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:,Immunologyro>is': the study~of4='the+`body•s-, defense mechanisms. - .r. Specitically, it is the"study of the white blood cells (neutrophils, lymphocytesr'and- macrophagc;) and cellular or }foreign, material,. ~ The., lung and cardiovascular system have _? .. antibodies that protect the body from pathogenic microorganisms .~ . . . " . , ,Z i. ,. ; • ~... p. defective immune system (e,.g.,, pneumonia . in combined . diseases affecting these systems that the immune system helps overcome. Additionally, some-diseases are the,result of a" to Foreign compounds may cause tissue damage resulting in a secondary inflammatory response (a natural defense that attemptss to remove debris and to heal tissue damage). This can occur in the lung, for,example, following.exposure to inhaled~gases such as chlorine. Acute tissue damage, cell death, and subsequent, .:+ fibrosis (scaring) of the lungs can occur from inhalation of chlorine gas or other noxious gases. The immune system is intimately involved in this process. The acute damage and tissue damage attracts white blood cells such as neutrophils and macrophages. These cells engulf or eat tissue debris; however, enzymes can leak from these cells that may cause further damage. This inflammation stimulates fibroblasts to lay down connective tissue in the form of scar tissue. Any inflammatory process in the lung including pneumonia can result in fibrosis or scaring, which is a irreversible change in the lung.

'0a,~ +,f"'r~ t; Why sf~ould R. J. ~V Reynolds be interested tin;;<,immunology? n .... f . . +'r . . . . . ,. ~' . .. ' _ ` . ~ ,.. There are several diseasesass,ocia.ted., wi th smoking by. ~. . <. ,.. , . , . .. , ;, epidemiological;',studies,~'that, involve the •immune system. Althosr ~# ug .:, ., , . . , . ,, .. F , . ., . , . . ; ~ ,. ,. .f.. the exact relationship of;smoking to these diseases~is now known,' many of the changes are hypothesized to be related to inflammatory cells and therefore, the immune,system. diseases a're , ~~.. chronic brohii, chronic onic obstructive pulmonary ncts disease, and emphysema. Inflammatory cells ara seen in chronic bronchitis. Chronic obstructive pulmonary dissase i long-term inflammatory changes. Emphysema is hypothesized to result from increased transit time of white blood cells in certain areas of the lung which is beli3ved to result in increased concentration of proteases and free radicals from white` blood cells. These proteases and free."radicalsrare hypothesized to break down elastin and other connective tissue. In`addition, another concern is recent epidemiological studies that suggest smoking by parents may lead to an increased risk of colds and other infections in infants less than six months of a g e . A04V#x~ -- ` , The study of immunology in relationship to these disease enti ties could help elucidatu Oe mechanism of these diseases and help determine the relationship, if any, between cigarette smoking and onset of these diseases. Other product-related diseases where the immune system has been suggested as a factor include life-style related abnormalities resulting from excesses due to alcohol, food, salt, etc. These, a0

r ® e , `' r. ~ ri '" ~~. ~Why~immunology., "ini E e Scholar's Program? the , . ,. '~3*,l!: initial focus.for'this,; program-.. because of, the.. rapid:.progreas being nade in.ti. the' field,""` particularly as it relates to understanding chronic pulmonary "y,:. Idise as Other frontiers in biomedical sciences will be the focus of .future scholar's programs but initially in'order to not diffuse - L--- - -- - - -- - - - -. the RJR effort a single focus was selected. With the limited resources available, a single focus .area., was ,,chosen.c to, enable:.. . , _ , . . ~., , .,. . r,,; better selection of a few highly qualified individuals. Furthermore, this focus complements the current emphasis on,the chronic degenerative disease program and allows our Scientific Advisors to focus their search for talented, scientists',within; a limited area.

© " ~' .r~ 'F W ,. , Al,~a, "E'eins,tei$n,,;~;.H;.D,:;;. Pro~essor~of~LEled ic i ne' Epidemiology` Yale University.',x, School' "of;' Medicine n ; New Haven,;`Connecticut ogy`of chronic degenerative'' Professional Interests.- Epidemiol ' . . . d Zspases,:.:" Fred Se i tz°, , M. D. ~ P5esideiit~Enaeritus ~''` ockelr' RfeleUniversity The New York, New York ;..."~ Professional Interests: Development and methodology._ ac yn c ar y, M.D. Professor Emeritus The Rockefeller University New` York';~"'New `York Professional Interests: Biochemistry cf diseases and co-developerywith Avery, MacLeod role4'of ` DNA'jin `"cell" replication. ~ Leon °Golbekg; M.D., Ph.D. q Professor `•of `'Comrauni ty Occupa tional Duke University Medical Center Durham.North Carol ina Professional Interests: Mechanisms of carcinogenesis. n. .„,ySb'iypst•a4!M~~Sta Medicine evaluation of research of the,

he`"immune system is the basic host defense mechanism and can be establishment of immunological memory perpetrated by long lived lymphocytes` to recognize and `re'spond to anagens (foreign compounds/proteins) in a highly specific manner and; the Wai characteristics of specific immunity are: the ability of divided into specific and non-specific immunity. The central lymphocytes (memory cells) which allow the host to respond to a second contact with the anagen in an anamnestic manner with ".enhanced,.cellular,activity. Non-specific immunity refers to generalized host defense mechanisms. The specific immune system is composed of two major components, derived lymphocyte system. Basically, this is a system which now referred to as -ar thymist derived and a, berca equivalent allows the human organism to respond to and to defeat insult from foreign chemicals. This is a major problem that one sees in organ transplants. 1 »