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Sp 15-Micro Final > Adaptive Immune Response to Intra- and Extracellular Pathogens > Flashcards

Adaptive Immune Response to Intra- and Extracellular Pathogens Flashcards

1
Q

The goal of the immune response to intracellular pathogens are to _____ against infection (B Cells) and _____ an established infection (NK Cells or CD8+).

A

Protect

Eradicate

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2
Q

NK cells are used by the _____ immune system; whereas CD8+ CTL are used by the _____ immune system to eradicate an established infection.

A

innate

adaptive

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3
Q

_____ mediates enhancement of the cytotoxic activity of NK cells and CD8+ cytotoxic T lymphocytes

A

IL-12

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4
Q

Activation of NK cells lead to __________ which kills the infected cell.

A

Degranulation

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5
Q

Antigen specific ______T Cells and cytotoxic ______ T Cells are involved with eradicating intracellular pathogens.

A

CD4+

CD8+

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6
Q

How is NK cell activity inhibited?

A

The inhibitory receptor binds Self MHC I-self peptide complex

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7
Q

If the NK cell is activated, what has the virus inhibited?

A

MHC Class I Expression

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8
Q

Naive T cells come into contact with _____ in lymph nodes which is necessary for activation of the T cell.

A

Antigen Presenting Cell

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9
Q

T cells become activated by:

  1. TCR recognition of _______ on APC
  2. _________ molecule binding
A

Peptide:MHC

Co-Stimulatory (ex. CD28-B7)

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10
Q

The interaction between dendritic cell and naive T cell and binding of co-stimulatory molecules CD28 and _____ causes activation of the T cell.

A

B7

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11
Q

Which co-stimulatory molecules are necessary for the T cell dependent pathway to activate B cells?

A

CD40L with CD40

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12
Q

If an infected cell is negative for MHC class I, what will happen to the cell?

A

The infected cell will be killed by NK cells

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13
Q

The receptor for naive T cells is ___-selectin; whereas, the receptor for activated T cells is ____ or ____ selectin ligand.

A 
Naive = L-selectin
Effector = E- and P-selectin Ligand
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14
Q

The receptor for naive T cells is ___-selectin; whereas, the receptor for activated T cells is ____ or ____ selectin ligand.

A 
Naive = L-selectin
Effector = E- and P-selectin Ligand
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15
Q

Activated T cells must migrate to __________ and be retained so that they can express their effector functions and eradicate virally infected cells.

A

the site of infection

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16
Q

Macrophages ______ and T cells ________.

A

Kill

Protect

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17
Q

Macrophages are activated by CD___: CD_____ and by ______.

A

CD40L:CD40

IFN-gamma

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18
Q

What are three responses that occur due to activation of macrophages?

A
  1. Killing of phagocytosed microbes
  2. Increased expression of MHC molecules and co-stimulatory molecules (B7)
  3. Secretion of cytokines (TNF, chemokines, IL-1, IL-2)
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19
Q

If a dendritic cell or macrophage ingests a microbe, it will release IL-12 and cause the differentiation of Naive CD4+ T Cell into ______ which will release IFN-gamma for the activation of macrophage.

A

Effector T Cell (T helper I Cell)

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20
Q

What are the three common cytokines that Th2 Cells will release in order to inhibit macrophage activation?

A

IL-10
IL-4
IL-13

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21
Q

What is CTL targeting?

A

A CTL will kill targets that express the same Class I-associated antigen that triggered the proliferation and differentiation of naive CD8+T cells to become CTLs.

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22
Q

What is CTL targeting?

A

A CTL will kill targets that express the same Class I-associated antigen that triggered the proliferation and differentiation of naive CD8+T cells to become CTLs.

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23
Q

What are the three important biochemical signals (kinases) that activate CD8+T cells to proliferate and differentiate into CTLs?

A

MAP kinases (AP-1)
Protein Kinase C (NF-kB)
Calcineurin (NFAT)

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24
Q

How does the CTL lyse a target cell?

A

Lytic Granules

Fas-FasL

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25
Q

What are the proteins within lytic granules of cytotoxic T Cells?

A

Perforin
Granzymes
Granulysin

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26
Q

What is perforin?

A

A protein in lytic granules that polymerizes to form a pore in the target membrane

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27
Q

What is a granzyme?

A

A serine protease (protein in lytic granule of T cell) that activates apoptosis in the cytoplasm of the target cell

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28
Q

What is granulysin?

A

A lytic granule protein of cytotoxic T cells that induces apoptosis of the target cell

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29
Q

What is granulysin?

A

A lytic granule protein of cytotoxic T cells that induces apoptosis of the target cell

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30
Q

How do granzymes enter the target cell?

A

A cytotoxic T lymphocyte releases Granzyme B and Perforin (lytic granules) via exocytosis.

  1. Perforin molecules create a Polyperforin Pore in the target cells membrane that allows entry of apoptotic Granzyme molecules
  2. ALSO, CI-MPR (receptor) will bind Granzyme and the complex will be engulfed in a vesicle and brought into the target cell
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31
Q

______ creates pores in the target cell membrane.

A

Perforin

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32
Q

What are the three pathways that Granzyme B uses to induce apoptosis of the target cell?

