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MICR 341 > THE INNATE IMMUNE SYSTEM > Flashcards

THE INNATE IMMUNE SYSTEM Flashcards

1
Q

What is the primary goal of the innate immune system?

A

To fight the pathogen/kill it off

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2
Q

What differentiates the innate immune system from the adaptive immune system?

A

The innate immune system is unspecified and always available for any pathogen. The adaptive immune system is specified, will take time to recruit and is specific to pathogens.

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3
Q

What are a few cells/components of the innate immune system?

A

Monocytes/Macrophages, Neutrophils, Natural Killer cells, Accessory Proteins

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4
Q

What are some “accessory” proteins used by the innate immune system?

A

Cytokines, chemokines and complement proteins.

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5
Q

What is the main function of mast cells?

A

Induce an inflammatory response at the site of infection

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6
Q

What is the main function of macrophages/monocytes?

A

Engulf proteins via phagocytosis

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7
Q

What are the functions of dendritic cells

A
  1. Induce phagocytosis and engulf bacteria via phagocytosis
  2. Present antigens to T cells to activate the adaptive immune system.
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8
Q

Where can dendritic cells be found?

A

Anywhere in the body, but most popularly in the lymph nodes

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9
Q

Where can monocytes/macrophage cells be found?

A

Liver, spleen and lungs

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10
Q

What is the complement system?

A

A series of 9 proteins that create the MAC complex or membrane attacking complex

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11
Q

What does the MAC complex do?

A

The MAC complex creates a pore on the membrane of pathogens, which allows nutrients to flow out and water to flow in eventually destroying it.

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12
Q

In the classical pathway, what protein/proteins activates C3?

A

C3 Convertase or C4bC2a

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13
Q

In the classical pathway, what protein/proteins activates C5?

A

C5 Convertase or C4bC2aC3b

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14
Q

What are the 3 remaining proteins from the classical pathway of the complement system that are NOT used?

A

C3a, C3b, C5a

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15
Q

What function does C3a have in the innate immune system?

A

C3a induces the release of vasoactive molecules like histamine by mast cells. This triggers inflammation.

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16
Q

What function does C3b have in the innate immune system?

A

Stimulates opsonization of bacteria - tagging of the pathogens for macrophages.

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17
Q

What function does C5a have in the innate immune system?

A

C5a attracts phagocytes to the site of infection.

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18
Q

What triggers the alternative pathway of the complement system?

A

Self-activation of C3 protein

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19
Q

What is the C3 Convertase of the alternative pathway?

A

C3bBb

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20
Q

What is the C5 Convertase of the alternative pathway?

A

C3bBbC3b

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21
Q

Why is the classical pathway of the complement system so complicated?

A

So that the host can not mistake the cell it is attacking for a host cell. It is a fail-safe.

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22
Q

How does the body protect itself from the alternative pathway (ie. self-activation of C3?)

A

Host cells are protected by sialic acid which stops activity of C3bBbC3b.

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23
Q

What is a defense that pathogens have adapted to combat the MAC complex?

A

Pathogens will produce capsules made of sialic acid so the host is unable to detect a foreign body.

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24
Q

What is an example of a pathogen that uses sialic acid capsules?

A

Neisseria meningitidis is a pathogen that infects the brain. It uses a sialic acid capsule to camouflage throughout the body and reach the brain.

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25
Q

Which cytokines trigger an inflammatory response?

A

IL-1, IL-6 and TNF-alpha

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26
Q

What effect do cytokines have on the body during the immune response?

A

Cytokines trigger inflammation, redness, fever and pain.

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27
Q

What are PAMPs?

A

Pathogen Associated Membrane Proteins. They are patterns that are recognized by the host to identify bacteria.

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28
Q

How does the host use PAMPs to increase its defense?

A

The host detects characteristics that are most associated with pathogens to determine if a foreign body is present.

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29
Q

What are some PAMPs?

A
  1. peptidoglycan fragments
  2. flagellin from flagella
  3. CpG-rich DNA
  4. LPS/lipoteichoic acid
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30
Q

What receptors are used to identify extracellular pathogens?

A

TLRs or toll-like receptors

31
Q

What receptors are used to identify intracellular pathogens?

A

NOD2 or NOD-like receptors

32
Q

True or False: all cells contain TLRs and NOD2/NOD-like receptors

A

False: only neutrophils and monocytes have TLRs and all cells have NOD2/NOD like receptors

33
Q

What are the 4 steps that come after recognition of PAMPs by receptors?

A
  1. Increased production of NF-kB
  2. Increased release of cytokines
  3. Increased phagocytosis
  4. Induced oxidative bursts
34
Q

What TLR is used to detect flagellin?

A

TLR5

35
Q

What TLR is used to detect LPS

A

TLR4

36
Q

What TLRs are used to detect peptidoglycan

A

TLR1-TLR2 complex, and TLR2-TLR6 complex

37
Q

How are LPS binding proteins useful to the host?

A

They are free floating in the blood, so they are able to pick up fragments of LPS anywhere in the body - even if the site of infection is remote.

38
Q

How does LPS binding protein trigger an immune response?

