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3rd yr- IWB- Microbiology > Immunity to microbial infection. > Flashcards

Immunity to microbial infection. Flashcards

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1
Q

Name some antimicrobial factors present within the oral cavity

A
  1. Lysozymes
  2. IgA, IgM, IgG
  3. Defensins
  4. Histatins
  5. LL-37
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2
Q

What does lysozyme fo?

A

It cleaves the bond between the peptidoglycan layer and bacterial cell wall
This allows access for antimicrobial peptides to reach the bacteria

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3
Q

Name the most abundant class of antibodies present in our saliva

A

IgA

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4
Q

Describe host defence peptides (HDPs)

A

Short cationic peptides present in the saliva and GCD

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5
Q

Where are host defence peptides (HDPs) produced?

A

Produced from the salivary glands, leukocytes and epithelial cells

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6
Q

What does it mean when we describe a molecule as cationic?

A

It has an overall positive charge

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7
Q

Name the 3 main families of host defence peptides (HDPs)

A
  1. LL-37 (Cathelicidin)
  2. Defensins
  3. Histatins
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8
Q

What can host defence peptides (HDPs) do?

A
  1. They have direct bactericidal activity
  2. Antiviral activity
  3. They can recruit immune cells
  4. Can actuate immune cells
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9
Q

Name the 2 main families of Defensins

A

Alpha

Beta

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10
Q

Describe human defensins

A

They are short peptides with a conserved pattern of 6 paired cysteine residues and 3 disulphide bonds

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11
Q

Where is human Defensin found

A

Expressed widely throughout the whole body

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12
Q

For human Defensins to be activated what needs to happen

A

They need to be proteolytically cut to release the active molecule

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13
Q

Where are alpha defensins made

A

Produced by neutrophils

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14
Q

What is another name for alpha defensins

A

Human neutrophil peptide (HNP)

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15
Q

How many alpha defensins are expressed orally?

A

4

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16
Q

What encodes the 4 HNPs that are expressed orally?

A

3 defensin alpha gens (DEFA)

They are 29-35 amino acids Long

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17
Q

Name the 3 HNPs that are present in high abundance in the oral cavity

A

HNP1
HNP2
HNP3

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18
Q

What are the differences between HNP1, HNP2, HNP3

A

HNP1 and HNP3 differ by one amino acid only (they are the same length)
Removal of that one amino acid forms HNP2 (This means HNP2 is one amino acid shorter than the other 2)

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19
Q

How are alpha defensins stored?

A

In primary azurophil granules

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20
Q

What happens to alpha defensins in periodontitis

A

Found increased levels of alpha defensin

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21
Q

List some of the antimicrobial activities of alpha defensins

A
  1. Active in vitro against a range of bacteria including oral pathogens like S mutans, P gingivalis and A. actinomycetescomitans
  2. Active against Candida albicans
  3. Some antiviral activity
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22
Q

What is Morbus Kostmann?

A

A generalised neutropenia

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23
Q

What happens to alpha denfesins in a patent with Morbus Kostmann?

A

Alpha defensin levels decrease

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24
Q

What happens to alpha denfesins in an edentulous patient?

A

Alpha defensin levels decrease

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25
Q

Other than antimicrobial activity what else can alpha Defensins do?

A

They have an immune regulatory activity

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26
Q

List some of the immune regulatory activities of alpha defensins

A
  1. HNP1-3 are directly chemotactic for monocytes
  2. They can increase neutrophil recruitment
  3. Promote the induction of adaptive immune response through the activation of dendritic cells
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27
Q

How do alpha defensins increase neutrophil recruitment

A
  1. Increase CXCL-8 production
  2. Regulated cytokine expression increasing pro inflammatory cytokine expression
    3, Inhibit anti inflammatory IL-10
  3. Induce mast cell degeneration (histamine release, vasodilation)
28
Q

How long are beta defensins?

A

36-45 amino acids long

29
Q

What are beta defensins expressed by in the oral cavity?

A

Expressed by cells of the :

  1. Gingiva
  2. Salivary glands
  3. Tongue
  4. Mucosa
  5. Epithelial cells
30
Q

When is HBP2 expressed in the oral cavity?

