Immune Reactions in Aging Brain and Senile Dementia

  • Kalidas Nandy
Part of the Advances in Behavioral Biology book series (ABBI, volume 23)


The immune system which provides specific defense mechanisms in our body may prove destructive in senescence. Immunologic competence is a growth-related process and may undergo deteriorative changes during aging. Such a self-destructive immunological reaction, often referred to as an autoimmune phenomenon, may give rise to pathological changes and reduction of life expectancy. There is considerable evidence in the literature to indicate that autoimmune reactions occur with increased frequency in the aged (Comfort, 1963). Although controversy exists on the processes underlying these changes, it is generally believed to result from the emergence of new antigenic stimuli or from the loss of acquired immunologic tolerance associated with aging. The autoimmune theory was first proposed by Burnet (1959). He described these changes as being due to the formation of ‘forbidden clones of cells’ arising from the derranged stem cells located in the reticulo-endothelial system, lymph nodes, spleen or bone marrow. Burch (1968), the leading proponent of the autoimmune theory of aging, proposed that several factors acting throughout life may significantly alter the process of acquired immunologic tolerance resulting in the increase of forbidden clones and incidence of autoimmune disorders. Walford (1962, 1967 and 1970), on the other hand, hypothesized that aging may be due to long-term low-grade histo-incompatability reactions among the body’s population of cells resulting in cell death. The possible deterioration of the immune system during aging in mammals has been studied by Makinodan (1976) who suggested that this might be due to either intrinsic changes in T and B cells or their interaction, thus making them less efficient.


Senile Plaque Aging Brain Senile Dementia Stumptail Macaque Antineuron Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Brody, H. Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. J. Comp. Neurol. 102:511–556, 1955.PubMedCrossRefGoogle Scholar
  2. Bruce, M.E. and Fraser, H. Amyloid plaque in brain of mice infected with scrapie morphological variation and staining properties. Neuropathol. Appl. Neurobiol. 1:189–192, 1975.CrossRefGoogle Scholar
  3. Burch, P.R.J. An inquiry concerning growth, disease and aging. Oliver and Boyd, Ltd., Edinburgh, 1968.Google Scholar
  4. Burnet, F.M. Auto-immune disease. II. Pathology of the immune response. Brit. Med. Journal 2:720–725, 1959.CrossRefGoogle Scholar
  5. Burnet, F.M. An immunological aspect of aging. Lancet 2:358–360, 1970.PubMedCrossRefGoogle Scholar
  6. Colon, E.J. The cerebral cortex in presenile dementia. Acta Neuropath. (Berl) 23:281–290, 1973.CrossRefGoogle Scholar
  7. Comfort, A. Mutation, autoimmunity and aging. Lancet 2:138–140, 1963.PubMedCrossRefGoogle Scholar
  8. Diederichsen, H. and Pyndt, I.C. Antibodies against neuron in a patient with systemic lupus erythematosis, cerebral palsy and epilepsy. Brain 93:407–412, 1968.CrossRefGoogle Scholar
  9. Divry, P. La pathochimie generale et cellular des processus senile et preseniles. In: Proc. First International Congress, Neuropath., Rome, 2:313, 1952.Google Scholar
  10. Eddington, T.S. and Dalessio, D.J. The assessment of immunofluorescence methods of humoral and antimyelin antibodies in man. J. Immunol. 105:248–255, 1970.Google Scholar
  11. Ellis, R.S. Norms for some structural changes in the human cerebellum from birth to age. J. Comp. Neurol. 32:1–33, 1920-1921.CrossRefGoogle Scholar
