Haem Week 11 Flashcards

1
Q

Describe the development and differentiation of HSCs into neutrophils

A

HSC

Then, common myeloid progenitor

Then, myeloblast

Then, N.promyelocyte

Then, N.myelocyte

Then, N.metamyelocyte

Then, N.band

Then, neutrophil

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2
Q

Describe the development and differentiation of HSCs into monocyte/macrophages

A

HSC

Then, common myeloid progenitor

Then, myeloblast

Then, monoblast

Then, promonocyte

Then, monocyte

Then, macrophage

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3
Q

Describe the development and differentiation of HSCs into basophils

A

HSC

Then, common myeloid progenitor

Then, myeloblast

Then, B.promyelocyte

Then, B.myelocyte

Then, B.metamyelocyte

Then, B.band

Then, basophil

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4
Q

Describe the development and differentiation of HSCs into eosinophils

A

HSC

Then, common myeloid progenitor

Then, myeloblast

Then, E.promyelocyte

Then, E.myelocyte

Then, E.metamyelocyte

Then, E.band

Then, eosinophil

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5
Q

Describe the development and differentiation of HSCs into platelets

A

HSC

Then, common myeloid progenitor

Then, megakaryoblast

Then, promegakaryocyte

Then, megakaryocyte

Then, thrombocytes (platelets)

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6
Q

Describe the development and differentiation of HSCs into erythrocytes

A

HSC

Then, common myeloid progenitor

Then, proerythroblast

Then, basophilic erythroblast

Then, polychromatic erythroblast

Then, orthochromatic erythroblast (normoblast)

Then, polychromatic erythrocyte (reticulocyte)

Then, erythrocyte

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7
Q

Describe the development and differentiation of HSCs into B lymphocytes

A

HSC

Then, common lymphoid progenitor

Then, lymphoblast

Then, prolymphocyte

Then, small lymphocyte

Then, B lymphocyte

Then, plasma cell

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8
Q

Describe the development and differentiation of HSCs into T lymphocytes

A

HSC

Then, common lymphoid progenitor

Then, lymphoblast

Then, prolymphocyte

Then, small lymphocyte

Then, T lymphocyte

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9
Q

Describe the development and differentiation of HSCs into NKCs

A

HSC

Then, common lymphoid progenitor

Then, lymphoblast

Then, prolymphocyte

Then, NKC

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10
Q

Define leukopoiesis

A

The physiological process of WBC formation and maturation within the bone marrow

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11
Q

Outline the morphology of neutrophils

A

Polymorphonuclear w granules

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12
Q

Outline the function of neutrophils

A

Migrate to sites of infection through chemotaxis, engage in phagocytosis to engulf and ingest foreign materials like bacteria, and kill pathogens by releasing antimicrobial substances

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13
Q

Outline the location of neutrophils

A

Circulate in the blood and migrate to sites of infection

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14
Q

Outline the lifespan of neutrophils

A

Relatively short of around 6-8 hrs in circulation

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15
Q

Outline the morphology of monocytes

A

Kidney-shaped nucleus

Fine granules

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16
Q

Outline the function of monocytes

A

Precursors of tissue macrophages and dendritic cells, involved in immune responses

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17
Q

Outline the location of monocytes

A

Circulate in the blood and migrate to tissues when needed

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18
Q

Outline the lifespan of monocytes

A

Can circulate for a few days before entering tissues, where they can live for weeks to months

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19
Q

Outline the morphology of macrophages

A

Irregularly shaped nucleus and abundant cytoplasm

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20
Q

Outline the function of macrophages

A

Respond to chemotactic signals to migrate to areas of infection, conduct phagocytosis to engulf foreign materials, and play a central role in antigen presentation, inflammation regulation and tissue repair in addition to destroying pathogens

