Hoffbrand's Essential Haematology Review

Questions and Answers

What is the primary site of haemopoiesis?

Bone marrow

Which of the following cells are formed from pluripotent stem cells? (Select all that apply)

Red blood cells (correct)

Neurons

Platelets (correct)

B lymphocytes (correct)

Haemopoietic growth factors are not relevant to the process of blood cell formation.

False

The cells that give rise to red blood cells, granulocytes, monocytes, and platelets are called ______.

progenitor cells Signup and view all the answers

Which proteins are frequently mutated in haemopoietic malignancies? (Select all that apply)

p53 Signup and view all the answers

What role does autophagy play in cells?

It is involved in the digestion of cell organelles and recycling nutrients. Signup and view all the answers

Which of the following proteins are part of the Janus-associated G-CSF kinase family?

JAK1 Signup and view all the answers

What do growth factors induce in progenitor cells?

Proliferation and differentiation Signup and view all the answers

JAK proteins act on ______ cells.

progenitor Signup and view all the answers

Which signal transducer is activated by phosphorylated JAK proteins?

STAT Signup and view all the answers

The JAK2 gene mutation is the cause of polycythemia vera.

True Signup and view all the answers

What is interphase divided into?

G1 phase, S phase, and G2 phase Signup and view all the answers

Which process describes programmed cell death?

Apoptosis Signup and view all the answers

What do adhesion molecules mediate?

The attachment of cells Signup and view all the answers

The gene ______ is overexpressed in follicular lymphoma to prevent apoptosis.

BCL-2 Signup and view all the answers

What are the main pathways that activate caspases?

Signaling through membrane proteins and cytochrome c release Signup and view all the answers

What is the approximate number of mature blood cells produced by one stem cell after 20 cell divisions?

1,000,000 Signup and view all the answers

Where does haemopoiesis occur in adults?

Bone marrow Signup and view all the answers

What occurs to the number of stem cells with aging?

The number of stem cells falls. Signup and view all the answers

Stem cells can accumulate genetic mutations with age.

True Signup and view all the answers

What binds to its receptor CXCR4 on HSC?

SDF-1 Signup and view all the answers

Which transcription factor is involved in erythropoietic and megakaryocytic differentiation?

GATA-1 Signup and view all the answers

Haemopoietic growth factors only act locally.

False Signup and view all the answers

Which of the following is NOT a characteristic of myeloid and lymphoid growth factors?

They are produced only by one cell type. Signup and view all the answers

What is required for stem cell survival and differentiation?

Growth factors, adhesion molecules, and cytokines. Signup and view all the answers

Which factors are involved in mediating apoptosis following DNA damage?

All of the above Signup and view all the answers

Necrosis is a form of programmed cell death.

False Signup and view all the answers

What initiates apoptosis?

Signalling through cell membrane receptors or release of cytochrome c from mitochondria. Signup and view all the answers

The intracellular ratio of pro-apoptotic proteins like ______ to anti-apoptotic proteins like BCL-2 affects cytochrome c release.

BAX Signup and view all the answers

What role do growth factors play in apoptosis?

They raise the level of BCL-2. Signup and view all the answers

What is haemopoiesis?

Blood cell formation from pluripotent stem cells. Signup and view all the answers

Match the following components with their roles in apoptosis:

Caspases = Digest DNA during apoptosis Cytochrome c = Signals apoptosis from mitochondria BAX = Pro-apoptotic protein BCL-2 = Anti-apoptotic protein Signup and view all the answers

What is autophagy?

The digestion of cell organelles by lysosomes. Signup and view all the answers

Where does haemopoiesis occur in adults?

In the bone marrow Signup and view all the answers

What are the progeny of centrocytes known as?

Plasma cells Signup and view all the answers

Which infections are associated with acute lymphocytosis?

Rubella Signup and view all the answers

Which of the following is a chronic infection associated with lymphocytosis?

Toxoplasmosis Signup and view all the answers

What causes Infectious mononucleosis?

Primary infection with Epstein-Barr virus (EBV) Signup and view all the answers

EBV infection rarely causes symptomatic disease.

True Signup and view all the answers

Chronic lymphoid leukaemias can lead to __________.

lymphocytosis Signup and view all the answers

What is the role of intrinsic factor in B12 absorption?

