POM MOCK 3 - lymphoid tissues, haemostasis, lymphocytes, Flashcards
Primary lymphoid organs?
Thymus, Bone marrow and foetal liver.
What does ‘repertoire’ mean in immunology?
The range of genetically distinct BCRs or TCRs present in a given host.
Where do B cell mature?
Start of maturation occurs in bone marrow where B cell progenitor is created. Final maturation occurs in periphery in spleen or lymph nodes.
What is a germinal centre?
Anatomically restricted site where B cells undergo mutation and selection to generate high affinity antibodies.
How do naïve T cells enter lymph nodes?
Selectin binding to endothelial cells. Switch to integrin binding. Transendothelial migration through high endothelial venule.
What is primary haemostasis?
Formation of unstable platelet plug.
What is secondary haemostasis?
Formation of stable fibrin mesh.
What is the first way platelets can bind to collagen?
Directly using their glycoprotein Ia receptor.
What is the second way platelets can bind to collagen?
Indirectly using their glycoprotein Ib receptor to bind to Von Willebrand factor (VWF).
Where is Von Willebrand factor (VWF) found?
Produced and released from endothelial cells. Produced in megakaryocytes and released from alpha granules in platelets.
What happens after platelets become activated?
They become more rounded and form spicules to encourage platelet-platelet interaction. Contents of platelet granules are also released.
What are released from platelet granules?
ADP, fibrinogen and von Willebrand factor.
What else along with content from granules is produced and released from platelets?
Thromboxane A2
What does thromboxane A2 do?
Vasoconstrictor and aids with platelet aggregation.
What 2 main molecules encourage platelet platelet aggregation?
ADP and Thromboxane A2
What receptor does ADP bind to promote platelet aggregation?
P2Y12 receptor found on platelets.
What receptor does Thromboxane A2 bind to promote platelet aggregation?
Thromboxane A2 receptor
What does fibrinogen do in primary haemostasis?
Binds to glycoprotein IIb/IIIa which further activates platelets. Also has a key role in linking platelets together to form a platelet plug.
How is platelet activation and aggregation counterbalanced?
Active flow of blood and the release of prostacyclin (PGI2) from endothelial cells; prostacyclin is a powerful vasodilator and suppresses platelet activation, thus preventing inappropriate platelet aggregation.
How does aspirin work as an anti platelet drug?
Aspirin inhibits the production of thromboxane A2 by irreversibly blocking the action of cyclo-oxygenase (COX) in platelets, resulting in a reduction in platelet aggregation.
How does clopidogrel work?
Blocks P2Y12 Receptor and so ADP can’t bind therefore reducing platelet aggregation.
Which factors require vitamin K?
Factors II (prothrombin), VII, IX and X
What factor initiates coagulation?
Tissue factor (TF).
What does TF bind to?
Factor VIIa.
What does binding of TF do?
Activates factors IX,X. This leads to factor II (prothrombin) being converted to small amounts of factor IIa (thrombin).
What do calcium ions do?
Aid in binding of activated clotting factors to the phospholipid surfaces of platelets.
What happens in the amplification step?
Small amount of thrombin mediates the activation of the co-factors V and VIII, the zymogen factor XI and platelets.
What happens in the propagation phase?
Factor XI converts more factor IX to IXa, which in concert with factor VIIIa,amplifies the conversion of factor X to Xa, and there is consequently a rapid burst in thrombin generation which cleaves the circulating fibrinogen (soluble) to form the insoluble fibrin clot.
What are the three main natural anticoagulant molecules?
Protein C, Protein S and antithrombin.
What activates protein C?
Thrombin binding to thrombomodulin on the endothelial cell surface.
What does activated protein C do?
Inactivates factors Va and VIIIa in the presence of a co-factor protein S.
What does antithrombin do?
Inactivates thrombin and factor Xa.
What makes antithrombin work?
Binding of antithrombin to endothelial cell-associated heparins.
Main anticoagulant drugs?
Heparin, Warfarin and direct oral anticoagulants.
How does heparin work?
Works indirectly by potentiating the action of antithrombin leading to the inactivation of factors Xa and IIa (thrombin).
How is heparin administered?
Intravenously or by subcutaneous injection.
How does warfarin work?
Vitamin K antagonist that works by interfering with protein carboxylation. It therefore reduces synthesis of functional factors II, VII, IX and X by the liver.
How is warfarin administered?
Given as an oral tablet and its anticoagulant effect needs to be monitored by regular blood testing
Why does warfarin take longer to take effect compared to heparin?
Reduces synthesis of coagulation factors in the liver rather than inhibiting existing factor molecules.
How do direct oral anticoagulants work?
Directly inhibit either thrombin or factor Xa.
What lyses fibrin?
Plasmin.
What is key for fibrin to be lysed?
Both plasminogen and t-PA need to bind to lysine residues on fibrin.
Why do plasmin levels need to be regulated?
Plasmin isn’t specific for fibrin. They can cause break down fibrinogen, factor Va and VIIIa.
