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Immunology 7070 > Lecture 2 > Flashcards

Lecture 2 Flashcards

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1
Q

How quickly does the innate immunity develop?

A

Within hours

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2
Q

Why are vaccines sometimes now directed at the innate immunity?

A

Innate and adaptive immunities are linked. The innate immunity is able to influence the adaptive immunity and how it responds.

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3
Q

What are the four major components of the innate immune system?

A

Barriers, Effector cells, cytokines, and effector proteins

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4
Q

What is the function of the barrier epithelial layers?

A

Prevents microbial entry

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5
Q

What is the function of the barrier defencins and intraepithelial lymphocytes?

A

Microbial killing

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6
Q

What is the function of neutrophils?

A

Early phagocytosis and killing of microbes

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7
Q

What is the function of macrophages?

A

Efficient phagocytosis and killing of microbes. Secretion of cytokines that stimulate inflammation.

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8
Q

What is the function of NK cells?

A

Lysis of infected cells. Activation of macrophages

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9
Q

What is the function of innate lymphoid cells?

A

Immunoregulatory cytokines that respond early on in infections

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10
Q

What is the function of platelets?

A

Regulator of inflammation/immunity

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11
Q

What are the three mechanisms that effector cells use to act on microbes?

A

Phagocytosis, Cytotoxicity, and cell mediated production of cytokines

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12
Q

What cells of the innate immunity can use phagocytosis?

A

DCs, neutrophils, and macrophages

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13
Q

What cells of the innate immune system are cytotoxic?

A

NKs

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14
Q

What are the four kinds of effector proteins?

A

Complement, mannose-binding lectin, C-reactive protein, and coagulation proteins

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15
Q

What is the brief function of complement proteins?

A

Killing of microbes, opsonisation of microbes, and activation of leukocytes

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16
Q

What is the brief function of mannose-binding lectin proteins?

A

Opsonization of microbes, and the activation of complement proteins

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17
Q

What is the brief function of C-reactive proteins?

A

Opsonization of microbes and the activation of complement proteins

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18
Q

What is the brief function of coagulation proteins?

A

Walling off of infected tissues

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19
Q

Describe complement proteins and their functions

A

Complement proteins are a system of plama proteins that can be activated directly by pathogens or indirectly by antibodies.
Lead to a cascade of reactions that occurs on the surface of pathogens
Generate active components with various effector functions

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20
Q

What is the principal cell source, cellular targets, and biological effects of TNF?

A

Macrophages and T cells

Activation of endothelial cells and neutrophils, create fever in the hypothalamus catabolise fat, and apoptosis.

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21
Q

What is the principal cell source, cellular targets, and biological effects of IL-1?

A 
Macrophages, endothelial cells, some spithelial cells
Activation of endothelial cells
fever in hypothalamus
synthesis of proteins in the liver
TH17 cell differentiation
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22
Q

What is the principal cell source, cellular targets, and biological effects of chemokines?

A

Macrophages, DCs, endothelial cells, T cells, fibroblasts, and platelets
Increased integrin affinity, chemotaxis, and activation in leukocytes

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23
Q

What is the principal cell source, cellular targets, and biological effects of IL-12?

A

DCs and macrophages
NK and T cells: IFNgamma production and increased cytotoxic activity
Th1 cell differentiation

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24
Q

What is the principal cell source, cellular targets, and biological effects of IFNgamma?

