Outsmarting the host: bacteria modulating the immune response

Pathogenic bacteria and their hosts have had a two-way conversation for millions of years. This interaction has led to many measure/counter-measure responses by the host and bacteria. The host immune response has developed many mechanisms to neutralize and remove pathogen bacteria. In turn pathogenic bacteria have developed mechanisms to alter and evade the host immune response. We will review some of the mechanisms utilized by bacteria to accomplish this goal. We will also examine the current state of understanding of Francisella tularensis mediated immune evasion.     

Fighting HIV with HIV

This article presents a new possibility for therapy and treatment of human immunodeficiency virus infection.     

HIV antibodies for treatment of HIV infection

The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure.     

Mechanisms of HIV persistence in HIV reservoirs

The establishment and maintenance of HIV reservoirs that lead to persistent viremia in patients on antiretroviral drugs remains the greatest challenge of the highly active antiretroviral therapy era. Cellular reservoirs include resting memory CD4+ T lymphocytes, implicated as the major HIV reservoir, having a half‐life of approximately 44 months while this is less than 6 hours for HIV in plasma. In some individuals, persistent viremia consists of invariant HIV clones not detected in circulating resting CD4+ T lymphocytes suggesting other possible sources of residual viremia. Some anatomical reservoirs that may harbor such cells include the brain and the central nervous system, the gastrointestinal tract and the gut‐associated lymphoid tissue and other lymphoid organs, and the genital tract. The presence of immune cells and other HIV susceptible cells, occurring in differing compositions in anatomical reservoirs, coupled with variable and poor drug penetration that results in suboptimal drug concentrations in some sites, are all likely factors that fuel the continued low‐level replication and persistent viremia during treatment. Latently, HIV‐infected CD4+ T cells harboring replication‐competent virus, HIV cell‐to‐cell spread, and HIV‐infected T cell homeostatic proliferation due to chronic immune activation represent further drivers of this persistent HIV viremia during highly active antiretroviral therapy.     

Pediatric HIV

The experiences of several HIV-infected children are highlighted to illustrate the importance of parents' and guardians' understanding the need for treating their HIV-infected children. Children face the same treatment issues as adults, but sometimes react differently to medications, and may require treatment changes if problems occur. Healthcare providers agree that HIV-infected children live longer and avoid illness when treated with HIV drugs. Those on no therapy become more withdrawn, miss school more often, and become increasingly dependent on their guardians. Theoretically, children may be able to achieve more immune cell restoration than do adults whose nervous and immune systems are mature. Children who are HIV-treated have shown considerable growth and development compared to untreated children who may develop complications such as cancer. Early HIV treatment before age one may lessen disease severity. A list of resources for parents and guardians is provided.     

Overview of HIV

This article provides an overview and reviews the HIV pandemic, the basic biology and immunology of the virus (e.g., genetic diversity of HIV and the viral life cycle), the phases of disease progression, modes of HIV transmission, HIV testing, immune response to the infection, and current therapeutic strategies. HIV is occurring in epidemic proportions, especially in Sub-Saharan Africa. In the US, men who have sex with men account for over half of AIDS diagnoses; racial and ethnic minorities are disproportionally affected. Factors influencing the progression and severity of HIV infection include type of immune response, coinfection (e.g., another sexually transmitted infection, including hepatitis B or C), age and behavioral and psychosocial factors. Antiretroviral therapies can achieve reduction in blood levels of the HIV virus below the limits of detection by current technology. However, effective treatment requires adherence to therapy. Patient failure to adhere to treatment regimens results in detectible circulating virus and in HIV disease progression, and is the primary cause of drug resistance. In addition to research on the immunology and virology of the disease, other studies focus on behavioral and psychosocial factors that may affect medication adherence and risk behaviors.     

Modeling HIV risk

OBJECTIVE: To provide HIV risk estimates for specific local population subgroups using an HIV risk index combining HIV risk behaviors, prevalence rates, and transmission probabilities. METHODS: A sample of 270 individuals was studied. Respondents described sexual and injection risk behaviors and partners in the previous 30 days. An HIV risk index was computed for each individual, combining reported sexual and injecting risk behaviors, HIV prevalence estimates for partners and HIV transmission probabilities for each of the risk behaviors. Partner HIV prevalence rates were estimated from a national sample, and HIV transmission probabilities were obtained from previously published studies. RESULTS: Projected risk estimates were found to differ a great deal within major demographic categories. Highest 10-year risk was found among African-American male gay injectors (72%) and the lowest among white male heterosexual noninjectors (<.01%). CONCLUSIONS: The method used here for estimating HIV risk can be calculated for specific at-risk population subgroups of any size and composition, including individuals. By understanding which specific subpopulations are at risk, specific interventions and public health campaigns may be better targeted.