U.S. Environmental Protection Agency, Program Contract Service Center (3803R), 401 M Street, SW, Washington, DC 20460-0001

B -- ACQUIRED IMMUNITY AND IMMUNOTOXICITY STUDY SOL RFQ-DC-99-00101 DUE 083099 POC Yvonne Stiso/stiso.yvonne@epa.gov/Contract Specialist WEB: click here RFQ, http://www.epa.gov/oamhpod1/oppts_grp/dc9900101/index.htm. E-MAIL: click here to contact the contract specialist, stiso.yvonne@epa.gov. The U.S. Environmental Protection Agency under the Simplified Acquisition Procedures of FAR Part 13 is seeking a contractor to provide technical support for an assessment of the state of the science on acquired immunity and immunotoxicity in development and children's health protection. The SIC code for this requirement is 8733. The EPA is FACNET certified. You may e-mail the contract specialist at: stiso.yvonne@epamail.epa.gov. Please include the following: Company name, address, phone number, business class, and e-mail address. NO PHONE CALLS WILL BE ACCEPTED. Two copies of the proposal must be submitted by the due date. US MAIL ADDRESS is- US EPA, 401 M Street, SW, Mail Code 3803R, Washington, DC 20460, ATTN: Yvonne D. Stiso. HANDCARRY (such as fed-ex) should be submitted to Ronald Reagan Building, 1300 Pennsylvania Avenue, NW, Bid and Proposal Room, 6th floor, Room 61107. Proposals are due NLT 2:00 PM /EST August 30,1999. BACKGROUND An Assessment of the State of the Science on Acquired Immunity andImmunotoxicity in Development and Children's Health Protection: The immune system is designed to ward off invasive organisms, combat diseases and perform other bodily defense functions. The immune response process is complex and the end result of a response is the combined product of both internal and external factors and their interactions with a foreign agent. Some of the recent findings are suggesting that external factors (such as chemicals, radiation) combining with the timing of the exposure could affect the course of the organism's response to conferring protective immunity, inducing allergic or other types of immune responses. The net effect is that the type and pattern of environmental exposures are likely to alter or compromise an immune response process resulting in a different outcome. This observation has public health importance, because to the extent that we can understand the mechanisms at work in these processes will dictate how we develop our strategy on how to prevent exposures, control diseases and ensuring health protection. Understanding how environmental exposures may impact the functional aspects of the immune system at different stages of development is important. The formation of structural components in an immune system occurs during fetal development, but the process of attaining functional immunity generally begins with birth. While the newborn is quite capable of differentiating an agent as different from itself, the process of acquiring protective immunity and other types of immune responses will take time. Full development is not reached until all the structural and functional components needed to support a competent immune system is put in place. In man, this period extends over a number of years during childhood. A body of evidence now gathering suggest that the immune system may be particularly sensitive to the toxic effects of certain environmental agents at the time of development or during the time of a normal immune response. The duration of the acquired immunity can vary, depending on a number of factors such as the nature of the agent, potency and the frequency of the encounter. It is generally accepted that a strong anti-microbial immunity is desirable, but allergies and some of the other auto-immune types of immune responses are not. The capacity for producing a desirable or undesirable response is believed by some to be closely related to early life events, life styles, and exposures during critical pre- and post-natal developmental periods. Other types of responses, such as auto-immunity, tolerance, and perhaps chemical sensitivity, may have origins linking to events from critical developmental periods. Developing infants and children are thought to be potentially more sensitive to undesirable external effects that may alter the course of the immune process, leading to immunity that may be weakly protective, and exaggerated responses that may be counter-productive or undesirable for the well-being of the host. The net result is that, depending on the state of immunity andthe nature of the exposure, altered immune responses may lead to a variety of unpredictable end results. The purpose of this acquisition is to commission the writing of a report that is based on documented literature, processes that would lead to normal and altered immune functions, factors that could lead to altered processes because of early life events and exposures, the types and magnitude of these outcomes, and their immediate or long-term health consequences. WORK STATEMENT The contractor will review the scientific literature for the body of bio-medical, clinical and epidemiologic data on the developing fetus, infant, adolescent, and adult, for normal and abnormal immune processes that may have environmental origins, and the consequences as a result of process alterations or modifications. Where possible, human data should be reinforced with supporting animal studies. Write a detailed report (about 400-500 pages) on the subject, and discuss each one of the major areas with case examples using an "if"..."then" logic flow format. Where possible, use