Unit 6 Flashcards
How does the site of erythropoiesis change through life?
Early weeks - yolk sac
Middle trimester - mainly liver (some in spleen and LNs)
Last month of gestation and after birth - bone marrow
How does IL-3 act on the bone marrow?
Promotes growth and reproduction of nearly all types of committed stem cells
What is the developmental journey of a RBC?
MHSC => CFU-S => CFU-B => CFU-E => pro erythroblast => basophil erythroblast => polychromatophil erythroblast => orthochromatic erythroblast => reticulocyte => erythrocyte
Which RBC precursor is the first to contain haemoglobin?
Polychromatophil erythroblast
After release from the marrow, how long does it take a reticulocyte to mature?
1-2 days
Where is EPO produced?
90% kidneys
10% liver
What are the steps for EPO production?
Renal hypoxia => increased tissue HIF-1 - transcription factor for hypoxia-inducible genes
HIF-1 binds hypoxia response element in EPO gene, inducing transcription and EPO synthesis
How can non-renal hypoxia stimulate RBC production?
Norepinephrine, epinephrine and several prostaglandins stimulate EPO production
How does EPO increase RBC count?
Stimulates production of pro erythroblasts from stem cells, and increases rate of maturation
What is needed for final maturation of RBCs?
Vitamin B12 and folic acid
What molecules are needed for haemoglobin formation? Describe the steps
2 x succinyl-CoA (from Kreb’s cycle)
2 x glycine
Combine to form pyrrole
4 x pyrrole combine => protoporphyrin IX
Combines with Fe => heme
Heme combines with globin
How many oxygen molecules can one haemoglobin molecule bind?
4
Describe iron transport and metabolism
pg 444, F 33-7
How and where is iron absorbed?
All of small intestine
Liver secretes apotransferrin in bile - combines => transferrin
Complex absorbed by pinocytosis
How do the lysosomes of macrophages and neutrophils differ?
Macrophage lysosomes contain lipases - capable of digesting thick lipid membranes
What cytokines play dominant roles in the control of the macrophage response to inflammation?
TNF, IL-1, GM-CSF, C-CSF, M-CSF
What are the components of the innate immune system?
Phagocytosis
Destruction of swallowed organisms by stomach acid/digestive secretions
The skin
Presence of lysozyme, basic polypeptides, complement and NK lymphocytes in the blood
What are the requirements for a substance to be antigenic?
Large molecular weight
Must have regularly recurring molecular groups - epitopes
Where are lymphocytes processed?
T - thymus
B - liver then bone marrow
Where is IL-1 produced and what is it’s role?
Macrophages
Promotes growth and reproduction of lymphocytes
Which antibody class is associated with the primary response to an antigen?
IgM
What component of the complement cascade activates phagocytosis?
C3b
What complement factors are responsible for lysis of invading organisms?
C5b6789
What complement factors are responsible for initiating chemotaxis of neutrophils and macrophages?
C5a
What complement components activate mast cells and basophils?
C3a, C$a abd C5a
What are the 7 effects of the compliment cascade?
1 - opsonisation and phagocytosis
2 - lysis
3 - agglutination
4 - neutralisation
5 - chemotaxis
6 - mast cell/basophil activation
7 - inflammation
What are the 3 major types of antigen presenting cells? Which cells respond to them?
Macrophages, B lymphocytes and dendritic cells
T lymphocytes
How do APCs present antigen?
On MHCs
What are the two types of MHC and what id their purpose?
MHC I - present to cytotoxic T cells
MHC II - present to T-helper cells
What are the most numerous T cells?
T helper cells
What T cell is CD4+?
T helper cell
What lymphokine stimulates growth and proliferation of cytotoxic and regulatory T cells?
IL-2
Which lymphokines stimulate the B-cell response?
IL-4, 5 and 6
What T cell is CD8+?
Cytotoxic T cell
How to cytotoxic T cells exert their effect?
Secrete hole-forming proteins - perforins
Release cytotoxic substances into the attacked cell
What are the mechanisms causing vascular constriction after trauma to a blood vessel?
Local myogenic spasm
Local autacoid factors (including thromboxane A2 from platelets
Nervous reflexes
What is found in the platelet cytoplasm?
1 - actin, myosin and thrombosthenin
2 - ER and Golgi apparatus
3 - mitochondria
4 - enzyme systems for prostaglandin synthesis
5 - fibrin-stabilising factor
6 - growth factor
What components make up the platelet surface membrane? What are their function?
Glycoproteins - repulse adherence to normal endothelium but adhere to injured areas
Phospholipids - role in activating clotting
What is the half life of a circulating platelet?
8-12 days
What happens to platelets following contact with a damaged vascular surface?
Swell and assume irregular form with multiple protruding pseudopods
Contractile proteins contract and release granules
Become ‘sticky’ - adhere to collagen and vWF
Secrete ADP, PAF and thromboxane-A2
What are the possible sequelae following blood clot formation?
Invasion by fibroblasts and connective tissue formation
Dissolution
What are the three essential steps to clotting?
Following vessel damage there is a cascade of chemical reactions, resulting in the formation of prothrombin activator
This catalyses the conversion of prothrombin to thrombin
This converts fibrinogen into fibrin
What is factor I?
Fibrinogen
What is factor II?
Prothrombin
What is factor III?
Tissue factor
What is factor IV?
Calcium
Where is prothrombin formed?
Liver
Where is fibrinogen formed?
Liver
What activates fibrin stabilising factor?
Thrombin
Briefly describe the extrinsic pathway
Tissue factor (FIII) released from traumatised tissue
Complexes with FVII, in the presence of calcium activated FX
Xa complexes with V to form prothrombin activator
Briefly describe the intrinsic pathway
Blood trauma causes activation of FXII and release of platelet phospholipids
Activates FXI
Activates FIX
Activates FX (alongside FVIII, FIII and platelet phospholipids)
What is needed for the activation of FXI?
FXIIa
High-molecular weight kininogen
Accelerated by prekallikrein
Which steps of the coagulation cascade are dependent on calcium?
All except first 2 steps of intrinsic pathway
Which clotting pathway is fastest?
Extrinsic
What factors prevent blood clotting in the normal vascular system?
Endothelial factors
1 - smoothness of endothelial cell surface
2 - layer of glycocalyx on the endothelium
3 - thrombomodulin - binds thrombin
4 - production of prostacyclin and NO by norma intact endothelial cells
Blood-based factors
Fibrin fibres
ATIII
Heparin (not normally significant)
What is heparin’s action?
Binds to ATIII and increases activity 100-1000x
Removes thrombin and FIX-XIIa
What are the vitamin K-dependent factors?
II, VII, IX, X, protein C
Where is vita normally produced?
Intestine
How does liver disease cause vit K deficiency?
Lack of bile prevents adequate fat digestion and depresses vitK absorption
