2015 Medsci TEST Answers PDF

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THE UNIVERSITY OF AUCKLANDFIRST SEMESTER, 2015Campus: HEALTHMEDSCI 203Mechanisms of DiseaseMID SEMESTER TEST(Time Allowed: 50 MINUTES)MULTIPLE CHOICE QUESTIONSNOTE: Write your NAME , AUID NUMBER and the VERSION NUMBER on the Scantron sheet provided.Use a 2B pencil for all marking on the answer sheet...

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THE UNIVERSITY OF AUCKLAND FIRST SEMESTER, 2015 Campus: HEALTH

MEDSCI 203

Mechanisms of Disease MID SEMESTER TEST (Time Allowed: 50 MINUTES)

MULTIPLE CHOICE QUESTIONS

NOTE: Write your NAME, AUID NUMBER and the VERSION NUMBER on the Scantron sheet provided. Use a 2B pencil for all marking on the answer sheet. Each question contains five suggested answers. Indicate your choice on the Scantron Sheet by shading in the box for the correct answer. Responses are either correct = 1 mark, or incorrect = 0 marks 1. An adequate intake of vitamins B9 (folic acid) and B12 is important for health because they are required for: (a) maintenance of DNA synthesis and repair (b) synthesis and export of lipids (c) the unfolded protein response (d) detoxification of reactive oxygen species (e) glycation of proteins Lecture 6, Manual page 6.2: Dietary deficiency involving these vitamins was given as an example of a biological condition affecting the integrity of DNA.

2. The enzyme known as catalase is important in: (a) the repair of DNA breaks

(b) protection against oxidants (c) degradation of extracellular matrix proteins (d) generating energy for cell metabolism (e) helping damaged proteins to re-nature Lecture 6, page 6.2, diagram on 6.3: Catalase detoxifies the reactive oxygen species known as hydrogen peroxide. It degrades H2O2 to oxygen and water.

3. Acute intracellular oedema is found in cells that: (a) are undergoing apoptotic cell death (b) have died from massive trauma (c) have reduced control of sodium ion movement (d) are storing large amounts of carbohydrates, lipids or abnormal proteins (e) cannot make proteins due to severe energy malnutrition (kwashiorkor) Lecture 6, page 6.5: Acute intracellular oedema (or hydropic change) is a sign of reversible injury. So options (a) and (b) have to be wrong. (Death is irreversible.) This condition happens when membranes become leaky, the Na+/K+ ATPase is damaged, or ATP concentrations are insufficient to support the Na+/K+ ATPase. The result is a temporary imbalance of Na+ and cell swelling.

4. Adaptive responses to cell stress include the responses to DNA damage, oxidant stress, heat shock, hypoxia, and endoplasmic stress. A feature common to all of these is: (a) the activation of the p53 molecule (b) cell swelling, membrane permeability and lysis (c) an insufficiency of glucose with loss of ATP synthesis (d) an increase in the activity of glucose transporters and glycolytic enzymes (e) the induction of gene transcription Lecture 6, page 6.5: All of the five responses to stress involve activation of transcription factors and the induction of proteins with protective effects. The p53 molecule (a) is but one

of these factors. Oncotic death (described by (b)) is not a stress response. The option (c) does not feature in any of the stress responses. Glucose transport and glycolysis (d) are integral to the hypoxia response only - not to the others.

5. A form of cell death that involves activation of inflammasomes and of caspase 1, followed by cell lysis is: (a) necrosis (b) oncosis (c) necroptosis (d) pyroptosis

(e) autophagic cell death Lecture 7, page 7.1: Pyroptosis implies fever (pyro, fire). This form of cell death involves microbes that activate inflammasomes and caspase 1. Cell death may prevent intracellular microbes from replicating, and will induce inflammation. Caspase 1 processes pro inflammatory cytokines such as IL-1β (see page 9.3).

6. Apoptosis will generate inflammation under conditions in which: (a) it is triggered by death receptors such as Fas (b) it is triggered by detachment from the extracellular matrix in a process called anoikis (c) apoptotic bodies are released (d) apoptotic bodies cannot be phagocytosed by neighbouring cells (e) cytochrome C is released from mitochondria Lecture 7, Manual page 7.1: Options (a), (b), (c) and (e) are all true of apoptosis, at least in some situations. However none is necessarily involved in inflammation. But when apoptotic bodies cannot be cleared by adjacent phagocytes, their membranes will eventually degenerate, the cytoplasmic or nuclear contents will leak out, and the resulting detection of DAMPs will excite inflammation.

7. In the presence of signals such as histamine and tryptases, arterioles contribute to the development of the cardinal signs of inflammation when: (a) they undergo dilatation (b) they are denuded of endothelial cells (c) cells comprising their endothelial lining retract to become leaky (d) their endothelial cells become adherent for neutrophils (e) they are occluded by thrombus Lecture 8, page 8.2: This question assessed your knowledge that redness and heat (from hyperaemia) arises from increased blood flow into an area. This must involve the dilation (or dilatation) of arteries in response to smooth muscle relaxation.

