Block 4 ALS Revision Questions

What are the main innate immunity cells?

• Neutrophils

• Monocytes

• Natural killer cells

• Mast cells

• Basophils

• Eosinophils

What cells give rise to platelets, erythrocytes and monocytes?

Haematopoietic stem cells

Where is the primary site of haematopoiesis in a foetus?

Liver

What are the main growth factors that regulate haematopoiesis?

• Interleukins 1-3

• Stem cell factor

• Erythropoietin

What are the four components of an erythrocyte membrane?

• Spectrin

• Ankyrin

• Band 4.1 protein

• Band 3 protein

What is the function of spectrin in the erythrocyte membrane?

Forms scaffold that maintains integrity and shape of membrane

What is the function of ankyrin in the erythrocyte membrane?

Anchors ion channels to spectrin skeleton

What is the function of band 4.1 protein in the erythrocyte membrane?

Regulates membrane stability by stabilising spectrin-actin cytoskeleton

What is the function of band 3 protein in the erythrocyte membrane?

Exchanges chloride and bicarbonate ions across the membrane

What type of blood cells are these?

Erythrocytes

Biconcave with no nucleus

Where are damaged erythrocytes removed from the blood?

Spleen

What class of antigens determine the blood type of a person?

ABO antigens

Split into A and B

What are the eight blood types?

A+, A-, B+, B-, O+, O-, AB+, AB-

What antibodies target non-present ABO antigens?

IgM

What is haematocrit?

The percentage volume of erythrocytes in the blood

What are the normal haematocrit levels?

Female - 40%

Male - 45%

What are platelets derived from?

Megakaryocytes

What regulates platelet production?

Thrombopoietin

What is the primary function of platelets?

Aggregation at site of wound repair to stop bleeding

What clotting components are required for platelet aggregation?

von Willebrand factor

Fibrinogen

What are the three types of granules found in platelets?

• Dense

• Lambda

• Alpha

What is the function of dense granules in platelets?

• Stimulate aggregation

• Contain ATP, calcium and 5-HT

What is the function of lambda granules in platelets?

Contain hydrolytic enzymes

What is the function of alpha granules in platelets?

Contain coagulation factors

What are the four types of phagocyte?

• Neutrophils

• Eosinophils

• Basophils

• Monocytes

What do neutrophils induce?

Inflammatory response

What is microcytic anaemia?

Form of anaemia marked by erythrocytes with a MCV < 80 fL

What is iron deficiency anaemia?

Anaemia caused by inadequate absorption of iron

Indicated by a low haemoglobin

What is thalassaemia?

Deficient synthesis of haemoglobin

Genetic condition

What is aplastic anaemia?

Anaemia caused by damage to bone marrow

What is the normal structure of haemoglobin?

• Globin ring of 4 polypeptide chains - 2 alpha, 2 beta

• Haem ring with Fe²⁺ ion in centre

How does foetal haemoglobin differ from adult haemoglobin?

2 gamma chains in place of 2 beta chains

What is indicated by a rise in HbA₂?

Sickle cell anaemia

What are the three main forms of beta thalassaemia?

• Minor - mild or absent anaemia

• Intermedia - moderate anaemia

• Major - severe anaemia requiring regular transfusions

What is the lifecycle of erythrocytes?

• Damaged RBCs removed from circulation by macrophages in spleen, liver and red bone marrow

• Globin and haem are split and globin further broken down into amino acids

• Iron is removed from haem in the form of Fe³⁺ associated with transferrin

• In the spleen, liver and muscle fibres Fe³⁺ detaches from transferrin and binds to ferritin

• At the storage site Fe³⁺ is released from ferritin and reattaches to transferrin

• This complex is transported to the red bone marrow

• RBC precursor cells take up the complex by receptor-mediated endocytosis and use Fe³⁺ to form haem and globin is produced from amino acids

• RBCs are produced in the red bone marrow by erythropoiesis

• The non-iron portion of old haem is converted into biliverdin and then bilirubin and enters the blood

• Bilirubin is transported to hepatocytes and placed in the bile where it is released into the small intestine

• Bilirubin is converted into urobilinogen and some is reabsorbed and excreted in urine as urobilin, with the majority converted to stercobilin and excreted in faeces

What is the precursor for erythrocytes?

