Local Humoral Immunity Research Articles

Immunological study of histologically non-involved jejunum during Crohn's disease: evidence for reduced in vivo secretion of secretory IgA

We studied the local humoral immunity of histologically non-involved jejunum in patients with Crohn's disease. Normal subjects and patients with ulcerative colitis served as controls. Jejunal fluid samples were collected during segmental jejunal perfusion, under an occluding balloon and the in vivo jejunal secretion of the following proteins was determined: albumin, orosomucoid, transferrin, alpha 2-macroglobulin, secretory component, monomeric and polymeric IgA, IgG, and IgM. The densities and number of IgA-, IgG-, and IgM-containing cells in the lamina propria of the jejunum were measured on perendoscopic biopsies. Jejunal secretion of polymeric IgA and the density of IgA-containing plasma cells in the lamina propria were significantly lower in patients with Crohn's disease than in both control groups. This abnormal intestinal immune response, which was not correlated to the activity of the disease, might be involved in its pathogenesis.

Mucosal immunization with recombinant heparin-binding haemagglutinin adhesin suppresses extrapulmonary dissemination of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in infected mice

It is generally accepted that cellular immunity plays a critical role in the protection against Mycobacterium tuberculosis, an intracellular pathogen. Recently, however, an increasing number of reports indicate the important contribution of humoral immunity against mycobacterial infection. Since M. tuberculosis establishes its primary lesion in the lung, induction of humoral immunity in the airway tract by mucosal immunization regime could provide protective immunity against tuberculosis. In this study, mycobacterial heparin-binding haemagglutinin adhesin (HBHA) was used as an immunization antigen because HBHA is an essential virulence factor required for the infection of lung epithelial cells and extrapulmonary dissemination of mycobacteria. The effects of intranasal immunization with a yeast-expressed recombinant (r) HBHA co-administered with a mucosal adjuvant cholera toxin (CT) on the induction of humoral and cellular immunity were examined, and its protective efficacy against pulmonary challenge infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) was evaluated. HBHA-specific antibodies were induced in serum and airway tract of immunized mice, which specifically recognized native HBHA expressed on M. bovis BCG. Th1-type immunity against mycobacterial antigens was also enhanced in the lung of immunized mice after pulmonary BCG infection. Furthermore, the immunization suppressed bacterial load in the spleen after pulmonary BCG infection. These results indicate that systemic and local humoral immunity induced by the HBHA-based mucosal vaccine impairs extrapulmonary dissemination, thus providing immune protection against mycobacterial infection.

No Evidence for Consistent Virus-Specific Immunity in Simian Immunodeficiency Virus-Exposed, Uninfected Rhesus Monkeys

Defining the immune correlates of the protection against human immunodeficiency virus type 1 (HIV-1) acquisition in individuals who are exposed to HIV-1 but do not become infected may provide important direction for the creation of an HIV-1 vaccine. We have employed the simian immunodeficiency virus (SIV)/rhesus monkey model to determine whether monkeys can be repeatedly exposed to a primate lentivirus by a mucosal route and escape infection and whether virus-specific immune correlates of protection from infection can be identified in uninfected monkeys. Five of 18 rhesus monkeys exposed 18 times by intrarectal inoculation to SIVmac251 or SIVsmE660 were resistant to infection, indicating that the exposed/uninfected phenotype can be reproduced in a nonhuman primate AIDS model. However, routine peripheral blood lymphocyte gamma interferon enzyme-linked immunospot (ELISPOT), tetramer, and intracellular cytokine staining assays, as well as cytokine-augmented ELISPOT and peptide-stimulated tetramer assays, failed to define a systemic antigen-specific cellular immune correlate to this protection. Further, local cell-mediated immunity could not be demonstrated by tetramer assays of these protected monkeys, and local humoral immunity was not associated with protection against acquisition of virus in another cohort of mucosally exposed monkeys. Therefore, resistance to mucosal infection in these monkeys may not be mediated by adaptive virus-specific immune mechanisms. Rather, innate immune mechanisms or an intact epithelial barrier may be responsible for protection against mucosal infection in this population of monkeys.