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21
Q

Outline the location of macrophages

A

Found in various tissues such as lungs, liver and spleen

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22
Q

Outline the lifespan of macrophages

A

Long lifespan, from months to years within tissues

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23
Q

Outline the morphology of eosinophils

A

Bilobed nucleus

Large granules

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24
Q

Outline the function of eosinophils

A

Defence against parasitic infections and involvement in allergies

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25
Outline the location of eosinophils
Found in tissues and the bloodstream, especially at sites of inflammation
26
Outline the lifespan of eosinophils
Relatively short of around 8-12 hours
27
Outline the morphology of basophils
Bilobed nucleus Large granules
28
Outline the function of basophils
Release histamine, heparin, and other mediators involved in allergic responses
29
Outline the location of basophils
Circulate in blood but are rare compared to other WBC
30
Outline the lifespan of basophils
Short lifespan, usually few hours to few days
31
What is chemotaxis
Biological process in which cells, such as immune cells, move in response to chemical signals or gradients
32
Outline the morphology of T lymphocytes
Round or irregularly shaped nucleus and minimal cytoplasm
33
Outline the function of T lymphocytes
Cell mediated immunity Central role in recognising and attacking infected or abnormal host cells Each type (cytotoxic, helper, regulatory) has distinct function
34
Outline the location of T lymphocytes
Blood and lymphatic system, but also present in lymphoid organs such as thymus, lymph nodes and spleen
35
Outline the lifespan of T lymphocytes
Varies, some circulate for weeks or months while memory T cells can persist for many years
36
Outline the morphology of B lymphocytes
Round nucleus and larger amount of cytoplasm compared to T cells
37
Outline the function of B lymphocytes
Humoral immunity Produce antibodies that can neutralise pathogens, mark them for destruction, or enhance phagocytosis, and has a role in antigen presentation to T cells
38
Outline the location of B lymphocytes
Found in lymphoid organs, lymph nodes, the spleen, and in bloodstream Can also be found in peripheral tissues
39
Outline the lifespan of B lymphocytes
Variable lifespans; some differentiate into short lived plasma cells that produce antibodies, while other form memory B cells that can persist for years
40
Define leukocytosis
Abnormal increase in number of WBC in blood, often indicative of immune response to infection or other underlying medical conditions WBC >11,000/microL
41
Define leukopaenia
Decrease in the total WBC count in the blood, potentially increasing the risk of infections and impairing the immune system’s function
42
Define neutropaenia
Condition characterised by a deficiency of neutrophils which can make individuals more susceptible to bacterial infections
43
Define monocytopaenia
Reduction in the number of monocytes in the blood, potentially affecting the body’s ability to fight certain infections and inflammatory conditions
44
Define lymphopaenia
Lower than normal count of lymphocytes, which can weaken the immune response and increase vulnerability to infections
45
What is netosis
When a neutrophil expels nuclear material in the form of neutrophil extracellular traps (NETs)
46
Outline the process of pathogen recognition
1. Pathogens exposure - immune system encounters pathogen 2. Antigen ID - immune cells equipped w PRRs recognise conserved molecular patterns found on pathogens 3. PRR binding - PRRs on immune cells bind to PAMPs on pathogen surface > activates immune cell which triggers series of intracellular signalling events to initiate immune response 4. Phagocytosis - engulf pathogen 5. Antigen presentation - dendritic cells present fragments of pathogen’s antigen on surface using MHC markers 6. T cell recognition - Th cells (CD4+) recognise antigen-MHC complexes on dendritic cells, so they then release cytokines that orchestrate immune response / T cytotoxic cells (CD8+) also recognise antigens presented by infected host cells 7. B cell recognition - B cells recognise antigens directly which activates them so that they can differentiate into plasma cells that can produce specific and complementary antibodies
47
Describe the role of the complement system in initiating an inflammatory response
