Photoperiod controls the induction, retention, and retrieval of antigen-specific immunological memory

2004 ◽  
Vol 286 (1) ◽  
pp. R54-R60 ◽  
Author(s):  
Brian J. Prendergast ◽  
Staci D. Bilbo ◽  
Randy J. Nelson

Changes in day length affect several measures of immunity in seasonally breeding mammals. In Siberian hamsters ( Phodopus sungorus), short day lengths suppress specific secondary antibody responses to the keyhole limpet hemocyanin (KLH) antigen and enhance cutaneous delayed-type hypersensitivity (DTH) responses to dinitrofluorobenzene (DNFB). These experiments tested whether day length affects secondary antibody and DTH responses by altering immune function solely during the interval after the initial exposure to each antigen, solely during the interval after the second exposure, or during both stages of the respective immune responses. Adult male Siberian hamsters were exposed to either a long (16 h light/day; LD) or a short (8 h light/day; SD) photoperiod for 7.5 wk before receiving an initial exposure to each antigen (KLH injection, cutaneous DNFB treatment; separate groups of animals for each antigen). A subset of LD hamsters was transferred to the SD photo-period, and a subset of SD hamsters was transferred to the LD photoperiod. Other hamsters remained in LD or SD. Eight weeks later, all hamsters were challenged with a second subcutaneous injection of KLH or a second application of DNFB to the ear, and immune responses were measured. Exposure to SD during the primary antibody response did not affect secondary IgG responses, but SD exposure during the secondary response significantly suppressed IgG production independent of day length during the initial KLH treatment. In contrast, exposure to SD during the DNFB challenge enhanced the ensuing DTH response, but this enhancement depended on the photoperiod prevailing during the initial exposure. Exposure to SD during the sensitization stage did not enhance DTH in hamsters subsequently exposed to LD. The data suggest that short photoperiods have enduring effects on immune responsiveness and on the establishment and retention of immunological memory.

2002 ◽  
Vol 9 (3) ◽  
pp. 119-125
Author(s):  
Carl De Trez ◽  
Annette Van Acker ◽  
Georgette Vansanten ◽  
Jacques Urbain ◽  
Maryse Brait

Immune responses developing in irradiated environment are profoundly altered. The memory anti-arsonate response of A/J mice is dominated by a major clonotype encoded by a single gene segment combination called CRIA. In irradiated and autoreconstituted A/J mice, the level of anti-ARS antibodies upon secondary immunization is normal but devoid of CRIA antibodies. The affinity maturation process and the somatic mutation frequency are reduced. Isotype switching and development of germinal centers (GC) are delayed.The primary antibody response of C57BL/6 mice to the hapten (4-hydroxy-3-nitrophenyl) acetyl (NP)-Keyhole Limpet Hemocyanin (KLH) is dominated by antibodies encoded by a family of closely related VH genes associated with the expression of the λ1 light chain.We investigated the anti-NP primary response in irradiated and autoreconstituted C57BL/6 mice. We observed some splenic alterations as previously described in the irradiated A/J model. Germinal center reaction is delayed although the extrafollicular foci appearance is unchanged. Irradiated C57BL/6 mice are able to mount a primary anti-NP response dominated by λ1 positive antibodies but fail to produce high affinity NP-binding IgGl antibodies. Following a second antigenic challenge, irradiated mice develop enlarged GC and foci. Furthermore, higher affinity NP-binding IgG1 antibodies are detected.


Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 673-683 ◽  
Author(s):  
Massimo Massaia ◽  
Paolo Borrione ◽  
Silvano Battaglio ◽  
Sara Mariani ◽  
Eloise Beggiato ◽  
...  

Abstract Igs contain unique portions, collectively termed idiotypes (Id), that can be recognized by the immune system. Id expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and a target for vaccine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KLH) as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first remission at the time of vaccination. They received subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reaction was observed in 8 of the 10 patients studied. DTH specificity was confirmed in 1 patient by investigating the reactivity to synthetic peptides derived from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation of soluble and cellular immune responses to KLH was observed in 100% and 80%, respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease progression (FFDP), measured from the date of first Id/KLH injection to the date of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM patients is still susceptible to specific immunization after high-dose chemotherapy and PBPC transplantation. It remains to be determined whether generation of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease.


2011 ◽  
Vol 7 (3) ◽  
pp. 468-471 ◽  
Author(s):  
Tracy A. Bedrosian ◽  
Laura K. Fonken ◽  
James C. Walton ◽  
Randy J. Nelson

Species have been adapted to specific niches optimizing survival and reproduction; however, urbanization by humans has dramatically altered natural habitats. Artificial light at night (LAN), termed ‘light pollution’, is an often overlooked, yet increasing disruptor of habitats, which perturbs physiological processes that rely on precise light information. For example, LAN alters the timing of reproduction and activity in some species, which decreases the odds of successful breeding and increases the threat of predation for these individuals, leading to reduced fitness. LAN also suppresses immune function, an important proxy for survival. To investigate the impact of LAN in a species naive to light pollution in its native habitat, immune function was examined in Siberian hamsters derived from wild-caught stock. After four weeks exposure to dim LAN, immune responses to three different challenges were assessed: (i) delayed-type hypersensitivity (DTH), (ii) lipopolysaccharide-induced fever, and (iii) bactericide activity of blood. LAN suppressed DTH response and reduced bactericide activity of blood after lipopolysaccharide treatment, in addition to altering daily patterns of locomotor activity, suggesting that human encroachment on habitats via night-time lighting may inadvertently compromise immune function and ultimately fitness.


