Chapter 41

1. Innate immunity is nonspecific, acts rapidly, and recognizes broad classes of molecules. Adaptive immunity is specific, acts more slowly, and is longer lasting.

2. The TLR pathway is involved in innate immunity to bacterial infections. Bacteria have molecules that act as pathogen-associated molecular patterns (PAMPs), and these normally activate the TLR pathway which results in white blood cells producing cytokines and other defensive molecules. If this does not occur, people will be especially susceptible to bacterial infections.

3. The genomes of both the insect and the human would have genes for innate immunity, such as barriers and the TLR pathway, but only the human would have genes for adaptive immunity: antibodies, T cell receptors, and T and B cells.

1. The physical barrier of skin prevents infection. Mucus traps and removes bacteria so they cannot infect. Lysozyme hydrolyzes bacterial cell walls. Defensins insert into the bacterial cell membranes, rendering them leaky. Once below the skin, the bacteria come in contact with complement proteins, which provoke phagocytosis, and phagocytes that ingest and destroy the bacteria.

2. The bacterium has an arrangement of atoms on its molecules called PAMPs. These are recognized by receptors on the human body cells, and they initiate a response. Dust particles lack PAMPs.

3. The splinter initiates the inflammatory response. See Figure 41.5.

1. Humoral immune response: Free virus binds to B cells already making antibodies that react with viral antigens (recognition). These B cells are selected to divide and form a clone. The clone produces more antibodies against the virus. These antibodies bind to free virus in the bloodstream, and phagocytes ingest and hydrolyze the virus–antibody complexes.

   Cellular immune response: Virus infects cells in the respiratory tract. Some of these cells break down the viral proteins and present fragments on their surfaces (antigen presentation). T cells with a T cell receptor that can bind to the viral fragment bind to the antigen-presenting cells. These T cells stimulate the formation of cytotoxic T cells that can then kill the virus-infected cells.

2. The older people had memory cells that could make antibodies to bind to the 1918 flu strain. Since the 1918 flu strain was similar to the 2009 virus, these people were able to mount a strong immune response to the 2009 virus.

3. Vaccines are inactive antigens that still provoke an immune response. Vaccination promotes a proliferation of clones that produce antibodies (B cells) or T cell receptors (T cells) that bind to the injected viral antigen. Some memory cells remain. These will be needed to mount a massive immune response when the virus (with antigen) infects later.

1. See Figure 41.8. The antigen-binding site of an antibody has heavy and light chains in a unique three-dimensional configuration that binds a particular antigenic determinant. This is similar to an enzyme active site that binds a substrate. In both cases, binding is noncovalent. A major difference is in the result of binding: an antigen does not change its covalent structure when it binds to an antibody, whereas a substrate does change covalently when it binds to an active site.

2. Both immunoglobulins and T cell receptors have constant and variable protein regions, bind antigens, and have great variability in primary structure. T cell receptors are membrane proteins of T cells. Immunoglobulins can be either membrane proteins of B cells or secreted proteins in the blood.

3. There are thousands of different enzymes in an individual but potentially millions of different specific antibodies. Every cell in an animal has the genetic information for all enzymes. Each immunoglobulin, however, is derived from a unique gene (produced by DNA rearrangements) in a B cell or a clone.

1. By inhibiting T cell development, cyclosporine blocks T_H cell binding to transplanted cells. This stops cellular immunity from occurring, because T_H cell binding releases cytokines to attract T_C cells that would kill the transplanted cells.

2. Inside the infected cell, the virus is broken down into fragments, and some peptide fragments are displayed on the cell surface along with MHC protein (class I). A cytotoxic T cell displaying a T cell receptor that is specific for the peptide on the target cell binds to the target cell and initiates the cellular immune response.

3. Increased Treg activity would inhibit the cellular immune response, so the tumor would evade the adaptive immune system.

1. An antigen in peanuts binds to a B cell displaying an anti-peanut protein antibody. This causes production of a clone of plasma cells that initially make IgG and then switch to IgE. The IgE binds to mast cells, which release histamine, causing symptoms of distress.

2. Desensitization involves giving the person a small amount of peanut protein that provokes IgG synthesis but not IgE, so mast cells are not stimulated.

3. The anti-CTLA4 treatment for cancer removes inhibition of the T cell cytotoxic response to self antigens. This causes T cells to bind to and kill cancer cells. A side effect might be generalized autoimmunity.

4. Experiments might involve testing vaccinated people for neutralizing antibodies against HIV (humoral immunity) and looking for T cell activity against HIV-infected cells (cellular immunity).

1. While some people had low titers and other had high titers of anti-Russian flu antibodies, the general trend over time was for the titers to increase. As these people were exposed to the typical flu strains year after year, their anti-flu virus responses, including to the Russian flu, increased. This indicates that there were some general antibodies that bind to all flu strains.

2. There was little change in the antibody titers to CMV. Note that the y axis is much lower quantitatively in this case than the y axis for anti-flu titers. CMV has epitopes unrelated to the flu virus, so anti-CMV antibodies will not be made when a person is exposed to flu. The data indicate that the increase in flu virus strain immunity was flu virus–specific.

3. The antibodies that developed were mostly broadly reactive. These antibodies could be used to develop a vaccine that might work on old as well as new strains of flu virus.

1. By 3 weeks after the initial treatment, ADA and deoxyadenosine levels were normal. Weekly injections were probably needed because ADA gets broken down in blood serum.

2. Matched sibling and matched family donors had almost the same survival percentage: 87% and 88%, respectively. Matched unrelated donors were not nearly as successful, with only 67% survival. However, even this was better than the mismatched family donors, which had only 43% survival. The lowest survival of all was shown by mismatched unrelated donors: 29%. The survivorship of untreated patients might be similar to that with mismatched unrelated donors, but perhaps with even lower survival.

3. In gene therapy, hematopoietic stem cells are the cells that receive the genetic modification. Thus they are the only cells that will be able to produce and maintain normal levels of ADA. However, all cells produce ADA, because all cells undergo a certain level of DNA metabolism. ERT could keep other body cells from reaching dangerously high levels of deoxyadenosine.