8. A lipid-derived signalling molecule that induces platelet aggregation and vasoconstriction, and so contributes to haemostasis, is: (a) thromboxane A 2 (b) prostaglandin E2 (c) phosphatidylcholine (d) phosphatidylserine (e) any leukotriene Lecture 8, page 8.2 and 8.3: Sorry – you just have to know this. The name thromboxane implies thrombus. Thrombus arises when blood coagulates inside blood vessels, and this requires platelet aggregation. TXA2 thus promotes platelet aggregation (leading to clots) and vasoconstriction, reducing blood loss after vascular injury. Thrombus (occurring inside blood vessels) is dangerous as it may lead to blockage, ischaemia and infarction.

9. The key protease in the fibrinolytic pathway is: (a) thrombin (b) plasmin (c) esterase (d) kallikrein (e) caspase 1 Lecture 8, page 8.4 and 8.5: Plasmin cleaves fibrin, and so can be a life-saver if thrombus blocks arteries.

10. The functions of C3a and C5a include: (a) vasopermeability and neutrophil attraction (b) digestion of extracellular matrix (c) the removal of fibrin aggregates (d) the direct killing of bacteria (e) platelet disaggregation and vasodilatation Lecture 8, page 8.4 and 8.5: These proteins are cleavage products of complement. They have a profound ability to induce vasopermeability and to act as chemoattractants (as in necrotaxis). Indeed widespread activation of complement in the bloodstream can make a major contribution to the dangerous condition of SIRS or sepsis.

11. Suppuration may be induced by neutrophil-derived hydrolytic enzymes and is characteristic of: (a) coagulative necrosis (b) ischaemic injury (c) diapedesis (d) fat necrosis (e) cellulitis and abscesses Lecture 9, page 9.5: Suppuration is the formation of pus, which is seen during infections that may be localised (in cystic structures called abscesses) or when they become delocalised and spread (as in cellulitis).

12. In sterile inflammation, N-formylated peptides act as strong chemotactic signals and are derived from: (a) degraded extracellular matrix (b) chromatin (c) the granules of phagocytes (d) mitochondria (e) advanced glycation end products

Lecture 9, page 9.3: Bacteria add a formyl group (HC=O) to the N-terminal methionine of the proteins they make. Mitochondria have bacterial-type protein synthesis machinery. So they make N-formulated proteins too. When mitochondria are broken during cell death, their NFPs leak out and are recognised as signalling a bacterial emergency. (Fascinating!) NFPs strongly recruit neutrophils. Note that ECM fragments (such as those derived form hyaluronan) and chromatin proteins (such as HMGB1) are also chemotactic.

13. Multiorgan failure is a lethal condition that may be seen in: (a) the acute phase response (b) systemic inflammatory response syndrome (c) leukocytosis (d) TH1-mediated chronic inflammation (e) the coagulation cascade Lecture 9, page 9.5 and 9.6: SIRS is a very serious condition. The whole vascular system shows acute inflammatory change. Widespread C5a activation will cause widespread vasopermeabilty (and loss of blood voume) for example. So the condition of multiorgan failure has to arise in the context of SIRS, (b). The other options may contribute to SIRS, but of course usually occur in the absence of SIRS.

14. During wound healing, the process of debridement typically occurs during: (a) haemostasis (b) the inflammatory phase (c) the proliferative phase (d) re-epithelialisation (e) remodelling Lecture 10, page 10.2: Debridement is the removal of damaged necrotic tissue. It requires neutrophils and macrophages (which phagocytose junk and release ROS and proteinases). This has to occur during (b). It must occur before (c) to (e) can get underway.

15. The cells responsible for the contraction of wounds are: (a) macrophages (b) fibroblasts (c) myofibroblasts (d) migrating epithelial cells (e) smooth muscle cells Lecture 10, page 10.3: Myofibroblasts are produced from fibroblasts, especially in the context of wound repair, and are contractile. Just think of the myo prefix.

16. During wound healing, regeneration involves:

(a) the formation of granulation tissue (b) scarring with a protracted period of tissue remodelling (c) proliferation of terminally differentiated cells (d) replacement of lost tissue by cells of the same kind (e) repair of tissue that has lost both epithelial and stromal components Lecture 10, page 10.1 and figures on 10.2: Regeneration involves healing in which damaged or lost tissue is wholly replaced. Tissue is reconstituted as new. The options (a), (b) and (e) all involve repair (which ends up with a scar). The option (c) may sometimes contribute to regeneration (as when differentiated hepatocytes proliferate to replace lost liver tissue) but is not definitive for regeneration.

