B11 - leukocytes: production and function Flashcards
Granulopoiesis
- The process by which cells that have granules are made in the bone marrow
- HSC (haemopoietic stem cells) undergoes specific differentiation in response to cytokines (cell hormones) with orderly sequence of maturation
○ HSC express CD34 - a marker of haemopoietic stem cells - Early precursors adjacent to bony trabeculae
- Maturing forms deeper in marrow space
- Nuclear maturation and cytoplasmic granulation
- Controlled as to number and where in the marrow it takes place
- Most immature cell is next to the trabecular bone
- Mature cells away from the trabecular bone - released into the blood vessels in the bone marrow and then circulate in the blood
- HSC (haemopoietic stem cells) undergoes specific differentiation in response to cytokines (cell hormones) with orderly sequence of maturation
Neutrophils
- Most common granulocytic - cells with granules
- Majority of the white blood cells in blood stream
neutrophil development stages
- Myeloblast
2. Promyelocyte
3. Myelocyte
4. Metamyelocyte
5. Band form
Neutrophil
- Neutrophil maturation
○ Reduction in size
○ Contain fine granules (azurophilic) - acquire granules
§ Present early are primary granules, as the cell mature further they become specific to that lineage and become secondary granules
○ Neutrophil nucleus segments (2-5 segments)
§ Nucleus goes from being round, to ovoid, to bent and then segmented
§ Vit B or folate deficiency causes hyper segmentation
○ females have drumstick-like appendage
○ Neutrophil made in the bone marrow released in blood migrates through endothelial cells to tissue
○ 9-15 micrometres diameter
○ phagocytic function
§ Engulf invading pathogen, discharge granule contents to kill the invading pathogen
nuetrophil granule contents
○ Primary - formed at promyelocyte stage, electron dense
○ Secondary - formed at myelocyte stage of differentiation
neutrophil number and life span
○ Number in blood varies by:
§ Age, gender, ethnicity
§ Caucasians, Chinese, Indians: comparable neutrophil counts
§ Ethnic neutropenia occurs - lower baseline set because the neutrophils sit against the edge of the blood cell wall, when a blood sample is taken from the middle of the blood vessel - neutrophils are equally as effective in these individuals - does not impact ability to combat infection
○ Mature neutrophil migrate from BM to blood
§ Migrates through the sinusoidal endothelium
§ Lifespan in PB: 7.2 hours
§ Don’t spend much time in the blood - use it as a transport system
§ Appear in secretions and tissues
§ Survive outside the blood for up to 30 hours
neutrophil number in blood varies by
§ Age, gender, ethnicity
§ Caucasians, Chinese, Indians: comparable neutrophil counts
§ Ethnic neutropenia occurs - lower baseline set because the neutrophils sit against the edge of the blood cell wall, when a blood sample is taken from the middle of the blood vessel - neutrophils are equally as effective in these individuals - does not impact ability to combat infection
mature neutrophil migrate from BM to blood
§ Migrates through the sinusoidal endothelium
§ Lifespan in PB: 7.2 hours
§ Don’t spend much time in the blood - use it as a transport system
§ Appear in secretions and tissues
§ Survive outside the blood for up to 30 hours
neutrophil function
○ Attracted to and move to sites of infections
○ Adhere to the foreign particle via receptors
○ Pseudopodia form and encircle the particles
○ Ingest foreign particles
○ Phagosome forms
○ Fusion of 1&2 granules
○ Granule contents discharged
○ Bacteria killed
○ Phagocytose invading pathogens and then form a vesicle around it, pseudopods totally engulf what it taken in, granule contents are discharged into phagocytic vesicle and pathogen killed
- Reactive neutrophilia - appropriate
○ Increased granulation ‘toxic’
○ Dohle bodies
○ Cytoplasmic vacuoles - neutrophils are doing their job, being phagocytic
○ Increase to 10-50 x 10^9 L
○ Higher than 50: may be cancer
○ ‘left shift’ - immature cells usually in the bone marrow coming out into the blood
○ Caused by
§ Infection - bacterial or viral
§ Acute inflammation
§ Stress, exertion
§ Pregnancy
§ Malignancies eg. Hodgkin’s lymphoma
§ Surgery, trauma, tissue damage or infarction
§ Steroids, cytokines (administered following chemotherapy)
bacterial infections
- Fever, lethargy
- Hypercellular bone marrow - responding by making more neutrophils
- Acute, chronic infections
- Localised: skin, tonsil, bone
- Generalised:
○ Hypotension, fluid shift
○ Organ failure - Heamotological response
○ Bone marrow granulocytic hyperplasia
○ Blood neutrophilia, left shift, toxic granulation dohle bodies - Staph, strep, neisseria etc.
