White Blood Cells Flashcards
What are granulocytes?
Leukocytes with granules in cytoplasm
(contain agents for microbicidal function)
What are the 4 types of granulocyte?
- Neutrophil
- Basophil
- Eosinophil
- Monocytes
What are the 3 myeloid growth factors?
- G-CSF (granulocyte-CSF)
- M-CSF (macrophage-CSF)
- GM-CSF
How do myeloblasts turn into granulocytes?
-Cell division to myelocyte
- Differentiation to band form then granulocyte
What is the lifespan of a neutrophil?
7-10 hours
How can neutrophils be identified on a blood film?
Segmentend nucleus (3-5 lobes)
What is the function of neutrophils?
Phagocytoses and kills microorganisms
What are the 6 steps of neutrophil chemotaxis?
- Adhesion - to vessel lumen
- Margination
- Rolling
- Diapedesis - squeezes through cell gaps in endothelium
- Migration - in tissue to microorganism
- Phagocytosis
What must happen to a neutrophils for phagocytosis to occur?
Cytokine-priming
What is the lifespan of an eosinophil?
<Neutrophil
What is the function of eosinophils?
Fight parasitic infections (eg. helminths)
Why are eosinophils important in hypersensitivity?
Regulate Type 1 hypersensitivity reactions
- Inactivate histamine and leukotrienes from basophils/mast cells
How are eosinophils identified on a blood film?
-Red
-Many granules
-Bilobed nucleus
What 3 things do basophil granules store?
- Histamine
- Heparin
- Proteolytic enzymes
What is the function of basophils?
Immune and inflammatory responses
What are the 2 reactions basophils influence and how?
- Type 1 hypersensitivity —> IgE-coated basophils release histamine and leukotrienes
- Inflammatory response —> release heparin and proteases
How are basophils identified on a blood film?
- Blue
- Packed with granules
What are mast cells?
Tissue-resident cells involved in hypersensitivity reactions
What is the circulation time of a monocyte?
Several days
Where do monocytes go when they leave circulation?
Reside in tissue —> macrophages
What are the 3 functions of monocytes?
- Phagocytosis of antibody and complement-coated micoorganisms
- Phagocytosis of bacteria/fungi
- Antigen presentation to immune cells
What is the 2 function of macrophages?
- Phagocytosis
- Store and release iron
How are macrophages arranged in the bone marrow?
Each encircled by erythrocytes —> delivers iron to them
What 3 cells to lymphoid progenitor cells give rise to?
- B lymphocytes
- T lymphocytes
- NK cells
Where do lymphocytes circulate?
- Recirculate to lymph nodes and tissues
- Then back to bloodstream
How are B and T lymphocytes identified on a blood film?
- Small
- Mostly nucleus
How in an NK cell identified on a blood film?
- Larger
- Granules
- Clumped nucleus
Where do B lymphocytes originate? (2)
- Fetal liver
- Bone marrow
Where do B lymphocytes mature?
Bone marrow
How do B lymphocytes acquire surface antibodies?
Ig heavy and light chain gene rearrangements
How do B lymphocytes develop further in the lymphatic system?
- Exposed to other antigens
- Mature to recognise non-self antigens
Where do T lymphocytes originate?
Fetal liver
Where do T lymphocytes mature?
Thymus
What is the function of T lymphocytes?
Cell-mediated immunity
What is the function of B lymphocytes?
Humoral immunity
What is the function of NK lymphocytes?
Innate immunity
- kill tumour cells
- kill virus-infected cells
What is the cause of transient leukocytosis?
Reactive cause
- Infection/inflammation/infarction
- Bone marrow responding to external stimulus
What is the cause of persistent leukocytosis?
Primary blood cell disorders
- Leukaemia/lymphoma/myeloma
- DNA damaged —> affects haemopoietic precursor cells
What is leukocytosis?
Too many white blood cells
What are the 5 types of leukocytosis?
- Neutrophilia
- Eosinophilia
- Basophilia
- Lymphocytosis
- Monocytosis
What is leukopenia?
Too few white blood cells
What are the 2 types of leukopenia?
- Neutropenia
- Lymphopenia
Why may those with leukopenia need isolation?
Very weak immune system
What is neutrophilia?
Too many neutrophils
What are the 3 causes of neutrophilia?
- Infection
- Inflammation
- Tissue damage
What 3 things is neutrophilia also a normal response to?
- Pregnancy
- Exercise
- Corticosteroids
What 2 things may accompany neutrophilia?
- ‘Left-shift’ —> presence of non-segmented neutrophils or neutrophil precursors
- Toxic granulation
What is chronic myeloid leukaemia? (CML)
Primary blood cancer
- Myeloproliferative
What 3 things can be identified on the blood film of a CML patient?
- Neutrophilia
- Basophilia
- Left-shift
What is neutropenia?
Too few neutrophils
Which 2 therapies can cause neutropenia?
- Chemotherapy
- Radiotherapy
What are the 5 causes of neutropenia?