illustrations and tables to help clarify or reinforce a concept. Provide a glossary of basic terms, and a list of the references used. Reader's technical comprehension should be at the college level, in both reading and writing. Task 1. Describe the structure and components comprising of the body's defense system. Define the human immune system developmental periods. Describe how in the developmental process a fully functional system is attained. Summarize the major theories describing the mechanisms involved in producing an immune response. Describe the dynamics of cellular and molecular interactions in producing various immune responses (humoral, acute and delayed hypersensitivity). Discuss the type of immune responses produced based on the nature of the antigenic moiety (microbial, allergic, particulate, immune complexes, transplantation immunity, tumor immunity, autoimmunity, tolerance, antigenic mimicry, UV light, etc.) Discuss the mechanisms that lead to activation, potentiation or suppression of humoral and cellular immune responses. Task 2. Discuss the immune system as a responsive and self-regulating mechanism. Examine the system's response characteristic to a stimulus, and describe how different internal and external factors may influence whether beneficial or detrimental effects are the expected outcomes in the developing organism. Discuss in the course of becoming fully immuno-competent, how diverse immune stimuli and competing mechanisms can alter or compromise the normal immune process. Discuss our current understanding of atopy and how exposure patterns and nature of the stimuli may alter the response and the course of a disease. Discuss risk factors and how they may alter the state of the immune response. Discuss the outcome on immune regulation between TH-1 and TH-2 activations. Task 3. The contractor should address the following questions in the report: How should one expect the outcome to an immune stimulus to differ during different stages of the developmental process? How do the timing, quality, and quantity of an exposure (to an environmental toxicant) vary the result of an immune response as a function of the immune status of the host? How might one be able to anticipate the effects of known stimuli in induction, potentiation, suppression, or in the production of tolerance under different immune states or different developmental periods? How do the effects of environmental exposures differ in the developing immune system, and how the action of agents such as radiation, chemicals and allergens differ? How does one attribute an effect to be a change in mechanism or a change in the variability in sensitivity? How do risk factors alter the level of protective immunity against microbial or other pathogenic agents? What are the time implications for early life exposures on latency of cancers in children and in the adult, or on non-cancer endpoints? How might long term environmental changes and pollution potentially affect the dynamic balance of pathogenic virulence and what are the implications for health? Deliverables: One page monthly written progress report. Draft written report, 26 weeks after award (2 hard copies). Final written report, 40 weeks after award (2 hard copies and one 3.5" floppy disk in DOS, WP 6.1 format). Period of Performance: From award through 40th week Travel: The contractor or his/her designee may be required to participate in up to two (2) one to two day meetings/conferences in the Washington, D.C. area. EVALUATION CRITERIA Evaluation will be made on the contractor's demonstration of his/her understanding of the subject matter and on the topics to be discussed, on the originality and thoughtfulness in responding to the proposal, and on his/her potential for completing the tasks as well as producing a high quality report in the time frame specified. 1. Experience- Provide evidence of training, practice, certification, and publication of immunological research demonstrating knowledge and competency in the area of functional immunity, allergy and aberrations, immunopathology, immune regulation, developmental immunology or developmental immunotoxicity. 2. Proposal- Prepare a work proposal that will include a two (2) page writeup demonstrating the breadth and depth of the contractor's knowledge of the subject matter, ability in organizing the scope of work and the major subject areas under discussion, and demonstrating his/her understanding of the specific concerns raised as part of this acquisition. (The contractor should use the key concepts found in each of the questions raised in Task 3 to help guide the development of the 2 page writeup). Prepare a detailed report outline on the topics to be discussed and as a guide to the writing of the report, as well as to be used as a basis for EPA's evaluation of the comprehensiveness of the intended work product. The two page writeup and outline should allow EPA the opportunity to evaluate the contractor's understanding of the concepts and problems with respect to environmental exposures from the standpoint of developmental immunology, developmental immunotoxicity, subsequent effects and health consequences. 3. Time Requirement- The proposed work must be completed within the prescribed time period of 6-9 months, without provision for an extension. A description of the resource and level of effort will be needed to help justify the claim for support of this requirement. See numbered Note 1. Posted 08/06/99 (W-SN364674). (0218)

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