Immune System and Bacteria Flashcards

1
Q

What are some non-specific exterior defences against bacteria?

A
  • Skin (barrier, epithelium, fatty acids, lysozyme, microbiota)
  • Tears (lysozyme)
  • Urinary tract (epithelium, flushing, low pH, microbiota)
  • Mucosal Surfaces (epithelium, mucus, with lysozyme and lactoferrin, ciliated epithelial cells, microbiota)
  • Gut (epithelium, acid, defensins, microbiota)
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2
Q

How do cells of the innate and adaptive immune systems differ to each other?

A
Innate	
Molecules:Shared by microbes/damaged host cells	
Diversity:Limited (encoded by germ line)
Memory:	None
Response:Rapid, constant size	
Barriers:	Skin, mucus, antimicrobial molecules
Blood proteins:Complement, etc.	
Cells:	Phagocytes, NK cells

Adaptive
Molecules:Antigens
Diversity:Large, somatic recombination possible
Memory: Yes
Response:Slower, more exposure increases size
Barriers: Lymphocytes (epithelia), antibodies
Blood proteins: Antibodies
Cells:Lymphocytes

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3
Q

What kinds of receptors distinguish self from non-self?

A

Pattern Recognition receptors (PRRs)

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4
Q

What are PRRs? What are examples of some?

A
  • Expressed by cells and soluble components of INNATE immune system
  • For PAMPs
  • TLR, NLR, RLH, collectins, scavenger receptors
  • Can bind DAMPs (molecular patterns produced by body during disease)
  • Binding lead to signalling cascades
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5
Q

What are PAMPs and DAMPs?

A

PAMPs: pattern associated molecular patterns
DAMPs: danger associated molecular patterns (produced by your body in response to disease)

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6
Q

What does the receptor CR1 on a phagocyte recognise on bacteria?

A

C3b

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7
Q

What does the receptor CR3 on a phagocyte recognise on bacteria?

A

iC3b

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8
Q

What does the receptor p150/95 on a phagocyte recognise on bacteria?

A

iC3b

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9
Q

What does the Fc receptor on a phagocyte recognise on bacteria?

A

Antibody

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10
Q

What does the C1q receptor on a phagocyte recognise on bacteria?

A

Mannose Binding Lectin

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11
Q

What does the Mannan receptor on a phagocyte recognise on bacteria?

A

Glycoconjugates

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12
Q

What does the Oligosaccharide receptor on a phagocyte recognise on bacteria?

A

Lectins

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13
Q

What does the PRR on a phagocyte recognise on bacteria?

A

PAMP

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14
Q

What does activation of the complement system result in? What are the 3 pathways?

A

• All lead to C3 convertase which activates C3 and allows for opsonisation (and activation of MAC)
• C3b is opsonin
• C5a
• Bacteria lysed by MAC (membrane attack complex)
• Lectin Pathway
o Collectins attached to mannose activate C2 and C4
• Classical Pathway
o Antibodies activate C1
• Alternative Pathway
o Bacterial surface molecules bind C3b

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15
Q

What is C3b?

A

Opsonin

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16
Q

What is C3a?

A

Helps chemotaxis, inflammation, B cell activation

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17
Q

What is the process of phagocytosis that kills bacteria?

A
  1. Engulf bacteria
  2. Phagosome formation, acidification
  3. Phagolysosome formation
  4. Death of bacteria by lysosomal proteins (degradative enzymes, defensins, myeloperoxidase)
  5. Release fragments
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18
Q

How does the timing of the release of cytokines and chemokines impact the immune response?

A
  • Early released up regulate response

* Late release down regulate response

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19
Q

What is the basic action of natural killer cells?

A
  1. Bind infected cell
  2. Release granules with toxic effectors (perforin, gransymes, granulysin)
  3. Kill bacteria and infected host cell
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20
Q

What occurs during the inflammatory response?

A
  • Complement activation
  • Cytokine release
  • Phagocyte transmigration and activation
  • Produce prostaglandins and leukotrienes
  • Symptoms = redness, swelling, heat, pain
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21
Q

What are the binding sites found on antibodies and where are they located?