17. Fibrin is an insoluble protein that is: (a) produced by fibroblasts (b) responsible for the bulk of scar tissue (c) present in clots and thrombi (d) a major constituent of basement membranes (e) responsible for the strength of normal skin Lecture 8, page 8.4 and 8.5: There is often confusion as to the nature of fibrin. It is the main product of the coagulation cascade, generated from fibrinogen by the proteinase thrombin. Despite the similarity in name, fibrin is not produced by fibroblasts, and does not contribute to fibrosis. Fibroblasts and fibrosis are associated with extracellular matrix proteins such as collagens.

18. Metaplasia arises during the progression of Barrett’s oesophagus, and is that condition in which: (a) stomach contents are regurgitated into the lower oesophagus (b) stomach acid induces inflammation (c) squamous epithelium is replaced by intestinal epithelium (d) bile acids cause injury to epithelial cells (e) N-nitroso compounds damage DNA and contribute to cancer development Lecture 11, page 11.4: Metaplasia is associated with a change in the type of tissue present. GERD may progress to chronic oesophagitis with Barrett’s oesophagus. The stress of continual inflammation may lead to the replacement of squamous epithelium by intestinal epithelium.

19. Every person has a level of background inflammation that may be increased by: (a) physical exercise (b) lifestyles that increase the ratio of symbionts to pathobionts (c) diets that generate abundant short chain fatty acids in the colon (d) dietary omega-3 fatty acids that stimulate GPR120 receptors (e) obesity

Lecture 11, page 11.3: Lifestyle features that decrease basal inflammation levels include exercise, symbiotic bacteria, SCFAs and omega-3 FAs. Obese adipose tissue is often the site of lipotoxicity, inflammation, and the release of TNF, IL-1, and Il-6.

20. The evidence that Crohn’s disease has a significant environmental component comes from the observation that: (a) the CARD15 gene is mutated mainly in Caucasians (b) the incidence has risen sharply in industrialised countries in 40 years (c) the immune system is over-activated (d) it appears in adolescence or later (e) it occurs throughout the digestive tract but especially at the end of the ileum Lecture 11, page 11.5: The frequencies of rare alleles can vary geographically, but in themselves do not tell us about environmental causes of a disease - so (a) is irrelevant. The options (c), (d) and (e) all relate to Crohn’s disease, but not specifically to environment. For example, activated immune systems are a constant feature of Crohn’s. The changing incidence of Crohn’s over the last generation is far too fast to be due to changes in allele frequencies. It is paralleled by lifestyle changes and must reflect environmental influences.

21. A liver condition, associated with abnormalities in metabolism, in which there is cell damage, inflammation and sometimes fibrosis is known as: (a) non-alcoholic steatohepatitis (b) steatosis (c) cirrhosis (d) end-stage liver disease (e) liver failure Lecture 12, page 12.1: Inflammation is identified by the suffix –itis. NASH is defined by inflammation, and although fibrosis may occur, it is not necessarily so. Fibrosis is a defining feature of cirrhosis, as well of end-stage liver disease (ESLD) and liver failure, to which cirrhosis may progress.

22. Lipotoxicity in the liver is considered to arise from elevated concentrations of: (a) cholesterol (b) free fatty acids (c) triglycerides (d) phospholipids (e) very low density lipoprotein Lecture 12, page 12.1 12.2: Free fatty acids are overproduced from adipose tissues and may be present in high concentrations in steatotic livers. The FFAs damage membranes. Unsaturated FFAs may lead to ER stress.

23. During infection with Mycobacterium tuberculosis, the change that allows infection of other individuals typically is: (a) formation of caseous necrosis (b) formation of a fibrous capsule (c) liquefaction resulting in cavitation (d) formation of a granuloma (e) development of TH1 cell-mediated immunity Lecture 12, page 12.4 and 12.5: Liquefaction of granulomas results in release of extracellular M tuberculosis, and damage to airways. Coughing generates aerosols in which bacteria are released into airways, and spread to people nearby. All other options relate to granulomas, but in general to containment of the bacteria.

24. The inability to distinguish between self-cells and nonself-cells may lead to: (a) hypersensitivity (b) auto-immune disease (c) immunodeficiency (d) tolerance (e) all of the above Lecture 13. The immune system must be tolerant of harmless environmental molecules, and of ‘self’ molecules. The breakdown of tolerance to self indicates that the immune system reacts aggressively to ‘self’ antigens.

25. Autoimmune disease can be triggered by cross-reactivity with a pathogenic antigen by the process of: (a) immune deficiency (b) anergy (c) molecular mimicry (d) hypersensitivity (e) antigen presentation Lecture 13: Molecular mimicry indicates that a foreign antigen and a ‘self’ antigen are

sufficiently similar in conformation that an immune response stimulated by the former will lead to targetting of the latter. A foreign immunogen effectively breaks tolerance to a component of the body.

