NIH GUIDE, Volume 21, Number 40, November 6, 1992

PA NUMBER:  PA-93-014

P.T. 34




  Immune System 


National Institute on Aging

National Institute of Allergy and Infectious Diseases


It has been well established that overall immune function declines with

advancing age.  However, because the immune system is highly complex,

it is essential to understand the multi-faceted nature of this

age-related loss of immune function and to identify the primary changes

in immune mechanisms leading to this decline in the immune responses.

It has been proposed that the decline and/or dysregulation of the

immune system may be a primary cause of aging or perhaps a pace-setter

of the aging process.  The possibility that changes in the immune

system may be a fundamental predisposing factor in the aging process is

also an appropriate field of scientific inquiry.  Research is also

indicated into the pathological consequences of age-related changes in

the immune system, such as decreased resistance to infection with

pathogens and an increased tendency toward autoimmunity and


The Biology of Aging Program (BAP) of the National Institute on Aging

(NIA) has responsibility for supporting extramural research and

training in the fundamental studies of immunology as related to aging.

The Geriatrics Program (GP) has responsibility for supporting clinical

studies of the immune competence of aging humans, the transfer of

promising immunological interventions, and the delivery of effective

vaccines to geriatric populations.  The Division of Allergy,

Immunology, and Transplantation (DAIT) of the National Institute of

Allergy and Infectious Diseases (NIAID) is responsible for promoting

research into the basic mechanisms of the immune system and the changes

that occur in the immune system that initiate or contribute to disease.

The two institutes share the goal of achieving a better understanding

of the behavior of the immune system and the specific deficits of

various components of the immune system that occur during aging to

permit intervention and prevent or reverse the immunologic deficits of



Applications may be submitted by foreign and domestic, for-profit and

non-profit, public and private organizations, such as universities,

colleges, hospitals, laboratories, units of State and local

governments, and eligible agencies of the Federal government.

Applications from minority individuals and women are encouraged.

Applicants for K and F awards must be U.S. citizens, non citizen

nationals, or have been lawfully admitted for permanent residence at

the time of award.  Applications related to the health of women and

minorities are particularly encouraged.


o  Research grant (R01)

o  Program Project grant (P01)

o  First Independent Research Support and Transition (FIRST) award


o  Career grants, which include:  Research Career Development Award

(K04); Clinical Investigator Award (K08); Physician Scientist Award

(individual K11)

o  Training grants (T32)

o  Fellowships (F32, F33)

Deadlines for applications are as follows:

F-series and T-series grants:        Jan 10, May 10, Sep 10

New R, K, and P-series:              Feb 1, Jun 1, Oct 1

Competing continuation and revised:  Mar 1, Jul 1, Nov 1

Foreign institutions are not eligible to apply for T32 Awards, Program

Project (P01) Awards, or FIRST Awards (R29).


The NIA and the NIAID invite investigators to submit applications for

research and research training in all areas of immunology that relate

to fundamental processes of aging.  Applications to study the aging of

the immune system in humans, animals, or cell culture systems are

welcome.  Applications that might lead to successful interventions in

the aging of the immune system are particularly encouraged.

The following topics are illustrative of appropriate research areas

covered by this Program Announcement.  However, applications need not

be limited to the issues listed below.

o  Age related changes in the functions of lymphoid organs (thymus,

spleen, lymph nodes, gut-associated lymphoid tissue)

o  The roles of changes in bone marrow cell production and thymic

involution in the aging immune response.  The possible role, source and

mechanism of extrathymic T cell repopulation

o  Age-related changes in the genetic and ontogenic control of T and B

cell production.  Selection and deletion of involved cell types.  The

nature and function of different T and B cell subtypes (naive, memory,

helper, and cytotoxic T cells)

o  Age-related changes in the mechanisms of antigen sequestration,

transport, processing, and presentation, including the accessory cells

involved (Langerhans cells, macrophages, dendritic cells, B cells)

o  Age-related changes in molecules involved in specific antigen

recognition (B-cell and T-cell receptors, MHC-encoded molecules) and in

lymphocyte and macrophage activation

o  Age-related changes in biochemical processes leading to lymphocyte

and macrophage activation

o  Age-related changes in the production of lymphokines and other

cytokines (and their receptors) involved in the immune response

o  The role of hormones and neuroendocrine factors in the regulation of

T and B cell activity and in age-related changes in immune function.

o  Age-related changes in the regulation of the immune response (e.g.,

regulatory cells, immunoglobulin isotypes, the idiotypic network).

Changes in the nature of the antibody repertoire with aging.

o  Immune responses to infectious agents and to vaccines in senescence;

development of vaccine delivery systems.

o  Immunologic tolerance, autoimmunity, and immunopathology in


o  The interrelationship between disease and immune function in the

aging process

o  The role of nutrition and caloric restriction in the potentiation or

prevention of age-associated deficits in immune function

o  Immune surveillance in aged individuals

o  Generalized immunosuppression due to viral, protozoal, and bacterial

infections in aged individuals

o  Attempts to prevent or reverse the immunologic deficits of aging by

immunotherapy (e.g., development of techniques for immune augmentation,

biological response modifiers, hormonal treatment)

o  Attempts to prevent or reverse the immunologic deficits of aging

through cellular or genetic engineering

o  Effects of drugs on the immune system of older individuals

o  Gender-related differences in any of the above areas of research.

