Importance Of Cell-mediated Immunity Research Articles

Interferon-γ Induced by In Vitro Re-Stimulation of CD4+ T-Cells Correlates with In Vivo FMD Vaccine Induced Protection of Cattle against Disease and Persistent Infection

The immune defense against FMDV has been correlated to the antibody mediated component. However, there are occasions when some animals with high virus neutralising (VN) antibody are not protected following challenge and some with low neutralising antibody which do not succumb to disease. The importance of cell mediated immunity in clinical protection is less clear and so we investigated the source and production of interferon-gamma (IFN-γ) in re-stimulated whole blood of FMDV immunized cattle and its correlation to vaccine induced protection and FMDV persistence. We were able to show a positive correlation between IFN-γ response and vaccine induced protection as well as reduction of long term persistence of FMD virus. When combining this IFN-γ response in re-stimulated blood with virus neutralizing antibody titer in serum on the day of challenge, a better correlation of vaccine-induced protection with IFN-γ and VN antibody was predicted. Our investigations also showed that CD4+ T-cells are the major proliferating phenotype and IFN-γ producing cells.

Immunity to Cytomegalovirus

Cytomegalovirus is one of the most immunodominant antigens that are encountered by the human immune system. The human cytomegalovirus (HCMV) exhibits a broad cellular tropism and can infect most major organ systems and cell types. Immunologic control of HCMV replication includes several distinct categories of effector cells: natural killer cells, macrophages, B cells and T cells however virus-specific CD8+ and CD4+ T cells appear to play a pivotal role. The importance of cell mediated immunity against CMV is exemplified by the occurrence of severe and prolonged HCMV infection in immunocompromised individuals, including transplant recipients, late stage -HIV patients, congenitally infected neonates, elderly subjects and/or septic patients. Severely impaired T-cell function leads to viral reactivation and consequences are widely variable, ranging from asymptomatic infections to life-threatening situations. Monitoring of protective HCMV-specific immune response may serve as an early predictive marker for identifying individuals at high risk for HCMV disease prior to the detection of increased viremia. The identification of patients who are at high risk of CMV is a more complex challenge for the laboratory. Mainly HCMV specific T cell immunity, resp. enumeration of CD8+ HCMV specific T cells would be expected to correlate with the incidence of HCMV disease. Recently, it has become possible to enumerate antigen-specific CD8+ T cells by using tetramers. HCMVspecific cellular immunity by evaluating the activation capacity of CD8+ T cells to a mitogenic stimulus or whole HCMV antigen or HCMV peptides assessed by IFNγ ELISPOT or ELISA seem to be promising in the assessment of HCMV specific function/immunity. However the clinical utility of these assays will need to be evaluated.

Why vaccines are not the answer – The failure of V520 and the importance of cell-mediated immunity in the fight against HIV

The recent failure of Merck's HIV vaccine, V520, left the future of HIV vaccine research in question. The current article offers a possible explanation for the failure of V520 and explores a potential alternative to the vaccine approach. Vaccines prior to V520 were designed to evoke strong antibody-mediated immune responses to HIV; that is, the generation of antibodies to attach to and disable the HIV virus before it infiltrates host cells. V520 represents a misguided, though well-intentioned, effort to evoke a cell-mediated immune response to HIV; that is, immune activity aimed at identifying proteins associated with HIV after it infiltrates host cells. In the body, these two immune responses, antibody-mediated (for extracellular infections) and cell-mediated (primarily for intracellular infections), operate in a teeter-totter fashion. When one is activated the other is suppressed. Because HIV quickly infects host cells near entrances to the body, it requires a strong cell-mediated response to defeat, not an antibody-mediated response. The driving hypothesis of this article is that the antibody-mediated immune response triggered by V520 suppressed the ability of the body to mount the cell-mediated immune response necessary to protect against HIV and created a window of opportunity for HIV infection, particularly in subjects previously exposed to the adenovirus vector used in the vaccine. While the immune system uses antibodies to identify extracellular pathogens, it uses transfer factors to label infected host cells. Hundred of papers indicate that pathogen-specific transfer factors can be used to stimulate cell-mediated immunity against a wide variety of viruses. The available research, reviewed in this manuscript, suggests that HIV-specific transfer factors could prove extremely useful, far more useful than vaccines, in preventing and treating HIV infections.