A

All the time (expression is constitutive)

31
Q

Where are HBD1 + 2 expressed?

A

Expressed within the differentiated epithelial cells layers SS and SG

32
Q

Where is HBD3 expressed

A

Expressed within stratified basal layer

33
Q

When is HBD expression increased?

A

In inflamed gingivae

34
Q

What are HBD3s active against

A

Gram positive and gram negative bacteria including:

  1. P gingivalis
  2. S mutans
  3. A actinomycetescomitans
  4. F nucleatum
  5. T denticola
35
Q

What are HBD2s active against ?

A

Gram negative and candida sp

36
Q

What are HBD1s active against?

A

P gingivalis

F nucleatum

37
Q

Which of the 3 HBDs is the most potent and which is the least?

A

HBD3 is the most potent

HBD1 is the least potent

38
Q

List some immune regulator activities of beta defensins

A
  1. Expression of HB2 and 3 are increased by pro inflammatory cytokines
  2. Activate dendritic cells and T cells
  3. Chemo taxis
39
Q

Other than bacteria what else do beta defensins target?

A

They have anti viral activity

40
Q

List some of the antiviral activity of defensins

A
  1. Can target the lipid envelope
  2. Extracellular aggregation
  3. Receptor blocking/ down regulation
  4. Inhibition of fusion
  5. Blocking uncoating
  6. Cellular changes
41
Q

Describe LL-37

A

Alpha helical structure

42
Q

Name the only HUMAN member of the cathelicidin family

A

LL-37

43
Q

Where is LL-37 present

A

Salivary glands
Saliva
GCF

44
Q

What is LL-37 produced by

A

Leucocytes

Epithelial cells

45
Q

How is LL-37 stored?

A

Stored as precursor hCAP-18 in secondary granules

46
Q

When do levels of LL-37 increase?

A

Increased levels in GCF and saliva in periodontal disease

47
Q

What bacteria does LL37 work against

A
  1. P intermedia
  2. P gingivalis
  3. F nucleatum
  4. S gardenia
  5. S sanguines
48
Q

Other than anti bacterial activity what else can LL37 do?

A
  1. Autoaggregation of candida albicans
  2. Reducses candida binding to epithelia
  3. Promotion of wound healing
  4. Stimulates pro inflammatory responses
  5. Inhibits inflammatory responses to gram negative LPS
  6. Neutralises gram negative LPS
  7. direct chemo attractant
49
Q

How does LL-37 stimulate pro inflammatory responses

A
  1. Stimulates epithelial cells to produce CXCL-8

2. Synergise with cytokines to enhance PBMCs responses

50
Q

Why does p gingivalis cause inflammation

A

So that it can take proteins from the increased GCF flow and use that to produce toxins and cause damage

51
Q

Name the three models we use to describe AMP insertion into lipid bilayers

A
  1. Barrel stave model
  2. Toroidal model
  3. Carpet model
52
Q

What is the barrel stave model thought to be a model for now?

A

Model for perforin

53
Q

Out of the 3 models which are most Likely to be the models for antimicrobial peptides (AMP) insertion

A
  1. Toroidal model

2. Carpet model

54
Q

What is another name for the toroidal model?

A

Wormhole model

55
Q

What does AMP stand fro

A

Antimicrobial peptide

56
Q

What form in the toroidal model

A

Holes form

57
Q

What is the carpet model based on

A

Based on the description of the lipid bilayer

58
Q

Describe histatins

A

They are histadine rich
They are cationic and 7-38 amino acids long
They are madly amphopathetic

59
Q

Where are histatins found

A

In the saliva

60
Q

What are histatins produced by

A

Parotid, submandibular and sub lingual glands

61
Q

Name the most prominent histatins in humans

A

Human histatin 1, 3 and 5

62
Q

To which fungi do histatins have the most potency to?

A

Candida species

63
Q

What are the activities of histatins

A
  1. Anti fungal
  2. Important in production of acquired enamel pellicle
  3. Important in wound healing
64
Q

How do histatins affect candida species

A

They inhibit mitochondrial respiration

65
Q

How do histatins help in would healing

A

They activate the migration of epithelial cells

3rd yr- IWB- Microbiology (12 decks)

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