POM MOCK 8 - Immune evasion, cell injury, plasma Flashcards

1
Q

How do neutrophils get from blood to pathogen in tissue?

A

Pathogen triggers release of C3a and C5a. Endothelial cells express ICAM allowing for neutrophil adhesion. Neutrophil transmigration occurs. Gradient of C3a and C5a detected by neutrophils via their C3aR and C5aR receptors. Neutrophils move towards gradient of complement and bacteria proteins.

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2
Q

Why is staphylococcus aureus regarded as an opportunistic pathogen?

A

Lives in our microbiota and is harmless however can become harmful in certain situations (immunocompromised or unhealthy individuals).

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3
Q

What can staphylococcus aureus cause?

A

Skin infections and can also lead to life threatening sepsis.

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4
Q

What can streptococcus pyogenes cause?

A

Pharyngitis, skin infection, scarlet fever and sepsis.

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5
Q

How does a capsule polysaccharide evade the immune system?

A

Hides antigenic structures. Antibodies or complement proteins can’t bind.

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6
Q

What surface protein does s.aureus express?

A

Protein A

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7
Q

What surface protein does S.pyogenes express?

A

M protein.

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8
Q

What do surface proteins expressed by bacteria do to evade immune system?

A

Binds antibodies by the fc region (constant region) rather than the fab region (variable region). This prevents normal opsonization and so neutrophils can’t detect.

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9
Q

What do proteases that are released do to evade immune system and what proteases does s.pyogenes release?

A

They cleave antibodies. Prevents normal opsonisation and so neutrophils can’t detect. S.pyogenes = Ides.

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10
Q

How does antigenic variation help evade immune system?

A

Prevents pathogen from being detected by immune cells.

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11
Q

What does C3a and C5a do?

A

Enhances inflammation. Chemoattraction by forming complement protein gradient.

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12
Q

3 ways in which bacteria evade complement system?

A

Cleave complement factors. Inhibit complement convertases. Recruit negative regulators of complement cascade to bacterial surface.

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13
Q

How does the bacterial protease ‘aur’ evade the immune system?

A

Cleaves C3. Prevents c3a and c3b deposition. Prevents c5a formation. This result in less inflammation, less recruitment of immune cells, less opsonisation and no MAC formation.

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14
Q

What do s.aureus and s.pyogenes produce that degrades complement protein C3?

A

Aur and SpeB.

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15
Q

Explain how s.aureus inhibits C3 or C5 convertases?

A

S. aureus produces SCIN protein which binds to C3bBb and inhibits formation of C3 convertase and C5 convertase.

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16
Q

What does inhibition of C3 or C5 convertases result in?

A

Prevents C3b deposition, C3a formation, C5a formation. This result in less inflammation, less recruitment of immune cells, less opsonisation and no MAC formation.

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17
Q

What does recruitment of complement negative regulators result in?

A

Inhibits formation of C3 convertase and C5 convertase. Prevents C3b deposition, C3a formation, C5a formation. This result in less inflammation, less recruitment of immune cells, less opsonisation and no MAC formation.

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18
Q

What do TLR detect?

A

Microbial structures.

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19
Q

What do CLEC receptors detect?

A

Microbial carbohydrates.

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20
Q

What do FPR detect?

A

Microbial peptides.

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21
Q

How can neutrophils indirectly detect microbes?

A

Detect opsonised microbes through their Fc receptors or complement receptors.

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22
Q

What is CXCL8?

A

Chemokine.

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23
Q

What does S.aureus CHIPs do

A

Releases CHIPs which binds to C5aR and prevents binding of C5a. This prevents neutrophils moving to the area of infection.

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24
Q

What does S.pyogenes do to inhibit chemotaxis?

A

Releases SpyCEP which cleaves CXCL8. CXCL8 can’t bind to CXR1/2 and so migration to site of infection doesn’t occur.

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25
Q

How does S.aureus prevent antibody mediated phagocytosis?

A

They release molecules that bind to Fc receptors on neutrophils and prevent detection of opsonised bacteria. FLIPR targets IgG Fc receptor and SSL5 target IgA Fc Receptor.

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26
Q

What toxins does s.aureus release to kill neutrophils?

A

PVL Toxin, LukAB, LukDE

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27
Q

What toxins does s.pyogenes release to kill neutrophils?

A

SLS and SLO

28
Q

What less common ways can bacteria evade immune system?

