This page is largely a review of the foregoing to help you organize your thinking.
One useful way of reviewing the various immunological mechanisms is to focus on the different possible locations in the body and analyze the mechanisms working in each situation.
Many pathogens infect the mucous membranes lining the digestive, respiratory, urinary or reproductive systems. Here they are isolated from phagocytes and some of the other potent mechanisms found in the internal environment. To deal with this, various innate mechanisms are found in secretions such as saliva, including the antibacterial enzyme, lysozyme, and antimicrobial peptides such as the defensins.
For the specific immune response, the key component is IgA. This is secreted into the lumen in the following way. First, in its dimeric form, it binds to the inner surface of epithelial cells lining the intestines and other mucosal surfaces. It is then engulfed by the cell by endocytosis. Next, it moves in a vesicle across the cell and is released into the lumen by exocytosis. IgA is also found in saliva and mother's milk. By binding to microbes, IgA prevents binding and causes agglutination. Without effective binding, the microbes are sweep along the mucous membrane and out of the body.
The epithelium also has lymphocytes embedded in it. These are a special population that respond mainly to a restricted set of antigens typically found in the lumen of the GI tract and respiratory airways. Most are CD8+ T cells that kill infected cells. But some secrete cytokines or activate macrophages.
Once a pathogen crosses a mucous membrane or the skin into the internal environment, phagocytosis by neutrophils or macrophages is its most likely fate. The various innate receptors and opsonins we have discussed play an important role. But by far the most effect opsonin is antibody in the form of IgG (or IgM). Agglutination by these antibodies helps phagocytosis as well.
The complement system also can be very effective, either via innate activation, IgG or especially IgM pentamer. Complement activation results in phagocytosis due in the opsonin C3b or sometimes lysis due to the membrane attack complex (MAC). Also, of course, the C3a and C5a peptides diffusing away serve as inflammatory paracrines and chemotactic factors
In the case of helminth worms, eosinophils become involved, especially if IgE is made. This tends to occur when the antigen presents the picture, as presented in class, that results in TH2 helper T cells forming. Eosinophils have some proteins in their vesicles that are chemically basic and somehow toxic to helminth worms. They also have myeloperoxidase in the vesicles, and the oxygen radical story is important here as well as in phagocytes. Mast cells also release inflammatory paracrines.
Here we are concerned mainly with viruses after they have infected a cell, although certain bacteria, such as listeria, and protozoa fall in this category too. One initial mechanism is to slow the spread of the infection with IFN-alpha and IFN-beta. These are released by infected cells and macrophages and induce in nearby cells an "anti-viral state", which includes the synthesis of certain proteins that slow viral replication and slow down cell growth and division.
But the ultimate solution is apoptosis of the infected cell. This is caused by natural killer cells of the innnate system and cytotoxic T cells of the specific immune system. Macrophages then engulf the remains. We did not attempt to discuss the molecules used by the natural killer cells to identify a virally infected cell. But with cytotoxic T cells, of course, it is the T cell receptor identifying peptide antigens on MHC I molecules.
In some cases, pathogens are phagocytized, but are able to evade the killing mechanisms of the phagocyte. The most important case here, of course, is tuberculosis. But there are a few others, such as leprosy. If the pathogen is not being destroyed inside the phagosome, then the "activation" of macrophages by TH1 helper T cells is the next step. The helper T cell travels to the infected tissue and recognizes the macrophage due to antigen displayed on an MHC II molecule. This should make sense since we are dealing with a phagocyte. Once attached to the macrophage, the most important cytokine released by the helper T cell is IFN-gamma. This increases the fusion of lysosomes with the phagosome and increases synthesis of oxygen radicals and other killing mechanisms. Cytokines are also released that cause inflammation and recruit further cells.
But if this turns out to be inadequate, then the remaining option is to wall off the pathogen through the formation of a granuloma. The bacteria might still be alive, but at least they are isolated. But there may be substantial inflammation and release of oxygen radicals and enzymes due to the ruckus caused by the helper T cells. Indeed, this is what causes the damage in tuberculosis, rather than the bacteria themselves.
The table below summarizes the mechanisms acting in each of the locations.
|Main Immune Response||Antimicrobial peptides
|IFN alpha and beta
Cytotoxic T cells