The Geriatrics Program of the NIA also supports research in the

clinical aspects of several of the preceding topics, particularly those

regarding immune responses to infectious agents in senescence and the

development and delivery of effective vaccines.  Inquiries considered

more appropriate for the Geriatrics Program will be referred to them.





NIH policy is that applicants for NIH clinical research grants and

cooperative agreements are required to include minorities and women in

study populations so that research findings can be of benefit to all

persons at risk of the disease, disorder or condition under study;

special emphasis must be placed on the need for inclusion of minorities

and women in studies of diseases, disorders and conditions which

disproportionately affect them.  This policy is intended to apply to

males and females of all ages. If women or minorities are excluded or

inadequately represented in clinical research, particularly in proposed

population-based studies, a clear compelling rationale must be


The composition of the proposed study population must be described in

terms of gender and racial/ethnic group.  In addition, gender and

racial/ethnic issues should be addressed in developing a research

design and sample size appropriate for the scientific objectives of the

study. This information must be included in the form PHS 398 in

Sections 1-4 of the Research Plan AND summarized in Section 3,

Recruitment of Individuals from Underrepresented Racial/Ethnic Groups,

and Section 5, Human Subjects.  Applicants are urged to assess

carefully the feasibility of including the broadest possible

representation of minority groups. However, NIH recognizes that it may

not be feasible or appropriate in ALL research projects to include

representation of the full array of United States racial/ethnic

minority populations (i.e., Native Americans including American Indians

or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The

rationale for studies on single minority population groups must be


For the purpose of this policy, clinical research is defined as human

biomedical and behavioral studies of etiology, epidemiology, prevention

and preventive strategies), diagnosis, or treatment of diseases,

disorders or conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded.  However,

every effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;

since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including

minorities.  If the required information is not contained within the

application, the review will be deferred until the information is


Peer reviewers will address specifically whether the research plan in

the application conforms to these policies. If the representation of

women or minorities in a study design is inadequate to answer the

scientific question(s) addressed AND the justification for the selected

study population is inadequate, it will be considered a scientific

weakness or deficiency in the study design and will be reflected in

assigning the priority score to the application.

All applications for clinical research submitted to NIH are required to

address these policies.  NIH funding components will not award grants

or cooperative agreements that do not comply with these policies.


Applications are to be submitted on the grant application form PHS 398

(rev. 9/91) and will be accepted at the standard application deadlines

as indicated in the application kit. The receipt dates for applications

for AIDS-related research are found in the PHS 398 instructions.

National Research Service Award (NRSA) (F32, F33) applications must be

submitted on grant application Form PHS 416 (rev. 10/91).

Application kits are available at most institutional offices of

sponsored research and may be obtained from the Office of Grants

Inquiries, Division of Research Grants, National Institutes of Health,

Westwood Building, Room  449, Bethesda, MD 20892, telephone

301/496-7441.  The title and number of the announcement must be typed

in Section 2a on the face page of the application.

Applications from institutions that have a General Clinical Research

Center (GCRC) funded by the NIH National Center for Research Resources

may wish to identify the GCRC as a resource for conducting the proposed

research.  In such a case, a letter of agreement from either the GCRC

program director or Principal Investigator could be included with the


The completed original application and five legible copies must be sent

or delivered to:

Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD 20892**


Other institutes may also have interest in several of the topics

mentioned here.  All applications in response to this Program

Announcement will be assigned to an Initial Review Group and reviewed

by the usual Public Health Service Peer Review (Study Section)

procedures.  They will also be given appropriate primary and secondary

Institute assignments in accordance with established PHS Referral

Guidelines.  The review criteria are the traditional criteria

appropriate to each mechanism.  In accordance with the standard NIH

peer review procedures, research project grant (R01 and R29)

applications, fellowships  (F32, F33) and research career development

awards (K04) will be reviewed for scientific and technical merit by an

appropriate study section in the Division of Research Grants.  All

other applications will be reviewed by review groups of the appropriate

funding component.  Following the Study Section review, the

applications will receive a second-level review by the appropriate

advisory council.  Funding decisions will be based on the above

evaluations and on the availability of funds.


Applications compete for available funds on the basis of scientific

merit.  The following will be considered in making funding decisions:

o  Quality of the proposed project as determined by peer review

o  Availability of funds

o  Program balance among research areas of the announcement


Researchers considering an application in response to this announcement

are strongly encouraged to discuss their project, and the range of

grant mechanisms available with NIA and/or NIAID staff.  This can be

done either through a telephone conversation or a brief letter.

Correspondence and inquiries may be directed to:

Dr. David Lavrin, Immunology Program Administrator

Biology of Aging Program

National Institute on Aging

Gateway Building, Room 2C231

7201 Wisconsin Avenue

Bethesda, MD  20892

Telephone:  (301) 496-6402

FAX:  (301) 402-0010

Dr. Joseph Albright

Program Administrator, Division of Allergy, Immunology and


National Institute of Allergy and Infectious Diseases

Solar Building, Room 4A20

Bethesda, MD  20892

Telephone:  (301) 496-7985

FAX:  (301) 402-0175


This program is described in the Catalog of Federal Domestic Assistance

Nos. 93.866 and 93.855.  Awards are made under authorization of the

Public Health Service Act, Title IV, Part A (Public Law 78-410, as

amended by Public Law 99-158, 42 USC 241 and 285) and administered

under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR

Part 74.  This program is not subject to the intergovernmental review

requirements of Executive Order 12372 or Health Systems Agency review.


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