26. Which of the following factors is/are known to predispose people to the development of systemic lupus erythematosus (SLE)?

(a) The presence of HLA-D2, HLA-D3 and HLA-D8 risk alleles (b) A single nucleotide polymorphism in the PTPN22 gene (c) Exposure to sunlight (d) Female gender (e) All of the above Lecture 13, slide 41: The genetic and environmental factors predisposing to SLE are all shown on this slide.

27. All hypersensitivities involve two stages. These are known as the: (a) sensitisation and effector stages (b) initiation and resolution stages (c) sensitisation and resolution stages (d) initiation and effector stages (e) initiation and sensitisation stages Lecture 14: Sensitisation is described in detail, from entry of allergen to binding of IgE to mast cell Fcε receptors (slide 17, and those following). The effector stage includes allergen biding to the IgE, mast cell degranulation with PAF release, eosinophil recruitment and tissue damage (as described in slides 22 and 23).

28. Another term for type I hypersensitivity is: (a) direct antibody-mediated cytotoxic hypersensitivity (b) IgE-mediated hypersensitivity (c) delayed type hypersensitivity (d) immune complex-mediated hypersensitivity (e) IgG-mediated hypersensitivity Lecture 14, slide 15: A classification of hypersensitivity types is given. Type I is also called IgE-mediated hypersensitivity, immediate hypersensitivity, allergy, or atopy. Allergens cross link IgE bound on mast cells/basophils and induce degranulation

29. During type I hypersensitivity, mast cells become sensitised by: (a) phagocytosis of allergen by mast cells (b) dendritic cells that express IL-4 (c) degranulating dendritic cells (d) IgE binding to FcεRs located on mast cells (e) dendritic cells that express IL-4, IL-5 and IL-13 Lecture 14, slide 15: Mast cells become sensitised to a particular allergen when their FcεRs bind IgE antibodies that specifically recognise that particular allergen. These mast cells are poised to respond to the presence of the allergen.

30. What is the major characteristic of staphylococcal food poisoning? (a) It is caused by protease and heat-sensitive toxins (b) It results from infection with Staphylococcus aureus (c) Disease symptoms start about 7 days after ingestion of toxins (d) Patients recover after 1-2 days (e) It can be prevented by vaccination Lecture 17, slide 10: The toxins are heat-resistant; the condition arises from ingestion of food, rather than an infection (and therefore cannot be prevented by vaccination). The course shows a rapid onset and a rapid recovery (no more than two days).

31. Cholera toxin causes watery diarrhoea by: (a) lysing enterocytes in the gut epithelium by pore formation (b) decreasing the intracellular cAMP concentration (c) inducing an apoptotic signal in the host cell (d) causing inflammation of the gut epithelium (e) deregulation of the cystic fibrosis transmembrane conductance regulator (CFTR) Lecture 17, manual page 17.2: The V cholerae toxin does not cause actual damage to cells - so (a), (c) and (d) cannot be correct. It modifies the Gαs protein, increasing cAMP concentrations - so (b) is incorrect. This leads to loss of ions from cells, and the corresponding loss of water. Patient death flows by dehydration

32. Staphylococcus aureus beta-toxin damages host cell membranes by which mechanism? (a) Phospholipase A activity (b) Phospholipase C activity (c) Serine-protease activity (d) Metalloprotease activity (e) Formation of pores into lipid membranes Lecture 17, slide 21: Staphylococcus aureus produces a phospholipase C (‘PL C’, see diagram) that degrades phospholipids in cell membranes .

33. Which of the following statements about acute rheumatic fever (ARF) is CORRECT? (a) ARF is characterized by a type II hypersensitivity reaction (b) ARF is an infectious disease with group A streptococcus (c) ARF is an inflammation caused by the release of endotoxin by the bacteria (d) Stimulation of Toll-like receptor 4 plays a major role (e) Secreted bacterial toxins contribute to inflammation Lecture 18, slide 32: The heading of this slide specifies that ‘Cross-reactive antibodies trigger a type II hypersensitivity reaction’.

34. Which of the following is an important cytokine involved in inflammation damage? (a) Interleukin 4 (IL-4) (b) Interleukin 10 (IL-10) (c) Tumour necrosis factor-α (TNF-α) (d) Endotoxin (e) Lipopolysaccharide (LPS) Lecture 18, manual page 18.3: TNF can be very damaging. Interleukins-4 and -10 are generally considered to be anti-inflammatory. You should know that endotoxin/LPS is a bacterial product, not a cytokine.

35. Superantigens produced by Staphylococcus aureus cause which of the following effects? (a) Haemolysis (destruction of red blood cells) (b) Strong activation of a pro-inflammatory cytokine response (c) Strong activation of an anti-inflammatory cytokine response (d) Induction of apoptosis in host epithelial cells (e) Rapid spreading of bact...