Essential role of Peyer's patches in the development of Helicobacter-induced gastritis

Helicobacter bacteria colonize in the stomach and induce strong, specific local and systemic humoral and cell-mediated immunity. Helicobacter binds to the host epithelial cells, directly triggering the recruitment of neutrophils. Local inflammatory processes in the gastric mucosa are followed by extensive immune cell infiltration, resulting in chronic active gastritis characterized by a marked infiltration of T(h)1 cytokine-producing CD4(+) T cells. The mechanisms underlying the development of T(h)1 cell-mediated chronic gastritis, however, are not clear. Peyer's patches (PPs), the major inductive sites for mucosal immunity in the gut system, might orchestrate Helicobacter-specific local and systemic humoral and cell-mediated immunity. To examine the roles of PPs in the development of Helicobacter-induced gastritis, we generated PP-null mice that normally develop well-organized lymphoid organs except for PPs and intra-gastrically infected the resulting PP-null mice with Helicobacter felis. PP deficiency severely impaired both the development of T(h)1 cell-mediated gastritis induced by Helicobacter and the production of anti-Helicobacter antibodies despite marked bacterial colonization of the gastric mucosa. Although PP deficiency did not impair the differentiation of Helicobacter-specific CD4(+) T cells into IFN-gamma--producing T(h)1 cells, Helicobacter-specific IFN-gamma--producing CD4(+) T cells in PP-null mice lacked the ability to migrate into Helicobacter-colonized gastric mucosa. These findings suggest that PPs have an important role in Helicobacter-specific local and systemic humoral and cell-mediated immunity, including the development of Helicobacter-induced gastritis.

Immunohistochemical characterization of Kisselev nodules (ectopic lymphoid follicles) in wild boar ( Sus scrofa L.)

This paper describes the histopathological features and cellular distribution of T lymphocytes (CD3), B cells (CD79), follicular dendritic cells (FDC) and macrophages (alpha-1-antitrypsin, lysozyme) in lymphoid aggregates (Kisselev nodules) found in the lung, kidney and liver of wild boar ( Sus scrofa L.). The distribution of immunoreactive cells, tested for antibodies, was similar to that found in the cortex of lymph nodes: lymphoid follicles with germinal centers mainly consisting of CD79 + B cells with sparse interfollicular tissue (CD3 + T lymphocytes). This finding and the association of these structures with helminthic infections suggests that local humoral immunity is central to the organism’s response to parasitic challenge. The presence of follicular dendritic cells confirms the high degree of organization of these lymphoid-like structures. The role of other pathogenic factors and the induction of chronic inflammatory reaction in these ectopic lymphoid sites is also discussed.

Morphological and immunological analysis of the oral mucosa in tobacco smoking and odontopreparation

Tobacco smoking causes pronounced structural reorganization of the gingival mucosa and its atrophic changes. Odontopreparation stimulates destructive processes in the gingival mucosa promoting activation of local immunity (stimulation of immunoglobulin synthesis). Significant differences in the local humoral immunity (IgG dysimmunoglobulinemia) and cytokine spectrum in nonsmoking and tobacco-smoking patients were detected. Subcompensated level of immune resistance in tobacco smokers prompts referring them to a group at a high risk of chronic pathological processes of the oral cavity.

A morphologic and immunohistochemical study of the bronchus-associated lymphoid tissue of pigs naturally infected with Mycoplasma hyopneumoniae.

Porcine enzootic pneumonia (PEN), caused by Mycoplasma hyopneumoniae (Mh), has been described in pigs in all geographic areas. The disease is characterized by high morbidity and low mortality rates in intensive swine production systems. A morphologic and immunohistochemical study was done to determine the cellular populations present in lung parenchyma of infected pigs, with special attention to the bronchus-associated lymphoid tissue (BALT). Polyclonal and monoclonal antibodies were used for the detection of antigens of Mh, T lymphocytes (CD3+, CD4+, and CD8+), IgG+ or IgA+ lymphocytes, and cells containing lysozyme, S-100 protein, major histocompatibility complex class II antigen or myeloid-histiocyte antigen. Findings in lung tissues associated with Mh infection were catarrhal bronchointerstitial pneumonia, with infiltration of inflammatory cells in the lamina propria of bronchi and bronchioles and alveolar septa. Hyperplasia of mononuclear cells in the BALT areas was the most significant histologic change. The BALT showed a high morphologic and cellular organization. Macrophages and B lymphocytes were the main cellular components of germinal centers. T lymphocytes were primarily located in perifollicular areas of the BALT, lamina propria and within the airway epithelium, and plasma cells containing IgG or IgA at the periphery of the BALT, in the lamina propria of bronchi and bronchioles, in alveolar septa, and around bronchial submucosal glands. The hyperplastic BALT in PEN cases consisted of macrophages, dendritic cells, T and B lymphocytes, and IgG+ and IgA+ plasma cells. CD4+ cells predominated over CD8+ cells. Local humoral immunity appears to play an important role in the infection.

