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IAHI Block 1 > 8 - Cytokines and Soluble Immune Mediators > Flashcards

8 - Cytokines and Soluble Immune Mediators Flashcards

1
Q

What are cytokines?

A

Principal mediators of communication between cells of the immune system.

Cytokines are proteins produced and secreted by different cell types.

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2
Q

Cytokines and their receptors are products of _____ encoded genes.

A

Germ-line.

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3
Q

What happens when a Toll-like receptor interacts with a bacterial or viral molecule?

A

The TLR signals the activation of TF NFKB pathway and transcription of additional pro-inflammatory genes.

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4
Q

What cytokines are downstream of the pathogen encounter and NFKB activation?

A

Secretion of:
TNF-alpha
IL-1
IL-6

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5
Q

What causes a neutrophil influx after the pathogen encounter and NFKB activation?

A

G-CSF and GM-CSF: induce proliferation in the bone marrow

IL-8: chemotactic, calls in circulating PMNs

Chemokines

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6
Q

What is the function of chemokines?

A

Function in a cell-contact independent manner.

They form a gradient to which PMNs are attracted.

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7
Q

What do chemokines CC, CXC, and CX3C do?

A

Secreted by macrophages, epithelial, and endothelial cells to promote the migration of PMNs and other lineages into the site of infection.

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8
Q

Inconcert with TNF-alpha and IL-1, chemokines promote four stages of leukocyte extravastation. What are these stages?

A
  1. Rolling
  2. Integrin activation by chemokines
  3. Stable adhesion
  4. Migration through endothelium into ECM of tissue
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9
Q

Is T cell activation cell-contact dependent or independent?

A

Cell-cell contact dependent.

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10
Q

What is the function of IL-2 in T cell activation?

A

It’s a cytokine that provides autocrine, cell-contact independent pro-proliferative feedback to the Th cell producing it.

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11
Q

What are the defining cytokines that cause Treg cell differentiation?

A

TGF-beta and IL-10

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12
Q

What is the defining cytokine that cause Th1 cell differentiation? What does this cell type protect against?

A

IFN-gamma

Intracellular pathogens.

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13
Q

What are the defining cytokines that cause Th2 cell differentiation? What does this cell protect against?

A

IL-4, IL-5, and IL-13

Parasites (helminths)

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14
Q

What are the defining cytokines that cause Th17 cell differentiation? What does this cell type protect against?

A

IL-17 and IL-22

Extracellular pathogens

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15
Q

What are the APC derived signals that influence the differentiation of Th cells? What is the role of each?

A

IL-12: promotes Th expression of IFN-gamma (Th1)

TGF-beta: produced by many cell types, including APCs. Promotes development of Treg cells.

IL-10: promotes Treg pathway.

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16
Q

What occurs if there are no APC cytokines by Th cells?

A

It will default to a Th2 cell.

17
Q

What are the Th derived signals involved in Th cell differentiation?

A

IFN-gamma: provides autocrine signal to promote Th1 gene expression. Suppresses expression of IL-4.

TGF-beta and IL-10: autocrine signal to promote further Treg development

IL-4 and IL-5: promotes autocrime skewing towards TH2

18
Q

Th1 cells are optimal for activating ______ to kill _____ pathogens.

A

Th1 cells are optimal for activating macrophages to kill intracellular bacterial pathogens.

19
Q

Th2 cells evolved primarily to eliminate ______ pathogens. Many people have Th2 cells that are directed at _____?

A

Eukaryotic pathogens (helminths).

Many people have Th2 cells that are directed at innocuous materials such as pollen and gluten, causing allergy.

20
Q

How are B cells activated?

A

Through antigen-induced clustering of membrane Ig receptors.

Triggers signals that are transduced by signaling molecules.

21
Q

How do helper T cells activate B cells?

A

They express CD40L and secrete cytokines that activate B cells causing proliferation and differentiation.

22
Q

What are the four isotypes that B cells make and the function of each?

A

IgM: complement activation

IgG: Fc receptor dependent phagocyte responses; complement, activation

IgE: immunity against helminths; mast cell degranulation

IgA: mucosal immunity

23
Q

What is the function of FcyRI (CD64) receptors? Where are they found?

A

Bind to antibodies and activate phagocytosis.

On macrophages, neutrophils, and eosinophils.

24
Q

What is the function of FcyRIIA (CD32) receptors? Where are they found?

A

Bind antibodies and activate phagocytosis. Also play a role in cell activation.

On macrophages, neutrophils, eosinophils, and platelets.

25
Q

What is the function of FcyRIIB (CD32) receptors? Where are they found?

A

Bind antibodies and function in feedback inhibition of B cells and attenuation of inflammation.

On B lymphocytes, DCs, mast cells, neutrophils, and macrophages.

26
Q

What is the function of FcyRIIIA (CD16) receptors? Where are they found?

A

Bind antibodies and function in antibody-dependent cellular cytotoxicity (ADCC).

Found in NK cells.

27
Q

What is the function of FcERI receptors? Where are they found?

A

Bind antibodies and function in activation (degranulation) of mast cells and basophils.

Mast cells, basophils, and eosinophils.

28
Q

In general, what happens when a microbe binds to an Fc receptor?

A

The microbe is phagocytosed and killed.

29
Q

Granulocyte degranulation is regulated by _____.

A

FCERI.

IgE binds to its cognate antigen while the Fc portion of the antigen binds to the FCERI receptor.

30
Q

What three soluble signals are found in granulocyte granules? What is the function of each?

A
  1. Histamine: vasoactive amine stored in mast cells and causes increased vascular permeability and contraction of bronchial and smooth muscles
  2. Prostaglandin D2: activate GPCRs on smooth muscle and act as vasodilator and bronchoconstrictor, promotes PMN chemotaxis
  3. Leukotriene C4: cause prolonged broncho-constriction
31
Q

What is the complement cascade pathway triggered by?

A

Binding of complement proteins to the Fc portion of the antibody on the microbial surface.

Is FcR-independent.

32
Q

What is antibody directed (B cell) phagocytosis dependent on?

A

FcYRI-recognition of IgG

33
Q

What is antibody-directed cytotoxicity dependent on?

A

FcYRIIIA recognition of IgG

34
Q

Where is interferon-gamma found? What is its action?

A

NK cells and T lymphocytes

Activation of macrophages and stimulates some antibody responses

35
Q

Where is Type I IFNs (alpha and beta) found? What is their action?

A

IFN-alpha is in DC cells and macrophages.

IFN-beta is in fibroblasts.

In all cells they cause an anti-viral state and increase class I MHC expression.

Also activate NK cells.

36
Q

Where is IL-15 found? What is it’s action?

A

Found in macrophages.

NK cell proliferation and T cell proliferation

37
Q

Where is IL-18 found? What is its action?

A

Macrophages

Causes IFN-gamma production in NK cells and T cells.

IAHI Block 1 (19 decks)

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