Facilitates B12 absorption by the ileum Signup and view all the answers

What is the most important site of haemopoiesis during fetal life?

Liver Signup and view all the answers

What is megaloblastic anaemia primarily characterized by?

Increased size of circulating red cells (MCV > 98 fL) Signup and view all the answers

The abnormal appearance of bone marrow erythroblasts in megaloblastic anaemia is typically caused by __________.

B12 or folate deficiency Signup and view all the answers

Alcohol consumption can lead to macrocytic anaemia.

True Signup and view all the answers

Which factor contributes to the need for injections of hydroxocobalamin?

B12 deficiency Signup and view all the answers

What are two important examples relevant to gene expression that do not affect DNA sequence?

Histone modification and DNA methylation. Signup and view all the answers

Haemopoiesis in adults is confined to the peripheral skeleton.

False Signup and view all the answers

What role do transcription factors play in gene expression?

They bind to DNA and control the transcription of specific genes or gene families. Signup and view all the answers

Apoptosis is a physiological process of cell death resulting from activation of __________.

caspases Signup and view all the answers

Which of these proteins determines the cell's susceptibility to apoptosis?

Both A and B Signup and view all the answers

Where do stem cells reside in the body?

In the bone marrow. Signup and view all the answers

B cells can recognize antigens through their surface immunoglobulin without any assistance.

False Signup and view all the answers

What occurs in the germinal centers as a result of continuing response to antigenic stimulation?

B cells undergo massive proliferation and somatic mutation of their immunoglobulin V genes. Signup and view all the answers

The antigen recognition site of the TCR is joined to several other __________ in the CD3 complex.

subunits Signup and view all the answers

What class of T helper cells produces IL-2, TNF-b, and g-interferon (IFN-g)?

Th1 cells Signup and view all the answers

Study Notes

Authors and Edition

A.Victor Hoffbrand: Emeritus Professor of Haematology at University College London.
Paul A.H. Moss: Professor of Haematology at the University of Birmingham.
Seventh Edition published in 2016, continuing from previous editions dating back to 1980.

Publication Details

Published by John Wiley & Sons, Ltd.
Copyright details ensure protection of content as per the UK Copyright, Designs and Patents Act 1988.

Important Content Topics

Advances in understanding blood and lymphatic diseases due to next-generation DNA sequencing.
Discovery of genetic mutations linked to conditions such as myeloproliferative diseases and Waldenström’s macroglobulinemia.

Key Developments in Treatment

Development of therapies that improve patient life expectancy, such as B cell receptor signaling inhibition and JAK2 inhibitors for chronic conditions.
Introduction of new anticoagulants that simplify treatment for arterial and venous thrombosis, minimizing monitoring needs.

Structure of the Textbook

Each chapter includes Key Topics and concludes with a Summary for study purposes.
Covers various aspects of haematology, including haemopoiesis, types of anaemias, hematological malignancies, and blood disorders.

Chapter Highlights

Haemopoiesis: Blood cell formation from pluripotent stem cells in the bone marrow.
Erythropoiesis and Anaemia: Discussion of red blood cell formation and associated conditions.
Malignant Conditions: Insights on acute and chronic leukaemias, lymphomas, and myeloma.
Coagulation Disorders: Overview of bleeding disorders, pathogenesis, and treatment strategies.

Educational Features

Inclusion of diagrams and tables for visual understanding.
Companion website offers additional resources like multiple-choice questions.

Research and Clinical Implications

Recognition of the impact of genetic mutations on disease progression and treatment responses.
Need for ongoing education and adaptation of practices in haematology due to evolving research and therapies.

Acknowledgments

Thanks to contributors who aided in the preparation of the book, including suggestions from experts in the field and providers of illustrative materials.### Stem Cells and Niches
Stem cells are located in the bone marrow, within microenvironments known as niches.
They are regulated by stromal cells that facilitate growth and differentiation.

Apoptosis Mechanism

Apoptosis is a deliberate process of programmed cell death activated by caspases.
The balance between pro-apoptotic (e.g., BAX) and anti-apoptotic proteins (e.g., BCL-2) influences a cell's likelihood of undergoing apoptosis.

