INSTRUCTOR: This patient's cold is caused by rhinoviruses, shown here in red, that entered her nasal passages and escaped the first line innate defenses such as mucus and cilia. Some of these rhinoviruses entered the respiratory epithelial cells, where they replicated, releasing more rhinoviruses into the patient's nasal passages and tissue fluids. In the tissue fluids, cells of the second line of innate defense, such as this dendritic cell, carry out surveillance for anything that appears foreign. Dendritic cells engulf the rhinovirus within an endosome. The endosome fuses with a lysosome, whose enzymes digest the rhinovirus. The resulting rhinovirus fragments are called epitopes. The dendritic cell then attaches the rhinovirus epitopes to presentation molecules called MHC-II. This complex folds outward so that it sits on the outside of the dendritic cell membrane. The dendritic cell then enters a lymphatic vessel and travels to a nearby lymph node. Here, the dendritic cell, part of the innate defenses, encounters a helper T cell, which is part of the adaptive defenses. The T Cell Receptor, or TCR, of this helper T cell recognizes the rhinovirus epitope, while the CD4 glycoprotein associated with the TCR recognizes the MHC-II. The dendritic cell then stimulates activation of this helper T cell. Adaptive defenses help to control the current infection, but also provide immunity against future infections by the same rhinovirus. They are carried out by two types of lymphocytes, B cells and T cells. Immature B cells conduct surveillance in the lymph nodes using B Cell Receptors, or BCR, to recognize only one specific epitope. The BCR on the left does not recognize the rhinovirus, but the BCR on the right does, and this B cell is selected for activation in a step called clonal selection. The selected B cell takes in the rhinovirus, degrades it, and presents the rhinovirus epitope with its MHC-II. Our mature helper T cell recognizes the rhinovirus epitope with its TCR and the MHC-II with its CD4. Then the helper T cell secretes chemical messengers known as cytokines that activate the B cell. The B cell proliferates and differentiates in a process called clonal expansion, resulting in two types of cell. Memory B cells carry the memory of this pathogen for many years. Plasma cells secrete antibodies that conduct surveillance for more rhinoviruses, grouping them together so they are easy targets for phagocytes. Antibodies in the blood and tissue fluids seek out free rhinoviruses. The antibodies neutralize the rhinovirus by binding to its surface molecules, thus preventing attachment to host cells. Antibodies are humoral defenses that target free pathogens. But what about the rhinoviruses that are already inside our patient's cells? Another type of adaptive defense cell called a cytotoxic T cell can locate and destroy rhinovirus-infected cells. It provides cell-mediated or cellular immunity. Let's return to our patient's lymph node to see how cytotoxic T cells become activated. The T cell receptor, or TCR, of this particular cytotoxic T cell is genetically programmed to recognize the rhinovirus epitope when presented by the dendritic cell. This time, the epitope is presented differently, with an MHC-I, which is recognized by a CD8 glycoprotein on the cytotoxic T cell. With the help of cytokines from a nearby helper T cell, the cytotoxic T cell is activated, and clonal expansion occurs, resulting in some long-lasting memory cells ready for a subsequent exposure and many active Cytotoxic T cells, or CTLs, that leave the patient's lymph vessel to search for infected cells that present rhinovirus epitope with their MHC-I. The epitope is recognized by the TCR of the cytotoxic T cell, and the MHC-I is recognized by the T cells' CD8 glycoprotein. The cytotoxic T cell then secretes perforin molecules, which form channels in the infected cell's membrane. Granzyme, also from the T cell, passes through the perforin channels and activates enzymes that lead to apoptosis, the programmed death of the infected cell. The cytotoxic T cell then moves on to look for another infected cell. Together, the humoral and cellular defenses are the body's third line of defense in fighting a very specific pathogen. The humoral defenses, ultimately in the form of antibodies, conduct surveillance for rhinoviruses that are outside the body cells, in the patient's tissue spaces and bloodstream. The cellular defenses, in the form of cytotoxic T cells, search for rhinovirus-infected cells, inducing apoptosis when they are found. Memory T and B cells help our patient's body to recognize and more rapidly fight the same rhinovirus should it infect her again.