  12. Espana, C., Gajdusek, C., Gibbs, C.J., Osburn, B.J., Gribble, D.H. and Cardinet, G.H. Transmission of Creutzfeldt-Jakob disease to the stumptail Macaque. Proc. Soc. Exp. Biol. Med. 149:723–724, 1975.PubMedGoogle Scholar
  13. Field, E.J., Caspary, E.A. and Ball, E.J. Some biological properties of a highly active encephalitogenic factor isolated from human brain. Lancet 2:11, 1963.PubMedCrossRefGoogle Scholar
  14. Filppi, J.A., Rheins, M.S. and Nyerges, C.A. Antigenic cross-reactivity among rodent brain tissues and stem cells. Transplantation 21:124–128, 1976.PubMedCrossRefGoogle Scholar
  15. Fraser, H. and Bruce, M.E. Argyrophilic plaques in mice inoculated with scrapie from particular sources. Lancet 1:617–618, 1973.PubMedCrossRefGoogle Scholar
  16. Fraser, H. and Dickinson, A.G. Scrapie in mice. Agent strain differences in the distribution and intensity of grey matter vacuolation. J. Comp. Pathol. 83:29–40, 1973.PubMedCrossRefGoogle Scholar
  17. Glenner, G.G., Ein, D. and Terry, R.D. The Immunoglobulin origin of amyloid. Am. J. Med. 52:141–147, 1972.PubMedCrossRefGoogle Scholar
  18. Glenner, G.G., Harbough, J., Ohms, J.I., Harada, M. and Cuatrecasas, P. Amyloid protein: the amino-terminal variable fragment of immunoglobulin light chain. Biochem. Biophys. Res. Commun. 41:1287–1289, 1970.PubMedCrossRefGoogle Scholar
  19. Goldberg, B. and Green, H. Cytotoxic action of immune gamma-globulin and complement on Krebs ascites tumor cells. J. Exp. Med. 109: 505–510, 1959.PubMedCrossRefGoogle Scholar
  20. Green, H., Fleischer, R.A., Barrow, P. and Goldberg, B. The cytotoxic action of immune gamma-globulin and complement of Krebs ascites tumor cells. J. Exp. Med. 109:511–521, 1959.PubMedCrossRefGoogle Scholar
  21. Grunnet, M.L. Nuclear bodies in Creutzfeldt-Jakob and Alzheimer’s disease. Neurology, Minn. 25(1):1091–1093, 1975.CrossRefGoogle Scholar
  22. Heath, R.G. and Krupp, I.M. Schizophrenia as an immunologic disorder. Arch. Gen. Psychiat. 16:1–9, 1967.PubMedCrossRefGoogle Scholar
  23. Husby, G., Rijn, I.V.E., Zabriskia, J.B., Abdin, Z.H. and Williams, R.C. Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. J. Exp. Med. 144:1094–1110, 1976.PubMedCrossRefGoogle Scholar
  24. Ingram, C.R., Phegan, K.J. and Blumenthal, H.T. Significance of an aging-linked neuron binding gamma-globulin fraction of human sera. J. Geront. 29:20–27, 1974.PubMedGoogle Scholar
  25. Ishii, T. Histochemistry of the senile changes of the brain of senile dementia. Psychiat. Neurol. Jap. 60:768–781, 1958.Google Scholar
  26. Ishii, T. and Haga, S. Immuno-electron microscopic localization of immunoglobulins in amyloid fibrils of senile plaques. Acta Neuropath. (Berl) 36:243–249, 1976.CrossRefGoogle Scholar
  27. Kalter, S. and Kelly, S. Alzheimer’s disease. Evaluation of immunologic indices. N.Y. State J. Med. pp. 1222-1225, July, 1975.Google Scholar
  28. Kidd, M. Alzheimer’s disease. An electron microscopic study. Brain 87:303–320, 1964.CrossRefGoogle Scholar
  29. Krigman, M.E., Feldman, R.G. and Bensch, K. Alzheimer’s presenile dementia. A histochemical and electron microscopic study. Lab. Invest. 14:381–396, 1965.PubMedGoogle Scholar
  30. Lennon, V.A. Immunology of the acetylcholine receptors. Immunol. Commun. 5(4):323–344, 1976.PubMedGoogle Scholar
  31. Makinodan, T. Immunobiology of aging. J. Am. Ger. Soc. 24:249–252, 1976.Google Scholar
  32. Makinodan, T., Perkins, E.H. and Chen, M.G. Immunologic activity in the aged. Adv. Gerontol. Res. 3:171, 1971.PubMedGoogle Scholar