A

NK and T cells

Activation of macrophages and the stimulation of some antibody responses

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25
What is the principal cell source, cellular targets, and biological effects of IFN alpha and beta?
IFN alpha in DCs and macrophages IFN beta in fibroblasts IFNs create an antiviral state and increased MHC I expression in all cells. They also activate NK cells
26
What component do complement proteins fulfil?
They are a part of the humoral component.
27
What are the three outcomes of complement proteins?
Lysis of microbes Inflammation Phagocytosis of complement coated microbes
28
What are the three pathways by which complement proteins are activated? How do they work (briefly)?
Classical pathway: antibodies recognize the microbe Alternative pathway: microbes activate the proteins on their own Lectin pathway: lectin proteins recognize and bind to the microbe to activate the proteins
29
What are the three complement proteins in the stages of the pathway activation? How big are the two parts of the activated proteins? At which stage of the pathway are they present?
C3 (C3a and 3b) – a is small, b is big. Early stage. C5 (C5a and 3b) – a is small, b is big. Mid stage. C9 – late stage – no separation of proteins.
30
Why does the innate immunity have limited diversity?
It must use the mechanisms that exist before infection and the receptors that are incoded in the germline.
31
What do the germlines use to recognize microbes?
Pattern recognition receptors
32
What are the two parts of the innate immunity target specificity?
``` Cellular receptors (cell mediated component) Soluble plasma proteins (humoral) ```
33
What are the kinds of PRRs in the innate immune system?
``` TLRs NLRs (NOD-like – nucleotide binding oligomerization domain) RLRs – Retinoic acid-inducible gene 1 (RIG-1)-like receptor/helicases (RLHs) ```
34
What are the components of a TLR?
Multiple leucine-rich repeats (LRRs) and one Toll-interleukin (IL)-1 receptor homology (TIR) domain
35
Where are LRRs in the TLR located?
1, 2, 4, 5, and 6 are on the outside of the cells | TLRs 3, 7, 8, and 9 re located on the inside of the membrane compartment
36
How many TLRs are there?
13 murine TLRs and 10 human TLRs
37
What does TLR 3 recognize? Where is it found?
dsRNA – endosomal membranes of cells
38
What does TLR 7 recognize? Where is it found?
ssRNA– endosomal membranes of cells
39
What does TLR 8 recognize? Where is it found?
ssRNA– endosomal membranes of cells
40
What does TLR 9 recognize? Where is it found?
CpG RNA– endosomal membranes of cells
41
What does TLR 1 recognize? Where is it found?
Bacterial LPS – on the surface membrane of cells
42
What does TLR 2 recognize? Where is it found?
Bacterial LPS and bacterial peptidoglycans – on the surface membrane of cells
43
What does TLR 4 recognize? Where is it found?
LPS – on the surface membrane of cells
44
What does TLR 5 recognize? Where is it found?
Bacterial flagellin – on the surface membrane of cells
45
What does TLR 6 recognize? Where is it found?
Bacterial LPS – on the surface membrane of cells
46
What non-TLR family recognizes bacterial peptidoglycans? What TLR family recognizes the same?
NODs | TLR-2
47
Why are viruses and bacteria able to be recognized by CpG DNA islands?
They have those available to them in their DNA while we have methylated versions in self.
48
What are the main steps to the TLR pathway?
TLR engagement Recruitment of adaptor proteins Activation of transcription factors Increased expression of cytokines, adhesion molecules, or co stimulators leading to inflammation and stimulation of adaptive immunity OR production of type 1 interferons (IFN alpha/beta) leading to the antiviral state.
49
What are NLRs characterized by?
A central NOD, a C-terminal LRR, and an N-terminal domain responsible for the signaling (like CARD and PYRIN domains)
50
What do mammalian NOD1 and NOD2 recognize?
Bacterial peptidoglycan components gamma-D-glutamyl-mesodiaminopimelic acid – NOD1 Muramyl dipeptide – NOD2
51
To what do NOD receptors transmit their signals and what do they activate?
To RIP2/RIPK kinase leading to activation of NFkB.
52
What is the principal cell source, cellular targets, and biological effects of IL-10?
IL-10 is secreted by macrophages, DCs, and T cells. | In Macrophages and DCs in inhibits IL-12 production and reduces expression of costimulators and MHC II molecules
53
What is the principal cell source, cellular targets, and biological effects of IL-6?
Macrophages, endothelial cells and T cells secrete IL-6. Liver: synthesis of acute-phase proteins B cells: proliferation of antibody producing cells
