White Blood Cells Flashcards
What are the myeloid lineage white cells?
Granulocytes
Monocytes
What are monocytes?
The precursors of macrophages
What are granulocytes?
Basophils, neutrophils, eosinophils
Why are they called granulocytes?
They all have granules in them which contain agents essential for their microbicidal function
And the killing of phagocytosed microorganisms
What are some of the growth factory’s that control the proliferation of granulocytes?
G-CSF
Granulocyte colony stimulating factor
M-CSF
Macrophage
GM-CSF
Granulocyte-macrophage
What is the first stage of granulocyte maturation?
Myeoblast
Largest
Undergoes cell division
Prominent nucleoli
Open chromatin pattern of their nuclei
Which un matured forms of granulocytes undergo cell division?
Myeloblast
Promyelocyte
Myelocyte
These along with metamuelocytes and band forms should only be present in the bone marrow
How long does a neutrophil survive in circulation before migrating to tissues?
7-10 hours
What is the nucleus of a neutrophil like?
Segmented/lobulated
What is the main function of a neutrophil?
To phagocytose and kills micro organisms
By what process do neutrophils migrate to an infected tissue?
Chemotaxis
They are marginated in the vessel lumen, adhere to the vessel wall and migrate to the tissues
Neutrophils phogocytose pathogens which are then killed by the toxic intra cellular contents by two mechanisms, what are the two ways phagocytosis occurs?
Super oxide dependant mechanism
Oxygen independent
What is the role of eosinophils?
Phagocytose and destroy microorganisms, usually parasitic
They spend a much shorter time in circulation than neutrophils
What do the granules in basophils contain?
Histamine
Heparin
Proteolytic enzymes
In which ways are basophils involved in the immune response?
Mediation of the immediate type hypersensitivity reaction
In which IgE coated basophils release histamine and leukotrienes
Modulation of inflammatory response by releasing heparin and proteases
How long do monocytes spend in circulation, and what roles do they play in immunity?
Several days
Phagocytosis
Antigen presentation to lymphoid cells
They migrate to tissues where they then develop into macrophages
What is the role of macrophages?
Scavenging and macrocytic function
They also store and release iron
What are the main functions of neutrophils?
Chemotaxis
Phagocytosis
Killing of phagocytosed bacteria
What are the main roles of monocytes and macrophages?
Chemotaxis
Phagocytosis
Killing of some microorganisms
Antigen presentation
What are the main functions of eosinophils?
Chemotaxis Phagocytosis Killing of phagocytosed bacteria Main defence against parasites Regulation of some immediate type hypersensitivity reactions
What are the main functions of basophils?
Mediation of immediate type hypersensitivity
Modulation of inflammatory responses by releasing heparin and proteases
Where do lymphocytes develop from?
Common lymphoid progenitor
In the bone marrow
Requires transcription factors
What do lymphoid stem cells turn into?
B cells
T cells
Natural killer cells (NK)
These circulate to lymph nodes and tissues then back to the blood stream
What can B cells matur into?
Plasma cells, which produce antibodies
Required exposure to specific antigens
B cells originally develop in the bone marrow of the foetus where the heavy and light globulin chains are arranged to provide immunity against a lot of antigens. These circulate in the lymph so they recognise what is self and non self.
What to T cells do?
Cell mediated immunity
Their development ends in the thymus
T helper cells gain CD4 markers, those release cytokines such as interferon, activating monocytes and macrophages
Cytotoxic T cells gain CD8 markers during development
What are NK cells?
Part of the innate immune system
They can kill Timor cells and virus infected cells
What abnormalities involving leukocytes can arise?
Numerical and/or morphological
What is leukocytosis?
Too many white blood cells
Neutrophilia Eosinophilia Basophilia Lymphocytosis Monocytosis
What is a reduction in white blood cell count called?
Leukopenia
Neutropenia
Lymphopenia
What are leukocytosis and leukopenia usually caused by?
Changes in number of neutrophils as these are the most abundant leukocyte in circulation
What are causes of neutrophilia?