A
  1. Activation of Caspase 3
  2. Activation of CAD directly
  3. Activation of BID (mitochondria)
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33
Q

Describe how Granzyme B induces apoptosis (starting with caspase 3).

A
  • Granzyme B activates Caspases, especially Caspase 3
  • Caspase 3 leads to Caspase Activated DNAse (CAD)
  • CAD causes DNA fragmentation = Apoptosis
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34
Q

What is the action of Caspase Activated DNAse?

A

CAD causes DNA fragmentation and, thus, apoptosis

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35
Q

What is the action of Caspase Activated DNAse?

A

CAD causes DNA fragmentation and, thus, apoptosis

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36
Q

Granzyme B has three pathways leading to apoptosis, two of which use CAD to fragment DNA. The third pathway cleaves DNA through activation of ________.

A

ENDOG

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37
Q

Describe the Granzyme B pathway that begins with activation of BH3-interacting domain death agonist (BID).

A
  • Granzyme B enters the target cell and activates BID
  • BID destroys the integrity of the mitochondrial outer membrane and induces the formation of the BAD/BAX channel
  • Pro-apoptotic factors are released from the mitochondrial membrane
  • Cytochrome C will activate Caspase 9 and endonuclease G (ENDOG) = cleaves DNA = apoptosis
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38
Q

Granzyme B cleaves DNA through either _____ or ______.

A

CAD
(two pathways: caspase 3 or CAD directly)
ENDOG
(BID >BAD/BAX>Cyto C > Caspase 9 >ENDOG)

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39
Q

Granzyme B cleaves DNA through either _____ or ______.

A

CAD
(two pathways: caspase 3 or CAD directly)
ENDOG
(BID >BAD/BAX>Cyto C > Caspase 9 >ENDOG)

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40
Q

The release of T cell granules occurs over a somewhat specific time line:
T zero = cell binds to target cell, no granules nearby
T 1min - 4min = granules move toward point of contact
T 40mins = ______________

A

Release of granules into space between T cell and Target cell. Target cell has begun apoptosis at this time.

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41
Q

Other than lytic granules, how can cytotoxic T cells lyse a target cell?

A

Fas:FasL

42
Q

FasL is on the ______ and Fas is on the ________.

A

CTL
Target Cell

Interaction = apoptosis (death receptor pathway)

43
Q

How do Fas:FasL interactions eradicate cells infected with intracellular pathogens?

A
  1. Fas receptor trimerization activates the death domain
  2. FADD leads to signaling cascade that activates caspase 8
  3. Caspase 8 activates BID and/or Caspase 3
  4. The caspase cascade leads to DNA fragmentation
44
Q

Bax/Bak is associated with the ________ pathway of apoptosis, whereas BAD/BAX is associated with the _____ pathway of apoptosis.

A

Fas/FasL

Granzyme B

45
Q

Bax/Bak is associated with the ________ pathway of apoptosis, whereas BAD/BAX is associated with the _____ pathway of apoptosis.

A

Fas/FasL

Granzyme B

46
Q

Fas-mediated killing is important for the maintenance of T Cell _______.

A

Self-tolerance

47
Q

Both Fas and FasL are members of the _____ family of proteins.

A

TNF

48
Q

Which cells produce IFN-gamma in order to activate macrophages?

A

CD4+ T Cells

49
Q

Which cells produce cytokines to provide stimulation for CD8+ T cell activation?

A

CD4+ T Cells

50
Q

Which cells produce cytokines to enhance the activity of APCs?

A

CD4+ T Cells

51
Q

Why are CD4+ T Cells important (3 main functions)?

A
  1. Production of cytokines to stimulate CD8+ T Cells
  2. Production of cytokines to enhance APC activity
  3. Production of IFN-gamma for activation of macrophages
52
Q

How do intracellular pathogens try to thwart the immune response?

  1. Inhibit ______ activity
  2. Block _____ transport
  3. Block _______ synthesis or retention
  4. Removal of _____ from the ER
  5. Interfere with ________ by “decoy”
A
  1. proteasomal
  2. TAP
  3. MHC
  4. Class I
  5. Cytotoxic T Lymphocytes
53
Q

The immune response to EXTRAcellular pathogens is initiated by ______ and _______.

A

Macrophages

Neutrophils

54
Q

The immune response to EXTRAcellular pathogens is initiated by ______ and _______.

A

Macrophages

Neutrophils

55
Q

Once inside a lysosome, microbes are killed via _____ and/or ______.

A

ROS

NO

56
Q

_____ Immunity is referred to as a driver of cell mediated immunity.

A

Th1

57
Q

Which cell type will activate IFN-gamma?

A

Th1

58
Q

What does IFN-gamma do?

A
  1. Increases MHC expression
  2. Activates macrophages
  3. Activates class switching
  4. Induces formation of Th1 effector cells
59
Q

Isotype switching occurs when _____ acts on B cells.

