Learning Objective:

Understand how Th1 cells activate macrophages and how macrophages, in turn, stimulate lymphocytes during cell-mediated immunity.

Th1 cells secrete IFN-γ

• The most important cytokine for activating macrophages.
• IFN-γ greatly enhances macrophage microbicidal activity, helping them kill ingested pathogens (especially intracellular organisms such as Mycobacterium tuberculosis).

CD40–CD40L interaction

• Provides a second activation signal:
• CD40L on Th1 cells binds CD40 on macrophages, further increasing their killing capacity.
• Dual signaling (IFN-γ + CD40L–CD40) produces “classically activated” macrophages (M1 phenotype).

Macrophages activate lymphocytes by:

• Antigen presentation on MHC II
• Costimulatory molecules (e.g., B7 binding CD28)
• Cytokine secretion (e.g., IL-12 promotes Th1 differentiation)

Activity

High-Yield Summary for Step 1

• Th1 → IFN-γ + CD40L → Macrophage activation → Enhanced intracellular killing
• Activated macrophages → Antigen presentation + IL-12 → More Th1 cells
• A positive feedback loop is crucial for defense against intracellular pathogens.

Activity