A

Inhibit effects of antimicrobials. Manipulate
intracellular signalling.

29
Q

What s.aureus protein inhibits C3 or C5 convertases?

A

SCIN protein.

30
Q

What complement negative regulator does s.aureus recruit?

A

Factor H.

31
Q

What complement negative regulator does s.pyogenes recruit?

A

Factor H and C4BP.

32
Q

What does S.auerus protein CHIP’s do?

A

CHIPs binds to C5aR and prevents binding of C5a. Neutrophils do not migrate to sites of infection

33
Q

What does s.pyogenes protease SpyCEP do?

A

Cleaves CXCL8 and so prevents binding to CXCR1/2. Neutrophils do not migrate to sites of infection.

34
Q

Consequences of an injurious stimulus depends on what?

A

Type of cell. Cell status (where in the cell cycle).

35
Q

What are the four intracellular systems that are particularly vulnerable to cell damage?

A

Cell membrane integrity, ATP generation, protein synthesis and integrity of genetic material.

36
Q

What is the common cause of physiological hyperplasia?

A

Hormonal or compensatory.

37
Q

What is the common cause of pathological hyperplasia?

A

Excessive hormonal or growth factor stimulation.

38
Q

What is metaplasia?

A

A reversible change when one cell type is replaced by another cell type.

39
Q

What is dysplasia?

A

Precancerous cells which show the genetic and cytological features of malignancy but do not invade underlying tissue.

40
Q

Key feature of dysplasia?

A

Increase in nuclear-cytoplasmic ratio.

41
Q

What are some changes you could see under a light microscope associated with reversible injury?

A

Fatty change and cellular swelling.

42
Q

What is coagulative necrosis?

A

Tissue architecture is maintained. Usually seen in hypoxic environments.

43
Q

What is liquefactive necrosis?

A

Complete loss of cell detail.

44
Q

What is caseous necrosis?

A

Combination of coagulative and liquefactive. Looks granular. Seen in TB.

45
Q

What is fat necrosis?

A

Seen calcifications due to calcium and fatty acids.

46
Q

How is apoptosis different to necrosis?

A

Apoptosis the cell membrane is contained and so apoptosis doesn’t produce inflammatory response. Apoptosis required ATP, necrosis doesn’t.

47
Q

What is necroptosis?

A

Programmed cell death that produces inflammation. Required ATP.

48
Q

How is plasma prepared?

A

Blood is collected, mixed with an anticoagulant and then centrifuged.

49
Q

What is serum?

A

Plasma without the clotting factors.

Serum = plasma - fibrinogen

50
Q

How is serum prepared?

A

Blood is left to clot and then centrifuged.

51
Q

What do serum tubes contain?

A

Silica coating to induce clotting. Gel to form physical barrier between serum and red blood cells.

52
Q

Serum vs plasma?

A

Serum better for longer storage. Serum takes longer to prepare.

53
Q

What are the two major types of plasma protein?

A

Serum albumin and globulins.

54
Q

What does albumin do?

A

Transports lipids, hormones and ions. Maintains osmotic pressure of plasma. Transports fatty acids released from adipocytes so they can be used in cells in the process of beta oxidation.

55
Q

Where is alpha-1 antitrypsin produced?

A

Liver.

56
Q

What does alpha-1 antitrypsin do?

A

Inhibits proteases, protects tissues from enzymes.

57
Q

What can a deficiency in alpha-1 antitrypsin do?

A

Degration of lung tissue leads to loss in elasticity. This is because neutrophil elastase isn’t heavily inhibited due to the deficiency.

58
Q

What are haptoglobin and alpha 2 macroglobulin examples of?

A

Alpha-2 globulins.

59
Q

Function of haptoglobin?

A

Binds to haemoglobin released from erythrocytes, haptoglobin-haemoglobin complex is removed by the spleen.

60
Q

What disease is haptoglobin used as diagnostic marker?

A

Haemolytic anaemia.

61
Q

What does alpha 2 macroglobulin do?

A

Protease inhibitor that can inactivate fibrinolysis.

62
Q

What is transferrin an example of?

A

Beta globulin.

63
Q

Complement proteins C3 and C4 are examples of?

A

Beta globulins.

64
Q

Immunoglobulins and c reative protein are examples of?

A

Gamma globulins.

65
Q

What is magnesium important for?

A

Cofactor for enzymes.

66
Q

What can we use plasma for?

A

Biomarkers, passive immunotherapy.