Clinic immunological comparison when studying erosive affections of gastro duodenal zone in patients with bronchial asthma

The aim of the work is to study the condition of the local immunity of stomach when there is bronchial asthma and the role of affection of some its factors in the formation of gastro duodenal pathology in this category of patients. 302 patients, both male and female were examined in the age of 18—60 with exogenous and mixed bronchial asthma. Gastro duodenal zone of all patients and local immunity of stomach in 65 patients were examined. The condition of the local immunity of the stomach was evaluated according to the content of secretory antibody A (sIgA), antibody G (IgG), circling immune complexes, activity of lysozyme in stomachic secretion. 68 patients (22,5%) have erosive affections of gastro duodenal zone. It is revealed that pathology of gastro duodenal zone is developed with the local deficit sIgA and rise of the content IgG in stomachic secretion. Dose-dependent effect of the long term peroral therapy by the systematic glucocorticosteroids at bronchial asthma on the pathology of gastro duodenal zone and local immunity of the stomach is revealed. Lowering the content of IgG and circling immune complexes in stomachic secretion and immune complex reactions in mucous membrane of the stomach, physiological doses lower the frequency of erosive affections of gastro duodenal zone. Treatment by supraphysiological doses of systematic glucocorticosteroids brings on disruption of specific protection section in mucous membrane of the stomach. It leads to the rise of erosive affections of gastro duodenal zone in this category of patients. Revealed affections of the local humoral immunity of the stomach in the patients have general characteristics and one-directed character of changes with the local immunity of respiratory tract when there is bronchial asthma. It gives the opportunity to suppose the participation of immune system of mucous membrane when having bronchial asthma.

Antibody Levels against Galactosyl (α1 → 3) Galactose Epitopes in Cervical Mucus from Patients with Human Papillomavirus Infection

Objectives. The general objective of the present study is to quantify antigalactosyl (α1 → 3) galactose (anti-Gal) antibody levels in the cervical mucus of patients with/without human papillomavirus (HPV) infection and, as specific objectives, to compare these levels in the different HPV subgroups and with the presence of intraepithelial lesions.Methods. Sixty women between 18 and 35 years old (mean: 26 years) were studied through the following methods: vaginal cytology, colposcopy, biopsy of suspicious lesions, sample taking for evaluating HPV presence through PCR and hybridization, and quantification of anti-Gal levels using ELISA with laminin antigen extracted from the Engelbreth–Horm–Swarm cell line.Results. The presence of HPV was detected in 55% of patients; 45% of them had intermediate/high oncogenic risk HPV, 12% had low oncogenic risk HPV, and the other 43% had both subgroups. There were significantly higher anti-Gal levels in the HPV+ group when compared with the HPV- group (P < 0.0001); also, when dividing the HPV+ group into one subgroup with normal cytology and another with cervical intraepithelial neoplasia (CIN) 1, we found higher values in the latter group (P < 0.0001). There was no significant difference in anti-Gal levels in the various HPV subgroups.Conclusion. High anti-Gal levels are found in the cervical mucus of patients with HPV infection and CIN 1, which suggests the participation of local humoral immunity in cervical lesions.

Immunity in the female lower genital tract and the impact of HIV infection.

This study investigates the distribution of immunocompetent cells in the ectocervix, and cytokine and immunoglobulin (Ig) levels in cervicovaginal secretions to determine whether they are altered in asymptomatic human immunodeficiency virus (HIV) infection. Ectocervical biopsies from 10 HIV+ and 10 presumed HIV-ve women were studied by immunocytochemistry. Levels of Igs in cervicovaginal secretions were quantified by radial immunodiffusion (RID) and cytokine levels by ELISA. HIV+ women had significantly increased numbers of CD8+ lymphocytes resulting in reversal of the CD4:CD8 ratio. There was a significant increase in the proportion of activated CD8+ HLA-DR+ and CD4+ HLA-DR + lymphocytes, but not in CD8+ TIA-1+ cells. The epithelium of the cervix from HIV+ subjects showed a significant increase in both numbers of macrophages (CD68+) and proportions of activated macrophages (CD68+ HLA-DR+) compared to normal. The stroma contained increased proportions of inductive (D1+) and suppressive (D1+ D7+) macrophages but a decrease in effector phagocyte (D7+) proportions and Langerhans' cells. Significantly lower tumour necrosis factor (TNF)-alpha levels were observed in cervicovaginal secretions from HIV+ subjects. IgG levels were 4 times higher and IgM levels twice higher in cervicovaginal secretions from HIV+ women, compared to results from normal subjects. These results suggest a response within the CD8+ cells in HIV+ women, yet these cells may have a low cytolytic capacity. The raised proportions of HLA-DR+ and D1+ CD4+ macrophages could act as antigen-presenting cells (APC) for CD4+ CD45RO+ lymphocytes, and represent a local acquired response. However, the close juxtaposition of these cells offers the potential for them to act as a local reservoir of virus and promote its proliferation. The increase of IgG over sIgA in secretions of HIV+ subjects provides evidence suggesting a dysregulation of local humoral immunity.

