Innate Immunity Flashcards
(52 cards)
1
Q
innate immunity (2)
A
- first line of defense in the immune response
- non-specific
2
Q
innate immunity: general characteristics of immunity (5)
A
- barriers keep harmful materials from entering the body
- direct engulfment of pathogen (phagocytosis) leads to destruction of the pathogen
- secretion of chemokines and cytokines
- sense the threat and type of threats using TLR receptors
- shape the adaptive immune response
3
Q
what kind of barriers are involved in mucosal defense (2)
A
- chemical
- mechanical
4
Q
what is mucus produced by
A
- sub-epithelial goblet cells
5
Q
how does mucus contribute to innate immunity (2)
A
- traps bacteria
- contains transferrin, lactoferrin, anti-microbial peptides and lactoperoxidase
6
Q
what are the three steps to eliminating infection in mucosal defense (3)
A
- plasma exudation
- immune exclusion
- immune elimination
7
Q
mucosal defense: plasma exudation (2)
A
- plasma is exuded from blood vessels into the mucus site during infection
- plasma can contain serum proteins, such as bactericidal antibodies and complement
8
Q
mucosal defense: immune exclusion (2)
A
- antibodies neutralize the bacteria
- prevent binding of bacteria to host receptors for uptake
9
Q
mucosal defense: immune elimination (2)
A
- breach in epithelial layer results in exposure to cells of the immune system
- elimination of bacteria by immune cells
10
Q
what is one of the first lines of mucosal defese
A
- nasopharynx contains mucus and cilia to prevent bacteria from entering lungs/intestines at all
11
Q
what are some ways that the bacteria can protect itself from the host innate immune system (5)
A
- prevent complement-mediated lysis
- prevent phagocytosis
- escape autophagy
- prevent lysosomal fusion
- prevent cytokine release
12
Q
why did the innate immune system evolve
A
- to recognize invariant structures in pathogens
13
Q
what are the invariant structures we recognize on pathogens called
A
- pathogen associated molecular patterns (PAMPs)
14
Q
what are some examples of PAMPs (3)
A
- carbohydrate-based (dsRNA, bacterial DNA, PG)
- lipid-based (lipoproteins, LPS)
- proteins (flagella)
15
Q
what does the innate immune system use to detect pathogens (2)
A
- pattern-recognition receptors (PRRs)
- recognize conserved epitopes
16
Q
what PRR recognizes the lipid A portion of LPS (a PAMP)
A
- TLR4 and MD-2 co-receptor
17
Q
what groups of molecules do PRRs recognize (2)
A
- PAMPs from pathogens
- DAMPs released from damaged cells
18
Q
what cells are PRRs found on (5)
A
- dendritic cells
- macrophages
- monocytes
- neutrophils
- epithelial cells
19
Q
what occurs after innate immune recognition of pathogen (2)
A
- direct engulfment of pathogen, leading to pathogen destruction
- secretion of cytokines and chemokines that shape the adaptive immune response
20
Q
TLR 4: ligand
A
- LPS
21
Q
TLR4 components (3)
A
- ectodomain binds lipid A
- transmembrane region
- cytoplasmic region contains a toll-interleukin 1-receptor (TIR) domain
22
Q
how does TLR4/MD-2 recognize LPS (4)
A
- LPS bind to LPS-binding protein, a free protein
- complex interacts with CD14, a membrane receptor
- CD14 delivers LPS to MD-2, which attaches to a TLR4
- TLR4/MD-2/LPS complex dimerizes with another complex
23
Q
what are important domains on TLR4 for dimerization (2)
A
- charged PO4- interface
- neutral acyl chain interface
24
Q
TLR4/MD-2/LPS: how does signaling work after dimerization (3)
A
- TIR domains come in close proximity
- domains act as a scaffold to recruit adaptor proteins
- activates two signaling pathways
25
what are the two signaling pathways activated by TLR4 (2)
