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lec 3- induced innate response Flashcards

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1
Q

what are ILC cells, where are they located, and what do they do?

A

-innate lymphoid cells
-resident in tissues, and do not circulate
-they secrete cytokines

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2
Q

do all immune cells express a subset of the hundreds of innate immune receptors?

A

yes

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3
Q

how do the immune cells increase the probability that a pathogen is recognized?

A

by functional heterogeneity, which is when each of the cell types expressed subsets of different receptors than their normal ones

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4
Q

what do immune receptors recognize?

A

-carbohydrates
-lipids
-proteins
-nucleic acids

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5
Q

when are macrophages formed?

A

during fetal development

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6
Q

what is seeded into every tissue in the body during embryonic development?

A

macrophage precursors

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7
Q

what do macrophage precursors give rise to?

A

long lived, self renewing macrophages

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8
Q

do macrophages have 100 different non specific PRRs and PAMPS?

A

yes

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9
Q

what are PRRs?

A

pattern recognition receptors

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10
Q

what are PAMPS?

A

pathogen associated molecular patterns

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11
Q

do macrophages play a role in maintenance by taking up dead and dying cells by recognizing DAMPs?

A

yes

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12
Q

what are DAMPs?

A

damage associated molecular patterns

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13
Q

are many PRRs scavenger receptors (SRs)?

A

yes

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14
Q

how many classes of scavenger receptors (SRs) are there?

A

11, A-L

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15
Q

what are lectins?

A

cell surface receptors and plasma proteins that recognize carbohydrates

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16
Q

are mannose receptors and Dectin-1 apart of the lectin family?

A

yes

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17
Q

explain the steps of a mannose receptor binding and internalizing pathogen:

A
  1. the mannose receptor has 10 extracellular domains of 4 types
  2. surface sugars of bacterium are bound by two CTLD domains
  3. macrophage ingests bacterium by receptor mediated endocytosis
  4. bacterial degradation begins in the endosome
  5. endosome fuses with lysosome to form a phagolysosome in which the bacterium can degrade
  6. the mannose receptors returns to the cell surface
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18
Q

what do CR1, CR3, and CR4 do?

A

-CR1 binds to C3b
-CR3 binds to iC3b
-CR4 binds to iC3b

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19
Q

what type of CRs are integrin?

A

CR3 and CR4, cell surface glycoproteins that mediate adhesive interactions

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20
Q

why do B cells also have complement receptors?

A

-because B cells must engulf pathogens in order to present antigen to helper T cells for B cell activation

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21
Q

what type of CR is found on B cells?

A

CR2, binds to iC3b and C3d (a cleavage product of iC3b)

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22
Q

what pathway/protein complex is the key player in activating the immune response in vertebrates?

A

NFkB pathway
-it controls transcription of DNA, cytokines production, and cell survival

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23
Q

what does the activation of TLRs (toll-like receptors) cause?

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A

-a signal cascade in the cell that can lead to a variety of protective immune responses, including enhanced transcription of inflammatory genes

24
Q

where are TLRs found and what do they bind to?

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A

-found on the plasma membrane and in the endocytic pathway
-bind to every type of pathogen

