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Host And Defense - Exam 2 > Quiz 4 - German - Induced Immunity - Cells And Cytokines > Flashcards

Quiz 4 - German - Induced Immunity - Cells And Cytokines Flashcards

1
Q

Generally, what do macrophages do?

A

Phagocytosis

Present antigen to lymph

Activation of T cells

Initiation of immune responses

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2
Q

Monocytes are __________ in the bone marrow.

A

UNDIFFERENTIATED

Move into tissue and then differentiate

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3
Q

Monocytes differentiate into what?

A

Macrophage

Dendritic cells

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4
Q

What do dendritic cells do?

A

Activate T cells

Initiate adaptive immune responses

(Act like a vacuum)

  • Drive ongoing inflammatory response to cease
  • Collect antigen, go to lymph nodes, and initiate T cells
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5
Q

What do NK cells do?

A

Kill cells infected with certain viruses

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6
Q

Neutrophils. Tell me.

A

PHAGOCYTOSIS
-Then degranulate

*1st cell recruited in an immune response

**Billions of these sit in bone marrow and are waiting to be mobilized

***Also can extend a NET to catch and hold pathogen

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7
Q

Mast cells do what?

A

Expulsion of parasites from body thru release of granules containing histamine and other active agents

Presenters, too

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8
Q

What do eosinophils do?

A

Kill antibody-coated parasites thru degranulation

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9
Q

What do basophils do?

A

Control immune response to parasites via degranulation

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10
Q

What are 3 local, tissue resident immune cells?

A

Macrophage

Dendritic cells

Mast cells - Release histamine

*Adaptive - T cells

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11
Q

What initiates the induced immune response?

A

Local, tissue resident immune cells

Complement

Pro-inflammatory signaling

  • Cytokines
  • Eicosanoids
  • Acute phase response

Infected, damaged, or diseased tissues

  • Interferon response
  • Altered MHC expression
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12
Q

What is the inflammatory response for a flesh wound?

A

Wound introduces bacteria

Resident effector cells secrete cytokines

Vasodilation and increased vascular permeability allow fluid, protein, and inflammatory cells to leave blood and enter tissue

Infected tissue becomes inflamed, causing redness, heat, swelling, and pain

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13
Q

Tell me about macrophages.

A
  • Come from monocytes
  • Most tissue have resident macrophages
  • Induce and direct inflammation
  • Pattern recognition receptors (PRRs)
  • Activate adaptive immune system
-Effector mechanisms
—Phagocytosis
—Cytokine release
—Degranulation
—Antigen presentation
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14
Q

What tissue have resident macrophages?

A

Brain - Microglia

Bone - Osteoclasts

Liver - Kupffer cells

Skin - Langerhans cells

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15
Q

Bound material is internalized in a macrophage and then what happens?

A

Internalized in phagosomes and broken down in phagolysosomes

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16
Q

T/F - Macrophage receptors recognize the cell-surface carbohydrates of bacterial cells, but not those of human cells. (This is considered extracellular)

A

TRUE

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17
Q

T/F - NK cell receptors recognize change at the surface of human cells that are caused by viral infection. (This is considered intracellular)

A

TRUE

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18
Q

What are some common PRRs that result in phagocytosis?

A

Mannose

Complement

LPS

Dectin

MARCO (Macrophage receptor with collagenous structure)

Scavenger receptors A and B

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19
Q

What is a common PRR that does NOT result in phagocytosis?

A

Toll-like receptors

  • These result in signaling
  • These are mediated by a family of 10 receptors with variable specificity for a range of pathogens
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20
Q

Tell me the gross process of phagocytosis?

A

Bacterium become attached to membrane evaginations called pseudopodia

It is ingested, forming a phagosome

The phagosome fuses with the lysosome

Bacterium is killed and then digested by lysosomal enzymes (Proteases, lipases, granules)

Digestion products are released from the cell via exocytosis

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21
Q

What agents are in phagolysosomes?

A

Acid

Toxic O2-derived products - H2O2, OHCL

Toxic NO

Antimicrobial peptides

Enzymes

Competitors

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22
Q

What do Toll-Like Receptors do?

A

Activate macrophages

*These are expressed widely throughout the immune system

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23
Q

What TLRs bind lipid?

A

TLR1

TLR2

TLR4

TLR6

TLR10

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24
Q

What TLRs bind nucleic acid?

A

TLR3

TLR7

TLR8

TLR9

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25
Q

What TLR bind protein?

A

TLR5

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26
Q

What TLRs are heterodimers?

What TLRs are homodimers?

A

Hetero:

  • TLR-1/TLR-2
  • TLR-2/TLR-6

Homo:

  • TLR-3
  • TLR-4
  • TLR-5
  • TLR-7
  • TLR-9
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27
Q

The heterodimers (TLR-1/TLR-2 and TLR-2/TLR-6) bind what?

A

Lipid

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28
Q

What homodimer binds protein?

What homodimers bind lipid?

What homodimers bind nucleic acid?