A

IFN-gamma

60
Q

Th2 immunity drives the ______ response.

A

antibody (humoral)

61
Q

Interleukin 4 and co-stimulatory molecules ________ induce the production of IgG and ______.

A

CD40/CD40L

IgE

62
Q

Which cytokine will activate eosinophils in the presence of parasites?

A

IL-5

63
Q

Which cytokine is closely associated with isotype switching?

A

IL-4

64
Q

What is the “default” antibody that does not require any isotype switching?

A

IgM

65
Q

The humoral immune response involves _____ production.

A

Antibody

66
Q

How are B cells activated?

A
  1. Recognition by B cells leads to a signal transduction cascade that ultimately activates the B cell
  2. Soluble antigen initiates crosslinking of immunoglobulin receptor which results in production of IgM
67
Q

B cells do not need MHC for activation because they themselves are ________ cells.

A

Antigen-Presenting

68
Q

______ are the receptors on B cells.

A

Antibodies

69
Q

True or False: All B Cells produce antibodies.

A

False. Naive B cells canNOT produce antibody, they must become activated.

70
Q

B cells can be activated by _______ or soluble _______.

A

Microbes

antigen

71
Q

When a soluble antigen activates B cells through its IgM receptor, proliferation will result in what kind of B cells?

A

B cells that have IgM receptors

72
Q

When a soluble antigen activates B cells through its IgM receptor, proliferation will result in what kind of B cells?

A

B cells that have IgM receptors

73
Q

What two changes can result from B Cell exposure to microbes?

A

Changes in phenotype and function

74
Q

Where do T cells and B cells interact?

A

Lymph Nodes

75
Q

How is Isotype switching in B cells dependent on T cell interactions?

A

A dendritic cell may present antigen to a helper T cell through interaction of B7 and CD28. The T cell expresses CD40 ligand and begins releasing cytokines. Through the CD40L and the cytokines, the T cell will now activate a specific B cell.

76
Q

Isotype switching in B cells is dependent on T cells (interaction through CD40-CD40L) and the released _______.

A

Cytokines

77
Q

Activated B cells will go through isotype switching after T helper cell interaction and will respond to different cytokines. To change to the IgG isotype, B cells will interact with _____ cytokine. To change to the IgE isotype, B Cells will interact with _____ cytokines.

A 
IFN-gamma = IgG
IL-4 = IgE
78
Q

_____ is secreted onto mucosal surfaces.

A

IgA

79
Q

What type of B cell-derived cells will produce and secrete antibody?

A

Plasma cells

80
Q

High-affinity Ig-expressing B cells are also known as _____.

A

Memory B cells

81
Q

Plasma cells take up residence in _______.

A

Bone marrow

82
Q

Memory B cells take up residence in _________.

A

Secondary Lymph Nodes

83
Q

What is the effect of complement activation?

A

Inflammation (due to “a fragments”) and cascade effect (due to “b fragments”)

84
Q

What is the effect of complement activation?

A

Inflammation (due to “a fragments”) and cascade effect (due to “b fragments”)

85
Q

NK cells are part of which arm of the immune system?

A

Innate (even though they are lymphoid derived)

86
Q

What is active immunization?

A

Vaccination

87
Q

What is induced by vaccination?

A

Adaptive Immunity
Immunological Memory
Protection

88
Q

Vaccinations can be of what two forms?

A

Live-attenuated

Killed (inactive)

89
Q

What is passive immunization?

A

Passive injection of preformed antibodies

90
Q

True or False: The two public health interventions that have had the greatest impact on the world’s health are clean water and vaccines.

A

True

91
Q

To which category of vaccines do most successful viral vaccines belong?

A

Live Attenuated

92
Q

What are heterologous vaccines?

A

Vaccination through the use of closely related organisms of lesser virulence that share many antigens with the virulent organism (i.e. Smallpox eradication through vaccinia or cowpox)

93
Q

What are live recombinant vaccines?

A

Vaccines that have been genetically engineered to contain a gene that codes for an immunogenic protein of interest but came from a different organism.

94
Q

Which category of vaccines has good immune response in a single dose, danger of reversion, and is inexpensive?

A

Live Vaccines

95
Q

Killed vaccines have a poor immune response because it has primarily an ______ response and very little ______ .

A

Antibody response

Very little cell-mediated

96
Q

A vaccine is considered to be very good if it produces what two responses?

A

Humoral Immunity: Protection against infection

Cell-Mediated Immunity: Eradication of infection

97
Q

True or False: Antibodies can only neutralize microbes.

A

False: antibodies can neutralize microbes or toxins

98
Q

True or False: Antibodies can only neutralize microbes.

A

False: antibodies can neutralize microbes or toxins

99
Q

Through which receptor will antibody-opsonized microbes bind to a phagocyte?

A

Fc Receptors will bind a microbe that has been opsonized by antibody.

100
Q

_______ Activity is enhanced by antibody.

A

Complement

101
Q

Which complement fragments will recruit and activate leukocytes?

A

C3a and C5a

Sp 15-Micro Final (12 decks)

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