells
• Divide into T cells (Thymus – lymphoid gland in chest) and B cells (Bone marrow or bursa)
• Rise in response to viral infections, and Chronic Lymphocytic Leukaemia
• T and B cell malignancies with circulating cells = leukaemia
• Part of the adaptive immunity

Question 9

Macrophages/Monocytes:

• What % of WBC in blood are these?
• What is the difference between the 2?
• What is their lifespan?
• What do they contain?
• What are their 2 roles?
• What kind of immunity are they part of?

Answer 9

• Make up 5-10% of WBC count in blood.
• Macrophages are monocytes that have migrates to any tissue in the body.
• Monocytes have a lifespan of a few days; macrophages have a lifespan of months to years.
• They have a vacuole containing hydrolases and myeloperoxidase
• They act as antigen presenting cells by ingesting material (phagocytosis) and presenting the peptides to T cells so antibodies can be made.
• Their role is to kill mycobacteria’s (e.g. TB), fungi and intracellular organisms e.g. listeria.
• Part of the innate immunity.

Question 10

What is innate and active immunity? What immunity are each type of WBC part of?

Answer 10

• Innate immunity – the organism is born with it (non-specific)
• Adaptive immunity – organism acquires this through disease exposure (specific)
• Innate immunity
• Neutrophils, eosinophils, basophils, monocytes
• Adaptive
• T and B lymphocytes

Question 11

What is a WBC differential?

What are 4 reasons why is it useful in clinical practise?

Answer 11

• A WBC differential determines the % of each type of WBC in the blood.
• A WBC differential and blood film can be useful clues for:
• Evidence of different types of infection and response to treatment
• Allergic response
• Leukaemia (malignant T and B cells in circulating blood is leukaemia)
• Marrow infiltration

Question 12

Chronic Myeloid Leukaemia (CML):

• What age group does it occur?
• What are symptoms?
• What are signs of it?
• How does it develop?
• What causes most cases?

Answer 12

• Occurs in all age groups.
• Symptoms of anaemia (tired, no energy), large spleen, bone pain
• Signs are anaemia, high WBC and platelet count (immature cells)
• Typically, a chronic phase and then an accelerated acute phase
• 95% of cases have an identical cytogenetic and molecular mutation.

Question 13

What is the cytogenetic mutation associated with Chronic myeloid leukaemia?

How does this cause CML?

How is this treated?

How is the effect monitored?

Answer 13

• Reciprocal translocation between chromosome 9 and 22.
• Each chromosome swaps a chunk.
• This results in the formation of a Philadelphia chromosome on chromosome 22
• This causes the tyrosine kinase gene to be activated which causes cell proliferation.
• The drug imatinib is used to treat CML by acting as a tyrosine kinase inhibitor
• Effect of drug monitored by PCR on blood test.

Question 14

Acute Myeloid Leukaemia (AML):

• What age group does it occur?
• What does it present with?
• What are symptoms?

Answer 14

• More common with increasing age
• Presents with symptoms of marrow failure:
• Anaemia
• Bleeding – purpura (small blood vessels bursting), bruises
• Infections – sepsis (life-threatening reaction to infection), pneumonia

Question 15

How is Acute Myeloid Leukaemia treated?

What are the problems when treating AML?

Answer 15

• Unlike CML, there are diverse cytogenetic changes, so there is no specific target for chemotherapy for AML
• Chemotherapy produces marrow aplasia, where the red marrow disappears and ceases to create new blood cells.
• It is hope that the marrow stem cells will regenerate bone marrow faster than the chemotherapy destroys it
• Under 60s patients can undergo bone marrow transplants.
• During chemo, patients can get infections, bleeds, psychological difficulties from long hospital stays, and suffer pain from venous access and frequent marrow tests to check response.

Question 16

Identify all the white blood cells on a blood film

Answer 16