Exam II: Lecture 5 Flashcards

1
Q

What are the two main components of the adaptive immune response?

A
  1. Cytotoxic T lymphocytes (CTLs)

2. Humoral antibodies

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2
Q

Is the innate response specific or non-specific? Does it render the host immune to future infection?

A

It is non-specific

Does not render the host immune to future infection

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3
Q

What does the innate response produce?

A

Cytokines such as interferon and interleukins

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4
Q

Not all genomes are the same, what does this imply for your immune system?

A

We all make antibodies differently

Think colonizers and smallpox

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5
Q

What are the 6 main components of the innate immunity?

A
  1. Apoptosis
  2. Natural killer cells
  3. Complement activation
  4. Complement production
  5. Interferons
  6. The antiviral state
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6
Q

How is apoptosis used as a defense mechanism?

A

Denies the virus the opportunity to replicate and spread

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7
Q

What is the mechanism for apoptosis in innate immunity?

A

Irreversible damage > Mdm2 degraded (p53 is always made and degraded via ubiquitination by Mdm2) > p53 stabilized > activates caspases = cystiene proteases > cleave target proteins after aspartic acid&raquo_space;> DNA degredation, cytoskeleton eaten > apoptosis

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8
Q

What genes regulated apoptosis? (2)

A
  1. Antiapoptotic: BCL2

2. Pro-apoptotic: BH123 (Bax, Bak)

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9
Q

Cytochrome C in mitochondria can activate what?

A

Caspases

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10
Q

Are NK cells antigen-independent or antigen-dependent?

A

Antigen independent

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11
Q

NK activation occurs within how many days after viral infection?

A

2-3 days

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12
Q

NK cells are believed to kill what kind of cells?

A

Cells that do not express MHC I

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13
Q

If the virus decreases the production of MHC I to escape detection, what cells are responsible for killing the virus-infected cells?

A

NK cells

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14
Q

Complement Cascade Mechanism

A

Antibody finds antigen > C1 complex forms > C2a and C4b fragments > C3 convertase > C3 hydrolysis > C3b and C3a fragments > C3b cleaves C5 > C5a and C5b > C5b, C6, C7, C8, C9 form the pore > cell swells and bursts

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15
Q

The complement cascade is a part of which system?

A

It can be a part of both the adaptive and innate immune system

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16
Q

Define Opsonization

A

Marking a pathogen for phagocytosis

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17
Q

What complement protein binds to the surface of pathogens?

A

C3b

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18
Q

What are the final results of complement activation? (4)

A
  1. Phagocytosis
  2. Virus neutralization
  3. Induction of inflammatory response
  4. Activation of B cells
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19
Q

What are cytokines?

A

A family of over 30 proteins that are induced by different stimuli

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20
Q

Why is cytokine production low or absent?

A

Because they lead to inflammation, cell proliferation, and differentiation state which can be bad for a healthy body

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21
Q

Upon induction, they are produced for a short or long period of time?

A

Short

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22
Q

They bind to receptors on the surface of target cells with low or high affinity?

A

High

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23
Q

What can cytokines cause? (3)

A
  1. Changes in gene expression
  2. Cell proliferation
  3. Differentiation state
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24
Q

