Cytokines

proinflammatory cytokines made by macrophages

-IL-1, IL-6, IL-8, and TNF-alpha (IL-10 and IL-12) -cause local and systemic effects

Cytokines made by Th2 cells

-IL-4, IL-5, IL-10, IL-6, CD40L, IL3, & GM-CSF

JAK/STAT pathway

-STAT 3 is required for IFNS, IL-5,6,10, LIF and hormones EGF, HGF, and BMP2 -*crucial for the development of Th17 cells*

What cytokines do mast cells make?

-TNF- α (might lead to the shock like reaction during systemic anaphylaxis). -TGF-β -IL-3 -IL-6 -IL-8, -IL-13 -GM-CSF.

Cytokine

-a mediator that is generated by cells of the immune system to influence growth, differentiation, or function of cell types inside and outside of the immune system. -generally soluble glycoproteins that bind to receptors on either the cell making the cytokine or neighboring cells. -generic term for over 180 immunomodulatory-signaling peptides

G-CSF

-cytokine that is the best at promoting the expansion of PMNs (neutrophils) -implicated in differentiation into neutrophils from -used during peripheral blood progenitor cell collection, they increase mobilization of hematopoietic progenitor cells into the peripheral blood for leukapheresis collection.

IL-12 Receptor deficiency

-decreased T cell differentiation -diminished Th response -decreased levels of IFN-gamma

CD40L

-made by Th1 cells -stimulates B cells to isotype switch: without it you don't make IgG, IgA, or IgE -induces macrophage activation (only from Th1 NOT Th2), and dendritic cells

Common gamma chain (gammaC)

-shared by IL-2, IL-4, IL-7, IL-9, and IL-15

NBT dye reduction Assay

-tests for the ability of the neutrophils to generate oxygen radicals and form hydrogen peroxide -useful in dx of CGD -mix PMNS, NBT, and PMN activator, prepare smears, and visualized blue formazan product

2 pathways that INF-gamma can come from

-the NK cells -the Th1 pathway (this allows it to become self-perpetuating

IL-4

Cytokines required for the production of IgE

Major activator of macrophages

IFN-gamma

What cytokines inhibits Th1

IL-10

Cytokines that DRIVE a Th1 response

IL-12

IL-____ is to T cells as IL-____ is to B cells

IL-2 is to T cells as IL-4 is to B cells

Cytokines made by Th1 cells

IL-2, IFN-gamma, TNF, CD40L (bound to the surface of the cell), IL-3, GM-CSF

Cytokines that DRIVE a Th2 response

IL-4, IL-13, IL-10

IL-6

Implicated in multiple myeloma

IL-3 and GM-CSF

Involved in hematopoesis

IL-12, type I IFNS (alpha and beta), and IL-15

NK activating cytokines

IL-15

NK cell maturation

Cytokines involved in hematopoiesis

SCF, IL-1, -3, -4, -5, -6, -7, EPO, GM-CSF, M-CSF, and G-CSF.

IL-3

differentiation factor for plasmacytoid dendritic cells.

M-CSF

implicated in the differentiation of myeloid stem cells into monocytes and macrophages

IL-2

source: *Th cells (naïve and Th1 and Th2)* • T cell: growth factor +++++ (CD4, CD8) *promotes both Th1 and Th2 proliferation* • NK cell: enhanced activity + • B cell: *growth factor induction of antibody production +/-* a monoclonal antibody against this would promote the greatest inhibition of T cell proliferation

IL-4

source: *Th2 cells* *basophils drive the initial flux*, mast cells/endothelial cells ? • B cell: proliferation and differentiation specifically the differentiation into *basophils* +++++ •*Increases antibody productions* • B cell: *IgE production and isotype switching to IgE*(and IgG1 production) • T cell: promotes Th2/inhibits Th1 pathway +++ • Mast cell and basophil: differentiation/activation (required for mast cells) • Goblet cells: proliferation and *increased mucus production* provides protection against *helminthic parasites* Inhibits macrophages and ROI More of an anti-inflammatory

