Let's first look at hepatitis A, which is an acute disorder in which the immune response usually manages to prevent a long term problem.
Before the person actually has hepatitis, phagocytosis would be important while viruses are in the extracellular fluid. This would follow the sequence we have described for any pathogen. But once the person has hepatitis A, liver cells are infected, and macrophages and neutrophils cannot get at the virus inside the cells.
With infected cells, the pertinent innate mechanism now is the release of IFN-alpha and IFN-beta. These are released by any virally infected cell (and also macrophages) and induces an "anti-viral state", as we have discussed. There are a number of proteins on and in cells that act as sensors for viruses and start the process leading to the release of the interferon. For example, there is a specific toll-like receptor that responds to viruses and a number of proteins inside the cytosol that respond, for example, to viral RNA. Recall also that natural killer cells can cause apoptosis of infected cells and in this way slow viral infections before the adaptive immune response begins. A low number of MHC I molecules on infected cells is an important factor activating the natural killer cells.
After one to two weeks, the adaptive, specific immune mechanisms begin and include both B cells and T cells. B cells at first make IgM and then eventually IgG. Both act as opsonins for phagocytosis for any viruses released into the extracellular spaces and provide immunity for decades, if not life. Also, IgA may provide mucosal immunity. In addition, cytotoxic T cells develop. These, of course, are CD8+ with T cell receptors that bind viral antigen on MHC I molecules on the surface of virally infected cells and induce apoptosis. It is this apoptosis and other immunological action that cause the usual flu-like symptoms, although there may be no apparent symptoms, especially in children. In low income countries, most adults have the IgG antibodies, while most adults in high income countries do not, unless they have been vaccinated with the effective, safe vaccine.
The immune responses for hepatitis A, in general, are going to work, which is why the disorder is acute. But with hepatitis B and C these immune responses may well not be enough, and thus the infection becomes chronic with long-term repercussions.
It's interesting to note that chronic hepatitis is often treated with IFN-alpha. An important action of this cytokine is to increase the placement of MHC I molecules on the surface of cells. This makes it much easier for cytotoxic T cells to attack the cells in which the virus is so effectively hiding. As the liver cells are attacked, the patient at first becomes ill, a necessary effect if the infected cells are to be removed. Antiviral drugs are also given at the same time.
As you know, tuberculosis bacteria, after they have been phagocytized, have a mechanism through which they can prevent lysosomes from fusing with the phagosomes. Thus, they can remain alive in the phagosome. But at the same time, a dendritic cell phagocytizes some of the bacteria and carries them to a lymph node where this leads to the creation of a clone of TH1 helper T cells.
Can you characterize the situation the dendritic cell "sees" that cause it to release cytokines that move the helper T cells in the TH1 direction (rather than the TH2 direction)?
Now some of the TH1 helper T cells travel out to the location of the macrophages and bind to them.
How does a helper T cels know which macrophage to bind to with its T cell receptor?
Once bound to the macrophages, the helper T cells release of IFN-gamma, which "activates" the macrophages.
Can you list some things that happen in the macrophage with this activation?
But if the activation of the macrophages does not wind up killing the bacteria, what tends to happen?
But if the bacteria are now walled off, why is the tissue damaged? Why might the patient, for example, be coughing up blood?
But if the formation of the granuloma is successful, with time the bacteria may remain contained, the stimulation by the helper T cells may decrease and the symptoms of tuberculosis disappear. However, later, if the immune system becomes comprised by old age or a disorder with immunodeficiency, the quiescent bacteria can emerge and cause secondary tuberculosis.
On the preceding page, we looked at how a particular viral disease, such as the H5N1 influenza A, readily can lead to a sequence of events that can be fatal. Now let's consider a bacterial example.
Anthrax is an example of a bacterium that causes considerable problems for the effector mechanisms. The spores of this bacterium are extremely hardy and can live for a long period in the environment. Upon entering the body, they are engulfed by macrophages and taken to lymph nodes. As this is going on, they enter their "vegetative" form and start dividing.
In the vegetative form, the capsules of the bacteria inhibit phagocytosis (various other pathogens have capsules too.) The population of the bacteria grow rapidly and in the lymph nodes causes hemorrhagic lymphadenitis. Soon the bacteria are entering the blood in large numbers. This by itself might trigger the issues discussed for fatal influenza.
But it is the toxins released by this rapidly growing population of bacteria that cause the main symptoms and death. One toxin acts on macrophages, and their response leads to a hyper-inflammatory response. One aspect of this is the release of oxygen radicals. But especially important (in one hypothesis), the macrophages release large amounts of the cytokines TNF-alpha and IL-1, which powerfully stimulate inflammation. Septic shock and disseminated intravascular coagulation can occur. Death often follows, typically within two days of the onset of symptoms.