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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
Which cytokines trigger an inflammatory response?
IL-1, IL-6 and TNF-alpha
26
What effect do cytokines have on the body during the immune response?
Cytokines trigger inflammation, redness, fever and pain.
27
What are PAMPs?
Pathogen Associated Membrane Proteins. They are patterns that are recognized by the host to identify bacteria.
28
How does the host use PAMPs to increase its defense?
The host detects characteristics that are most associated with pathogens to determine if a foreign body is present.
29
What are some PAMPs?
1. peptidoglycan fragments 2. flagellin from flagella 3. CpG-rich DNA 4. LPS/lipoteichoic acid
30
What receptors are used to identify extracellular pathogens?
TLRs or toll-like receptors
31
What receptors are used to identify intracellular pathogens?
NOD2 or NOD-like receptors
32
True or False: all cells contain TLRs and NOD2/NOD-like receptors
False: only neutrophils and monocytes have TLRs and all cells have NOD2/NOD like receptors
33
What are the 4 steps that come after recognition of PAMPs by receptors?
1. Increased production of NF-kB 2. Increased release of cytokines 3. Increased phagocytosis 4. Induced oxidative bursts
34
What TLR is used to detect flagellin?
TLR5
35
What TLR is used to detect LPS
TLR4
36
What TLRs are used to detect peptidoglycan
TLR1-TLR2 complex, and TLR2-TLR6 complex
37
How are LPS binding proteins useful to the host?
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
How does LPS binding protein trigger an immune response?
The LPS binding protein captures the LPS and presents it to TLR4. TLR4 will release cytokines responsible for signaling and attracting monocytes/neutrophils
39
When a TLR recognizes a PAMP what does it do?
Triggers the release of inflammatory cytokines
40
What are the cytokines responsible for an inflammatory response?
IL-1, TNF-alpha and IL-6
41
What cells/proteins trigger histamine production for vasodilatation?
Mast cells and C3a
42
What cytokines are responsible for reducing inflammation?
IL-4 and IL-10
43
What is transmigration?
The movement of neutrophils/monocytes from the blood vessel to the tissue
44
What is chemotaxis
The attraction of neutrophils/monocytes by increased concentration of cytokines and accessory proteins to the site of infection
45
What complement protein is responsible for attracting monocytes/neutrophils to the shite of infection?
C5a
46
What does IL-8 cytokine do to help monocytes/neutrophils move towards the infection?
Helps immune cells adhere to the endothelial cells of the tissue.
47
Why is vasodilatation so important for the immune system?
Opening the blood vessels allows more proteins and cells to be transported to the infection
48
What cytokine is responsible for replenishing used macrophages/neutrophils
GM-CSF cytokine
49
What is the first vacuole used by macrophages when phagocytosing pathogens?
Phagosome
50
What feature of the macrophage allows the bacteria to be engulfed?
The pseudopodia
51
Differentiate between the environmental conditions of a phagosome and phagolysosome
- 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
What is the product when a phagosome and a lysosome is fused?
Phagolysosome
53
What is V-ATPase's function in the phagolysosome?
Pulls protons from the cytoplasm into the phagolysosome to reduce the pH to be more acidic.
54
What are the benefits of a reduced pH in the phagolysosome?
1. Low pH degrades molecular structures of the bacteria. 2. Low pH triggers the activity of other destructive enzymes
55
What are some enzymes or proteins recruited by the phagolysosome to kill bacteria? (4)
Nucleases, peptidases, proteases, antimicrobial peptides
56
What does the oxidative mechanism of phagocytosis refer to?
The breakdown of NADPH to produce reactive oxygen species used to kill bacteria
57
What is the most powerful reactive oxygen species? What component is necessary to produce this species?
Hydroxyl radical is produced in the presence of iron
58
What are some pathogens that have bypassed the oxidative and non-oxidative mechanisms of phagocytosis?
Legionella and Yersinia pestis
59
How do pathogens bypass mechanisms of phagocytosis?
Prevent the fusion of the phagosome and the lysosome
60
What are 3 things that are stopped/slowed when pathogens prevent phagolysosome production?
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
What are NETs?
Neutrophil Extracellular Traps
62
What are NETs used for?
Capturing and killing bacteria in a confined region
63
What are NETs made of, and who are they made by?
NETs are made by neutrophils and are made of chromatin (DNA filament) covered in antimicrobial proteins
64
If a pathogen wanted to break through a NET, what would it use?
A DNAse could be use to break down the chromatin of a NET and allow the pathogen to break free.
65
What are three advantages/functions of a NET?
1. Limit movement of a pathogen by confining it to one region 2. Inactivates virulence factors of pathogens 3. Kills the bacteria
66
What is iron sequestration?
The protection of iron compounds by the host against pathogens
67
Why does the host use iron sequestration?
Bacteria require iron to grow, so keeping the iron protected limits the growth.
68
What proteins are used by the host to keep iron bound?
Lactoseferrrin, Transferrin and Heme
69
Why are bacteria that can hemolyse problematic?
If pathogens can hemolyse, they can free the iron present in the heme of hosts - gaining nutrients for growth.
70
What way does Borrelia Burgorforferi deal with iron sequestration?
The pathogen replaces iron with manganese in all metabolic pathways that require iron.
71
What is a main tactic used by pathogens to attain iron?
Siderophores from the pathogen itself or commensal pathogens steal the iron from hosts.
72
What about siderophores allows pathogens to steal iron?
Siderophores have a higher affinity for iron than some host proteins, so the iron is more likely to move to the siderophore.
73
How can a parasitic relationship between pathogen and commensal begin through iron sequestration?
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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