A
  • Antigen binding sites in variable region (fv)

* Complement binding site and phagocyte receptor binding site in constant region (fc)

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22
Q

What is the role of secretory component?

A

anchor, protection from degradation

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23
Q

What is the action of CD8+ T cells?

A
  • Recognise antigen via MHC I on infected cell
  • Release toxic effectors (perforin, gransymes, granulysin)
  • Cell can apoptosis due to gransymes
  • Bacteria can be killed by granulysin
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24
Q

What is the difference between CD8+ T cells and Natural Killer Cells?

A

Natural killer cells recognise a cell is infected, but they don’t know what with

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25
Q

What happens in the class MHC I antigen presentation pathway?

A
  • All nucleated cells
  • Cytosolic protein
  • Intracellular bacteria (Cytotoxic/CD8 T cells)
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26
Q

What happens in the class MHC II antigen presentation pathway?

A
  • Dendritic cells, macrophages, B cells
  • Endosomal proteins
  • Extracellular bacteria (T helper/CD4 cells)
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27
Q

What antigens use the CD1 pathway for antigen presentation?

A

• Lipid derived antigens

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28
Q

How does antigen presentation differ for intracellular and extracellular bacteria?

A

Intracellular use MHC I

Extracellular use MHC II

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29
Q

What encourages T cells to differentiate into Th1?

A

Il-12, IFNy

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30
Q

What encourages T cells to differentiate into Th2?

A

Il4, parasites

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31
Q

How does CD4 help B cells?

A
  • MHC II
  • Epitope binds to antibody on B cell surface
  • Epitope broken up and presented
  • T cell recognises, production of memory cells and plasma cells
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32
Q

What is involved in CD4 independent B cell activation?

A
  • No memory
  • Cross linking of molecules
  • IgG and IgM
33
Q

Which bacterial structures are important in innate and acquired responses?

A

Cell wall, flagella, pilli, capsule

34
Q

What happens as a result of PAMP-PRR interactions?

A

Lead to changes in cytokine gene expression and therefore inflammation

35
Q

What does TLR1 and 6 interact with?

A

o Triacyl lipopeptide

o Peptidoglycan

36
Q

What does TLR2 and 6 interact with?

A

o Diacyl lipopeptide

37
Q

What does TLR3 interact with?

A

dsRNA

38
Q

What does TLR4 interact with?

A

LPS

39
Q

What does TLR7/8 interact with?

A

ssRNA

imidazoquinolones

40
Q

What does TLR9 interact with?

A

o Cpg DNA

o Hemozoin

41
Q

What does TLR5 interact with?

A

Flagella

42
Q

What does TLR11 interact with?

A

Profilin like protein

Uropathogenic bacteria

43
Q

Where are TLR 1, 2, 6, 4 and 5 located?

A

On the cell surface

44
Q

Where are TLR 3, 7/8 and 9 located?

A

On the endosome

45
Q

What are NLRs?

A

Nod like Receptors (i.e. inflammasome)

46
Q

What does the ASC domain recruit?

A

Pro-caspase 1

47
Q

What does activated caspase 1 do?

A

 Pre IL-1b to Il-1b (promotes inflammation)

 IL-18 activation (with IL-12 promotes IFN-g production)

48
Q

What is an inflammasome? What domains does it have?

A
o	NLRP (NLR subfamily with N terminal and PYD domain)
o	Sensor protein: NLR family
o	NACHT domain: NLR oligomerisation
o	PYD domain: signal transduction, caspase recruitment
o	ASC domain: adapter protein, recruits pro-caspase 1
49
Q

What does NLRP3 respond to?

A

Cell stress

50
Q

What does NLRC4 respond to?

A

Flagella

51
Q

What does NLRP1 respond to?

A

Anthrax LT

52
Q

What does AIM2 respond to?

A

dsDNA

53
Q

What are the features of the bacterial cell wall?

A

• Shape, support, structure, pathogenicity, protection, antibiotic action site, rigidity (peptidoglycan)

54
Q

What is the structure of peptidoglycan? What PRRs recognise it?

A

o Repeating glycan chains cross linked by peptide fragments
o Strong but flexible support framework
o Recognised by TLRs and Nod1/2
o Made up of repeats of N-acetylmuramic acid and N-acetylglucosamine

55
Q

Why is peptidoglycan a good target to select against?