Immune System Responses

Antigen recognition is critical for immune responses, with CD4+ T cells (helper T cells) classified into Th1 and Th2 subtypes based on cytokine profiles.
Th1 cells release IL-2, TNF-β, and γ-interferon, enhancing cell-mediated immunity.
Th2 cells produce IL-4 and IL-10, primarily aiding in antibody production.

B Cell Activation

B cells recognize antigens via surface immunoglobulins, while T cells assist in producing antibodies for certain antigens.
Germinal centers within the secondary lymphoid organs form as a result of ongoing immune responses.

Germinal Center Formation

Activated B cells migrate to germinal centers, where they undergo division and somatic hypermutation to enhance antibody affinity.
Centroblasts in the dark zone mutate their immunoglobulin genes, while centrocytes in the light zone are selected based on antigen affinity.

Lymphocytosis

Lymphocytosis refers to an increased number of lymphocytes, often seen in children due to infections.
Common causes include viral infections (e.g., infectious mononucleosis, HIV) and chronic conditions (e.g., tuberculosis, non-Hodgkin lymphoma).
Conditions resulting in lymphocytosis can be categorized into acute and chronic infections, with specific examples noted for clarity.### Glandular Fever and Infectious Mononucleosis
Glandular fever refers to a disease characterized by fever, sore throat, lymphadenopathy, and atypical lymphocytes in the blood.
Infectious mononucleosis, often caused by Epstein-Barr virus (EBV), can occur following primary EBV infection.
Most EBV infections are subclinical; significant disease occurs in a minority of cases.
Atypical lymphocytosis is a hallmark of infectious mononucleosis and occurs due to T cell expansions reacting to infected B lymphocytes.

Macrocytic Anaemias

Macrocytic anaemias are identified by larger-than-normal red blood cells (MCV >98 fL).
Common causes include vitamin B12 and folate deficiencies, along with alcohol use, liver disease, and certain drugs.
Clinical features to consider: hypersegmented neutrophils, leukopenia, and thrombocytopenia.
Important diagnostic steps include assessing dietary history, conducting serum B12 and folate tests, and evaluating for autoimmune disorders or previous gastrointestinal issues.
Symptoms like jaundice, glossitis, and neuropathy may indicate megaloblastic anaemia.

Vitamin B12 and Folate Deficiency

Vitamin B12 malabsorption often occurs with pernicious anaemia, where intrinsic factor production is compromised.
Folate deficiency can arise from poor diet or malabsorption conditions like gluten-induced enteropathy.
Both deficiencies lead to megaloblastic anaemia, affecting the morphological appearance of bone marrow erythroblasts.
Treatment involves hydroxocobalamin injections for B12 deficiency and oral folate supplementation for folate deficiency.

Haemopoiesis Overview

Early haemopoiesis occurs in the yolk sac and later shifts to the AGM (aorta-gonads-mesonephros), liver, and spleen during development.
Bone marrow becomes the primary source of new blood cells from 6-7 months of fetal life onward through adulthood.
In adults, haemopoiesis is largely limited to the vertebrae, ribs, sternum, skull, sacrum, pelvis, and proximal humerus and femur.
Approximately 50% of bone marrow comprises fatty tissue, with potential for reactivation in certain diseases.

Hematopoietic Stem and Progenitor Cells

Haematopoiesis initiates with pluripotential hematopoietic stem cells (HSCs), which can self-renew and differentiate into various blood cell lineages.
HSCs are rare, constituting about 1 in every 20 million nucleated cells.
The differentiation process involves transitioning through committed progenitor cells, which have restricted developmental potential.
Many hematopoietic growth factors influence the production of different blood cells depending on physiological demands.

Bone Marrow Microenvironment

Bone marrow stroma provides a supportive environment for stem cell maintenance and differentiation.
Interactions between stem cells and stromal cells facilitate survival, self-renewal, and production of differentiated cells.
Key factors include the stem cell factor (SCF) and jagged proteins that interact with their respective receptors on HSCs, ensuring proper hematopoietic function.

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This quiz is designed to assess your understanding of Hoffbrand's Essential Haematology. It covers key concepts, terminology, and essential knowledge in the field of haematology as presented by A. Victor Hoffbrand and Paul A.H. Moss. Enhance your grasp of important topics and prepare for further studies in haematology.