IFN-alpha & Beta (Type I IFN)

source: Induced by virally infected cells • Antiviral +++++ • Increased MHC class I expression and presentation • NK cell: activation + • Macrophage: activation +

IL-6

source: Macrophage, endothelium, epithelium drives the generation of the myeloid lineage supresses Treg activites and in conjunction with TGF-Beta cna differentiation TH17 CD4+ T cells. • Endothelial cells: activation (inflammation, coagulation) • Hypothalamus: fever • Liver: synthesis of acute phase proteins • B cells: proliferation of antibody producing cells Part of the Lectin complement pathway. Bacterial induce macrophages to produce IL-6 which stimulates the synthesis of CRP and MBP which bind to components of bacterial or fungal cell walls.

IL-1

source: Macrophage, endothelium, epithelium • Endothelial cells: activation (inflammation, coagulation) • Hypothalamus: fever • Liver: synthesis of acute phase proteins

IL-12

source: Macrophages • T cells: promotes the differentiation of Th1 cells from naive CD4+ T cells. pathway • NK cell: activation and IFN- gamma synthesis

IL-8

source: Macrophages, Fibroblasts, Endothelial cells •Neutrophil: chemoattractant and activation • Endothelial cells: activation

IL-10

source: Macrophages, Th2 cells • Synthesized hours after IL-1, IL-6, IL-8 and TNF-α are produced *downregulates the immune response* • *Promotes Th2 functions*

TNF-alpha

source: Macrophages,T cells * • Endothelial cells: activation (inflammation, coagulation) • Hypothalamus: fever • Liver: synthesis of acute phase proteins • Killing of tumor cells • Muscle, fat: catabolism (cachexia, wasting)

TGF-Beta

source: Th cells, Tregs • Inhibits much of innate immunity • Anti-inflammatory • Recruits macrophages promoting clean up, fibroblast proliferation, and extracellular matrix deposition (healing & fibrosis) • Promotes sIgA • supresses the activities of T cells.

TNF

source: Th1 cells, CD8 cells, NK cells Causes changes in metabolism, causes wasting and depletion of fat stores • Macrophage: activation +++++ • NK cell: activation and enhancement of activities +++ • Antiviral ++ • Increased expression and presentation by class I & II MHC • T cell: promotes Th1/inhibits Th2 pathway • B cell: promotes class switching to IgG2 while inhibiting IgE Can kill virus infected as well as malignant cells

IFN-gamma

source: Th1 cells, CD8 cells, NK cells Type: Type 2 Part of the innate immune response (NK cells, and Th1 cells) • Macrophage: activation +++++ • NK cell: activation and enhancement of activities; *prompts macrophages to make IL-12 and drive the Th1 response* • Antiviral ++ (not as good as the others) • Increased expression and presentation by class I & II MHC • T cell: *promotes Th1*/inhibits Th2 pathway • B cell: promotes class switching to IgG2 while inhibiting IgE

IL-17

source: Th17 cells (and others) • Stimulates neutrophil recruitment • Stimulates cytokine/chemokine production by fibroblasts and epithelial cells • Dendritic cells induce Th17 cells by exposing naïve CD4 cells to high levels of TGF-Beta, IL-23, and IL-6 during activation

IL-13

source: Th2 cells • B cell growth and differentiation • Inhibits Th1 cells and macrophage inflammatory cytokines • Associated with asthma/allergy

IL-5

source: Th2 cells • Eosinophil: terminal differentiation and activation (provides protection against helminthic parasites)

IL-10

source: Th2 cells, Tregs, macrophages • T cell: promotes Th2/inhibits Th1 • Macrophage: inhibits proinflammatory cytokine • Neutrophils: increased apoptotic death of neutrophils (inhibits the inhibitors of neutrophil apoptosis

IL-7

supports proliferation and differentiation of developing lymphocytes in the primary lymphoid tissue (differentiates lymphoid stem cells into precursor T cells and precursor B cells)