Epidemiologic and mucosal immunologic aspects of HPV infection and HPV-related cervical neoplasia in the lower female genital tract: a review.

Human papillomavirus (HPV) infections are known to play an important role in the pathogenesis of cervical neoplasia. Considering the morbidity and mortality of cervical cancer, infection with HPV can be regarded as a worldwide problem, especially in developing countries. Currently, many studies focus on the development of both prophylactic and therapeutic HPV vaccines. Crucial for these vaccination protocols to be successful is that they will result in a long-lasting ability to generate an immune response that will eliminate the virus. HPV transmission and subsequent infection is a local event in the lower female genital tract and therefore the efficacy of vaccines against this locally transmitted infection can be best assessed by parameters of local immunity. In this review we describe both the epidemiology of HPV-related cervical neoplasia and the general aspects of mucosal immunity in the female genital tract while focusing on the local humoral immunity in HPV-related cervical neoplasia.

Epidemiologic and mucosal immunologic aspects of HPV infection and HPV-related cervical neoplasia in the lower female genital tract: A review

Human papillomavirus (HPV) infections are known to play an important role in the pathogenesis of cervical neoplasia. Considering the morbidity and mortality of cervical cancer, infection with HPV can be regarded as a worldwide problem, especially in developing countries. Currently, many studies focus on the development of both prophylactic and therapeutic HPV vaccines. Crucial for these vaccination protocols to be successful is that they will result in a long-lasting ability to generate an immune response that will eliminate the virus. HPV transmission and subsequent infection is a local event in the lower female genital tract and therefore the efficacy of vaccines against this locally transmitted infection can be best assessed by parameters of local immunity. In this review we describe both the epidemiology of HPV-related cervical neoplasia and the general aspects of mucosal immunity in the female genital tract while focusing on the local humoral immunity in HPV-related cervical neoplasia.

Instillation of allogeneic lung antigen-presenting cells deficient in expression of major histocompatibility complex class I or II antigens have differential effects on local cellular and humoral immunity and on pathology in recipient murine lungs.

Recognition of allogeneic major histocompatibility complex (MHC) molecules expressed on donor lung antigen-presenting cells (APCs) by host T lymphocytes is believed to stimulate lung allograft rejection. However, the specific roles of donor MHC molecules in the rejection response is unknown. We report a murine model in which instilling allogeneic lung APCs into recipient lungs induces pathology analogous to acute rejection, and the production of interferon (IFN)-gamma, immunoglobulin (Ig) G2a, and alloantibodies in recipient lungs. Using allogeneic lung APCs (C57BL/6, I-a(b), H-2(b)) deficient in MHC class I, II, or both for instillation into lungs of BALB/c mice (I-a(d), H-2(d)), the purpose of the current study was to determine the specific roles of donor MHC molecules in stimulating local alloimmune responses. The data show that MHC class I or II on donor APCs induced IFN-gamma and IgG2a synthesis locally, though less than that induced by wild-type cells. Both MHC class I and II were required to induce alloantibody production. Instillation of wild-type or class I- or class II-deficient APCs induced comparable pathologic lesions in recipient lungs, and more severe than that induced by MHC-deficient cells. These data show that donor MHC class I and II molecules have differential effects in the stimulation of local alloimmune responses.

Mammary gland immunology and neonate protection in pigs. Homing of lymphocytes into the MG.