- Blood count
○ Leucocytosis
○ Neutrophilia 10-50 x 109
○ Mild thrombocytosis 400-500 x 109
○ Thrombocytopenia in severe infections
§ Disseminated intravascular coagulation - DIC
§ Thrombocytopenia accompanying marked neutrophilia indicates severe sepsis
○ Chronic bacterial infections eg. Osteomyelitis
§ May have mild anaemia
□ Due to anaemia of chronic inflammatory process
§ May have mild monocytosis
Eosinophils
- Granulocytic
- Similar to neutrophil, nucleus does not have more than 3 segments
- Granules are more orange (eosinophilic - loving eosin dye)
- Eosinophilic differentiation (specific granules) at myelocyte
○ Same as the neutrophil
○ Have their own set of specific granules
○ Different granules means they stain a different colour
eosinophil morphology
§ Slightly larger that neutrophils
○ Cytoplasm packed with large round granules
○ Red-orange with Romanowsky stains
○ 2-lobed nucleus
eosinophil lifespan and function
○ Granule contents: phospholipases, hoistaminase, ribonuclease, b-glucoronidase, cathepsin, collagenase (don’t memorise)
○ Motile cells: respond to chemotactic agents, phagocytose and kill microorganisms, slower at ingesting and killing bacteria than neutrophils
○ Involved with allergy: role in regulating immediate-type hypersensitivity reactions
○ Eosinophilia: allergy, drugs, asthma, dermatitis, parasites, neoplastic, hayfever
- Because they are only in the bloodstream for a short period of time, after they have been treated the eosinophil count returns to normal within a matter of hours
Basophils
- Deeply stained deep purple granules that overly the nucleus
- Most infrequent leukocyte (0.1x10^9)
- Diameter of 12 micro meters
- Large round purple black cytoplasmic granules that overly the nucleus
- Nucleus has two segments
- Cell surface receptors for IgE, IgG, C5a
basophils function
- Role in immediate-type hypersensitivity reactions
- Role in immune response to parasites
- Release histamine on activation
- A major source of IL-4 role in immunity
- Basophilia: chronic myeloid leukemia (increase in basophils in blood and bone marrow, don’t have any granules as normal) - cause them to look like neutrophils, but they’re actually abnormal hypo-granular basophils
- We don’t know what they do - normal blood film might not present a basophil
monocytes
- Some have granules - 10%
- Horseshoe nucleus with indentation
- 2-8% of white cells
- Maturation from stem cell - monoblast - monocyte
- Diameter 15-30 micro meters
- Maturation from stem cell - monoblast, monocyte
- Diameter 15-30 micro meters
- Cytoplasm: grey, few granules, vacuoles
- Blood average T of 70 hours - a bit longer than most cells
- Maturation to macrophage in tissue (months/years) - reticuloendothelial system
○ In spleen and liver - 3.6 times more marginated than circulating cells in PB
monocyte function
○ Granules - own set of enzymes
○ Role is phagocytosis and killing
○ Monocytosis
§ Increase monocyte count is rare - usually for chronic infections
§ TB - tuberculosis - patients with HIV
§ Chronic infections/ inflammation
§ Chronic myelomonocytic leukaemia
§ Myodisplasia - dysfunctional bone marrow, elderly people
□ Increase in monocytes in the blood, don’t look normal
monocytosis
§ Increase monocyte count is rare - usually for chronic infections
§ TB - tuberculosis - patients with HIV
§ Chronic infections/ inflammation
§ Chronic myelomonocytic leukaemia
§ Myodisplasia - dysfunctional bone marrow, elderly people
□ Increase in monocytes in the blood, don’t look normal
Lymphocytes
- Don’t have granules
- Smallest white blood cell
- Vary in size
- Round with round nucleus and blueish cytoplasm
- Immune cells
- Immunocologically competent cells
- B produced in bone marrow, T start in bone marrow and then migrate to thymus
- Produced in bone marrow and thymus
- BM: 10-15% of BM cells, T:B ratio = 6:1
Patients with lymphocytic or lymphoblastic leukemia will have far more B cells
- Because b cells are functional in trying to make immunoglobulin - they are more activated and therefore likely to have a mutation leading to a malignancy, usually happening in the lymph node
® Epstein barr virus infection EBV - mono
◊ Most common
◊ Low platelet count, immune mediated haemolytic anaemia, bone marrow failure - rare
◊ Usually just a mild infection that resolves and is self limiting
◊ Teenagers and young adults
◊ Lassitude, fever, pharyngitis, lymphadenopathy, hepatosplenomegaly
◊ Thrombocytopenia is common
◊ Haemolytic anaemia (immune-mediated, spherocytes)
◊ Blood film: virally infected B lymphocytes and activated reactive T lymphocytes
◊ Dutch skirting - scalloped blue edge (enhanced blue/basophilia)
◊ Mononucleosis
◊ Occurring in young people
® Cytomegalovirus CMV
◊ Similar clinical features to EBV
◊ Pharyngitis and lymphadenopathy: rare
◊ Ages 20-50 years
◊ Virus infects the neutrophils, which spread the infection to the macrophages
◊ Reactive T-lymphocytes morphologically indistinguishable from EBV
◊ Reactive T lymphocytes in the blood
◊ Thrombocytopenia is common
® Varicella
◊ Common in young children may occur in adults
◊ Thrombocytopenia
◊ Reactive T lymphocytes in the peripheral blood
◊ Activated T lymphocytes closely resemble those in EBV and CMV infections
® Viral hepatitis
◊ Hepatitis A and B cause mononucleosis like syndrome
◊ Reactive lymphocytes on the blood film
◊ Morphology is different - cells are larger with more cytoplasm
