Introduction to Macrophages
- Macrophages are a type of white blood cell of the immune system.
- They engulf and digest pathogens, cancer cells, microbes, cellular debris, and foreign substances.
- Macrophages are involved in phagocytosis, which helps defend the body against infection and injury.
- They are found in all tissues and patrol for potential pathogens.
- Macrophages have various forms and names in different parts of the body.

Types and Development of Macrophages
- Macrophages can be classified as M1 macrophages, M2 macrophages, and regulatory macrophages.
- M1 macrophages increase inflammation and stimulate the immune system.
- M2 macrophages decrease inflammation and encourage tissue repair.
- Macrophages have different metabolic abilities depending on their type.
- Macrophages in healthy tissues can derive from circulating monocytes or be established before birth.
- Macrophages that accumulate at diseased sites typically derive from circulating monocytes.
- Monocytes enter damaged tissue and become macrophages through leukocyte extravasation.
- Macrophages can populate certain organs through proliferation.
- Macrophages have a longer lifespan compared to neutrophils.

Functions and Role in Innate Immune Response
- Macrophages are specialised in removing dying or dead cells and cellular debris.
- They play a crucial role in chronic inflammation and the early stages of inflammation.
- Macrophages can phagocytize neutrophils and foreign materials, such as pathogens.
- When a pathogen is ingested, it becomes trapped in a phagosome and is digested by enzymes.
- Macrophages are among the first cells to respond to a pathogen invasion.
- Tissue resident macrophages are among the first cells to respond to a pathogen invasion.
- They phagocytose incoming antigens and secrete proinflammatory cytokines.
- Phagocytosis of pathogens is an important function of macrophages.
- Macrophages can internalize antigens through receptor-mediated phagocytosis.
- They can also secrete proinflammatory cytokines to induce inflammation and recruit other immune cells.

Macrophage Recruitment of Immune Cells
- Macrophages recruit neutrophils to the infection site through chemokines such as CXCL1, CXCL2, and CXCL8.
- Other immune cells recruited by macrophages include monocytes, dendritic cells, natural killer cells, basophils, eosinophils, and T cells.
- Chemokines such as CCL2, CCL4, CCL5, CXCL8, CXCL9, CXCL10, and CXCL11 are involved in the recruitment of these immune cells.
- Macrophages, along with dendritic cells, help activate natural killer (NK) cells through secretion of type I interferons (IFN-α and IFN-β) and IL-12.
- IFN-γ produced by NK cells enhances the innate immune response by inducing a more aggressive phenotype in macrophages.

Macrophages and Adaptive Immunity
- Macrophages are professional antigen presenting cells (APC) that present peptides from phagocytosed antigens on MHC II molecules.
- Macrophages interact mostly with previously activated T helper cells or tissue resident memory T cells.
- Macrophages provide both signals required for T helper cell activation: antigen presentation through MHC II molecules and co-stimulatory signals through CD80 and CD86 molecules.
- These interactions allow T helper cells to achieve full effector function and receive survival and differentiation signals.
- Macrophages in lymphoid tissues are involved in preventing antigen entry into the blood and clearing debris from apoptotic lymphocytes.
- Macrophages can achieve different activation phenotypes through interactions with different subsets of T helper cells.
- The two major phenotypes are classically activated macrophages (M1 macrophages) and alternatively activated macrophages (M2 macrophages).
- M1 macrophages are proinflammatory, while M2 macrophages are mostly anti-inflammatory.
- T helper cells of the T1 subset play a role in classical macrophage activation against intracellular pathogens.
- Interaction between T1 cells and macrophages leads to the secretion of IFN-γ and upregulation of CD40 expression, activating macrophages and enhancing their ability to kill intracellular pathogens.