Requirement for CD4(+) T lymphocytes in host resistance against Cryptococcus neoformans in the central nervous system of immunized mice.

The importance of cell-mediated immunity (CMI) and CD4(+) T lymphocytes in host resistance against Cryptococcus neoformans is well documented and is exemplified by the high susceptibility to progressive infection with this pathogen of AIDS patients with reduced CD4(+) T-cell numbers. Although much has been learned about the role of CMI in the clearance of C. neoformans from the lungs and other internal organs, less is known about the protective mechanisms in the brain, the organ most frequently involved with a fatal outcome of cryptococcosis. We hypothesized that host resistance mechanisms against C. neoformans in the central nervous system (CNS) were similar to those outside the CNS (i.e., gamma interferon [IFN-gamma], CD4(+) T cells, and others). To test this hypothesis, we used a murine model of cryptococcal meningitis whereby cryptococci are introduced directly into the CNS. In experiments where mice were immunized to mount an anticryptococcal CMI response, our results indicate that immunization induced protective mechanisms that could be detected in the CNS by inhibition of the growth of viable yeast cells. Flow cytometric analyses of leukocytes in brain and spinal cord homogenates revealed that T lymphocytes, macrophages, and neutrophils accumulated in C. neoformans-infected brains of immune mice. In vivo depletion of CD4(+) T cells, but not CD8(+) T cells, resulted in significantly reduced leukocyte accumulation in the brains of immune mice. Furthermore, depletion of CD4(+) T cells or neutralization of IFN-gamma exacerbated CNS infection in immune mice, suggesting a critical role for CMI mechanisms in acquired protection in the CNS.

Importance of Cell-Mediated Immunity in Marek's Disease and Other Viral Tumor Diseases

Cell-mediated immune (CMI) responses to viral tumor diseases are often used as examples of the importance of antiviral and antitumor immunity in chickens. Especially, reticuloendotheliosis virus (REV) and Marek's disease herpesvirus (MDV) are used as models to study the development of cytotoxic T-lymphocytes against viral and tumor antigens and activation of natural killer (NK) cells. Major histocompatibility complex Class I-restricted, antiviral cytotoxic T-lymphocytes expressing CD4–/CD8+ markers are induced after infection with REV. Thus far, this is the only example of Class I-restricted cytotoxic T-lymphocytes in chickens. Antiviral cytotoxic T-lymphocytes may be induced by infection with MDV or by vaccination, but conclusive evidence has not yet been provided. Antitumor responses have not been demonstrated against REV-induced tumors. Although Marek's disease is often used as an example for the importance of antitumor immunity, there is a lack of convincing data demonstrating antitumor immunity mediated by cytotoxic T-lymphocytes. Activation of NK cells by MDV infection or vaccination is probably an important part of CMI responses against Marek's disease viral antigens but not against tumor antigens.

Interactions of cytomegalovirus with the human immune system.

Infection of the normal host with human cytomegalovirus (HCMV) is followed by both humoral and cellular immune responses against this herpesvirus. The importance of cell-mediated immunity against HCMV is exemplified by the occurrence of severe and prolonged HCMV infections in individuals with congenital, iatrogenic, or acquired deficiencies of this arm of host immunity. In contrast, infection in most individuals with primary B cell disorders usually is not severe. The nature of different aspects of cell-mediated immunity, including cytotoxic T cell (CTL) responses and levels of natural killer cell (NKC) and antibody-dependent cellular cytotoxicity (ADCC) during infection, has been characterized in detail in susceptible populations. To a high degree, the presence or absence of CMV-specific CTL responses correlates inversely with the severity of infection, as do levels of NKC and ADCC activity. Clinical correlates of these immune responses will be discussed. In addition, recent observations implicating HCMV as an immunosuppressive virus will be presented.