2005 ◽  
Vol 83 (10) ◽  
pp. 1271-1278 ◽  
Author(s):  
L M Pyter ◽  
Z M Weil ◽  
R J Nelson

Animals use day length (photoperiod) to time seasonal adaptations to annual changes in their environment. Reproductive adjustments in deer mice (Peromyscus maniculatus (Wagner, 1845)) from high latitudes are more extensive in response to short days than in deer mice from low latitudes. These adjustments may permit individuals to survive the severe seasonal changes (e.g., temperature and food abundance) in high-latitude environments. Immune function is also affected by photoperiod. Short days were predicted to result in elevated immune and reproductive responses in meadow voles (Microtus pennsylvanicus (Ord, 1815)) from the Northwest Territories (NWT), Canada (~62°N), compared with voles from Ohio (OH), USA (~39°N). Male voles from both latitudes were maintained in long or short days for 10 weeks prior to a delayed-type hypersensitivity (DTH) immune challenge. Both populations displayed similar testicular regression and reduction of testosterone concentrations in short days. DTH immune responses, however, diverged between the two populations. DTH immune responses were enhanced in long-day NWT voles and short-day OH voles, but decreased in short-day NWT voles and long-day OH voles. Total and free corticosterone concentrations did not explain the latitudinal differences in immune responses. These results suggest that photoperiod affects reproductive and immune systems differently and that immune responses may reflect other environmental factors.


Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 673-683 ◽  
Author(s):  
Massimo Massaia ◽  
Paolo Borrione ◽  
Silvano Battaglio ◽  
Sara Mariani ◽  
Eloise Beggiato ◽  
...  

Igs contain unique portions, collectively termed idiotypes (Id), that can be recognized by the immune system. Id expressed by tumor cells in B-cell malignancies can be regarded as tumor-specific antigens and a target for vaccine immunotherapy. We have started a vaccination trial in multiple myeloma (MM) using Id-specific proteins conjugated to keyhole limpet hemocyanin (KLH) as immunogens and low doses of subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2 (IL-2) as immunoadjuvants. Twelve patients who had previously been treated with high-dose chemotherapy followed by peripheral blood progenitor cell (PBPC) transplantation entered this study from August 1995 to January 1998. All patients were in first remission at the time of vaccination. They received subcutaneous injections of Id vaccines and immunoadjuvants in an outpatient setting. The generation of Id-specific T-cell proliferative responses was documented in 2 patients, whereas a positive Id-specific delayed-type hypersensitivity (DTH) reaction was observed in 8 of the 10 patients studied. DTH specificity was confirmed in 1 patient by investigating the reactivity to synthetic peptides derived from the VDJ sequence of the tumor-specific Ig heavy chain. None of the patients generated soluble immune responses to Id, whereas the generation of soluble and cellular immune responses to KLH was observed in 100% and 80%, respectively. Eleven patients completed the treatment, whereas 1 patient failed to finish owing to progression of disease. Freedom from disease progression (FFDP), measured from the date of first Id/KLH injection to the date of first treatment after vaccination or last follow-up, ranged from 9 to 36 months. These data indicate that the immune competence status of MM patients is still susceptible to specific immunization after high-dose chemotherapy and PBPC transplantation. It remains to be determined whether generation of Id-specific immune responses can reduce the relapse rate of patients with minimal residual disease.


2007 ◽  
Vol 292 (1) ◽  
pp. R316-R320 ◽  
Author(s):  
Lynn B. Martin ◽  
Kristen J. Navara ◽  
Zachary M. Weil ◽  
Randy J. Nelson

The immune system protects organisms against infection, but this protection presumably comes at a cost. Here, we asked whether food restriction would compromise the ability of an organism to generate an immune response on reexposure to an antigen, which would represent a functional cost of immunological memory. Immunological memory is generated when B and T lymphocytes sensitive to components of pathogens (i.e., antigens) proliferate after exposure and persist in circulation to hinder reinfection. To test the possibility that B cell memory, the component of the immune system responsible for antibody production, is expensive to maintain, secondary antibody production against a novel protein [keyhole limpet hemocyanin (KLH)] was compared in food-restricted and ad libitum-fed male deer mice ( Peromyscus maniculatus). To determine whether compromised secondary antibody production was solely due to elevated corticosterone independent of resource availability, some food-restricted and ad libitum-fed mice were subjected to unpredictable, chronic (2 h/day) restraint. Mice fed 70% of their ad libitum diet 2 wk after primary antigen challenge produced ∼95% less IgG against KLH after a second antigen challenge than mice fed ad libitum, even though all mice were fed ad libitum during the secondary antibody response period. Restraint had no effect on secondary IgG production in response to KLH, and corticosterone concentrations 1 day after food restriction did not differ between food-restricted and ad libitum-fed mice. Together, these data imply that secondary antibody responses and the benefits of immunological memory are energetically costly in this species.


