Blood and body defences Flashcards
What is a myeloproliferative neoplasms?
Abnormal overproduction of the myeloproliferative cells
What are the signs of polycythaemia?
Itching, flushed skin, splenogamaly, dizziness, headache
What is primary polycythaemia and the cause?
Primary polycythaemia is generally a congenital/genetic condition.
What are the types of primary polycythaemias?
It can be caused by a congenital defect where the cells which respond to EPO have a defect in the gene coding for the EPO receptor. Polycythaemia vera is a congenital condition where there is a JAK2V617F mutation.
What is secondary polycythaemia?
Acquired polycythaemia as a result of other conditions.
What are the types of secondary polycythaemias?
Hypoxia induced- related to COPD, CHF or kidney transplant
Carcinoma of the liver (which is the site of EPO production) and liver (which is the site of HIF-alpha production that drives EPO levels)
Neonatal- transfusion with maternal blood
What is relative polycythaemia?
Reduction of plasma volume caused by vomiting or diarrhoea leads to greater volume of RBCs
What is thrombocythaemia?
Excess platelets caused by mutation in the AK2V617F. Generally asymptomatic but extreme symptoms are haemorrhage, thrombosis and progression into myelofibrosis or leukemia.
What is idiopathic myelofibrosis?
Abnormal platelets, bone marrow fibrosis, splenogamaly caused by JAK2V617F mutation
What is the similary between thrombocythemia and idiopathic myelofibrosis?
Both caused by the JAK2V617F mutation.
What is myelofibrosis?
Scar tissue forming in the bone marrow which impairs the myeloid progenitor proliferation.
What is JAK2?
A non-receptor protein kinase found on the EPO receptor which acts as a signal transductor for the transcription of the JAK-2 protein to control RBC proliferation.
What is V617F?
An autoinhibitory domain encoded in JAK-2 that regulates downstream signalling following EPO/TPO binding to initiate RBC/platelet proliferation.
What increases risk of developing Polycythaemia with V617F Jak 2 mutation?
Sex and V617F mutation homozygous inheritance
What increases risk of developing Thrombocythaemia with V617F Jak 2 mutation?
Depleted iron stores, EPO levels and genetic modifiers
What is hypersensitvity?
Overexcessive immune response to an antigen or allergen.
What is type 1 hypersensitivity?
IgE antibody driven- binds to soluble antigen and via its Fc receptor to activate mast cells and cause degranulation.
What is type 2 hypersensitvity?
IgG/ IgM antibody binds to a cell-associated antigen or cell surface antigen and via its Fc receptor activates the complement system or Natural killer cells to induce destruction. This drives drug allergy
What is type 3 hypersensitvity?
Immune complex where IgG antibody binds to cell surface antigen and is deposited in regions of the body and this allows C1q to bind to initiate the complement cascade for inflammation or opsonisation.
What are the consequences of type 3 hypersenstivity?
Inflammation at the site of the immune complex deposit. Eg vasculitis, in the glomeluri it is nephritis, in the lungs it is called farmer’s lungs and in the subcutaneous layer it is arthus’ disease.
What is type 4 hypersensitivity?
Driven by T cells. TH1 binds to soluble antigen and induces macrophage activation. TH2 binds to soluble antigen and induces neutrophil activation. CTL binds to cell-surface antigen and induces cytotoxicity.
What are the consequences of type 4 hypersensitivity?
Formation of granuloma where macrophage/eosinophils create clumps around the site and present as large swellings.
What is a schistosome?
Flatworm pathogen which leads to formation of granuloma.
Why is there a delay in lymphocyte recruitment?
Antigen must be processed first by antigen presenting cells for clonal selection of T cells which produce lymphokines.
What is primary immunodeficieny?
Impaired immune response caused by genetic defect
What is secondary immunodeficiency?
Impaired immune response caused by environmental factor
What is chronic granulomatous?
Primary immunodeficiency where there is Type 4 hypersensitvity that leads to chronic granuloma formation. Caused by mutation in the -phox enzymes for NADPH oxidase for respiratory bursts by phagocytes.
What is sex linked chronic granulomatous disease?
Mutations of GP91- phox enzyme for NADPH oxidase production
What are the signs of chornic ganulomatous disease?
Skin and rectal abscess, reccurrent pneumonia, granuloma, impetigo (skin infection)
What is the role of NADPH oxidase?
Respiratory burst for phagocytic cells
What is HIV and AIDS?
Retroviral disease that leads to reduction of CD4+ T cells.
What is the impact of HIV associated immunodeficiency?
Normal CD4+ T cells is 500-1500 mm3. HIV reduces CD4+ T cells increases risk for infection which can be indicative of disease
How does deficiency affect T cell regulation?
Leads to a decline in T cell population
What is the impact of an overactive immune response in cancer?
Development of acute lymphoblastic leukemia of B and T cells. This is the production of immature lymphocytes
What is the impact of an underactive immune response in cancer?
Insufficient B and T cell response to destroy tumour cells.
What is autoinflammation?
Overactive immune response
What is autoimmunity?
Loss of recognition
What is familial mediterranean fever?
Mutation in the FMF gene encodes pyrin, a protein produced by WBC for infection. Common in Turkish, Arab and Jewish populations and causes fever, peritonitis and pleurisy.
What is neonatal onset multisystem inflammatory disease?
Enhanced IL-1 production that causes joint damage, hearing loss and poor survival
What is molecular mimicry?
Pathogen produces antigens similar in structure to self cells that results in immune activation against self antigens.
How is autoimmunity induced by infection?
Molecular mimicry, bystander activation, superantigens and cryptic antigens.
What are cryptic antigens?
Tissue damage by infection causes formerly hidden epitopes in dendritic cells become available for T and B lymphocytes to recognise and attack
What are superantigens?
Antigens produced by pathogens that bind to MHC Class II on dendritic cells and TCR and cause an excessive immune T cell activation. It bypasses macrophages and DCs for lymphocyte activation
What is bystander activation?
Antigen-independent activation of lymphocytes caused by Inflammation and cytokines generated during immune response.
How can autoimmune conditions be treated?
Cytokine therapy such as anti-TNF or anti-IL1
Disrupting the signalling pathway using steroids, cell surface receptor antagonists or inducing tolerance
Anti-B cell therapy using Rituximab