Reticulocytes

What do proerythroblasts divide into?

Haemoglobin synthesising cells

What is polycythaemia?

Excess of red blood cells in production

• Absolute - overproduction of red blood cells

  • Primary - due to neoplastic proliferation of haematopoietic cells in the bone marrow

  • Secondary - due to increased erythropoietin, e.g. in hypoxia

• Relative - apparent rise in red blood cells, actually due to reduction in blood plasma

What are the clinical signs of polycythaemia?

• Breathing difficulties

• Dizziness

• Excessive bleeding

• Splenomegaly

• Headache

What is the difference between primary and secondary polycythaemia?

Primary - genetic problem resulting in excess production of erythrocytes

Secondary - due to conditions that promote erythrocyte development

What is relative polycythaemia?

Normal red blood cell levels but reduced plasma volume, e.g. due to dehydration

What is essential thrombocythaemia?

Overproduction of platelets by megakaryocytes

What is thrombocytopenia?

Decreased platelet levels

What blood disorders are associated with mutations in the JAK2 gene?

• Polycythaemia vera

• Essential thrombocythaemia

What causes primary immunodeficiency?

Chronic granulomatous diseases

What causes secondary immunodeficiency?

Viral diseases, e.g. HIV/AIDS

What is autoinflammation?

Prolonged, unwanted innate immunity

What is autoimmunity?

Loss or failure of self recognition

What is the principle site of haematopoiesis in adults?

Long bones

What are primary lymphoid tissues?

Sites where lymphocytes differentiate to express antigen receptors

e.g. thymus and bone marrow

What are secondary lymphoid tissues?

Specialised sites for turning on the acquired immune response

e.g. lymph nodes, spleen, mucosal associated lymphoid tissue (MALT)

What do superficial lymphatics follow?

Superficial veins

What do deep lymphatics follow?

Main vessels, e.g. aorta

Where does the majority (3/4) of lymph from the body drain into?

Left brachiocephalic vein via the thoracic duct

Where does lymph from the upper right quadrant drain into?

Right brachiocephalic vein

What do lymph nodes represent?

Anatomical meeting place for cells of the immune system and their exposure to antigens

Where in a lymph node do B cells circulate?

Follicles

Where in a lymph node are T cells found?

Periarteriolar region

What is the largest lymphoid organ?

Spleen

What are the main functions of the spleen?

• Direct immune response to antigens in blood

• Clearance of old or damaged red blood cells

What is the role of haemostasis?

• Limitation of blood loss

• Removal of damaged tissue

• Re-growth and repair of tissue

What are the four haemostatic components?

• Vascular system

• Coagulation proteins

• Platelets

• Fibrinolytic system and coagulation inhibitors

What are the three pathways of the coagulation cascade?

• Extrinsic

• Intrinsic

• Common

What is haemangioblasts?

Stem cells within the blood vessel that give rise to endothelial and haematopoietic cells

Exist in tunica intima

What is the extrinsic pathway?

• Tissue trauma

• Tissue factor leaks into blood from cells outside vessels

• Presence of Ca²⁺ results in TF activating factor X

• Activating factor X combines with factor V in presence of Ca²⁺ to form active enzyme prothrombinase

How fast is the extrinsic pathway?

Very fast - can occur in seconds if trauma is severe enough

What is the intrinsic pathway?

• Damage to endothelial cells exposes collagen fibres and blood comes into with them

• This also damages platelets which release phospholipids

• Blood contact with collagen activates factor XII

• Factor XII in presence of Ca²⁺ and platelet phospholipids eventually activates factor X

• Activated factor X combines with factor V in presence of Ca²⁺ to form active enzyme prothrombinase

What marks the beginning of common pathway?

