Antibody-Forming Potential of Lymph Nodes in Aged Mice, with Special Reference to the Influence of Adjuvant

Abstract

The secondary antibody-forming potential of non-splenic lymphatic tissues during senescence was investigated in NMRI/Han mice, both at the cellular and humoral levels. The mean life span of conventionally reared NMRI/Han mice amounts to 19.86 months. After primary immunization of aged (20-month-old) NMRI mice with 4 X 10⁸ sheep erythrocytes (SE) by the intraperitoneal (i.p.) route, the primary antibody-forming potential of both spleen and lymph nodes was significantly reduced, as compared to young adult (3-month-old) controls. In contrast, the anamnestic response elicited by an i.p. booster injection of 4 X 10⁸ SE at the 44th day after primary immunization was not significantly diminished in comparison to the controls. When killed cells of Bordetella pertussis were given as an adjuvant in conjunction with the primarily injected erythrocyte antigen, both the primary immune response and the process of priming for the secondary response were found to be significantly increased in young adult as well as in aged mice. These data obtained at the cellular level were in accordance with corresponding serological findings. The impressive restitution of the antibody-forming potential evident after secondary antigenic stimulation was associated with a remarkable restitution of the lymph node morphology. This was particularly pronounced in the parathymic lymph nodes which represent the draining nodes for the peritoneal cavity. These findings indicate that the lymph nodes of the senescent individual also possess remarkable reserves in immunocompetence.

Age-Related Defense against Infection with Intracellular Pathogens

“…It is remarkable that the immune system of the aged organism is evidently capable of producing effective priming for a long-term and marked anamnestic response as already demonstrated for inanimate antigens in previous studies (5,6). The rela tively faster decrease in the reactivity of aged mice to secondary infection as compared to young adult controls became detectable only when secondary infection was transmitted as late as 13 weeks after primary infection.…”

“…On the other hand, several reports describe a striking restoration of the secondary anti body-forming potential in senescent individuals, associated with a remarkable restoration of the lymphatic structures, although the preceding primary response was found to be significantly decreased (5,6,14,15). This immunologic rejuvenation of the aged was especially pronounced with the additional administration of immunologic adjuvants (5,6). But the results of investigations on the primary and secondary immune potential against inanimate antigens certainly do not allow any conclusions con cerning the capacity of the defense apparatus against living pathogens.…”

“…This might be interpreted as an expression of the decreasing precision work of the immune system in the superintendence of the body's integrity (12,17,18). On the other hand, several reports describe a striking restoration of the secondary anti body-forming potential in senescent individuals, associated with a remarkable restoration of the lymphatic structures, although the preceding primary response was found to be significantly decreased (5,6,14,15). This immunologic rejuvenation of the aged was especially pronounced with the additional administration of immunologic adjuvants (5,6).…”

Macrophage Function in Senescence

“…These findings evidently support the concept of a general immunologic defi ciency in senescence. However, more re cently it was observed that the defense reac tivity of conventionally reared NMRI mice with a mean lifespan of 19.86 months [6] against a mouse-virulent strain of L. monocy togenes appeared to be even stronger than that of young adult controls [5], Thus, it may be concluded that at least two components of the defense system are functionally intact in aged NMRI mice, specifically sensitized T lymphocytes and activated macrophages. On the basis of such results it is conceivable that the aged individual compensates a possibly reduced T cell function by an increased activ ity of the mononuclear phagocytes, as already demonstrated in nude mice with congenital dysplasia of the thymus [2][3][4]13], Such an assumption is strongly supported by the ex periments reported here, showing that pre treatment of aged mice with DS 500 before listeric infection did not lead to such a dra matic result, as observed in identically pre treated young adult controls.…”

“…In contrast, the secondary immune response does not differ signifi cantly from that of young adult animals, indi cating a fast recovery of the lymphatic tissue function by secondary antigenic stimulation 1 This investigation was supported by a grant from the Schutzkommission beim Bundesminister des Inneren. [6,7,21,22], Such rejuvenation of the im mune system is especially pronounced when immunological adjuvants are applied in con junction with the antigen [6,7]. Surprisingly, little is known about the function of macrophages and antibacterial re sistance in the aged.…”