54
What is the principal cell source, cellular targets, and biological effects of IL-15?
Macrophages and others produce IL15 | IL-15 causes proliferation in NK and T cells
55
What is the principal cell source, cellular targets, and biological effects of IL-18?
Macrophages | Causes IFN gamma synthesis in NK and T cells
56
What is the principal cell source, cellular targets, and biological effects of TGF beta?
Many cell types produce TGFbeta. Causes inhibition of inflammation Causes differentiaiton of Th17s and Tregs
57
Describe the average TLR signaling pathway and the steps it takes.
TLR is engaged by bacterial/viral molecules Recruitment of adaptor proteins Activation of transcription factors (like NFkB/IRFs) Causes acute inflammation/stimulation of adaptive immunity Causes antiviral state
58
Which domain does the NALP family of NLRs possess? | Instead of which domain?
PYRIN domain instead of a CARD
59
What is the function of most NALP members of the NLR family?
We don't know!
60
What is the function of NALP 1, 2, and 3?
involved in cleavage of prointerleukin 1beta and prointerleukin 18 to mature forms using caspase 1
61
What kind of NLRs do microbial constituents signal?
So far, all of them
62
What kind of NLRs do danger signals alert?
NALP3
63
Which signalling cascade to NOD1 and NOD2 use? What do they result in?
They use RIP2 and NFkB resulting in an inflammatory response
64
NLRs result in which three outcomes?
Inflammatory responses Cell death Cytokine processing
65
What is the function of caspase-1
incurs cell death OR helps process immature IL1beta and IL18 into mature forms via processing
66
What are RLRs comprised of?
RIG-I, MDA5, and LGP2
67
The helicase domains of RLHs show high similarity to those of which protein? What does this protein do?
Dicer protein | It is a nuclease essential for the generation of small interference RNA
68
What is the main thing RLRs recognize?
Viruses
69
Describe briefly a very approximate RLR pathway.
A virus triggers RIG-I or MDA5 signalling cascade IRF3/IRF7 gets triggered which results in type I IFNs AND/OR NFkB gets triggered and induces proinflammatory cytokines
70
In an RLR signaling cascade, what do IRFs 3 and 7 result in?
Type I IFNs
71
In an RLR signaling cascade, what does NFkB result in?
Proinflammatory cytokines
72
Describe very simply an example of how an extracellular something might trigger acute inflammation.
Pathogenic bacterial triggers a sensor which transmits the signal to its adaptor and possibly an internal protein gets activated and causes the induction of proinflammatory cytokines.
73
What are NK cells activator receptors?
Ly49H and NKG2D
74
What are NK cells inhibitory receptors?
Ly49A and p58 KIR
75
Discuss the 2 signals that are required for the activation of lymphocytes in the adaptive immunity. (Two signal hypothesis)
Two signals are required: 1. Antigen 2. Co-stimulatory molecules (Secret signal 3 = the microbial products or components of innate responses to microbes)
76
What is the role of innate immunity in stimulating adaptive immune responses?
Works along with antigen to initiate the T and B cells The "second signal" generated during innate immunity enhances magnitude and nature of adaptive response. Basis of action of adjuvants
77
How are the innate and adaptive immunities linked?
Macrophages and dendritic cells will express cytokines and costimulators in the innate immunity. Adaptive immunity will recognize the costimulator and be activated by the cytokine and proliferate/differentiate and use cell mediated immunity
78
What kind of cytokines do Th1 cells produce?
IFNgamma
79
What kind of cytokines do Th2 cells produce?
IL-4
80
Take home message: Why do we need innate immunity?
To provide a rapid response, and link to adaptive immunity
81
Take home message: What are the components of the innate immunity?
Barriers, cell mediated, and humoral components lead to | phagocytosis, cytotoxicity, and cytokines
82
Take home message: What is the specificity of the innate immunity?
Germline encoded PRRs evolved to recognize pathogens
83
Take home message: What are the differences between the innate immunity and adaptive immunity?
Innate:recognizes structures shared by groups, limited diversity, no memory Adaptive: specific antigens for microbes and other antigens, very diverse, has memory
84
Take home message: What is the role of the innate immune system in stimulating adaptive responses?
Initiates responses Enhances magnitude and nature of adaptive response Cross-talk between adaptor cells

Immunology 7070 (15 decks)

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