A

Protein - TLR-5

Lipid - TLR4, TLR10

Nucleic acid - TLR3, TLR7, TLR8, TLR9

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29
Q

What TLRs bind the plasma membrane? (Extracellular)

A

TLR1/TLR2

TLR2/TLR6

TLR5

TLR4

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30
Q

What TLRs bind the endosome? (Intracellular)

A

TLR3 - dsRNA

TLR7 - ssRNA

TLR9 - CpG-DNA

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31
Q

How does heterodimerization happen?

A

TLRs have binding sites for lipopeptides

Once the two TLRs bind the same lipopeptides, then dimerization is induced

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32
Q

Know this pathway

NF-kappaB

LOOK AT SLIDE 17 IF YOU NEED TO

A

Complex of TLR4, MD2, CD14, LPS is assembled at the macrophage surface

MyD88 binds TLR4 and activates IRAK4 to phosphorylation TRAF6 and that leads to phosphorylation and activation of IKK

IKK phosphorylates IkappaB, leading to its degradation and release of NFkappaB

NFkappaB enters the nucleus

NFkappaB activates transcription of genes for inflammatory cytokines which are synthesized in cytoplasm and secreted via the ER

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33
Q

What do NOD receptors do?

A

Detect degraded antigens

Recognize intracellular PAMPs and DAMPs

  • Microbial toxins
  • Viruses
  • Cell stress proteins

Form inflammasome which cooperates with TLRs

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34
Q

What do inflammasomes do?

A

Activate and promote cytokine release

They turn the prointerleukin into an interleukin

35
Q

What are cytokines?

A

Signaling molecules of the immune system

  • Mostly soluble
  • Predominantly paracrine and autocrine
  • Called interleukins, chemokines, etc.
  • Effect immune and non-immune tissues

-3 common intracellular signaling pathways
—JAK-STAT
—MAPK
—NFkappaB

36
Q

What are the 6 families of cytokine receptors?

A

Class I

Class II

Interleukin 1

Interleukin 17

Tumor Necrosis Factor (TNF)

Chemokines

37
Q

What are the 5 pro-inflammatory cytokines?

A

IL-1beta

TNF-alpha

IL-6

CXCL8

IL-12

38
Q

Pro-inflammatory cytokines act in what way?

A

Locally and systemically

39
Q

What cell releases inflammatory cytokines?

A

Macrophage

40
Q

Which cytokines act both locally AND systemically?

A

IL-1beta

TNF-alpha

IL-6

41
Q

Which cytokines only act locally?

A

CXCL8

IL-12

42
Q

IL-1beta, TNF-alpha, and IL-6 have what shared effects?

A

Local - Activates vascular endothelium, increase lymphocyte and immune cell activation

Systemic - FEVER
—IL-1beta - Production of IL-6
—TNF-alpha - Mobilize metabolites, shock
—IL-6 - Induces acute-phase protein production

43
Q

CXCL8 and IL-12 produce what local effects?

A

CXCL8 - Chemotactic factor recruits neutrophils, basophils, and T cells to infection site

IL-12 - Activates NK cells, induces the differentiation of CD4, T cells into Th1 cells

44
Q

The systemic inflammatory cytokines (IL-1beta, IL-6, TNF-alpha) affect what organs we discussed?

A

Liver

Bone marrow endothelium

Hypothalamus

Fat, muscle

Dendritic cells

45
Q

Which systemic inflammatory cytokine stimulates the liver acute phase response?

A

IL-6

  • Drives production of acute phase proteins
  • Surfactant proteins
  • Mannose-binding lectins
  • Fibrinogen
  • C-reactive protein
  • Serum amyloid protein
46
Q

Cytokines initiate _________ recruitment.

A

Leukocyte

47
Q

How is leukocyte recruitment initiated?

A

Macrophages produce cytokines
-Dilation of local small blood vessels

Leukocytes move to periphery of blood vessel due to increased expression of adhesion molecules by endothelium

Leukocytes extravasate at site of infection

Blood clotting occurs in the microvessels

48
Q

Extravasation depends on what 3 things?

A

Chemokines - chemoattractants (CL, CCL, CXCL, CX3CL)

Adhesion molecules - Tether leukocytes

Proteases - Opening bsmt membranes
—Matrix metalloproteases
—Elastase

49
Q

What recruits immune cells to tissues?

A

Chemokines gradients

50
Q

Tell me about leukocyte extravasation to sites of inflammation. 3 things.

A

Chemokines receptor activation leads to binding

Binding triggers protease release

Bsmt membrane degradation and chemokines induce diapedesis and tissue entry

51
Q

Excessive TNF-alpha in plasma causes what?

A

Septic Shock Syndrome

  • Systemic extravasation
  • Systemic neutrophil infiltration

-Vascular collapse
—Decreased blood volume
—Hypoproteinemia
—Neutrompenia

-Death

52
Q

What is the primary cell of the induced response?

A

Neutrophils

53
Q

T/F - Large reserves of neutrophils are stored in the bone marrow and are released when needed to fight infection.

A

TRUE

54
Q

What is the mnemonic to remember the quantity (%) of immune cells in the blood?