What inhibits plasmin?
alpha 2 macroglobulin and anti-plasmin.
When would thrombolytic agents like t-PA be used?
To treat PE or ischaemic stroke.
Risks of thromobolytic agents?
Bleeding.
When would anti-fibrinolytic drugs be used?
Trauma, surgical patients and patients with bleeding disorders.
Examples of anti-fibrinolytic drugs?
Tranexamic acid and aminocaproic acid.
How do anti-fibrinolytic drugs work?
Competitive inhibition. Bind to plasminogen and so plasminogen can’t bind to fibrin and so fibrin isn’t lysed.
When is prothrombin time used?
To evaluate extrinsic pathway and common pathway.
What factors does pro thrombin test for?
VII, X, V, II and fibrinogen.
What does recombinant thromboplastin contain?
Tissue factor and phospholipids.
What pathway does APTT (Activated partial thromboplastin time) test for?
Intrinsic and common pathway.
What factors does APTT (Activated partial thromboplastin time) test for?
XII, XI, IX, VIII, X, V, II and fibrinogen.
Difference in preparation of PT and APTT?
PT tissue factor is used. APTT a contact activator is used.
Prolonged APTT causes?
Haemophilia A (Factor VIII deficiency). Haemophilia B (Factor IX deficiency). Haemophilia C (Factor XI deficiency)
Increased bleeding causes?
Thrombocytopenia. Use of anti platelet drugs (e.g aspirin). Reduction in coagulation factors. Increased fibrinolysis (Use of t-PA).
3 principle causes of thrombosis (Virchow’s triad)
Stasis of blood flow (veins). Endothelial injury (artery). Hyper-coagulability (both).
Causes of thromobosis?
Inherited thrombophilia (reduced levels of anticoagulant proteins such as antithrombin). Reduced fibrinolytic activity (seen in pregnancy). Hyperviscocity (polycthaemia).
How do B cell recognise antigens?
Recognise structural 3D epitopes - native antigens.
How do T cells recognise antigens?
Recognise linear epitopes that are peptides derived from proteins processed by APC’s
What happens when lymphocyte receptor binds to antigen?
Leads to activation of cell and clonal expansion which results in differentiated effector cells of that lineage that bear the same receptor.
What generates the diverse b cell repertoire?
Immunoglobulin gene rearrangement. DNA is rearranged before transcription.
Explain production of BCR receptor chain?
Each BCR receptor chain is encoded by separate multigene families on different chromosomes. During B cell maturation these gene segments are rearranged and brought together. Transcription of B cell DNA then occurs. RNA is then spliced and mRNA is translated to produce polypeptide for that chain that will make up part of the B cell receptor.
Where are MHC I peptides processed?
Cytosol.
Where are MHC II peptides processed?
Endosomes.
What class of T helper cell would be involved in a viral and intracellular bacteria infections?
Th1.
What immune cells would be seen in a viral/intracellular bacterial infection?
CD8 T cells, NK cells, Th1 cells, neutrophils and macrophages.
What immune cells would be seen in a parasitic infection such as a helminth?
Eosinophils, basophils, Th2 cells, B cells and macrophages.
What immune cells would be seen in an extracellular bacterial infection or fungal infection?
Th17, neutrophils and macrophage.
T reg role and cytokines?
IL-10 and TGF beta.
Th1 role and cytokines?
Boosts cellular immune response. IF gamma, TNF and IL-12.
Th2 role and cytokines?
Pro allergic. IL-4, IL-5 and IL-13.
Th17 role and cytokines?
Pro Inflammatory (controls bacterial and viral infection). IL-17, IL-23 and IL-6.
Tfh role and cytokines?
Pro antibody. Produces the cytokine IL-21 which drives B cell proliferation.
Where are t follicular helper cells found?
Secondary lymphoid organs in b cell zones.
How does CD8 T cells kill infected cells?
Apoptosis. Released perforin which polymerise and form pores in the pathogen cell membrane, then released granzymes through pore that create a cascade that leads to apoptosis by fragmentation of nuclear DNA.
What are the 3 functions of antibodies?
Neutralisation, Opsonization and complement activation.
What class of antibody do thymus independent antigens stimulate production of?
Induce IgM synthesis by B cells.
What class of antibody do thymus dependent antigens stimulate production of?
All Ig-classes.
What do thymus independent antigens not stimulate?
They do not stimulate immunological memory.
How do thymus independent antigens activate B cell?
B cell receptor binds to repetitive structure present on bacterial surface. Second signal provided by PAMP such as LPS which binds to toll like receptor on b cell.
Explain thymus dependent antigen pathway?
B cell ingest pathogen and antigen is internalised and degraded into peptides. Displays antigen peptides on its b cell receptor. DC ingests pathogen and displays peptides on MHC II. CD4 T cell that has complementary TCR to antigen gets activated by DC cell. T helper cell then activated B cell by costimulation and cytokines. B cell turns into plasma cell and produces antibodies for that antigen.