A

The LPS binding protein captures the LPS and presents it to TLR4. TLR4 will release cytokines responsible for signaling and attracting monocytes/neutrophils

39
Q

When a TLR recognizes a PAMP what does it do?

A

Triggers the release of inflammatory cytokines

40
Q

What are the cytokines responsible for an inflammatory response?

A

IL-1, TNF-alpha and IL-6

41
Q

What cells/proteins trigger histamine production for vasodilatation?

A

Mast cells and C3a

42
Q

What cytokines are responsible for reducing inflammation?

A

IL-4 and IL-10

43
Q

What is transmigration?

A

The movement of neutrophils/monocytes from the blood vessel to the tissue

44
Q

What is chemotaxis

A

The attraction of neutrophils/monocytes by increased concentration of cytokines and accessory proteins to the site of infection

45
Q

What complement protein is responsible for attracting monocytes/neutrophils to the shite of infection?

A

C5a

46
Q

What does IL-8 cytokine do to help monocytes/neutrophils move towards the infection?

A

Helps immune cells adhere to the endothelial cells of the tissue.

47
Q

Why is vasodilatation so important for the immune system?

A

Opening the blood vessels allows more proteins and cells to be transported to the infection

48
Q

What cytokine is responsible for replenishing used macrophages/neutrophils

A

GM-CSF cytokine

49
Q

What is the first vacuole used by macrophages when phagocytosing pathogens?

A

Phagosome

50
Q

What feature of the macrophage allows the bacteria to be engulfed?

A

The pseudopodia

51
Q

Differentiate between the environmental conditions of a phagosome and phagolysosome

A
  • Phagosomes have similar conditions to the cytoplasm. No features are present to harm the bacteria.
  • Phagolysosomes have acidic environments that trigger the destruction of bacteria through several mechanisms
52
Q

What is the product when a phagosome and a lysosome is fused?

A

Phagolysosome

53
Q

What is V-ATPase’s function in the phagolysosome?

A

Pulls protons from the cytoplasm into the phagolysosome to reduce the pH to be more acidic.

54
Q

What are the benefits of a reduced pH in the phagolysosome?

A
  1. Low pH degrades molecular structures of the bacteria.
  2. Low pH triggers the activity of other destructive enzymes
55
Q

What are some enzymes or proteins recruited by the phagolysosome to kill bacteria? (4)

A

Nucleases, peptidases, proteases, antimicrobial peptides

56
Q

What does the oxidative mechanism of phagocytosis refer to?

A

The breakdown of NADPH to produce reactive oxygen species used to kill bacteria

57
Q

What is the most powerful reactive oxygen species? What component is necessary to produce this species?

A

Hydroxyl radical is produced in the presence of iron

58
Q

What are some pathogens that have bypassed the oxidative and non-oxidative mechanisms of phagocytosis?

A

Legionella and Yersinia pestis

59
Q

How do pathogens bypass mechanisms of phagocytosis?

A

Prevent the fusion of the phagosome and the lysosome

60
Q

What are 3 things that are stopped/slowed when pathogens prevent phagolysosome production?

A
  1. V-ATPase can not reduce the pH in the vacuole
  2. NADPH is not broken down to induce oxidative bursts
  3. MHC-1 does not present antigens to the surface of the cell
61
Q

What are NETs?

A

Neutrophil Extracellular Traps

62
Q

What are NETs used for?

A

Capturing and killing bacteria in a confined region

63
Q

What are NETs made of, and who are they made by?

A

NETs are made by neutrophils and are made of chromatin (DNA filament) covered in antimicrobial proteins

64
Q

If a pathogen wanted to break through a NET, what would it use?

A

A DNAse could be use to break down the chromatin of a NET and allow the pathogen to break free.

65
Q

What are three advantages/functions of a NET?

A
  1. Limit movement of a pathogen by confining it to one region
  2. Inactivates virulence factors of pathogens
  3. Kills the bacteria
66
Q

What is iron sequestration?

A

The protection of iron compounds by the host against pathogens

67
Q

Why does the host use iron sequestration?

A

Bacteria require iron to grow, so keeping the iron protected limits the growth.

68
Q

What proteins are used by the host to keep iron bound?

A

Lactoseferrrin, Transferrin and Heme

69
Q

Why are bacteria that can hemolyse problematic?

A

If pathogens can hemolyse, they can free the iron present in the heme of hosts - gaining nutrients for growth.

70
Q

What way does Borrelia Burgorforferi deal with iron sequestration?

A

The pathogen replaces iron with manganese in all metabolic pathways that require iron.

71
Q

What is a main tactic used by pathogens to attain iron?

A

Siderophores from the pathogen itself or commensal pathogens steal the iron from hosts.

72
Q

What about siderophores allows pathogens to steal iron?

A

Siderophores have a higher affinity for iron than some host proteins, so the iron is more likely to move to the siderophore.

73
Q

How can a parasitic relationship between pathogen and commensal begin through iron sequestration?

A

Commensals that use siderophores without harming the host can have their siderophores be stolen by pathogenic bacteria causing a parasitic relationship.

MICR 341 (4 decks)

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