The interaction between most antigens and antibodies is insufficient to stimulate immune responses. The antigen must be broken into small peptides and presented in conjunction with MHC II molecules by specialized APCs to the appropriate helper CD4 T lymphocytes. Antigen can also be processed as a part of the B-cell activation pathway. Most APCs belong to the mononuclear phagocytotic system (MPS; described in Chapter 6, Connective Tissue, page 185). APCs include macrophages, perisinusoidal macrophages (Kupffer cells) of the liver, Langerhans’ cells in the epidermis, and dendritic cells of spleen and lymph nodes. Two APCs that do not belong to the MPS are B lymphocytes and type II and type III epithelioreticular cells of the thymus.
To present an antigen to a helper T cell, the APC first processes the antigen intracellularly and then displays antigen peptides on its surface. Antigen processing begins when the APC endocytoses the antigen and breaks it down into 8 to 10 amino acid peptides. In the endosomal compartment of the APC, the peptides bind to MHC II molecules. The anti-gen–MHC II complex is then translocated to the plasma membrane of the APC and displayed on the cell surface (Fig. 14.9).
In addition to acting as APCs, macrophages perform other crucial functions in the immune response.
In addition to presenting antigens to both T and B lymphocytes, macrophages have other important, although nonspecific, functions in the immune response: conjunction with MHC II molecules to helper CD4
T lymphocytes.  They digest pathogenic microorganisms through lyso somal action in combination with the helper CD4
T lymphocytes. They secrete multiple cytokines including lymphokines, complement components, and interleukins, as well as acid hydrolases, proteases, and lipases.
After contact with an antigen, macrophages undergo an activation process characterized by multiple functional and morphologic changes. The macrophage increases in size, as do the number of lysosomes and cytoplasmic vacuoles. The  activated macrophage becomes avidly phagocytotic with a greater ability to lyse ingested pathogenic microorganisms (Fig. 14.10).
Activated macrophages destroy phagocytosed bacteria and foreign antigens.
Macrophages also play a vital role in sequestering and removing foreign materials and organisms that either do not provoke an immune response or are ingested but not  digested.
These include both organic and inorganic particulate materials (e.g., carbon particles), pigment (e.g., from tattoos), cellulose, and asbestos, as well as tuberculosis and leprosy bacilli and the organisms that cause malaria and other diseases. In these instances, macrophages often fuse to form multinucleate, foreign body giant cells called Langerhans’ giant cells that isolate these pathogens from the body.
Lymphatic vessels are the route by which cells and large molecules pass from the tissue spaces back to the blood.
Lymphatic vessels begin as networks of blind capillaries in loose connective tissue. They are most numerous beneath the epithelium of skin and mucous membranes. These vessels remove substances and fluid from the extracellular spaces of the connective tissues, thus producing lymph. Because the walls of the lymphatic capillaries are more permeable than the walls of blood capillaries, large molecules, including antigens and cells, gain entry more readily into the lymphatic capillaries than into blood capillaries.
As lymph circulates through the lymphatic vessels, it passes through lymph nodes. Within the lymph nodes, foreign substances (antigens) conveyed in the lymph are trapped by the follicular dendritic cells. The antigen exposed on the surface of follicular dendritic cells can be processed by APCs present within the lymph node.