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POM (Principles of Medicine) > Immune evasion > Flashcards

Immune evasion Flashcards

1
Q

What are the three preformed antimicrobial agents?

A

Interferons
Complement
Opsonin

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2
Q

What is the innate immune system?

A

Non-antigen specific, functions on the basis of recognising pathogenic and molecular patterns.
There is no immunological memory conferred through this system.

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3
Q

What are PAMPs?

A

Diverse set of microbial molecules, whereby general structural and biochemical patterns are shared through pathogen recognition receptors.

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4
Q

Which type of receptors detect PAMPs?

A

Pathogen recognition receptors (PRR)

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5
Q

Which type of transmembrane proteins located on leukocytes recognise conserves molecules through bacterial structures and viral structures?

A

Toll-like receptors

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6
Q

What are the examples of bacterial PAMPs? (4)

A

Flagellum (protein flagellin)
Lipopolysaccharide (Endotoxin)
Peptidoglycan
Glycolipids

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7
Q

What are the examples of viral PAMPs? (3)

A 
Glycoproteins
Double stranded (ds) DNA
Single stranded (ss) DNA
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8
Q

What type of bacteria is S.aureus?

A

Gram positive, coagulase and catalase positive

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9
Q

Which type of coagulase bacteria is s.aureus?

A

Coagulase positive

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10
Q

What is the structure of s.aureus?

A

Consists of polysaccharide capsule, cell protein A, has catalase, coagulase proteins embedded within coat.

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11
Q

What is the function of the polysaccharide capsule within s.aureus?

A

Protective against phagocytes

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12
Q

What is protein A?

A

Clumping factor proteins, mediates adherence of bacteria to host tissues.

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13
Q

What is the function of catalase?

A

Protects the bacterium from peroxides produced by neutrophils and macrophages

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14
Q

What is the function of coagulase?

A

Converts fibrinogen to insoluble fibrin resulting in clot formation, protects from phagocytosis

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15
Q

Which enzymes secreted by s.aureus stimulate tissue destruction?

A

Lipases, nucleases and hyaluronidase

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16
Q

Which cytotoxins lyses erythrocytes, neutrophils, macrophages and host cells?

A

Cytotoxin, alpha, beta, delta, gamma and leucocidin

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17
Q

Which type of toxins are heat stable and acid-resistant?

A

Enterotoxins

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18
Q

Which type of toxins cause scalded skin syndrome?

A

Exfoliative toxins A and B

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19
Q

What is scalded skin syndrome?

A

The superficial layers of skin peel off

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20
Q

What is a pyogenic?

A

Pus forming

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21
Q

What two groups of diseases are formed from s.aureus?

A

Localised pyogenic diseases

Systemic diseases

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22
Q

What are localised pyogenic diseases?

A

Diseases characterised by tissue destruction mediated by hydrolytic enzymes and cytotoxins

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23
Q

What types of antigens do toxins behave as?

A

Superantigens

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24
Q

What type of disease is impetigo?

A

Pyogenic disease; localised skin infection characterised by pus-filled vesicles on a erythematous base.

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25
Q

What type of disease is pneumonia?

A

Pyogenic

Abscess formation in the lungs, secondary infection succeeding viral infections of the respiratory tract.

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26
Q

What type of pyogenic disease concerns hair follicles?

A

Folliculitis.

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27
Q

What type of disease are furuncle and carbuncles?

A

Large pus filled skin nodules progress deeper skin layers and spread into circulation.

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28
Q

Which S.areus pyogenic disease is associated with abscess formation in the lungs?

A

Pneumonia

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29
Q

What is osteomyelitis?

A

Bone degradation, primarily in highly vascularized areas of long bones

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30
Q

What is septic arthritis?

A

Infection of joint regions characterized by a swollen reddened join with an accumulation of pus

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31
Q

What are the three main toxin-mediated diseases of s.aureus?

A

Toxic shock syndrome
Food poisoning
Scalded skin syndrome

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32
Q

Why does food poisoning occur with s.aueus?

A

Consumption of heat-stable enterotoxin contamination results in the onset of severe vomiting, diarrhea, and stomach cramps

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33
Q

What is scalded skin syndrome?

A

Localised infections produce the toxin that traverses into circulation and causes outermost skin layer to blister and peel off

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34
Q

What is toxic shock syndrome?

A

Produced toxin that affects multiple organs, characterised by fever, hypotension, and a diffuse , macular, erythematous rash.

35
Q

Which protein molecule assists with pathogen recognition for neutrophils & phagocytes?

A

Complement

36
Q

How does s.aureus evade antibodies?

A

Contains polysaccharide capsule on cell surface membrane, resulting in masking the antigenic structures, preventing detection by the innate immune and adaptive immune components (complement and antibodies)
Capsule enhances microbial virulence

SpA secretion binds onto fc regions of antibodies
Antibody degradation
Antigenic variability

37
Q

Which s.aureus protein binds to the respective Fc region expressed on antibodies?

A

SpA

38
Q

What does SpA surface protein do?

A

Inhibits opsonization, and thereby preventing neutrophil detection of S.aureus (Associated Fc receptor cannot bind to unavailable Fc region)

39
Q

Which immunoglobulin does SSL10 bind on the Fc region to?

A

IgG

40
Q

Which antibody region does SSL10 bind onto?

A

Fc region of igG

41
Q

What is the mechanism of SSL10?