Since placenta of pregnant sows are impermeable to immunoglobulin passage, the neonates are born agammaglobulinemic; although immunocompetent, they are unable to develop rapidly an immune response which will protect their systemic and mucosal compartments; thus their survival depend upon the passive acquisition of maternal immunity including at least 3 components: i) a systemic humoral immunity, transmitted through colostrum conveying mainly by IgG; these IgG are transferred from maternal serum via Fc gamma receptors on the epithelial cells of mammary gland (MG). ii) a local humoral immunity, especially secretory IgA (IgAs), transmitted mainly by milk (lactogenic immunity) until weaning. IgAs are secreted by MG recruited plasma cells and are excreted in milk via secretory component of epithelial cells: these IgA exhibit a specificity for the antigens present in the maternal digestive tract, the so-called "entero-mammary link"; this link is due to the migration of lymphocytes from the gut to the mammary gland; they are recruited from the blood via the interaction of their homing receptor (alpha 4 beta 7) with the developmentally regulated mucosal vascular addresin MadCAM-1. In the MG, MadCAM-1 increased in pregnancy (probably under oestrogenic stimulation) but regressed in lactation; its density is closely related to the T cell numbers in MG; in contrast the increase in plasma cell numbers is not related to MadCAM-1 density. Thus IgA precursor cells (alpha 4 beta 7 B cells) seem to be recruited by a milk B cell chemoattractant. On the other hand, presence of T and B lymphocytes in MG (some of them originating from the systemic compartment), sustains the attempts of MG immunization and the results sustain the view of a true local immune response. iii) possibly but not formally proved, a cellular immunity transmitted via maternal immunocompetent cells present in mammary secretions; the exported lymphocytes may represent a selected population of lymphocytes after their passage through the MG epithelium.

Recombinant Mycobacterium bovis BCG producing the N-terminal half of SIVmac251 Env antigen induces neutralizing antibodies and cytotoxic T lymphocyte responses in mice and guinea pigs.

Recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) represents a good candidate for the development of vaccines against AIDS. Several HIV or SIV genes including nef, gag, and env have already been expressed by rBCG strains and shown to induce strong humoral and cellular immune responses in experimental animals. Because a broad immune response directed to multiple HIV/SIV antigens is highly desirable in order to develop effective vaccines, we have also investigated the immune response induced by an rBCG strain expressing a large N-terminal portion of the SIVmac251 Env gp110-encoding gene. The rBCG(SIVmac251Env) strain obtained was able to induce strong CTL responses in mice as well as humoral immune responses in mice and guinea pigs immunized by parenteral routes. The anti-gp110 IgGs produced were able to neutralize in vitro growth of virulent SIVmac251 field isolates. Moreover, guinea pigs immunized by the oral route produced significant levels of anti-gp110 IgAs in the feces, demonstrating that rBCG is able to induce local humoral immunity in the intestinal mucosa. These data provide further evidence of the utility of BCG as a candidate vaccine vector against AIDS.

Role of passenger leukocytes in allograft rejection: effect of depletion of donor alveolar macrophages on the local production of TNF-alpha, T helper 1/T helper 2 cytokines, IgG subclasses, and pathology in a rat model of lung transplantation.

Acute lung allograft rejection is believed to be initiated by passenger leukocytes, such as alveolar macrophages (AM), in the donor organ, which release TNF-alpha, and present alloantigens to host lymphocytes, to up-regulated Th1 cellular and humoral immunity. However, the role of donor AM in local TNF-alpha synthesis, and their ability to induce local Th1 cellular and humoral immunity have not been evaluated. By depleting Brown Norway (BN, RT1n) rat lung allografts of AM before transplantation into Lewis rat (LEW, RT1(1)) recipients, the current study determined the role of donor AM in including the production of TNF-alpha, IFN-gamma (Th1 cytokine), IL-4 (Th2 cytokine), IgG subtypes, and rejection pathology in the allograft. The data show that compared with untreated BN allografts, pretransplant depletion of donor lung AM resulted in significantly less TNF-alpha, and IFN-gamma production in allograft bronchoalveolar lavage fluid with variable effects on local IL-4 production. Depletion of AM in the donor lung before transplantation affected the local production of several IgG subclasses. However, pretransplant depletion of donor AM had no effect on the development of the pathology of severe acute rejection. These data show that donor AM have a central role in the local synthesis of TNF-alpha and induce the production of IFN-gamma and IgG subtypes, locally, during acute lung allograft rejection. However, depletion of AM before transplantation does not prevent the development of severe acute rejection in BN rat lungs, transplanted into LEW recipients.

