White Blood Cells Flashcards
(40 cards)
How are granulocytes and monocytes created?
The multipotent haemopoietic stem cell gives rise to a myeloblast, which in turn can give rise to granulocytes and monocytes.
What are granulocytes?
Granulocytes refer to neutrophils, basophils and eosinophils, which have granules present in the cytoplasm that contain agents essential for their microbicidal function.
What growth factors influence granulocytes?
Signalling through myeloid growth factors such as as G-CSF, M-CSF, GM-CSF is essential for the proliferation and survival of myeloid cells.
G-CSF granulocyte colony-stimulating factor;
M-CSF, macrophage colony-stimulating factor;
GM-CSF, granulocyte-macrophage colony stimulating factor
Whta are the features of normal granulocyte maturation?
Maturation of granulocytes associated with reduction in size and development of granules that contain agents essential for cell function. Cell division occurs in myeloblasts, promyelocytes and myelocytes but does not occur in metamyelocytes or band forms. Precursors not found in bloodstream.
What is the earliest recognisable form of a granulocyte?
Myeloblast earliest recognisable granulocytic cell in bone marrow - these cells are recognisable by their large size, open chromatin pattern of their nuclei and their prominent nucleoli.
What are 3 features of the neutrophil?
- The neutrophil granulocyte survives 7–10 hours in the circulation before migrating to tissues.
- The nucleus of the mature neutrophil is segmented (sometimes referred to as lobulated).
- Its main function is defence against infection; it phagocytoses and then kills micro-organisms.
How does the neutrophil act?
The first step in neutrophil migration to tissues is chemotaxis. Neutrophils become marginated in the vessel lumen, adhere to the endothelium and migrate into tissues. Adhesion occurs via selectins, integrins and other adhesion molecules. Phagocytosis of micro-organisms occurs following cytokine priming. Neutrophils phagocytose microorganisms by the release of the neutrophil’s toxic intracellular contents via 2 mechanisms:
- Superoxide dep mech – release of ROS known as respiratory burst and this provides substrate for enzyme MPO (Myeloperoxidase) leading to prod of toxic acidic substances
- Oxygen indep – variety of antimicrobials released
What is the purpose of the eosinophil?
A myeloblast can also give rise to eosinophil granulocytes. The eosinophil spends less time in the circulation than does the neutrophil. Its main function is defence against parasitic infection.
What is the purpose of the basophil?
A myeloblast can also give rise to basophil granulocytes. Its granules contains stores of histamine and heparin, as well as proteolytic enzymes. Basophils are involved in a 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.
What is the structure and purpose of a monocyte?
Monocytes spend several days in the circulation.
Monocytes play several key roles that include phagocytosis and antigen presentation to lymphoid cells. Monocytes migrate to tissues where they develop into macrophages (also known as histiocytes) and other specialised cells that have a phagocytic and scavenging function. Macrophages also store and release iron.
What is the origin of the lymphocyte?
The multipotent haemopoietic stem cell also gives rise to a lymphoid stem cell. The lymphoid stem cell gives rise to T cells, B cells and natural killer (NK) cells. Lymphocytes recirculate to lymph nodes and other tissues and then back to the blood stream. Intravascular life span is very variable.
What is the purpose of B-lymphocytes and how do they develop?
B lymphocytes mature into plasma cells, which produce antibodies. Progenitor B cells develop sequentially into pre-B cells and mature B cells during which there is gene rearrangement of the immunoglobulin heavy and light chains leading to the production of surface immunoglobulins against many different antigens. This is known as humoral immunity.
What is the purpose of T-lymphocytes and NK cells?
T lymphocytes are involved in cell-mediated immunity. NK cells are part of the innate immune system ‒ they can kill tumour cells and virus-infected cells.
What is leukocytosis and leukopenia?
Leukocytosis - too many WBCs in circulation
Leukopenia - too few WBCs in circulation
When is transient leukocytosis seen?
Usually associated with infection.
Bacterial: Neutrophila/Monocytosis
Viral: Lymphocytosis
Parasitic: Eosinophilia
When is persistent leukocytosis seen?
Persistent leukocytosis may be caused by leukaemia.
Chronic myeloid leukaemia, CML (neutrophilia, basophilia, eosinophilia)
Acute lymphoblastic leukaemia, ALL (blast cells – lymphoblasts - are found in the blood)
Chronic lymphocytic leukaemia, CLL (lymphocytosis)
Name forms of leukocytosis and leukopenia
Leukocytosis:
neutrophilia, eosinophilia, basophilia, lymphocytosis, monocytosis
Leukopenia:
neutropenia, lymphopenia
What is often the cause of leukocytosis and leukopenia?
leukocytosis and leukopenia usually result from changes in the neutrophil count since this is usually the most abundant leucocyte in the circulation.
What are causes of neutrophilia?
infection (particularly bacterial infection), inflammation, infarction or other tissue damage, myeloproliferative disorders (chronic myeloid leukaemia)
When is an increase in neutrophils usually seen?
Neutrophilia is also a normal feature in pregnancy and may be seen following exercise (caused by a rapid shift of neutrophils from the marginated pool to the circulating pool) and after administration of corticosteroids. Toxic granulation is heavy coarse granulation of neutrophils (it can be a feature of pregnancy).
What can neutrophilia be accompanied by?
Neutrophilia may be accompanied by toxic changes and ‘left shift’ i.e. the presence of early myeloid cells such as metamyelocytes. Left shift means that there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood.
What characterises CML and what is it caused by?
There is an increase in all granulocytes —neutrophils, eosinophils and basophils—and their precursors in both the blood and the bone marrow. CML results from a translocation (exchange of material) between chromosomes 9 and 22, occurring in a single haemopoietic stem cell. The gene product gives the cell a growth and survival advantage and gives rise to a leukaemic clone.
Describe genetics of CML
Chr9 contains the ABL1 gene which codes for tyrosine kinase, an enzyme whose activity is tightly regulated. Chr22 contains the BCR gene. During a translocation, part of the ABL1 gene is transferred to Chr22 while a reciprocal change takes place on Chr9. Hence, BCR-ABL1 gene on Chr22 (Philadelphia Chr) encodes a protein with uncontrolled tyrosine kinase activity, which gives rise to leukaemic clone.
What is a feature of CML and how is it treated?
There is an enlarged spleen (splenomegaly).
The BCR-ABL1 protein signals between the cell surface and the nucleus, enabling division but it can be inhibited by specific tyrosine kinase inhibitors leading to remission, and potentially cure, of the disease.
