Cytokine and Chemokines

Th1 Cytokines

Th1 Cytokines

IL-2, IL-12, TNF-a, LT-a. LT-B, IFN-y

IL-2

Critical for T-cell survival/proliferation/differentiation

IL-12

Activates natural killer cells and helps polarize helper T-cells to be more Type-1 Like

TNF-alpha

Can cause cell death and has broad pro-inflammatory effects

LT-alpha

can signal in soluble form as a homodimer or membrane-bound form

LT-beta

Kills chronically infected cells, activated macrophages, lymphoid tissue development

IFN-y (gamma)

antiviral activity, activates macrophages, blocks polarization of type 2 helper T-cells

Th1 cytokine Response

generate a Type 1 immune system, promotes cellular immunity against intracellular (inside of cells) pathogens, geared toward the activation of CD8 T cells, Natural Killer/macrophages

Th2 cytokine response

Activate humoral responses (antibodies produced by B cells). Strong presence of Eosinophils, basophils and Mast cells. Response to helminths and promote wound healing/tissue repair. Responsible for the negative effects of allergies and asthma.

Th2 cytokines

IL-4, IL-5, IL-13, IL-25, IL-10

IL-4

Polarize helper T-cells to type 2 phenotype, promotes mast cell growth and development in the bone marrow, stimulates eosinophils and activates B cells

IL-5

Drives Eosinophil development in the bone marrow

IL-13

Signals B cells to make IgE antibodies

IL-25

Amplifies the Th2 response by inducing IL-4, IL-5 and IL-13 and activates type 2 innate lymphoid cells

IL-10

enhances B cell activation/antibody production and suppresses Th1 cytokine expression

Th17 response

Involves helper T cells which secrete IL-17. Controls fungi/bacteria via ability to recruit neutrophil response. Overly active Th17 response leads to irritable bowel syndrome

Th17 cytokines

IL-17, IL-22 and IL-23

IL-17

Stimulates production of chemokine IL-8 (CXCL8) which is a strong neutrophil chemoattractant

IL-22

Acts of epithelial cells in gut/skin/lung to promote cell proliferation and tissue healing and production of anti-microbial peptides

IL-23

helps polarize helper T-cells to Th17 phenotype

Treg (regulatory T cells) response

IL-10 and TGF-B

TGF-beta (tumor necrosis factor-beta)

Promotes tissue repair/wound healing. Has anti-inflammatory properties. Promotes Treg development. Inhibits B-cell proliferation. Inhibits activated macrophages

Chemokine and receptor difference

CCL2 (L stands for ligand) CCR2 (R stands for receptor)

CCL2 (MCP-1)

Promotes Th2 immunity and release of histamine by basophils

CCL3 (MIP-1alpha)

recruits monocytes/macrophages/neutrophils, promotes Th1 immunity

CCL4 (MIP-1beta)

recruits monocytes and natural killer cells

CCL5 (RANTES)

recruits eosinophils/T-cells/basophils, activates natural killer cells

CCL21

secreted by stromal cells to recruit dendritic cells

CCL18/CCL19

secreted by dendritic cells to recruit T/B to lymph nodes

CC chemokines function

induce migration of lymphocytes and monocytes

CXC chemokines function

induce migration of neutrophils

CXCL8 (IL-8)

recruits neutrophils to infected tissues

CXCL7

Released from activated platelets. Activates neutrophils, promotes angiogenesis

CXCL1, CXCL2, CXCL3

Promotes angiogenesis, activate neutrophils. Stimulate fibroblast proliferation. Released by endothelial cells/fibroblasts/monocytes

CXCL13

Secreted by follicular dendritic cells to recruit B cells to B cells zone by binding to CXCR5