3: White Blood Cells Flashcards
Covers Granulocytes and monocytes, Lymphocytes and WBC diseases
What do myeloid growth factors do?
Signalling controls proliferation and survival of myeloid cells
3 myeloid growth factors
G-CSF : granulocyte colony stimulating factor
M-CSF: macrophage colony stimulating factor
GM-CSF : both granulocyte and macrophage colony stimulating factor
Myeloblasts are initial granulocytes, where do they develop
in the bone marrow
cell size reduced and granules develop as they mature
Neutrophils are
primary immune defence cells
- lobulated nucleus
-survive 7-10h in circulation
- migrate in tissue to carry out pathogen phagocytosis
what is chemotaxis
first step of neutrophil migration into tissues
- primed by cytokines ready to phagocytose pathogens
Characteristics of eosinophils
pink granules in stains
bilobed nucleus
less time circulating than neutrophils
2 functions of eosinophils
1) defence against parasitic infections and phagocytosis
2) regulation of type 1 hypersensitivity reactions - inactivate histamine and leukotrienes released by basophils and mast cells
Components of basophils
contain granules storing :
histamine
heparin
proteolytic enzymes
2 inflammatory responses of basophils
mediation of T1 hypersensitivity reaction where IgE-coated basophils release histamine and leukotrines
modulation of inflammatory responses by releasing heparin and proteases
3 functions of Monocytes
1)Phagocytosis of micro-organisms covered in antibody and complement
2)Phagocytosis of bacteria and fungi
3)Antigen presentation to lymphoid cells
Macrophages are formed from
Developed monocytes migrated in tissues with other cells that have a phagocytic scavenging function
4 types of granulocytes
Basophil
Neutrophil
Eosinophil
Monocyte
3 types of lymphocytes
B
T
natural killer cells
B lymphocytes originate form
foetal liver and bone marrow
Where do B lymphocytes develop
in bone marrow
- differentiate into plasma cells involving Ig heavy and light chain rearrangement
Function of mature B lymphocytes
mature after being exposed to antigens in lymphoid tissue e.g. lymph nodes
recognition of non-self antigens triggers production of specific Igs and antibodies
function of T lymphocytes
cell mediated immunity
Where do foetal lymphocyte progenitors migrate from to develop
from the liver to the thymus to develop
Function of natural killer cells
part of innate immune system
kill tumour cells and cells infected with viruses
Leukocytosis means
Too many WBCs
Normal leukocytosis
Occurs during infections, levels rise and then fall back down
- Transient leukocytosis
Infections, inflammation, infarction
Bacterial infection : neutrophilia/ monocytosis
Viral infection : lymphocytosis
Parasitic infection : eosinophilia
Abnormal leukocytosis
Leukaemia, lymphoma, myeloma
Examples -
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic lymphocytic leukaemia
Chronic myeloid leukaemia
Neutrophilia is
Too many neutrophils
Causes of neutrophilia
Infection
Inflammation
Exercise
Infarction or tissue damage
Myeloproliferative disorders (CML)
Pregnancy - heavy toxic granulation of neutrophils
Use of corticosteroids
How to spot neutrophilia on a blood film
Left shift - non-segmented neutrophil precursors due to increased output from bone marrow
When can eosinophilia occur
Due to allergy / parasitic infection
Asthma / eczema / drugs
But can occur in leukaemia
Blood film in patients with basophilia
Myelocytes seen
Band forms
Neutrophilia
Left shift
What does basophilia occur due to
Leukaemia
(uncommon)
3 causes of monocytosis
Infection esp chronic
Chronic inflammation
Some types of leukaemia
Two main types of lymphocytosis
Transient lymphocytosis
Persistent lymphocytosis
Transient lymphocytosis is caused by
Viral infections
often atypical lymphocytes present
Persistent lymphocytosis is a
Lymphoproliferative disorder
Infectious mononucleosis is also known as
Mono
Or
Glandular fever
glandular fever
Lymphocytosis due to viral infection - resulting in atypical lymphocytes
WBCs in mono
Scalloped margins and hugging of nearby RBCS
Leukaemia is
Cancer or WBC - can be myeloid or lymphoid
How does a leukaemia clone arise ?
