Innate Immunity Protection Flashcards

1
Q

Definition of innate immunity

A

Non specific defense mechanisms that a host uses immediately/within several hours after exposure to an antigen (0-96hours)

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2
Q

Definition of complement

A

Series of proteins that circulate in blood and tissue fluids.
Synthesised in response to inflammation in the liver

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3
Q

Definition of cascade

A

1 product induces the formation of the next

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4
Q

Definition of opsonization

A

A molecule that enhances phagocytosis by marking an antigen for an immune response or marking dead cells for recycling

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5
Q

Definition of immunogenic

A

A protein that further escalates the immune response

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6
Q

Definition of pleotropic

A

Many cytokines and chemokine can exert similar actions

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7
Q

What is the innate immune system and what is made up of?

What processes does it precede?

A

1st part of the immune system

  • Epithelial barriers to infection
  • Components that are induced upon infection (cells, secreted compounds)

Precedes adaptive and specific immune response

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8
Q

Characteristics of the innate immune system

A

Born with it
V fast, within hours
Ancient evolution, found in invertebrates, snails, fruit flies
Same response every time
Molecules used to recognize infection
Induces, directs acquired/adaptive immune response

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9
Q

What are the physical/mechanical/anatomical components of the innate immune system

A

Skin
GI tract
Resp tract
Mucosal epithelia

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10
Q

What are the secreted compounds in the innate immune system

A

Antibactreial
Complement
Natural antibodies
Cytokines

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11
Q

What are the cellular compounds in the innate immune system

A

Phagocytes

NK cells

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12
Q

How does the skin attempt to prevent entry of pathogens into the body

A

Keratin
Antimicrobial compounds
-Psoriasin kills Ecoli
-Burn patients more likely to get Ecoli infections

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13
Q

How does the respiratory tract attempt to prevent entry of pathogens into the body

A

V tight junctions, cells cannot be penetrated easily
Motile cilia waft pathogens out
-Primary ciliary dyskinesis, pathogens can’t be moved out
Mucus traps bacteria and wafted away

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14
Q

How does the GI tract attempt to prevent entry of pathogens into the body

A

Peristalsis

HCl , low pH activates acid hydrolases which can digest bacteria

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15
Q

How do mechanical and secretory methods attempt to prevent entry of pathogens into the body

A

Blinking

Crying, lysozymes break down cell walls

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16
Q

How does microbial competition prevent entry of pathogens into the body

A

Friendly bacteria will compete against them for
Light
Space
Nutrients

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17
Q

How are pathogens recognised

A

Cannot recognize all possible antigens
Recognizes a few highly conserved molecular structures in many different microorganisms

PAMPS (pathogen associated molecular patterns)

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18
Q

What is the criteria for a PAMP

A

Must be present in the microbe and not the host
Must be essential for the survival of the pathogen
-Genetic material can mutate under stress

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19
Q

PAMPs in gram -ve bacteria

A

Lipopolysaccharide LPS

Made up of an O polysaccharide and lipid A
PAMP = lipid A
Type of gram -ve bacteria = O polysaccharide

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20
Q

PAMPs in gram +ve bacteria

A

Lipoteichoic acid

Found in all gram +ve bacteria cell walls

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21
Q

How are pathogens recognized?

What are the types and where are they found?

A

PRR (pattern recognition receptors)

Collecting, in serum
Toll like receptors, in membrane
Nod like receptors, in cytoplasm

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22
Q

Describe how collectins work

What are collectins made up of

A

Collagen like + lectin region

Collagen interacts with effector parts of immune system
Lectin binds to sugar molecules on pathogen surface (mannose, fucose)
-Spacing is also considered

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23
Q

Describe how Toll like receptors work

A

Each TLR on the cell surface recognizes specific molecules

Found on membrane bound surface and vesicles in cells

24
Q

What TLR recognizes gram +ve bacteria?