Formation of prothrombinase

What is the common pathway?

• Prothrombinase and Ca²⁺ catalyse conversion of prothrombin to thrombin

• Thrombin converts soluble fibrinogen to insoluble loose fibrin strands

• Thrombin also activates factor XIII

• Factor XIII strengthens and stabilises fibrin strands into a clot

What is clot retraction?

Consolidation or tightening of fibrin clot

What do natural killer cells attack?

Any body cells displaying abnormal or unusual plasma membrane proteins

What is the role of perforin?

Inserted into plasma membrane of infected cell and creates channels

Extracellular matrix enters cell and causes it to burst in cytolysis

What are granzymes?

Protein-digesting enzymes that induce apoptosis in target cells

What are the two main phagocytes?

• Neutrophils

• Macrophages

What is the difference between wandering and fixed macrophages?

• Wandering - actively phagocytic, move around the body

• Fixed - stay in specific tissue

What are the five stages of phagocytosis?

• Chemotaxis

• Adherence

• Ingestion

• Digestion

• Killing

What is the process of chemotaxis in phagocytosis?

Chemically stimulated movement of phagocytes to site of damage

What is the process of adherence in phagocytosis?

Attachment of phagocyte to microbe or other foreign material

What is the process of ingestion in phagocytosis?

Phagocyte extends pseudopods and engulfs microbe

Microbe is eventually surrounded by phagosome

What is the process of digestion in phagocytosis?

Phagosome enters cytoplasm and merges with lysosomes to form phagolysosome

Lysozyme is secreted to break down cell wall, along with other compounds to degrade microbe

What is the process of killing in phagocytosis?

Microbe killed

Remaining structures kept in residual bodies

What are the characteristic symptoms of inflammation?

• Redness

• Pain

• Heat

• Swelling

• Loss of function

What are the two immediate changes in blood vessels in the region of tissue injury?

• Vasodilation - allows greater blood flow to area

• Increased permeability - allows defensive proteins (antibodies, clotting factors) to enter injured area from the blood

What are the five substances that contribute to the inflammatory response?

• Histamine

• Kinins

• Prostaglandins

• Leukotrienes

• Complements

What is the effect of histamine in the inflammatory response?

Vasodilation and increased permeability of blood vessels

What is the effect of kinins in the inflammatory response?

Induce vasodilation and increased permeability

Chemotactic agents for phagocytes

What is the effect of prostaglandins in the inflammatory response?

Intensify effects of histamine and kinins

Stimulate emigration of phagocytes through capillary walls

What is the effect of leukotrienes in the inflammatory response?

Increase permeability

Chemotactic agents

Enhance adherence of phagocytes to pathogens

What is the effect of complements in the inflammatory response?

Stimulate histamine release

Chemotactic agents

Promote phagocytosis

What are the three stages of inflammation?

• Vasodilation and increased permeability

• Phagocyte emigration

• Tissue repair

Where do B cells form and mature?

Bone marrow

Where do T cells form and mature?

• Form - bone marrow

• Mature - thymus

What is immunocompetence?

Ability to carry out immune responses

What are the two types of T cell?

• Helper T cells - CD4

• Cytotoxic T cells - CD8

What are the two types of adaptive immunity?

• Cell-mediated

• Antibody-mediated

What is clonal selection?

Proliferation and differentiation of a lymphocyte in response to a specific antigen

What is antigen processing?

Breakdown of antigenic proteins into peptide fragments that associate with MHC molecules

What do MHC class 1 molecules process?

Endogenous antigens, e.g. viral, intracellular bacterial

What do MHC class 2 molecules process?

Exogenous antigens, e.g. bacteria, parasiticl

When do T cells ignore an antigen-MHC complex?

When the peptide fragment is from a self-protein