Exam 13: Failures of Host Defense Mechanisms

Studies performed in mice have revealed one important component affecting the altered immune response in individuals undergoing malnutrition or starvation. In these studies, mice were placed on a starvation diet for several days, and then immunized with a protein antigen in an adjuvant. One group of starved mice were given injections of 'compound X' for 48 hours, starting at the time of immunization. Seven days later, draining lymph nodes were isolated, and T cell responses were measured in vitro following stimulation with antigen. The results are shown in Figure . 'Compound X' is most likely:

Individuals with a complete absence of B cells and antibodies, such as patients with XLA, show a limited range of susceptibilities to infection rather than a global immunodeficiency to all categories of pathogens. For example, XLA patients show increased susceptibility to pyogenic bacterial infections, as antibody binding to these microbes is critical for their uptake and destruction by phagocytes. Clinicians caring for these patients are advised regarding their vaccinations, some of which could be highly dangerous to the antibody-deficient patient. In particular, XLA patients should never receive:

Listeria monocytogenes is a bacterial pathogen that causes a variety of diseases including gastroenteritis, encephalitis, and sepsis. The bacterium has evolved a strategy to replicate in the cytosol of macrophages, and to spread from one macrophage to another using the host's actin machinery to facilitate direct transfer between cells, thereby avoiding the extracellular space. This unique lifestyle of L. monocytogenes is dependent on the bacteria encoding enzymes that:

HIV-infected patients that progress to AIDS suffer from a variety of opportunistic infections that rarely cause disease in healthy individuals. In addition, many of these patients acquire malignancies, such as B-cell lymphomas or Kaposi's sarcoma. A common feature of these two malignancies is that they are:

The population of HIV viral variants circulating in the human population is extremely diverse, a phenomenon that contributes to the difficulties in generating an HIV vaccine. However, within a given individual, all HIV viruses are genetically identical.

Muckle-Wells syndrome is an autosomal dominantly inherited disease due to mutations in NLRP3. Individuals with this disease suffer from episodes of fever, as well as urticarial rash, joint pains, and conjunctivitis. What is the explanation for the beneficial effects of anakinra (IL-1 receptor antagonist) treatment in these patients?

Individuals with defects in ubiquitously expressed DNA repair proteins have a form of SCID known as RS-SCID (radiation-sensitive SCID). Studies have shown that, in addition to immune deficiencies, these patients have an increased rate of cancer. Yet, in general, they are diagnosed first based on their immunodeficiency disease, not on their susceptibility to getting cancer. This is due to the fact that:

In 1918, a worldwide epidemic of influenza A resulted in the deaths of 40-50 million people. This strain of influenza A, known as H1N1-referring to the genotypes of the viral surface proteins, hemagglutinin (H) and neuraminidase (N)-was shown to be derived from an avian virus that adapted to infect and grow in human cells. Interestingly, by 1957, the H1N1 strains of Influenza A had completely disappeared from the human population, to be replaced by new strains (H2N2) that contained three gene segments from avian origin. The most likely explanation for the disappearance of the early twentieth century form of H1N1 Influenza A virus is:

Antiretroviral drugs are effective at blocking HIV replication in infected individuals, and in reducing the rate of HIV transmission. Physical barriers to transmission have also been shown to be effective at blocking HIV transmission. An additional strategy for reducing the rate of new HIV infections in high-risk populations utilizes a strategy to prevent the virus from establishing a permanent infection, once an individual has been exposed. This strategy utilizes:

A small group of HIV-infected individuals are known as 'elite controllers.' These individuals have HIV viral RNA copy numbers that persistently remain <50 copies/ml of plasma. Studies examining the immune response to the virus in these individuals would likely reveal:

In the case of HIV infection by sexual transmission, a key step in the establishment of disseminated HIV infection is the replication of the virus in regional lymph nodes draining the mucosal site of initial virus entry. The ability of the virus to spread from the mucosa to the regional lymph node is made possible by:

Unlike defects in antibodies or T cell functions, defects in complement components often lead to autoimmune-like symptoms, rather than to increased susceptibility to infections. This is because:

One group of immune deficiency diseases is caused by an inability of CD8 effector T cells to kill virus-infected target cells, due to defects in cytotoxic vesicle exocytosis. Because of the inflammatory response that accompanies a normal virus infection, together with the prolongation of this response due to the inability to control the infection, patients with these disorders suffer from tissue damage caused by the infiltration of effector CD8 cells and activated macrophages into multiple organs. In addition, a subset of these patients also show increased susceptibility to extracellular and intracellular bacterial infections. This is because:

One HIV vaccine trial provided some small measure of hope for the development of an effective HIV vaccine. This vaccine, known as RV144, was administered to a high risk population in Thailand, and reduced new infections by ~30%. To address the mechanism of immune protection correlating with vaccine efficacy, a series of studies were performed. In one study, total IgG antibodies from four non-infected vaccinees were isolated and were mixed with HIV-infected cells plus peripheral blood lymphocytes from healthy unrelated donors. As a control, IgG antibodies were purified from four donors receiving the placebo, rather than the RV144 vaccine. Six hours later, lysis of the HIV-infected target cells was assessed, as shown in Figure Q40). Figure Q40) The immune mechanism that correlates with protection based on these data is:

A mutant mouse line (Mutant-X) is discovered that is defective in generating IgG or IgA antibody responses to immunization with the inactivated influenza A virus vaccine. As a first step in determining the gene responsible for the immunodeficiency, T lymphocytes and B lymphocytes are separately isolated from wild-type or Mutant-X mice and mixtures of cells are transferred into Rag-deficient recipients, which are then immunized with the Influenza A vaccine as shown in Figure. Fourteen days later, serum from the immunized mice is collected, and tested for anti-influenza IgG and IgA antibody titers. The results are shown in Figure : mice is:

Evidence indicates that HIV-1 and HIV-2 originated in non-human primates, and only made the jump to infecting humans in the early twentieth century. As a consequence, these viruses are not well adapted to co-exist in equilibrium with their human hosts.

Individuals that lack all T cells have the most severe form of immunodeficiency (SCID) and will not survive past their first birthday without a bone marrow transplant from a healthy donor. These individuals fail to make antibody responses to the normal childhood vaccines because:

Studies have shown that secondary lymphoid tissues are a major reservoir of HIV in infected individuals. In part, this is due to the high numbers of viral target cells expressing CD4, such as T cells, macrophages, and dendritic cells. Surprisingly, secondary lymphoid tissues were also found to contain large numbers of infectious virus particles in the form of immune complexes. A comparison of the viral species found in these immune complexes indicates that they include virus particles that have been retained for over a year. The cells responsible for this reservoir of infectious HIV are:

Malaria is caused by protozoan parasites, Plasmodium falciparum and Plasmodium vivax. These pathogens are transmitted when an individual is bitten by a Plasmodium-infected mosquito. This route of transmission:

HAART therapy is widely used in the US to treat HIV-infected individuals. This treatment is quite effective at inhibiting HIV replication, thereby preventing the progression to AIDS. However, HAART treatment is unable to completely eradicate all viral stores; consequently, patients must remain on this treatment indefinitely, as cessation of treatment leads to a rapid rebound in viral replication. One additional important side benefit of HAART treatment is its ability to: