Question

Provide two examples of how the immune response to bacterial antigens or toxins can cause severe disease and pathology. For each example, name the disease, the bacterial species, the corresponding bacterial toxin or antigen associated with the disease, and the immune response driving the pathology.

Answer 1

•AIDS

Primary immunodeficiencies (PIDs) are due to genetic defects that compromise innate and/or adaptive leukocytes or the complement system, whereas secondary immunodeficiencies have an external cause, such as malnutrition or infection with HIV. PIDs are treated by restoration of the missing immune component via immunoglobulin replacement therapy, enzyme replacement therapy, or HSCT. Somatic gene therapy is another therapeutic possibility but remains experimental. The retrovirus HIV causes AIDS in humans, and although treatment has improved greatly, development of an effective vaccine remains elusive. Interaction of HIV gp120 with CD4 and CCR5 or CXCR4 allows viral entry into macrophages, DCs and CD4+ T cells, followed by provirus integration into the genome. When the infected host cell is stimulated, viral transcription and translation produce virions that bud from the cell prior to its death. HIV-specific antibodies and CTLs are insufficient to contain the virus. If untreated, HIV causes mononucleosis-like illness followed by asymptomatic latency, viral reactivation, and then death due to opportunistic infections or malignancy. Treatment with antiretroviral drugs extends life but does not eliminate HIV. Factors confounding HIV vaccine development include antigenic variation, T cell depletion, and a lack of suitable animal models.

•Human T cell Lymphocytotropic virus (HTLV-1)

Infection by the HTLV-1 induces activation and intense cellular proliferation of infected T lymphocytes. This phenomenon is related mainly to the function of the virus' Tax gene, whose property is to transactivate IL-2 and IL-2-receptor genes. These T-cell proliferation anomalies may lead to the appearance of leukemia in adult T cells. Indiscriminate cell proliferation may also provoke an expansion of self-reactive T cells and accentuated secretion of pro-inflammatory cytokines like TNF-alpha. These abnormalities may associate with cutaneous and neurological tissue lesions.23

Owing to the strong Th1 cell activation in HTLV-1 infection, there is reduced production of IL-4 and IL-5, and a drop in IgE synthesis, in mastocytes and in eosinophil activation. Both these components are features of the protective response against helminthes. Accordingly, there exists a higher prevalence of schistosomiasis and strongyloidiases in patients infected by HTLV-1.24 There may also be a dissemination of S. stercoralis with severe forms of strongyloidiasis.