- Autoimmune disorder
- Severe bacterial infection
- Viral infections (some)
- Drugs
- Thrombocytopenia
Which ethnicities may have a blood film wrongly suggesting neutropenia and why?
African/Afro-Caribbean —> benign ethnic neutropenia
- More neutrophils parked in vasculature (not actually less neutrophils)
What is the biggest risk of neutropenia and how is this combatted?
Serious infection
- urgent intravenous antibiotics
How many lobes does the nucleus of a normal neutrophil have?
3-5
What is neutrophil hypersegmentation?
Increased number of lobes in neutrophil nuclei
- ‘Right-shift’
What causes neutrophil hypersegmentation?
Megaloblastic anaemia
- vit B12/folic acid deficiency — >affect DNA replication —> nuclei lobes keep dividing
What are the 3 neutrophil abnormalities?
- Neutrophilia
- Neutropenia
- Neutrophil hypersegmentation
What is ‘right shift’ and ‘left shift’ in neutrophils?
- Right-shift = too many nucleus lobes (overdeveloped)
- Left-shift = unsegmented nucleus or neutrophil precursors present in blood (underdeveloped)
What is eosinophilia?
Too many eosinophils
What are the 2 causes of eosinophilia?
- Allergy (asthma, eczema, drugs)
- Parasitic infection
Which type of leukaemia can present eosinophilia?
CML
What is basophilia?
Too many basophils
What is the cause of basophilia?
Leukaemia - eg. CML
Which leukocytosis is uncommon?
Basophilia
What are band forms?
Immature neutrophils
How can band forms be identified on a blood film?
- Snake-like nucleus (unsegmented)
- Granules
How can myelocytes be identified on a blood film?
- Rounded ‘triangle’ nucleus
What is monocytosis?
Too many monocytes
What are the 3 causes of monocytosis?
- Infection
- Inflammation
- Leukaemia (some)
What is lymphocytosis?
Too many lymphocytes
What is the cause of transient lymphocytosis?
Viral infection
What is the cause of persistent lymphocytosis?
Lymphoproliferative disorder - eg. CLL
What are the 4 symptoms of chronic lymphocytic leukaemia (CLL)?
- Weight loss
- Fevers
- Night sweats
- Straw-coloured blood
What is lymphopenia?
Too few lymphocytes
What are the 4 causes of lymphopenia?
- HIV
- Chemotherapy
- Radiotherapy
- Corticosteroids
Which patients may develop transient lymphopenia?
Severe infection
What is leukaemia?
Blood cancer
What are the 2 classes of leukaemia?
- Myeloid
- Lymphoid
Which cells do leukaemic cells replace?
Normal HSCs
What proportion of cancers are leukaemias?
5%
How do leukaemic cells enter the blood?
Clone —> replace normal bone marrow cells —> spill into blood
Where do most leukaemias originate?
Bone marrow
How does leukaemia occur?
Somatic mutations in a usually oncogenes
Why may leukaemic clones replace normal cells? (3)
Growth or survival advantage
1. Don’t need usual growth factors
2. Disturbance in proliferation or maturation
3. Failure of apoptosis
What is important about the life expectancy of patients with leukaemia?
Shortest of all cancer
Why do the terms malignant and benign not apply to leukaemias?
Leukaemias will circulate in the bloodstream and migrate to other tissues (no solid tumour)
What 4 types of leukaemia?
- ALL - acute lymphoblastic leukaemia
- AML - acute myeloid leukaemia
- CLL - chronic leukocytic leukaemia
- CML - chronic myeloid leukaemia
What is the difference between the maturity of cells affected by acute vs chronic leukaemias?
- ALL/AML —> blast cells affected
- CLL/CML —> mature cells affected
Which age group does ALL usually affect and why?
Children
- mutations in utero
Which age group does CLL usually affect?
Elderly
Why does CML occur?
Fusion protein BCR-ABL1 —> activates signalling pathways
Why does CLL occur?
Steady expansion of leukaemic clone —> gradually replace normal cells
(B —> mutation usually in TF gene —> B won’t mature —> accumulation of blast cells)
What are the 4 consequences of leukaemia?
- Accumulation of abnormal cells
- Metabolic effects
- Crowding out of normal haemopoiesis
- Lose T and B lymphocyte function (CLL)
What are the 7 consequences of accumulation of abnormal cells in leukaemia?
(Leukaemia Stops Happiness Because Tumours Stop Life)
- Leukocytosis
- Splenomegaly
- Hepatomegaly
- Bone pain (ALL/AML)
- Thymic enlargement (T-ALL/T-CLL)
- Skin infiltration
- Lymphadenopathy (ALL/CLL)
What are the 4 consequences of metabolic effects of leukaemia?
- Renal failure —> hyperuriacaemia
- Weight loss
- Fever (low-grade)
- Sweating
What are the 3 consequences of crowding out of normal haemopoiesis in leukaemia?
- Anaemia - fatigue, lethargy, pallor, breathlessness
- Neutropenia - fever
- Thrombocytopenia - bruising, petechiae, bleeding
What is the consequence of loss of T and B lymphocyte function in leukaemia?
Weak immune system (CLL)