A

TLR 1 and 2

25
What TLR recognizes gram -ve bacteria?
TLR 4
26
What TLR recognizes flagelli?
TLR 5
27
What TLR recognizes double stranded RNA
TLR 3
28
What TLR recognizes single stranded RNA
TLR 7 and 8
29
What TLR recognizes unmethylated GpG DNA
TLR 9
30
What TLR recognizes mycoplasma
TLR 2 and 6
31
How doe NOD like receptors work (nucleotide oligomerization domain) Which NOD like receptors recognize what?
In cytoplasm, recognize components of gram +ve, -ve bacteria - NOD1, y glutamyl diaminopimelic acid - NOD2, muramyl dipeptide Signals sent to nucleus so cytokine, chemokine, MHCs and constimulatory molecule production is upregulated -
32
What are the effector mechanisms of the innate immune response
Complement Phagocytosis and killing Cytokines Activation of adaptive immunity
33
What is a complement and how does it work?
Series of proteins that circulate in blood and tissue fluids Synthesised in response to inflammation in liver Operates via cascade All lead to formation of C3, activated by C3 convertase
34
What are the 3 pathways that lead to C3 converts activation
Classical, antigen antibody complex MB lectin, mannose on pathogen Alternative, pathogen causes spontaneous activation
35
What happens when C3 converts is activated?
C3 =C3 convertase=> C3a + C3b
36
What does C3a do
Diffuses away from site of inflammation Binds to C3a receptors on macrophages, neutrophils Activated cells recruited to site of infection
37
What does C3b do
C3b sits on pathogen surface (opsonization) More likely to be phagocytosed by neutrophils and macrophages
38
What do the terminal components (C5b, C6, 7, 8, 9) do?
Form the MAC (membrane attack complex) Form a pore that disrupts osmotic potential, pathogen cell lyses
39
What happens if you have a genetic C3 deficiency?
Have frequent bacterial infections
40
Describe the properties of monocytes/macrophages
Mature from circulating monocytes In large nos in GI, lung, liver, spleen Relatively long life span
41
Describe the properties of neutrophils
Found in blood but can enter tissues when signal from inflammation received Shorter lifespan than monocytes/macrophages
42
Describe the process of phagocytosis
Recognition of pathogen Chemotaxis and adherence towards pathogen Pseudopodia engulf pathogen into vesicle/phagosome Phagosome decreases in pH, recruitment of molecules on phagosome surface signals for lysozomes to fuse with the phagosome Phagolysozome pH activates hydrolytic enzymes, digests microbe Exocytosis of waste materials Immunogenic proteins are presented on cell surface to activate further immune response
43
What are the 2 killing mechanisms of macrophages and neutrophils
Generation of reactive oxygen radicals (more in neutrophils) | Generation of reactive nitrogen intermediates (more in macrophages)
44
How are reactive oxygen radicals generated
Following phagocytosis, increase in O2 uptake, respiratory burst O2 reduced by NADPH oxidase => hydroxyl radicals + hypochlorite Causes DNA damage and alternations in bacterial membranes, must be controlled
45
How is damage to the neutrophil/macrophage limited
When resting, the NADPH oxidase complex is separated 2 parts of complex in membrane Other components in cytoplasm When there is a respiratory burst, increase in microbes and inflammatory mediators, NADPH complex activated Complex comes together on phagosome membrane 2O2 => 2O2 - NADPH => NADP+ + H+ 2O2 - => H2O + O2 Assembly is on phagosomal membrane, near pathogen
46
How are reactive nitrogen intermediates generated
iNOS, NOS2 induced by cytokines and bacterial components (interferon y, tumor necrosis factor) Activates iNO synthetase O2 + L-arginine =tetrahydrobiopterin=> NO + citrulline Causes DNA damage and alterations in bacterial membranes
47
What are cytokines and what do they do
Proteins, intercellular messengers Bind to specific receptors Can activate and deactivate
48
What are the activating cytokines
``` IL 1 (interleukin 1) IL 6 (interleukin 6) TNF a (tumor necrosis factor a) ```
49
What are chemokines
Type of cytokine with chemoattractant properties Particular arrangement of cysteine residues Not specific to 1 receptor Chemokine receptors bind to more than 1 receptor (pleiotropic) Attracts cells to site of infection
50
What are the types of chemokines
CXC CC CX3C XC
51
What chemokine is produced by macrophages and endothelium and what do they do
IL 8 | Encourages neutrophils to come to site of inflammation
52
What are the types of interferons
Type 1 -IFa, IFb, both made in innate response to a viral infection. Activates NK cells TYpe 2 -IFy, activate macrophages for antimicrobial killing mainly made by T cells in the adaptive immune response
53
Describe the function of NK cells
Kill virally infected cells, tumor cells Respond to TNFa, IL12, IFNa, IFNb Produce IFNy which activates macrophages, unregulated MHC IFMy, IL12 stimukates differentiation of CD4 TH1 cells
54
How is the adaptive immune response activated
Signal 1 -Pathogen fragments from phagocytosis presented on APC surface with MHC Signal 2 - Pathogen recognized by PRR - Signal sent to nucleus to unregulated costimulatory signal production Both these signals can activate Naive T cells => Effector T cell Cytokines released by APC dictate what type of Effector T cell forms
55
What are the antigen presenting cells (APC)
Macrophages B cells Dendritic cells
56
How do the dendritic cells mature
Immature cells have MHCs but they are not displayed on the surface They display many PRRs When PRR recognizes a pathogen, dendritic cells mature Mature dendritic cells display many MHCs and costimulatory molecules