- MyD88 pathway
- TRIF pathway (MyD88-independent pathway)
26
TLR4/LPS: what protein orchestrates signaling
- the TIRAP/Mal protein
27
what kind of protein is TIRAP/Mal
- sorting adaptor protein
28
what kind of protein is MyD88
- signaling adaptor protein
29
TLR4/LPS: MyD88 pathway, up to MyD88 activity (3)
1. TIRAP/Mal binds to TIR domain of TLR4
2. MyD88 binds TIRAP
3. MyD88 associates with series of kinases
30
TLR4/LPS MyD88 pathway: what occurs due to MyD88 associating with kinases (2)
- activation of I kappa B kinases (IKK-1 and IKK-2)
- results in phosphorylation of IKB
31
TLR4/LPS MyD88 pathway: how is IKB normally found in the cytosol
- found in complex with NFkB
32
TLR4/LPS MyD88 pathway: what is NFkB
- transcription factor
33
TLR4/LPS MyD88 pathway: what occurs after IKB phosphorylation
1. IKB is marked as degradation target for proteasomes
2. NFkB is released and translocates to the nucleus
34
TLR4/LPS MyD88 pathway: what is the result of NFkB translocation to the nucleus (3)
- expression of pro-inflammatory cytokines
- tumour necrosis factor (TNF-α), IL-12, IL-6
- increased expression of co-stimulatory molecules
35
TLR4/LPS: what is a general result of the MyD88 pathway
- activation of adaptive immunity
36
TLR4/LPS: when is the TRIF pathway triggered
- after endocytosis of dimerized TLR4/MD-2/LPS complex into an endosome
37
TLR4/LPS pathway: first half of the TRIF pathway (3)
1. TRAM adaptor binds to TIR domain of TLR4
2. TRIF binds to TRAM and leads to series of signaling events (phosphorylation events)
3. results in activation of IRF-3 TF and translocation to the nucleus
38
TLR4/LPS TRIF pathway: what is the results of IRF-3 translocation to the nucleus (3)
- leads to expression of interferon-β (a type-I interferon)
- activates expression of interferon-β inducible genes and chemokines
- late induction of NFkB
39
TLR4/LPS TRIF pathway: what is the benefit of the delayed response
- ensure system isn't overwhelmed, causing more damage
40
TLR4/LPS TRIF pathway: what is the general result of this pathway
- influence the adaptive immune response
41
what can be the result of uncontrolled innate immune responses (3)
- endothelial damage leading to multiple-organ system failure
- acute respiratory distress syndrome (ARDS)
- disseminated intravascular coagulation (DIC)
42
what is ways that bacteria can avoid the TLR4/LPS signaling pathways (2)
- innate mimicry to interfere with TLR signaling
- lipid A modifications in LPS to affect recognition by PRRs
43
TLR4/LPS: innate mimicry (2)
- bacterial genomes contains genes encoding TIR-like domains
- make TIR-containing proteins (TCPs)
44
what types of bacteria practice innate mimicry against the TLR4/LPS pathway
- uropathogenic E. coli (UPEC)
45
monocyte model: WT bacteria vs TCP mutant
- WT induced lower levels of pro-inflammatory cytokines, whereas mutants induced higher levels
46
mouse model: WT bacteria vs TCP mutant
- mutant was less virulent compared to the wild type
47
innate mimicry: how does TCP function (3)
- binds MyD88
- reduces normal signaling in response to infection
- reduces inflammation
48
how can lipid A be modified in LPS (2)
- number of acyl chains
- charge of lipid A
49
where can lipid A modifications be made in LPS (2)
- modifications of acyl chains in the outer membrane
- modifications of phosphates in the inner membrane
50
endocytosis (2)
- ingestion of large particles (such as bacteria)
- uptake of fluids or macromolecules in small vesicles
51
phagocytosis (2)
- ingestion of large particles
- "cell eating"
52
pinocytosis (2)
- uptake of fluids or macromolecules in small vesicles
- "cell drinking"