Cell-mediated immunity in cat-scratch disease

The importance of cell-mediated immunity in cat-scratch disease (CSD) is suggested by the positive skin test reactions and granulomatous histopathology noted in patients with this disease. However, an earlier investigation found that lymphocytes from patients with CSD and control subjects were equally unresponsive in vitro to cat-scratch antigen. In contrast, we found that 16 patients with CSD had significantly increased lymphocyte transformation responses to cat-scratch antigen when patients were compared to control subjects. This cell-mediated immune response may be directed against nonviable bacteria in the involved lymph nodes and may be the major mechanism responsible for the granulomatous reaction and clinical features of CSD.

Trial of specific antigen-mediated leukocyte adherence inhibition test in patients with chronic active hepatitis and hepatitis B carrier.

In the pathogenesis of chronic active hepatitis, the importance of cell mediated immunity (CMI) has been emphasized. Leukocyte adherence inhibition (LAI) assay, which is one of the methods for analysis of the reaction of CMI, has been used to analysie the CMI of cancer patients.The authors tried the specific antigen-mediated LAI assay in 40 patients with chronic active hepatitis, 19 patients carriers of hepatitis B virus, and in the 5 persons who have no anti-HBs in spite of receiving vaccination against HBV, and these were compared with 7 normal control subjects who had been exposed to hepatitis B virus previously.The results were as follows: The NAI was 52.4±14 (mean ± standard deviation) in 7 normal control subjects who had been exposed to hepatitis B virus previously.The NAI was 20.6 ± 11 (mean ± standard deviation) in 40 patients with chronic active hepatitis. The value was significantly lower than that of the normal control group (P<0.001).The NAI was 49.7±17.8 (mean ± standard deviation) in 19 patients carriers of hepatitis B virus. The value was not significantly different from that of the normal control group (P>0.05).The NAI was 25.1±11 (mean ± standard deviation) in 5 persons who have no anti-HBs in spite of receiving vaccination against HBV. The value was significantly lower than that of the normal control group (P<0.05).In patients with chronic active hepatitis and hepatitis B virus carriers, we checked the LAI assay serially. The value of NAI was increased according to the improvement of clinical symptoms and normalization of transaminase, but the value of NAI was decreased according to the worsening of clinical symptoms and elevation of transaminase.

Dermatophyte antigens and cell-mediated immunity in dermatophytosis.

Recent advances in immunology have increased our present knowledge of host-parasite relationships in human dermatophytosis. Evidence is now accumulating regarding the importance of cell-mediated immunity (CMI) in the eradication of cutaneous infections. Thus, the main theme of this chapter will be cell-mediated responses and their different facets as expressed by delayed skin hypersensitivity reactions, in vitro lymphocyte reactivity, and to some extent T- cell function. These parameters will be considered in relationship to the clinical and mycologic aspects of dermatophyte infections in an attempt to establish the clinical significance of CMI. Furthermore, the important—but sometimes neglected—problems concerning the dermatophyte antigen and its production and standardization will be considered in some detail. All of these topics will be discussed using personal observations and previous research experience.

Effect of Corynebacterium granulosum immunopotentiation on the pathogenesis of herpes simplex virus type 2 in BALB/c mice.

Treatment of 4- to 6-week-old, 18- to 22-g male BALB/c mice with 0.6 mg of Corynebacterium granulosum resulted in a significant decrease in mortality due to challenge with herpes simplex virus type 2 (HSV-2). Optimal protection occurred when C. granulosum was injected 1 week before HSV-2 infection. C. granulosum-induced resistance to HSV-2 lasted up to 4.5 weeks. Studies involving immune spleen cell transfer and treatment with antilymphocyte serum demonstrated the importance of cell-mediated immunity in HSV-2 infection. However, C. granulosum protection was not transferable with spleen cells from C. granulosum-treated animals nor was C. granulosum treatment capable of completely overcoming the increased mortality which resulted from antilymphocyte serum treatment of HSV-2 infected mice. Under our experimental conditions, silica did not affect the mortality in BALB/c mice due to HSV-2 but significantly reduced the protective effects induced by C. granulosum. Attempts to transfer protection of HSV-2 challenge in suckling mice by using either glass-adherent or mixed peritoneal cells from either HSV-2-immunized or C. granulosum-treated animals were unsuccessful.