  33. Margolis, F. Senile cerebral disease: A critical survey of traditional concepts based upon observation with newer technique. Lab. Invest. 8:335, 1959.PubMedGoogle Scholar
  34. Motycka, A. and Jezkova, Z. Autoantibodies and brain ischaemia topography. Cas. Lek. Ces. 114:1455–1457, 1975.Google Scholar
  35. Nandy, K. Brain-reactive antibodies in mouse serum as a function of age. J. Geront. 27:173–177, 1972a.PubMedGoogle Scholar
  36. Nandy, K. Neuronal degeneration in aging and after experimental injury. Exp. Geront. 7:303–311, 1972b.CrossRefGoogle Scholar
  37. Nandy, K. Brain-reactive antibodies in serum of germ-free mice. Mech. Age. Dev. 1:133–138, 1972c.CrossRefGoogle Scholar
  38. Nandy, K. Significance of brain-reactive antibodies in serum of aged mice. J. Geront. 30:412–416, 1975a.PubMedGoogle Scholar
  39. Nandy, K., Fritz, R.B. and Threatt, J. Specificity of brain-reactive antibodies in serum in old mice. J. Geront. 30:269–274, 1975b.PubMedGoogle Scholar
  40. Price, G.B. and Makinodan, T. Immunologic deficiencies in senescence. I. Characterization of intrinsic deficiencies. II. Characterization of extrinsic deficiencies. J. Immunol. 108:403–413, 1975.Google Scholar
  41. Rapport, M.M. and Karpiak, S.E. Discriminative effects of antisera to brain constituents on behavior and EEG activity in the rat. Res. Commun. in Psych. Psychiat. and Behavior 1:115–124, 1976.Google Scholar
  42. Shafer, V.P. Absolute number of neurons and thickness of the cerebral cortex during aging, senile and vascular dementia, and Pick’s and Alzheimer’s diseases. Zhurnal Nevropatologii i Psikkiatrii imeni S.S. Korsakova 72:1024–1029, 1972.Google Scholar
  43. Simon, J. and Simon, O. Effect of passive transfer of anti-brain antibodies to a normal recipient. Exp. Neurol. 47:523–534, 1975.PubMedCrossRefGoogle Scholar
  44. Suzuki, K. and Terry, R.D. Fine structural localization of acid Phosphatase in senile plaques in Alzheimer’s presenile dementia. Acta Neuropaths (Berl) 8:276–284, 1967.CrossRefGoogle Scholar
  45. Terry, R.D., Gonatas, N.K., Weiss, M. Ultrastructure of senile plaques in Alzhimer’s presenile dementia. Amer. J. Path. 44: 269–281, 1964.PubMedGoogle Scholar
  46. Threatt, J., Nandy, K. and Fritz, R. Brain-reactive antibodies in serum of old mice demonstrated by immunofluorescence. J. Geront. 26:316–323, 1971.PubMedGoogle Scholar
  47. Walford, R.L. Autoimmunty and aging. J. Geront. 17:281–285, 1962.PubMedGoogle Scholar
  48. Walford, R.L. General immunology of aging. In: Advances in Gerontological Research, (Ed. B. L. Strehler), Vol. 2, Academic Press, New York, pp. 159–204, 1967.Google Scholar
  49. Walford, R.L. Immunologische aspekte des alterns. Klin. Wschr. 47: 599–605, 1969.PubMedCrossRefGoogle Scholar
  50. Walford, R.L. Immunologic theory of aging. Williams and Wilkins, Co., Baltimore, 1970.Google Scholar
  51. Walford, R.L. and Hildemann, W.H. Chronic and subacute parabiotic reactions in the Syrian hamster: Significance with regard to transplantation immunology, experimental amyloidosis and an immunologic theory of aging. Transplantation 2:87–115, 1964.PubMedCrossRefGoogle Scholar
  52. Weksler, M. and Hutteroth, T.H. Impaired lymphocyte function in aged human. J. Clin. Invest. 53:99–104, 1974.PubMedCrossRefGoogle Scholar
  53. Wisniewski, H. Infectious etiology of neuritic (senile) plaques in mice. Science 190:1108–1110, 1975.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Kalidas Nandy
    • 1
  1. 1.Geriatric Research, Educational and Clinical CenterVeterans Administration HospitalBedfordUSA

Personalised recommendations