Contributes to host defence by enhancing body’s ability to fight infections and remove damaged cells Activation of complement system leads to cascade of events, including opsonisation of pathogens, inflammation, and formation of membrane attack complexes to directly lyse and destroy target cells
48
Describe the classical activation pathway of complement system
C1 recognises immune complexes formed by binding of IgG or IgM to an antigen
49
Describe the alternative activation pathway for complement system
Non-specific activation by bacteria, fungi, and parasites via C3b deposition on the surface of microbes
50
Describe the lectin activation pathway for complement system
Mannose binding lectin (MBL) attaches to the mannose sugar residues on bacterial surfaces
51
What are 3 key mechanisms of action of the complement system and provide a brief description of each
Opsonisation - process by which complement proteins coat pathogens, making them more susceptible to phagocytosis Inflammation - increased blood flow and increased recruitment of immune cells and release of inflammatory mediators Punching holes - complement components create pores in membranes of target cells leading to their lysis
52
What is HLA
Genes that code for MHC proteins in humans
53
What are two classes of HLA/MHC, give 3 examples, and a brief description of their function
HLA/MHC class 1: HLA-A, HLA-B, HLA-C —> present on almost all nucleated cells and present endogenous peptides to CD8+ cytotoxic cells HLA/MHC class 2: HLA-DP, HLA-DQ, HLA-DR —> primarily found on APCs where they present exogenous peptides to CD4+ helper T cells
54
What does idiotype mean
Refers to the unique set of characteristics that define an antibody, including the specific shape and structure of its variable domains It is determined by the combination of CDRs within an antibody, and it plays a crucial role in the antibody’s ability to bind to a specific antigen
55
Describe how antigen-antibody complexes are formed
Epitopes (specific regions on antigens recognised by antibodies) bind to CDRs on antibodies. These interactions are highly specific, like a lock and key mechanism ensuring that each antibody binds only to its corresponding antigen
56
Distinguish between innate and adaptive immune response with regards to time course, specificity and discrimination between self and non self
Innate immunity has a rapid defence whereas adaptive is slower acting Innate immunity is non specific whereas adaptive is tailored to a pathogen Innate immunity has tolerance to self antigens whereas adaptive immunity can distinguish between self and non self
57
What is AML
Acute myeloblastic leukaemia Fast growing cancer of the blood and bone marrow characterised by the rapid proliferation of immature myeloid WBC
58
what is ALL
Acute lymphoblastic leukaemia Rapidly progressing cancer of the blood and bone marrow, primarily affecting lymphoid WBC and often seen in children
59
What is CML
Chronic myelogenous leukaemia Slow growing form of leukaemia that originates in myeloid WBC, characterised by the presence of the Philadelphia chromosome and a chronic phase that can transform into an acute phase
60
What is CLL
Chronic lymphocytic leukaemia A slowly progressing leukaemia primarily affecting lymphocytes, characterised by the accumulation of abnormal WBC in the blood and bone marrow
61
What is MM
Multiple myeloma Cancer of plasma cells in the bone marrow, leading to overproduction of abnormal monoclonal antibodies and weakened bone structure
62
Define leukaemia
Malignancy characterised by an excess of clonal WBC
63
Define lymphoma
A heterogenous group of malignancies that arise from the clonal proliferation of various cell subsets of lymphocytes at different stages of maturation
64
Define indolent lymphoid malignancy
Malignancies that refer to cancers that have a slow and relatively non-aggressive growth pattern
65
Define aggressive lymphoid malignancy
Malignancies that are characterised by a faster growth rate and a more invasive nature
66
Define acute lymphoid malignancies
Lymphoid malignancies that progress rapidly and involve immature or underdeveloped cells
67
Define chronic lymphoid malignancies
Lymphoid malignancies that progress more slowly and involve mature but abnormal cells
68
What are two types of acute leukaemias
ALL AML
69
Describe the pathogenesis of acute leukaemias
Leukaemia cells (arising from early HSCs) lose their ability to differentiate, resulting in an early block, however they retain their ability to replicate Then, these myeloblasts or lymphoblasts proliferate uncontrollably, occupying space in the bone marrow Then, these cells replace most of the bone marrow cells, crowding sites of normal haematopoiesis Then, they enter peripheral blood Then, they metastasise throughout the body, forming a malignant leukaemia
