Review of innate system Flashcards

1
Q

Why is the adaptive immune system not apt for new pathogens?

A

→too slow

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2
Q

Compare innate and adaptive immune system

A

→Adaptive immunity – involves very specific recognition of infectious agent
→Innate immunity – no specific antigen recognition

→Innate immunity involves recognition of broadly conserved features of different classes of pathogens

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3
Q

How is pattern recognition done in innate response?

A

→PAMPs

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4
Q

What are PAMPs?

A

→Molecules present only on pathogens and not on host cells

→Essential for survival of pathogens

→Invariant structures shared by entire class of pathogens

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5
Q

What type of bacteria have PAMPs?

A

→gram negative or positive

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6
Q

Example of PAMPs in gram negative bacteria

A

→lipopolysaccharides (LPSs) outer membrane

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7
Q

Examples of gram positive bacteria cell wall components

A

→teichoic acid
→lipoteichoic acid
→peptidoglycan found in outer membrane

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8
Q

What are other PAMPs?

A

→Bacterial flagellin
→Abnormal protein glycosylation
→Abnormal nucleic acids - viruses

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9
Q

What are PRRs?

A

→Host factors that specifically recognise a particular type of PAMP

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10
Q

How are PRRs encoded?

A

→germ line encoded

→no rearrangement unlike antibodies

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11
Q

What are the 3 types of PRRs?

A

→Extracellular
→intracellular
→secreted

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12
Q

What are secreted PRRs?

A

→they act to tag circulating pathogens for elimination

→eg complements

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13
Q

What are the components of innate immunity?

A
→The inflammatory response
→Phagocytes
Monocytes/granulocytes/neutrophils
→Complement
→Cytokines, chemokines and anti-microbial peptides (AMPs)
→Natural Killer cells
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14
Q

What is an inflammatory response?

A

→localize and eliminate injurious agents and to remove damaged tissue components

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15
Q

What are the features of inflammatory response?

A

→Enhanced permeability and extravasation
→Neutrophil recruitment
→Enhanced cell adhesion
→Enhance clotting

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16
Q

What is the inflammatory response trigger?

A

→the release of pro-inflammatory cytokines and chemokines

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17
Q

What is the difference between cytokines and chemokines?

A

→cytokines enhance inflammatory

→chemokines act to create chemical concentration gradient for neutrophils to migrate to

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18
Q

What are TLRs not involved in?

A

→phagocytosis

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19
Q

What is a distinct feature of phagocytic recognition?

A

→they use different pattern recognition receptors

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20
Q

What are neutrophils involved in?

A

→Neutrophils involved in tissue damage not involved in priming adaptive response

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21
Q

What are the three distinct roles of macrophages and dendritic cells?

A

→Phagocytosis; material is destroyed in lysosomes
→activated macrophages produce cytokines and chemokines

→Peptides from broken down pathogens can be presented through MHC and promote the development or recall of an adaptive T cell response

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22
Q

How do Phagocytes know what to eat?

A

→By detecting phosphatidylserine on exterior membrane surface (cells undergoing apoptosis)

→By detecting “atypical sugars” (e.g. mannose, fucose, b-glucan) on cell surfaces

→By Scavenger receptors

→By “passive sampling”

→By detecting complement
proteins bound to the
pathogen surface

23
Q

What are examples of atypical sugars?

A

→mannose,
→fucose,
→b-glucan

24
Q

Which virus doesn’t present phosphatidylserine?

25
What is the complement system?
→Complement proteins act as secreted Pattern recognition receptors (PRRs) →can be activated by a range of PAMPs, and can also be activated by “altered self”
26
Which organ makes the complement system?
→liver
27
What are the PAMP targets of the complement system?
``` →antigens →LPS →abnormal phospholipids →atypical glycosylation →lack of host control factors ```
28
What are the three pathways of complement system?
→The Classical Pathway →The Mannose-Binding Lectin Pathway →The Alternative Pathway
29
What is the classical pathway of complements?
→activated when a complement protein called C1q binds either directly to a pathogen, or onto an antigen-antibody complex
30
What do all the pathways have in common?
→produce C3 convertase
31
What is the MBL/ficolins pathway?
→detect carbohydrates containing mannose on the surface of pathogens, →activating a protease called MASP →MASP is responsible for cleaving complement components →activates cascade
32
What is the alternative pathway of the complement system?
→activated by bacterial endotoxin | →lipopolysaccharide present on the outer membrane of gram negative bacteria
33
How do Phagocytes know when they are infected and when to produce cytokines and chemokines?
→PAMPs are recognised by a distinct group of Pattern Recognition Receptors
34
What are the PRRs on phagocytes?
→TLRS →NOD-like →RIG like
35
What is the TLR ligands?
→LPS →Unmethylated CpG- viral infection →flagelin →dsRNA or ssRNA
36
What is the outcome of TLR activation?
→inflammation: cytokine release (TNF, IL-1, IL-12) →enhanced killing: reactive oxygen species, NO)
37
What are the ligands for NOD-like receptors?
→Peptidoglycan from Gram positive and negative bacteria →Some viral DNA and RNA (indirect?)
38
What is the outcome of NOD-like receptors?
→inflammation: cytokine release (IL-1, IL-8)
39
What is the outcome of RIG-like receptors?
→type I interferon production
40
What is the ligand for RIG-like receptors?
→Viral dsRNA and 5’-triphospho RNA(inproperly capped)
41
What are cytokines?
→Act to modify the behaviour of cells in the immune response →Most of these are called interleukins (eg. IL-1)
42
What do type 3 interferons protect?
→epithelial surfaces
43
What are interferons induced by?
→viral infection
44
How are interferons released?
→Secreted hormone factors (type I and type III)
45
What are anti-microbial peptides?
→Secreted short peptides (18-45 amino acids) →Offer broad protection →Some are induced by bacterial infection​
46
How do anti-microbial peptides work?
→by disrupting cell wall leading to lysis​
47
What are NK cells?
→Lymphocyte-like but larger with granular cytoplasm​
48
What pathogens do NK cells kill?
→certain tumour | →virally infected cells​
49
How do NK cells cause destruction?
→cytotoxic molecules called granzymes & perforins​ ​
50
How are NK cells activated?
→loss of self MHC molecules on target cell surfaces →upregulation of ligands ​
51
What are the two types of complement core defects?
→core defects (e.g. C3) linked to development of autoimmune diseases such as lupus​ →non-core defects linked to suseptibility to specific types of pathogens such as Neisseria​
52
What are two macrophage deficiencies?
→Chronic granulomatous disease (CGD); No oxidative burst for bacterial killing​ →IRF8 mutations linked to susceptibility to TB​
53
What is Aicardi-Goutieres syndrome?
→associated with constitutive production of inflammatory cytokines​
54
What are the receptors used in innate and adaptive immunity?
``` →innate= pattern recognition →adaptive= Igs and TCR ```