What are some common cytokines? 3 categories and examples

A
  1. Antivirial; IFN I and IFN II
  2. Inflammatory; TNF, IL-1, IL-6
  3. Lympokines; Interlukins
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25
What is a PAMP?
Pathogen Associated Molecular Pathway
26
What is a PRR?
Pattern Recognition Receptor
27
What is an example of a PAMP? (2)
Triphosphorylated RNA, LPS
28
What are the two categories of PRRs?
1. Cytoplasmic | 2. Membrane Bound
29
What is an example of a cytoplasmic PRR? What do they contain? What kind of activity do they possess?
RIG-I, Mda5 Contain CARD domains RNA helicase activity
30
What is an example of a membrane-bound PRR? What kind of PAMP do they detect?
Toll-like receptors (TLRs) | Detect extracellular PAMPS
31
What is a DAMP?
Damage Associated Molecular Pathway
32
What is a general example of a DAMP?
Stick yourself with a needle > Split cells > DNA escapes nucleus > triggers the immune response
33
Define Edema
Swelling due to liquid accumulation from blood vessels
34
Talk me through the RIG-I pathway
DNA/RNA virus enters cell > releases genome = PAMP = triphosphorylated ds RNA > activate RIG-I / MOAS > Uq chains come over > Uq chains act as a scaffold > RIG-I binds to MAVS on surface of mitochondrial membrane = assembly point > TRAPs assemble > TRAP activate TDK > TDK phosphorylate and activate IKK > IKK phosphylates IR3 and IkB >>> production of interferons
35
When RIG-I is inactive what does it look like? How does this change when its active?
RIG-I has a CARD domain and its folded up when in active When it is active it is unfolded which exposes its CARD domain MAVS CARD domain finds RIG-I CARD domain
36
What are the 2 uses for ubiquinization in the cell?
1. Degredation | 2. Localization
37
What are interferons?
Members of the cytokine family | Induce the antiviral state
38
What are the two groups of the interferons?
1. IFN I | 2. IFN II
39
What is IFN I involved in?
Defense against viruses and bacteria
40
What is IFN II involved in?
Defense against bacteria only
41
What are the two IFN I family members?
IFNalpha | IFNbeta
42
What members of the IFN II family?
IFNgamma
43
Which interferon is the main activator of the antiviral state?
IFNbeta
44
What is the general signaling pathway from PRR to antiviral response?
PAMP > recognized by PRR >>> IFN I > autocrine I paracrine signaling > secondary set of genes > more proteins > produce antiviral state
45
Type I IFNs are induced by what type of viral genome OR what type of cytokine?
ds RNA | TNF-alpha
46
IFNalpha and IFNbeta are produced by what cell types? What is the inducing agent? What are their functions (3)?
All cell types Viral infection, dsRNA Antiviral, increases MHC I, antitumor
47
IFNgamma is produced by what cell types? What is the inducing agent? What is its function (3)?
T-cells Antigen or mitogen Increase MHC I and II, decrease MHC II in B cells, NK cell activation
48
What is unique about the interferon promoter? Why?
It requires a complex enhanceosome because it needs to be highly regulated
49
What are the 4 main components of the interferon enhanceosome?
1. ATF2 2. C-JUN 3. IRF-3 4. NFKB
50
How do interferons effect their response?
By binding to receptors on the surface of cells
51
Do type I and type II interferons bind to the same receptors?
No, they bind to different receptors
52
Binding of an IFN leads to the activation of what?
A tyrosine kinase domain within the receptor
53
What is the ISRE?
Interferon stimulated responsive element
54
Talk me through the generalized mechanism after an interferon binds to a cell
IFN bind to receptor > activate tyrosine kinase domain > phosphrylation cascade > activation of TF > bind to ISRE sequence in DNA > expression of IFN responsive genes
55
What makes RNA unstable?
RNA has a built in AU rich element at the 3' end which causes its destruction
56
What does the AU rich region on the RNA signal for?
Signals for an RNAase to come degrade it
57
Induction by the type I interferons is short or long lived? How does this differ compared to type II (IFN gamma)?
IFN I induction is transient = short lived | IFN gamma = long lived, slower
58
What are the 3 ways IFN I signal transduction is regulated?
1. Complex enhanceosome 2. AU rich region > mRNA degradation 3. Makes its own inhibitor (NFKB makes IKK)
59
Talk me through the Jak/Stat pathway
IFNalpha/beta > IFNR > JAKI > STAT I + STAT II localize and dimerize > enter nucleus > bind to ISRE > turn on genes IFNgamma > IFNR > JAK I > STAT I > Dimerize > enter nucleus > bind GAS > turn on genes
60
IFN I turn on which gene sequence? What about IFN II?
IFN I : ISRE | IFN II : GAS
61
What are the 5 specific genes stimulated by IFN disucess in class? Which IFN are they stimulated by?
1. 2'-5' Oligo A synthetase ; IFN I 2. MxA ; IFN I 3. IRF-2 ; IFN I and II 4. MHC I ; IFN I and II 5. MHC II ; IFN II
62
What is the function of 2'-5'OligoA synthetase?
Induction of antiviral state
63
What is the function of MxA?
Inhibits replication of Influenza and BZV by binding to polymerase
64
What is the function of IRF-2?
Transcription factor that turns on antiviral state gens
65
Waht is the function of MHC I?
Increases antigen presentation
66
What is the function of MHC II?
Increase antigen presentation
67
What is one detectable biological effect of interferons? What does this do?
IFNs induce a fever | The high temperature inhibits replication of many viruses
68
What does TAP do?
Presents peptides on the surface of cells
69
What is APC?
Antigen-presenting Cell
70
Both IFN types lead to the activation of what 5 immune cells?
1. Monocytes 2. Macrophages 3. NK cells 4. CTLs 5. Synthesis of Ig by B cells
71
What is an evolutionary reason why inflammation cannot go on forever?
Anhedonia?
72
IFN can inhibit cell growth and was found to be effective against some forms of cancer
True
73
What does 2'-5'OligoA synthetase do once made in response to IFN stimulation?
IFN I/II > promoter > OAS (OligoAsynthetase) > polymerizes ATP > 2'-5'OligoA > activates RNAaseL > RNAase L cleaves ss mRNA > decreases production of viral proteins >>> apoptosis
74
What does PKR do once made in response to IFN stimulation?
dsRNA > PKR > phosphorylates eIF-2alpha ( eIF-2alpha recognizes eIF-4 which is on the mRNA cap > switches out GTP for GDP > ribosomal translation) > eIF-2 cannot switch out GTP for GDP > ribosome freezes > translation shuts down >>> apoptosis
75
IFN turns on the transcription of what 3 proteins which help ready the cell before it is infected with virus?
1. Inactive OAS 2. Latent PKR 3. Inactive RNAase L
76
Talk to me through the process by which an infected cell will protect other cells around it
Cell becomes infected > PAMP > PRR > IFN I > autocrine/paracrine signaling > JAK/STAT > promoter > OAS, PKR, RNAase L > ds RNA enters second cell > activation of PKR, OAS > active RNAaseL >>> apoptosis
77
Apoptosis
cells sacrifice themselves to save the organism
78
Natural Killer Cells
Attack cells that harbor virus (but do not display antigen)
79
Complement activation
Activate immune cells and act as chemokines
80
Interferons
first line of defense against infection
81
Antiviral state
prepares the cell to destroy viral RNA and prevent translation of viral proteins