1999 ◽  
Vol 189 (8) ◽  
pp. 1285-1294 ◽  
Author(s):  
Laurie L. Hill ◽  
Vijay K. Shreedhar ◽  
Margaret L. Kripke ◽  
Laurie B. Owen-Schaub

Induction of antigen-specific suppression elicited by environmental insults, such as ultraviolet (UV)-B radiation in sunlight, can inhibit an effective immune response in vivo and may contribute to the outgrowth of UV-induced skin cancer. Although UV-induced DNA damage is known to be an initiating event in the immune suppression of most antigen responses, the underlying mechanism(s) of such suppression remain undefined. In this report, we document that Fas ligand (FasL) is critical for UV-induced systemic immune suppression. Normal mice acutely exposed to UV exhibit a profound suppression of both contact hypersensitivity and delayed type hypersensitivity (DTH) reactions and the development of transferable antigen-specific suppressor cells. FasL-deficient mice exposed to UV lack both transferable suppressor cell activity and primary suppression to all antigens tested, with the exception of the DTH response to allogeneic spleen cells. Interestingly, suppression of this response is also known to occur independently of UV-induced DNA damage. Delivery of alloantigen as protein, rather than intact cells, restored the requirement for FasL in UV-induced immune suppression of this response. These results substantiate that FasL/Fas interactions are essential for systemic UV-induced suppression of immune responses that involve host antigen presentation and suggest an interrelationship between UV-induced DNA damage and FasL in this phenomenon. Collectively, our results suggest a model whereby UV-induced DNA damage disarms the immune system in a manner similar to that observed in immunologically privileged sites.


2010 ◽  
Vol 104 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Mohammad Hossein Yazdi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Zuhair Mohammad Hassan ◽  
Marzieh Holakuyee ◽  
Solmaz Agha Amiri ◽  
...  

Lactic acid bacteria can affect the maturation of immune cells and their products not only in the gut but also on the systemic immune organs such as lymph nodes and spleen. In the present work, we studied the effects of oral administration ofLactobacillus acidophiluson the immune responses of BALB/c mice bearing transplanted breast tumour. Two groups of female inbred BALB/c mice, each containing nine mice as test and control, were used. TheL. acidophilusATCC4356 strain was inoculated in DeMan–Rogosa–Sharpe broth and cultivated for 24 h at 37°C. Then, it was collected by centrifugation, and was washed and suspended in PBS. Afterwards, 0·5 ml/d of this suspension, which contained 2·7 × 108 colony forming units/ml of bacteria, was orally administered to the mice by gavage, 14 d before tumour transplantation and 30 d after that with 3-d intervals. Similar to the test mice, the control mice received an equal volume of PBS. The results showed that oral administration ofL. acidophilusincreased the production of IL-12 (P < 0·05) and decreased the level of transforming growth factor β (P = 0·05) in the splenocyte culture. Moreover, the growth rate of tumour in the test mice decreased (P < 0·01), and the results of delayed-type hypersensitivity assay after 48 h were risen (P < 0·05) in comparison with the controls. Results suggest that daily consumption ofL. acidophiluscan improve the production of immunomodulatory cytokine IL-12 in the splenocyte culture, which was stimulated by tumour antigen in BALB/c mice bearing transplanted breast tumour. But further studies are needed to find out some other possible mechanisms of this effect.


1997 ◽  
Vol 8 (7) ◽  
pp. 1101-1108 ◽  
Author(s):  
X R Huang ◽  
S R Holdsworth ◽  
P G Tipping

Acute autologous phase anti-glomerular basement membrane glomerulonephritis was compared in Th1-prone (C57BL/6) and Th2-prone (BALB/c) mice. Sensitized BALB/c mice, given a subnephritogenic intravenous dose of anti-mouse glomerular basement membrane globulin, developed acute glomerulonephritis characterized by marked proteinuria and glomerular deposition of mouse immunoglobulin and complement. A significant glomerular neutrophil influx was observed, but few T cells and macrophages were present. C57BL/6 mice, given the same dose of disease-inducing globulin, also developed acute glomerulonephritis, although their proteinuria was significantly less. Glomerular deposition of mouse immunoglobulin and complement and the influx of neutrophils were also significantly less than in BALB/c mice. However, their glomerular accumulation of macrophages and T cells was significantly greater. Complement depletion attenuated neutrophil influx and proteinuria in BALB/c mice but did not affect T cell or macrophage accumulation or proteinuria in C57BL/6 mice. CD4+ T cell depletion significantly reduced glomerular macrophage, T cell influx, and proteinuria in C57BL/6 mice, but had no effect on proteinuria or neutrophil influx in BALB/c mice. Thus, immune responses to planted glomerular antigens in Th2-prone mice induce acute injury as a result of antibody deposition, complement activation, and neutrophil influx, whereas immune responses to the same antigen in Th1-prone mice induce delayed-type hypersensitivity-like lesions in affected glomeruli.


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