25
how many types of TLRs exist in humans?
10 types
26
what roles do the 10 TLRs have?
1-9 have inflammatory roles 10 has an anti-inflammatory role
27
why do TLRs induce signaling in innate immune cells?
1. activate them to acquire features that increase their pathogen-clearing capabilities 2. induce the secretion of cytokines that activate inflammation and adaptive immunity
28
what is the structure of TLRs?what are the domains?
-2 polypeptides that form either heterodimers or homodimers -pathogen recognizing domain called leucine-rich repeat region (LRR) -intracellular domain for signalling called Toll interleukin-1 receptor (TIR) domain
29
explain the 12 steps of TLR activation and the signal cascade that leads to the release of the transcription factor NFkB and the production of cytokines:
1. lipopolysaccharide (LPS) found on gram-negative bacteria is released from bacterial cells surface after phagocytosis 2. LPS binds to a binding proteins (LBP) 3. the endocytic vesicle fuses with an exocytic vesicle carrying CD14 and LPS is transferred to CD14 (a co-receptor) 4. MD2 (a co-receptor on TLR) now binds to LPS, allowing for adaptor proteins to bind to TLR 5. MyD88 (adaptor protein) binds to TIR domain of TLR4 6. IRAK4 (a protein kinases) binds to MyD88, causing its activation 7. IRAK4 binds to and phosphorylates TRAF6 (an adaptor protein) which dissociates from IRAK4 8. TRAF6 initiates a kinase cascade 9. the cascade activates IKK (IkB kinase) by phosphorylation 10. IKK phosphorylates IkB of the IkB/NFkB complex 11. the phosphorylation causes the dissociation and degredation of IkB, resulting in the release of the transcription factor NFkB 12. NFkB enters the nucleus and initiates transcription of genes for the synthesis of cytokines and other proteins involved in inflammation
30
are most TLRs activated by the NFkB pathway?
yes
31
what TLR is activated by the TRIF-IRF3 pathway?
TLR3
32
what does the TRIF-IRF3 pathway induce?
Interferon response
33
are all TLRs induced to dimerize?
no, some are pre-formed dimers
34
are TLRs found in the cytosol?
no
35
what does the NOD in NOD-like receptors stand for?
nucleotide oligomerization domain
36
what do NOD-like receptors do?
recognize bacterial components in the cytosol
37
explain the 5 steps of how NOD-like receptors cause the release of NFkB which initiates the synthesis of cytokines:
1. ligand binds to NOD2 and causes it to dimerize 2. dimerization causes NOD2 to recruit RIPK2 3. RIPK 2 phosphorylates TAK1 4. TAK1 activates NFkB 5. NFkB travels to the nucleus and initiates transcription of genes for the synthesis of inflammatory molecules
38
what does interleukin-1B (IL-1B) activate the secretion of?
inflammatory cytokines
39
name the 5 inflammatory cytokines and what they do?
IL-12: activates NK cells to secrete cytokines CCL2: recruits monocytes CXCL8: recruits neutrophils IL-6: generates heat and raises temperature TNF-a: induces blood vessels to be more permeable
40
which of the 5 inflammatory cytokines are chemokines?
CXCL8 and CCL2
41
what are cytokines?
-small soluble proteins that communicate between cells -synthesized by one cell and bind to another cell
42
what are interferons (INFs)?
-a type of cytokine -produced in response to viral infections -3 types: alpha, beta, and gamma
43
what are chemokines (CXCs, CCs, CX3Cs, XCs)?
-a type of cytokine -chemoattractants important in cell migration (chemotaxis) and other functions -over 40 known and 23 chemo receptors -chemokine receptors are GPCRs
44
what are Tumour Necrosis Factors (TNF)?
-a type of cytokine -superfamily of receptors and ligands -29 known receptors and 19 known ligands
45
what are interleukins (IL)?
-a type of cytokine -40 known
46
what makes the interferon response?
cells infected with a virus
47
what are IRF3 and IRF7?
transcription factors for type 1 interferons, which includes IFN-beta and IFN-alpha
48
what does IRF3 generate?
the IFN-beta response
49
what does IRF-7 generate?
the IFN-alpha response
50
what does the IFN-beta response do?
-IFN-B binding to its receptors causes a signal transduction cascade that result in the induction of IFN-a ad both type 1 interferons induce the synthesis of a number of cellular proteins that inhibit viral replication in a cell
51
what do plasmacytoid dendritic cells do? where are they found?
-produce IFNs -found in blood and lymphoid tissue and use TLR7 and TLR8 to detect viral infection
52
where are most cytokines synthesized? how are they secreted?
-in the ER -via the endomembrane system
53
what are the steps needed for IL-1B to activate the synthesis of cytokines?
1. IL-B is synthesized by macrophages and stored in the cytosol in an inactive state until cleaved by caspase 1 2. once IL-1B is active, Gasdermin will form pores on the membrane of the macrophage to allow IL-1B to exit and be released into circulation 3. after IL-1B I released, the original macrophage dies (pyroptosis), and the IL-1B triggers the activation of other macrophages to synthesize the release of the 5 cytokines
54
why do few macrophages undergo pyroptosis?
-to get the immune response to move quickly by letting the IL-1B bind to other receptors on different macrophages which can activate the release of cytokines
55
why is too many cytokines (cytokines storm) bad?
-hyperactivation of the immune response causes the epithelial cells and blood vessels to become more permeable, which can cause blood to leak and organ dysfunction, ultimately leading to death

mbb 326 (6 decks)

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