70
What are 8 clinical features of acute leukaemias
Fatigue - due to decrease healthy RBC leading to decreased O2 transport Infection - due to fewer functional WBC Bleeding - due to decrease platelets Hepatosplenomegaly - due to infiltration of leukemic cells in these organs Lymphadenopathy - swelling of lymph nodes in response to abnormal proliferation of leukaemia cells Headache - due to increased ICP due to accumulation of leukemic cells and reduced blood flow Arthralgia - joint pain due to leukemic cells infiltration leading to inflammation Skin rashes - T cell infiltration to peripheral skin
71
Outline the pathogenesis of chronic leukaemias
Same as acute but it is a monoclonal disorder of LATE HSCs rather than early, meaning the cells are more mature but non-functional
72
What are 4 clinical features of chronic leukaemia
Fatigue - due to reduced healthy RBC and O2 transport Hepatosplenomegaly - infiltration of leukemic cells in these organs Lymphadenopathy - swelling of lymph nodes due to abnormal proliferation of leukaemia cells Arthralgia - joint pain due to leukemic cell infiltration leading to inflammation and discomfort
73
What are 6 common complications of haematologic malignancies
Organomegaly - due to uncontrolled growth and accumulation of cancerous cells within an organ Bleeding/bruising - malignant tumours invade blood vessels, impairing their integrity or when cancer disrupts normal clotting processes Infection - underproduction of immune cells > weakened immune system Anaemia - abnormal cancerous cells crowd out healthy blood-forming cells in bone marrow Renal failure - abnormal proteins produced by cancer cells > clog and damage filtering units of kidneys Bone pain - infiltration of abnormal cells into bone marrow and subsequent disruption of normal bone structure
74
What are 6 risk factors for haematological malignancies
Chemicals/radiation - damages DNA increasing risk of mutations Genetic abnormalities - ppl w trisomy 21 have an increased risk of haematological cancers due to genetic factors and abnormal immune function Smoking - carcinogens which increases the risk of developing haematological cancers Viruses - can lead to genetic changes which increases risk of developing haematological cancers Past medical history - history of certain conditions like myelodysplastic syndrome can increase risk of progression to more aggressive cancers Family history - indicate genetic predisposition
75
Describe peripheral blood films
Lab test in which a drop of blood is spread thinly on a glass slide and then stained to allow for the microscopic examination of blood ells Enables observation of size, shape, colour, arrangement and inclusions of blood cells
76
Describe how erythrocytes are seen in peripheral blood films
Darker cells with central pallor
77
Describe how neutrophils are seen on peripheral blood films
Larger, segmented purple nuclei
78
Describe how platelets can be seen on peripheral blood films
Represented as small dots
79
Outline the role of bone marrow biopsies in the investigation of suspected haematological malignancy
Diagnosis - crucial for confirming or ruling out haematological malignancies such as leukemia, lymphoma and myeloma Classification - classify specific subtype and stage of malignancy Staging - determine extent and progression of malignancy and spread Monitoring - response to Rx, assess disease remission, and detect relapse Rx guidance - determine most appropriate Rx strategies, including chemotherapy, targeted therapy, or bone marrow transplantation
80
Describe flow cytometry
Enables the analysis of cell surface markers and intracellular proteins on individual cells in a blood or bone marrow sample Detect and quantify abnormal cell populations such as leukemic blasts, lymphoma cells, and myeloma cells Helps differentiate b/w diff types of haem malignancies Allows assessment of Rx response Provides immunophenotypic info which is crucial for tailoring Rx
81
CD34 marker viewed on flow cytometry indicates what
Immaturity of cell
82
CD19 marker viewed on flow cytometry indicates what
Lymphoid lineage
83
CD117 marker viewed on flow cytometry indicates what
Myeloid lineage
84
What are 5 investigative methods that can be used to differentiate between different haem malignancies
Cytogenics Flow cytometry Next gen sequencing Gene profiling PCR
85
What is the Binet staging system