Bacterial infection Inflammation Infarction or tissue damage Myeloproliferative disorders (chronic myeloid leukaemia) (often accompanied by basophilia. Pregnancy Exercise Administration of corticosteroids
What toxic changes may accompany neutrophilia?
Left shift
Presence of early myeloid cells such as metamyelocytes
Cells usually only present In the bone marrow
Toxic granulation
Heavy coarse granulation of neutrocytes and maybe presence of vacuoles
What happens in chronic myeloid leukaemia, and what is it caused by? (CML)
Increased presence of all granulocyte and their precursors
Results from a translocation between chromosomes 9 and 22, occurs in a single haemopoietic stem cell (that undergoes clinal expansion). This leads to an abnormally short chromosome 22 (Philadelphia chromosome)
What happens to a patient with CML?
Enlarged spleen (splenomegaly)
The the BCR-ABL1 protein signals between the cell surface and the nucleus
It can be inhibited by specific tyrosine kinase inhibitors, leading to remission and potentially a cure
What are some causes of neutropenia?
Following chemotherapy or radiotherapy
Autoimmune disorders
Severe bacterial infections
Certain viral infections
Drugs (anticonvulsants, antimalerial, antipsychotic)
Physiology (e.g.african/Afro Caribbean ancestry can give lower counts normally)
Patents with very low neutrophil counts (<0.5x10^9 / L) are at risk of serious infection. May need to be treated with intravenous antibiotics
What Is a hypersegmented neutrophil?
Normal neutrophils should have between 3-5 segments or lobes
Neutrophil hypersegmentation (right shift) is when there is an increased average number of lobes
Usually results form a lack of vitamin B12 or folate: megaloblastic anaemia
What causes eosinophilia?
Allergy (Asthma, eczema,drugs)
Parasitic infection
Leukaemia
What causes basophilia?
Very unusual
Usually means leukaemia
What causes monocytosis?
Infection (especially chronic bacterial)
Chronic inflammation
Some types of leukaemia
What causes lymphocytosis?
Viral infection (transient) Lymphoproliferative disorders (persistent) (e.g. lymphoma)
Whooping cough (pertussis)
When lymphocytosis is caused by a viral infection it can lead to atypical lymphocytes, what does this mean?
Intensely basophilic cytoplasm (blue)
Scalloped margins and “hugging” of the surrounding red blood cells
Both present in response to glandular fever
Lymphocytosis can also be caused by chronic lymphocytic leukaemia, what atypical lymphocytes are present here?
Squashed CLL lymphocytes (smear or a smudge)
This is a lymphoproliferative disorder
CLL is the most common cause of persistent lymphocytosis in the elderly
What is the difference between acute and chronic lymphoid lukaemia?
Leukaemia is cancer originating in haemopoietic or lymphoid cells
In acute lymphoblastic anaemia (ALL) there is an increase in lymphobalsts (immature cells), which don’t develop into mature cells
These infiltrate the bone marrow leading to impaired haemopoiesis
Acute: severe and sudden in onset. Aggressive and lead to death quickly
In chronic lymphoid leukaemia (CLL) the cells are mature but some lymphocytes are abnormal
Chronic: disease and deterioration go on for a long period of time
What can cause ALL?
Mutation in the (B cell) progenitors so that mature B cells cannot be made
Summarise ALL?
Leukocytosis with lymphoblasts in the blood
Anaemia (normocytic, normochromic)
Neutropenia
Thrombocytopenia (low platelet count)
All caused by Replacement of normal bone marrow cells by lymphoblasts
Cytogenetic/molecular genetic analysis can be used to give information about the prognosis e.g. hyperdiploidy has a good prognosis but t(4,11) does not
What is the treatment for ALL?
Supportive:
Red cell and platelet transfusions
Antibiotics
Systemic and intrathecal chemotherapy
What is and what causes lymphopenia?
Decrease in the number of circulating lymphocytes
(Normal : 1x10^9 /L)
Most lymphocytes are CD4+ T cells
Causes include: HIV Chemotherapy Radiotherapy Corticosteroids Very severe infection (transient)
