Blood and body defences

Question 1

What is a myeloproliferative neoplasms?

Answer 1

Abnormal overproduction of the myeloproliferative cells

Question 2

What are the signs of polycythaemia?

Answer 2

Itching, flushed skin, splenogamaly, dizziness, headache

Question 2

What is primary polycythaemia and the cause?

Answer 2

Primary polycythaemia is generally a congenital/genetic condition.

Question 3

What are the types of primary polycythaemias?

Answer 3

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.

Question 4

What is secondary polycythaemia?

Answer 4

Acquired polycythaemia as a result of other conditions.

Question 5

What are the types of secondary polycythaemias?

Answer 5

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

Question 6

What is relative polycythaemia?

Answer 6

Reduction of plasma volume caused by vomiting or diarrhoea leads to greater volume of RBCs

Question 7

What is thrombocythaemia?

Answer 7

Excess platelets caused by mutation in the AK2V617F. Generally asymptomatic but extreme symptoms are haemorrhage, thrombosis and progression into myelofibrosis or leukemia.

Question 8

What is idiopathic myelofibrosis?

Answer 8

Abnormal platelets, bone marrow fibrosis, splenogamaly caused by JAK2V617F mutation

Question 9

What is the similary between thrombocythemia and idiopathic myelofibrosis?

Answer 9

Both caused by the JAK2V617F mutation.

Question 10

What is myelofibrosis?

Answer 10

Scar tissue forming in the bone marrow which impairs the myeloid progenitor proliferation.

Question 11

What is JAK2?

Answer 11

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.

Question 12

What is V617F?

Answer 12

An autoinhibitory domain encoded in JAK-2 that regulates downstream signalling following EPO/TPO binding to initiate RBC/platelet proliferation.

Question 13

What increases risk of developing Polycythaemia with V617F Jak 2 mutation?

Answer 13

Sex and V617F mutation homozygous inheritance

Question 14

What increases risk of developing Thrombocythaemia with V617F Jak 2 mutation?

Answer 14

Depleted iron stores, EPO levels and genetic modifiers

Question 15

What is hypersensitvity?

Answer 15

Overexcessive immune response to an antigen or allergen.

Question 16

What is type 1 hypersensitivity?

Answer 16

IgE antibody driven- binds to soluble antigen and via its Fc receptor to activate mast cells and cause degranulation.

Question 17

What is type 2 hypersensitvity?

Answer 17

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

Question 18

What is type 3 hypersensitvity?

Answer 18

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.

Question 19

What are the consequences of type 3 hypersenstivity?

Answer 19

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.

Question 20

What is type 4 hypersensitivity?

Answer 20

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.

Question 21

What are the consequences of type 4 hypersensitivity?

Answer 21

Formation of granuloma where macrophage/eosinophils create clumps around the site and present as large swellings.

Question 22

What is a schistosome?

Answer 22

Flatworm pathogen which leads to formation of granuloma.

Question 23

Why is there a delay in lymphocyte recruitment?

Answer 23

Antigen must be processed first by antigen presenting cells for clonal selection of T cells which produce lymphokines.

Question 24

What is primary immunodeficieny?

Answer 24

Impaired immune response caused by genetic defect

Question 25

What is secondary immunodeficiency?

Answer 25

Impaired immune response caused by environmental factor

Question 26

What is chronic granulomatous?

Answer 26

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.

Question 27

What is sex linked chronic granulomatous disease?

Answer 27

Mutations of GP91- phox enzyme for NADPH oxidase production

Question 28

What are the signs of chornic ganulomatous disease?

Answer 28

Skin and rectal abscess, reccurrent pneumonia, granuloma, impetigo (skin infection)

Question 29

What is the role of NADPH oxidase?

Answer 29

Respiratory burst for phagocytic cells

Question 30

What is HIV and AIDS?

Answer 30

Retroviral disease that leads to reduction of CD4+ T cells.

Question 31

What is the impact of HIV associated immunodeficiency?

Answer 31

Normal CD4+ T cells is 500-1500 mm3. HIV reduces CD4+ T cells increases risk for infection which can be indicative of disease

Question 32

How does deficiency affect T cell regulation?

Answer 32

Leads to a decline in T cell population

Question 33

What is the impact of an overactive immune response in cancer?

Answer 33

Development of acute lymphoblastic leukemia of B and T cells. This is the production of immature lymphocytes

Question 34

What is the impact of an underactive immune response in cancer?

Answer 34

Insufficient B and T cell response to destroy tumour cells.

Question 35

What is autoinflammation?

Answer 35

Overactive immune response

Question 36

What is autoimmunity?

Answer 36

Loss of recognition

Question 37

What is familial mediterranean fever?

Answer 37

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.

Question 38

What is neonatal onset multisystem inflammatory disease?

Answer 38

Enhanced IL-1 production that causes joint damage, hearing loss and poor survival

Question 39

What is molecular mimicry?

Answer 39

Pathogen produces antigens similar in structure to self cells that results in immune activation against self antigens.

Question 40

How is autoimmunity induced by infection?

Answer 40

Molecular mimicry, bystander activation, superantigens and cryptic antigens.

Question 41

What are cryptic antigens?

Answer 41

Tissue damage by infection causes formerly hidden epitopes in dendritic cells become available for T and B lymphocytes to recognise and attack

Question 42

What are superantigens?

Answer 42

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

Question 43

What is bystander activation?

Answer 43

Antigen-independent activation of lymphocytes caused by Inflammation and cytokines generated during immune response.

Question 44

How can autoimmune conditions be treated?

Answer 44

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