Used for staging CLL Categorises Pt into one of 3 clinical stages based on extent of lymphocyte involvement and presence of anaemia or thrombocytopaenia Helps in determine the prognosis and guiding Rx decisions w early typically requiring less aggressive Rx compared to late stages
86
Outline stage A (low risk) CLL according to the Binet staging system
Patients have fewer than 3 enlarged lymph node groups and no anaemia or thrombocytopenia Prognosis of >15 yrs
87
Outline stage B (intermediate risk) CLL according to the Binet staging system
Patients have 3 or more enlarged lymph node groups and no anaemia or thrombocytopenia Prognosis 7-8 years
88
Outline stage C (high risk) CLL according to the Binet staging system
Patients have anemia and/or thrombocytopenia regardless of number of enlarged lymph node groups Prognosis of 5-6 years
89
What are the 3 phases of Rx for haematological malignancies
Induction - primary goal is to rapidly reduce number of cancer cells using intensive therapy e.g chemo Consolidation - following success phase, aims to eliminate any remaining cancer cells often involving additional chemo or stem cell transplantation Maintenance - lower dose, long term therapy administer to prevent re-emergence of malignancy
90
Describe allogenic stem cell transplant
Curative option for some haematological malignancies, involving the infusion of healthy stem cells from a donor to replace the patients diseased bone marrow, enabling new blood and immune system to develop
91
Outline the use of monoclonal antibodies for Rx of haematologic
Targeted therapies that can be designed to recognise and bind to specific antigens present on surface of cancer cells Used as standalone Rx or combined w chemo Can exert therapeutic effects through various mechanisms including immune system activation, interference w cell signalling pathways and direct cytotoxicity against cancer cells E.g rituximab for B cell lymphomas and alemtuzumab for CLL
92
Describe the pathophysiology of CML
Reciprocal translocation between chromosomes 9 and 22 leads to the BCR-ABL fusion gene This encodes for a constitutively active tyrosine kinase This activation stimulates intracellular signalling pathways that promote cell growth, survival and division This results in uncontrolled proliferation of myeloid cells, especially granulocytes, in the bone marrow and peripheral blood The accumulation of these abnormal myeloid cells can lead to symptoms of CML such as fatigue, enlarged spleen, and increased WBC counts
93
Explain how tyrosine kinase inhibitors work
TKIs such as imatinib and dasatinib work by binding to active site of BCR-ABL protein, inhibiting its kinase activity By blocking the BCR-ABL kinase, these drugs effectively suppress the aberrant signalling pathways that drive uncontrolled cell proliferation in CML
94
What are myeloproliferative neoplasms
MPNs are a group of rare blood disorders characterised by the overproduction of mature blood cells in the bone marrow Caused by genetic mutations in HSCs leading to uncontrolled growth of blood cells
95
What are the 4 main types of MPNs
Essential thrombocythemia (ET) Polycythemia Vera (PV) Primary Myelofibrosis (PMF) Chronic myeloid leukemia (CML)
96
Describe polycythemia Vera
Rare blood disorder where the bone marrow produces too many RBC, WBC and platelets leading to an increased risk of blood clots and other complications Has raised haemtocrit, may have Splenomegaly, may have high platelets, may have high leukocytes
97
Describe essential thrombocythemia
Overproduction of platelets, potentially resulting in abnormal blood clotting or bleeding Has normal haematocrit, may have Splenomegaly, may have high leukocytes
98
Describe primary myelofibrosis
MPN where bone marrow develops fibrous tissue, impairing its ability to produce normal blood cells and leading to anaemia and an enlarged spleen
99
Provide an outline of aplastic anaemia
Rare and serious blood disorder characterised by a significant reduction in the number of blood cells, including RBC and platelets in the bone marrow Occurs when bone marrow fails to produce adequate amount of blood cells Can be acquired or congenital, but it can also be idiopathic
100
Describe the diagnosis of aplastic anaemia
CBC to assess low blood cell counts Bone marrow biopsy or aspiration to confirm reduction in haematopoietic cells
101
Outline Rx for aplastic anaemia
Blood transfusions Medications to stimulate blood cell production Immunosuppressive therapy Bone marrow transplantation
102
What are 7 signs/symptoms of aplastic anaemia
Fatigue Pallor Petechiae Infection Dyspnea Bleeding Headache