Leukaemic cells from in bone marrow and replace normal haemopoietic stem cells - can overspill into blood 🩸
Spontaneous mutations or exposure to mutagenic agents in oncogenes and tumour suppressor genes 🧬
Mutated cell has survival and growth advantage so replaces normal cell by clone 🧫
What issues can an leukaemic clone cause 🧫
Clones don’t require usual growth factors
Proliferation and maturation disturbance
Faliure of apoptosis
What type of cancer is leukaemia
Acute / chronic - depending on nature of mutation
As cells circulate in blood stream and migrate into tissues
4 types of leukaemia 🩸🧫
Acute lymphoblastic
Acute myeloid
Chronic lymphocytic
( Chronic myeloid )
Changes to cells in acute lymphoblastic leukaemia
Large
High nucleus to cytoplasm ratio
Blast means
Immature cells
Cystic means
Mature cells
In chronic myeloid leukaemia (CML)
Increase in granulocytes and their precursors in blood and bone marrow
Causes of CML
Translocation between (ABL1) gene on chr 9 (encoded tyrosine kinase enzyme)
(BCR) gene on chr22 causing chr 22 to have BCR-ABL1 (now called Philadelphia 🥯🧀 chromosome Ph) which causes uncontrolled tyrosine activity giving rise to a leukaemic clone
Causes of CLL
Causes of CLL
pluripotent HSC turns into Bcell progenitor in bone marrow due to common lymphoid progenitor
causing chronic lymphocytic leukaemia
(long period of time)
Characteristics of CLL on blood film
smudge / smear lymphocytes
what is the most common cause of leukaemia in elderly people
CLL
What is CLL staged according to
degree of lymph node/ liver/spleen involvement
and if Hb and platelet count is reduced
What is the most common cause of leukaemia in children
ALL
Cause of Acute lymphoblastic leukaemia
Pluripotent HSC changed into B cell acute lymphoblastic leukaemia (via common lymphoid progenitor)
progenitor cell picks up mutations (esp. in genes for TF)
cells unable to mature, but still proliferate, leading to lots of blast cells rapidly
What happens as there is a large number of B cell acute lymphoblastic leukaemia
Bone marrow inflitrated with lymphoblasts
resulting in impaired haemopoiesis
- only lymphoblasts in circulation
effects of ALL
leukocytosis of lymphoblasts
leading to :
neutropenia
thrombocytopenia
anaema
Clinical signs of ALL
prominent bruising due to thrombocytopenia
pale skin due to anaemia
Treatment for ALL
supportive therapy - red cell / platelet transfusion, antibiotics
systemic chemotherapy - through body
intrathecal chemotherapy - through spine (sanctuary site for lymphoblasts)
Clinical features of leukaemia due to accumulation of abnormal cells
leukocytosis
bone pain - acute leukaemia
hepatomegaly
splenomegaly
lymphadenopathy - if lymphoid
thymic enlargement if T lymphoid
skin infiltration
clinical features of leukaemia due to metabolic effects of leukaemic cell proliferation
Hyperuricaemia and renal faliure
weight loss
low grade fever
sweating
Clinical features of leukaemia due to crowding out of normal haemopoises
fatigue, lethargy, pallor, breathlessness (anaemia)
fever + features of infection (neutropenia)
bruising, petechiae, bleeding (thrombocytopenia)
Clinical fetaures of leaukemia due to loss of normal immune function
Loss of normal T and B cell function
- feature of chronic lymphocytic leukaemia
Neutropenia is
low neutrophil count
What are individuals with neutropenia at risk of
v low count below 0.5 x10^9 / L
risk of serious infection
urgent need for Iv Abx
what can result in neutropenia
-supressed bone marrow activity after chemo/radiotherapy
- Autoimmune disorders
-physiological effects e.g benign ethnic neutropenia in african heritage
Lymphopenia is
too few lymphocytes (below 1x10 L)
what cells are lymphocytes in normal blood
CD4+ T cells
Causes of lymphopenia
HIV Infection
Chemo / Radiotherapy
corticosteroids
severe infection (transient)
Neutrophil hypersegmentation
neutrophil has more than 3-5 lobes (normal)
- right shift
- results from lack of B12/folic acid (megaloblastic anaemia)
