Lecture Notes: Cytokines and Chemokines

Introduction

• Previous discussions: cytokine receptors and chemokine receptors
• Current focus: cytokines and chemokines, and naming strategies
• Cytokines: Communication between immune cells, non-immune cells can also release them
• Chemokines: Guide migration and localization of immune cells

Cytokine Nomenclature

• Grouped into families based on structure
• Named with prefix/suffix indicating family + identifier (number/Greek character)
• Major families include:
  • Interferons (IFN-)
  • Tumor necrosis factor (TNF-)
  • Colony stimulating factors (CSF)
  • Interleukins (IL-): Communication between leukocytes, used widely

Varieties of Immune Responses

• Defined by cytokine and cellular profiles, tailored to fight different pathogens
• Named after helper T cells orchestrating the response

Th1 Cytokines

• Th1 Response: Against intracellular pathogens (viruses/bacteria)
  • Activates CD8 T cells, natural killer cells, macrophages
• Key cytokines:
  • IL-2: T cell survival, proliferation, differentiation
  • IL-12: Activates NK cells, polarizes Th1 cells
  • TNF-α: Cell death, pro-inflammatory effects
  • Lymphotoxin-α (LT-α): Similar to TNF-α, kills infected cells, activates macrophages
  • IFN-γ: Antiviral activity, activates macrophages

Th2 Cytokines

• Th2 Response: Humoral response with antibodies, response to helminths, allergies/asthma
• Key cytokines:
  • IL-4: Polarizes Th2 cells, promotes mast cell growth, stimulates eosinophils, activates B cells
  • IL-5: Drives eosinophil development
  • IL-13: Signals B cells to produce IgE
  • IL-25: Amplifies Th2 responses
  • IL-10: Enhances B cell activation, suppresses Th1 cytokines

Th17 Cytokines

• Th17 Response: Controls fungi and extracellular bacteria, recruits neutrophils
• Key cytokines:
  • IL-17: Stimulates chemokine IL-8, recruits neutrophils
  • IL-22: Acts on epithelial cells, promotes cell proliferation, tissue healing
  • IL-23: Polarizes Th17 cells

Regulatory T Cells (Tregs)

• Tregs: Dampens immune response, prevent tissue damage, autoimmunity
• Key cytokines:
  • IL-10: Regulatory functions
  • TGF-β: Tissue repair, anti-inflammatory, promotes Treg development

Chemokines

• Regulate cell movement and migration
• Promote cell adhesion, motility, and guide cell movement (chemotaxis)
• Important for lymph node organization

Chemokine Nomenclature

• Two major families: CC and CXC
  • CC: Two adjacent cysteines
  • CXC: Two cysteines separated by one variable amino acid
• L stands for ligand, R for receptor

CC Chemokines

• Induce migration of lymphocytes, monocytes
• Key chemokines:
  • CCL2 (MCP-1): Promotes Th2 immunity
  • CCL3 (MIP-1α): Recruits monocytes, promotes Th1 immunity
  • CCL4 (MIP-1β): Recruits monocytes, NK cells
  • CCL5 (RANTES): Recruits eosinophils, T cells

CXC Chemokines

• Promote neutrophil migration
• Key chemokines:
  • CXCL8 (IL-8): Recruits neutrophils
  • CXCL7: Released from platelets, activates neutrophils
  • CXCL1/2/3: Similar to CXCL7, released by endothelial cells, fibroblasts

Chemokines in Lymphoid Tissues

• Direct lymphocytes to specific locations
• Key chemokines:
  • CCL21: Recruits dendritic cells
  • CCL18/19: Recruit T and B cells
  • CXCL13: Recruits B cells to B cell zone

Conclusion

• Cytokines and chemokines allow nuanced immune responses
• Understanding these is essential to delve into specifics of immune response
• Next topic: Innate immunity