A

Binds to fc region of IgG, prevents the Fc receptors on neutrophils from detecting igG, on the surface of S.aureus obviating neutrophil binding

42
Q

How are antibodies degraded by S.aureus?

A

Extracellular proteases are secreted resulting in the hydrolytic cleavage of antibodies
Enzymes: zinc-dependent metalloproteases aureolysin, cyteine proteases
Serine proteases

43
Q

How does antigenic variability confer antibody evasion?

A

Antigenic modification of cell surface membrane proteins prevents the binding mechanism of complement & opsonin due to structural incompatibility

44
Q

Which complement complex is formed which stimulates cell destruction?

A

Membrane attack complex (MAC)

45
Q

Which complement behaves as an opsonin?

A

C3b

46
Q

What is C3a?

A

An anaphylatoxin that promotes inflammation

47
Q

What does activated C3 do to cell membranes?

A

Triggers lytic pathway and damages plasma membranes of cells

48
Q

What effect does C5a have?

A

Attracts macrophages, and neutrophils –> Activates mast cells

49
Q

How is the classical complement cascade activated?

A

The antibody-antigen complex binds to C1

50
Q

What are three components of C1?

A

CIq, C1R, and C1s

51
Q

What does C3 convertase do?

A

Splits C3 into C3b and C3a (Activates mast cells, the release of histamine)

52
Q

Which protein factors are involved with the alternative complement pathway?

A

Factor, B,D,H, and I, interacts with each, and with C3b, forms C3 convertase, C3bBb activates C3

53
Q

What is c3 convertase?

A

C3bBb

54
Q

What are the stages of the alternative complement pathway?

A

Initiation, the formation of c3 convertase, formation of c5 convertase, and MAC formation

55
Q

Which s.aureus inhibitor protein binds to C3bBb?

A

SCIN

56
Q

What does SCIN do?

A

Binds to C3bBb and inhibits the formation of C3 convertase and c5 convertase
Therefore this prevents the deposition of C3b (opsonin) , and c5a formation

57
Q

Which protein prevents the binding of factor B to c3?

A

eFb (Extracellular fibrinogen binding protein)

This mechanism inhibits c3 processing

58
Q

Which s.aureus peptide inhibits MAC formation?

A

SSL7

59
Q

Which complement protein does SSL7 bind to

A

C5

60
Q

What is the function of C5?

A

C5b consists of essential binding sites for the continuation of the cascade to synthesise and activate further complements in the pathway to generate the cytolytic complex (MAC)

61
Q

What does SSL7 do?

A

Inhibit MAC formation

62
Q

What effect does proteases have on complement?

A

Hydrolytically cleaves the complement protein inhibiting opsonization and MAC formation

63
Q

What does factor H do?

A

Presented on the bacterial surface inhibits the action of C3B (opsonin cannot bind)

64
Q

What granules are neutrophil receptors found in?

A

Azurophillic and gelatinase granules

65
Q

What are pathogen recognition receptors?

A

Receptors directly detect microbial products & structures resulting in neutrophil priming or activation

66
Q

Which receptors detect conserved microbial structures?

A

Toll-like receptors

67
Q

How are microbial carbohydrates detected?

A

CLECs (C-type lectins)

68
Q

How are formulated peptides detected?

A

Detected by Formyl-peptide receptors
G-coupled protein receptor results in extracellular signaling upon cognate ligand binding. FPR 1 key regulator in inflammation

69
Q

What are fc receptors?

A

Fc receptors associate to complimentary fC regions of immunoglobulin opsonin antibodies that are attached to pathogens.
Complement receptors detect complement opsonin

70
Q

What are ITAMs?

A

Immunoreceptor tyrosine based activation motif
ITAM signalling is required for the differentiation and function of B & T cells in adaptive immunity, and regulates the function of innate immune cells

71
Q

What are the innate immune cells?

A

Macrophages, Nk cells, neutrophils and dendritic cells

72
Q

What are the 6 immune receptors?

A 
Cytokin receptors
Chemoattractant
LAIR
SIGLEC
LILR
CEACAM
73
Q

What are activator receptors?

A

Enhances immune cell activity

74
Q

What are inhibitory receptors?

A

Suppresses immune cell activity

75
Q

Which protein inhibits the chemotaxis of neutrophils and monocytes?

A

CHIPs

76
Q

What is the full name for CHIPs?

A

Chemotaxis inhibitory protein of staphylococcus aureus

77
Q

Which receptor does CHIPs bind onto?

A

C5aR and FPR

78
Q

What effect does CHIPs have on neutrophils?

A

CHIPs blocked binding actions of C5Ar, therefore this means that the receptor sites are not activated, and neutrophils subsequently do not migrate to the sites of infectons, and do not become activated through C5aR or FPR 1

79
Q

Which receptors do FLIPr bind onto?

A

Fc y receptors

80
Q

What effect does FLIPr have?

A

Binding onto Fc Y receptors prevents the detection of IgG opsonized bacteria

81
Q

What effect does SSL5 have?

A

Inhibits Fc alpha receptors, thereby reducing antibody-mediated phagocytosis and prevents s aureus destruction

82
Q

How does s.aureus evade neutrophils using antagonists?

A

Receptor antagonists bind and inhibits the function of activatory receptors

83
Q

What does SPIN do?

A

Inhibits the effects of mitochondrials

84
Q

What are the four main mechanisms of neutrophil evasion?

A

Inhibit chemotaxis
Inhibit detection of bacteria
Kill neutrophils
Stimulate inhibitory receptors

POM (Principles of Medicine) (34 decks)

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