Opsonic activity of sera and blister fluid from severely burned patients evaluated by a chemiluminescence method.

Burn wound sepsis is the most common and severe complication in the patients with severe burn. To know the systemic and local defect in immunity of burned patients, we measured the luminol-enhanced chemiluminescence (CL) response of normal polymorphonuclear leukocytes (PMNs) upon exposure to zymosan particles, bacteria or Candida albicans that were opsonized with any of patient's serum, blister fluid of burn wound or pooled normal serum (blood type AB). Sera from patients exhibited lower opsonic activities than those of pooled normal serum in the early postburn days. The levels of serum immunoglobulins, complement components and plasma fibronectin were found to correlate well with opsonin-index (OI), which was determined based on the CL response data obtained during the course of infusion therapy with fresh frozen plasma. Furthermore, patient's blister fluid showed much lower opsonic activity against bacteria such as Pseudomonas aeruginosa than patient's own serum. These results indicate that blister fluid is also not effective to opsonize bacteria because of the marked depression of the levels of immunoglobulins and complement components. Destruction of the skin barrier by thermal injury and impairment of systemic or local humoral immunity may predispose these patients to burn wound sepsis.

Humoral immune response patterns of human mucosae: induction and relation to bacterial respiratory tract infections.

Immunoglobulin-producing cells in mucosal tissues, quantitatively the body's most important humoral immune system, synthesize mainly dimers and larger polymers of IgA (poly-IgA) with incorporated J (joining) chain. Poly-IgA is actively transported to exocrine secretions by a transmembrane epithelial glycoprotein called secretory component. Enhancing secretory immunity by oral vaccination is an interesting possibility, but mucosal antigen uptake and local immune regulation are complex and only partly understood. Immunoglobulin isotype response patterns in the upper respiratory mucosa and distal gut are strikingly different. The preferential production of IgA1 in nasal and bronchial mucosae is intriguing in view of the frequent synthesis of IgA1-specific proteases by Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. A relationship of proneness to produce invasive disease and enzymatically induced deterioration of secretory immunity has been proposed. Differences in mucosal immune response patterns among patients with selective IgA deficiency or IgG subclass deficiencies also suggest that local humoral immunity is an important variable in resistance to infections.

Distribution of immunoglobulins and secretory component in gastric cancer of the aged

The secretory immune system plays an important role in the local humoral immunity of the gastrointestinal tract. In order to evaluate humoral immunity in gastric cancer, distribution of immunoglobulins (Ig) and secretory component was immunohistochemically studied in 74 early and 15 advanced primary gastric cancers. In non-cancerous gastric mucosa, IgA and IgM, and secretory component were mainly identified in the cytoplasm of the intestinal metaplasia. In early gastric cancer of well-differentiated type, the localization of IgA and IgM, and secretory component was similar to that of intestinal metaplasia. In advanced gastric cancer, they were faintly observed and showed low positivity. The number of Ig-containing cells infiltrating cancerous stroma was enumerated. Immunoglobulin A-containing cells were dominant in the stroma of early gastric cancer. On the other hand, there were few Ig-containing cells in the stroma of advanced gastric cancer, and the number of IgA-containing and IgM-containing cells was also decreased. These results suggest that local humoral immunity is suppressed in gastric cancer, especially in advanced gastric cancer.

Mucosal and systemic antiviral antibodies in mice inoculated intravaginally with herpes simplex virus type 2

Herpes simplex virus type 2 (HSV-2) causes lethal illness after intravaginal (IVAG) inoculation into BALB/cJ mice. In the present studies, we demonstrated in mice that primary IVAG vaccination with an attenuated strain of HSV-2 induced humoral immunity in sera and in vaginal secretions. Secondary genital exposure to HSV-2 enhanced this response. However, intraperitoneal exposure to attenuated HSV-2 elicited an antiviral antibody response in sera but not in vaginal secretions. In both sera and vaginal secretions, antiviral IgG antibodies were the major isotype. Systemic exposure to HSV-2 elicited antibodies only in sera that were specific for the major viral antigens whereas IVAG inoculation with HSV-2 stimulated both serum and vaginal antibody responses. Intravenous transfer of antiviral monoclonal antibodies protected against systemic HSV-2 infection but were ineffective against vaginal infection due to a lack of transudation into vaginal secretions. These results suggested that local humoral immunity in the genital tract is important in resistance to HSV-2.