A

 Unique to bacteria

 Needed for viability

56
Q

What do oligopeptides do? What are they made of?

A

o Oligopeptides have L and D AAs (resistant to normal proteolytic enzymes)
Crosslink glycan

57
Q

What is the action of lysozyme on peptidoglycan?

A

Hydrolyses polysaccharide bonds

58
Q

What are the 3 parts of LPS?

A

Lipid A (toxic), Core polysaccharide, O-specific polysaccharide side chain (distinguish strains)

59
Q

What is the action of penicillin on peptidoglycan?

A

Prevents formation of trans-peptide bond

60
Q

What are the features of gram positive cell walls?

A

o Thick peptidoglycan

Acidic polysacharides

61
Q

What are teichoic acids and lipoteichoic acids? What are they required for?

A
o	Acidic polysaccharide s
	Cell wall maintenance
	Enlargement of cell wall (cell division) 
	Acidic charge on cell surface
	TLR recognition 
o	Teichoic acid 
	Polymer of ribitol/glycerol and phosphate
	Imbedded in peptidoglycan 
o	Lipoteichoic acid
	Attached to lipids in PM
	Similar structure to teichoic acid
62
Q

What are the features of a gram negative cell wall?

A

o Large periplasmic space
o Thinner peptidoglycan
o Outer membrane

63
Q

What does the outer membrane of a G- cell wall contain?

A

 Protein
 Lipoprotein
 Phospholipid
 LPS

64
Q

What is LPS?

A

 Endotoxin

 Extended polysaccharide chains = receptors and antigens

65
Q

How does our immune system respond to LPS?

A

o Immune reaction
 Recognised TLR (TLR4)
 Very immunogenic, antibodies protective
o Toxic reaction
 Lots of lipid A, increase temp, fever and shock, death possible
o Endotoxic shock

66
Q

What occurs in endotoxic shock?

A

 IL-1, IL-6, TNFa act on endothelial cells
 Inflammatory response
 Monocytes can release tissue factor (thrombotic and fibrinolytic response)
 Endothelial damage
 Loss of fluid in tissues, blood pressure falls, circulatory collapse, organ failure

67
Q

What response does tissue factor stimulate during endotoxic shock?

A

thrombotic and fibrinolytic response

68
Q

What are the features on O-specific polysaccharide chain in LPS?

A

o Chain of sugar molecules

o Identify strains

69
Q

Which TLRs are activated by cell wall components?

A

1, 3, 4, 6

70
Q

What is the role of glycocalyxes? What are they?

A
  • Surround cell, sticky
  • Polysaccharide and/or polypeptides
  • Feature of blood borne pathogens
71
Q

What types of glycocalyxes are there?

A

Capsule: organised repeating units firmly attached to cell surface
• Slime layer: loose, water soluble

72
Q

How do capsules protect bacteria?

A
  • Protection from drying
  • Protect from phagocytosis
  • Prevent opsonisation
  • Promote adhesion
  • Promote biofilm formation
  • Poor antigens
73
Q

What are flagella?

A
  • Allow Motility for avoidance and favourable environment movement
  • 3 parts
74
Q

What are the components of prokaryotic flagella?

A

o Long thin filament (flagellin units)
o Hook
o Basal body

75
Q

How do flagella function?

A

360 degrees rotation
• Movement in series of runs (single direction)
• Movement in tumbles (random, adrupt)
• Movement is in response to stimuli

76
Q

How do we respond to flagella?

A
  • Serology: H type antigen (TLR5)

* Activate intracellular NLRs

77
Q

What are pili? What can they be used for and what is an example of a bacteria that uses pili?

A
  • Non-motile extensions
  • Sticky, proteinaceous bristle like projection
  • Gram neg bacteria use for adherence, sticking to environment, sticking to mucous membranes
  • E.g. ETEC
78
Q

What is the structure of pili?

A
  • Rod shaped, hollow
  • Ordered helical protein subunit (pilin) array
  • Tip mediate adhesion
  • Tip can be pilin or other proteins
  • Tip for host/tissue septicity