A

Never - Neutrophils - 40-75

Let - Lymphocytes - 20-50

Men - Monocytes - 2-10

Eat - Eosinophils - 1-6

Burritos - Basophils - <1

55
Q

What is the primary innate killer?

A

Neutrophils

56
Q

Tell me more about the role of neutrophils.

A

Potent pathogen killas

Small, numerous

Effectors

  • Phagocytosis
  • Degranulation
  • Extracellular traps
  • Cytokine release

Destined to die

57
Q

What are the three killing mechanisms of neutrophils?

A

Phagocytosis

Degranulation

NETs

58
Q

Granules serve what two purposes?

A

Phagocytosis

Degranulation

59
Q

What are the 4 types of neutrophil granules?

A

Azurophil

Specific

Gelatinase

Secretory

60
Q

The phagosome fuses with what two granules?

A

Azurophilic

Specific

61
Q

What other mechanism kills pathogens?

A

Oxidative burst

  • NADPH oxidase
  • Superoxide dismutase
  • Catalase
62
Q

What happens after neutrophils do their job?

A

They die
-Apoptosis

*Usually phagocytosed by a macrophage

63
Q

Three types of NETs. Name and tell me about them.

A

2 are non-lytic

1 is lytic

Non-lytic (30-60 min after activation)
-NET released by mitochondrial DNA
—No degranulation, no damage

-NET is chromatin from nucleus
—Some degranulation, little damage

Lytic (3-4 hrs after activation)
-Rupture of membrane, NET, and cell lysis
—Degranulation, a lot of damage
—Last thing the cell will do if it can’t phagocytose the bacterium

64
Q

Dendritic cells are basically what?

A

Vacuums and presenters

65
Q

Tell me more about dendritic cells. 7 things.

A

Resident in tissue

Derived from monocytes

A lot of PRRs

Phagocytes

Process pathogens into antigens

Present antigens to lymphocytes

Cytokine regulation

66
Q

What do activated NK cells target?

A

Infected, diseased, stressed cells

67
Q

Tell me more about NK cells.

A

Large, CYTOTOXIC lymphocytes

Diverse combination of activating and inhibitory receptors

Target and kill diseased self cells

Respond to interferons, MHC Class I, and unique stress ligands

68
Q

What causes the interferon response?

A

Viral infections

69
Q

Tell me about the interferon response.

A

Virus infected cells causes release of IFN-alpha and IFN-beta

This leads to an interferon response

  • Induce resistance to viral replication in all cells
  • Increase expression of ligands for receptors on NK cells
  • Activate NK cells to kill virus-infected cells
70
Q

What are interferons?

A

Cytokines

  • Reduce viral replication
  • Prevent cell division
  • Induce apoptosis
  • Activate NK cells, T cells, macrophages
  • Released by diseased or stressed cells
  • Intracellular infection
  • Cancer

*Release by leukocytes

71
Q

What are the types of interferons?

A

Type I
-IFN-alpha, beta, epsilon, kappa, omega

Type II
-IFN-gamma

Type III
-IFN-lambda

72
Q

Interferons activate what immune cells?

A

NK cells

Type I interferon drives proliferation of NK cells and then drives differentiation of NK cells into cytotoxic effector cells

Effector NK cells kill viral-infected cells via inducement of apoptosis

73
Q

T/F - Macrophage and NK cells are regulated bidirectionally.

What does this mean?

A

TRUE

Macrophage activated by viral infection and secretes cytokines thereby recruiting and stimulating NK cells

The macrophage and NK cells form a synapse, and NK cells proliferate and differentiate into effector NK cells and secrete IFN-gamma

IFN-gamma binds to its receptor on macrophages and activates them to increase phagocytosis and secretion of cytokines

74
Q

NK cells regulate ___________ cell recruitment of adaptive immunity.

A

Dendritic

75
Q

Tell me more about dendritic cell recruitment.

A

Dendritic cells locally activate NK cells

This is a checkpoint in the adaptive immune system

-Large NK response
—Dendritic cell presentation inhibited

-Small NK response
—Dendritic cells activated

76
Q

T/F - When NK cells outnumber dendritic cells, they can kill the dendritic cells.

A

TRUE

77
Q

When NK cells are less numerous than dendritic cells, what happens?

A

They drive the dendritic cells to mature into the form that initiates adaptive immunity

78
Q

T/F - Granulocytes protect local tissues (unless degranulation occurs) and are predominant in tissues, but rare in the blood.

A

TRUE

79
Q

What are the common granulocytes?

A

Neutrophils

Mast cells

Eosinophils

Basophils

80
Q

What do the granulocytes do?

A

Express PRRs

Degranulate when activated

Respond to parasitic organisms

Responsible for initiating type I hypersensitivity
—*Allergic reactions

81
Q

What granulocytes is responsible for allergies?

A

Mast cells

*Also do expulsion of parasites via degranulation, especially histamine

82
Q

Eosinophils do what?

A

Kill antibody-coated parasites thru release of granule contents

83
Q

What do basophils do?

A

Control immune responses to parasites

Host And Defense - Exam 2 (16 decks)

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