by Koo Sze Tak. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 148-165.

Influenza is a significant cause of morbidity and mortality worldwide. Individuals with underlying immune conditions, including the very young, are particularly vulnerable. Infection elicits lasting antibody and T cell-mediated immune responses although antibody-mediated protection is limited due to the mutagenic nature of influenza viral surface antigens. T cell responses, in contrast, target conserved viral proteins and can protect from highly disparate strains. Compared to circulating memory, non-circulating, lung tissue-resident memory T cells (TRM) generated following influenza infection mediate enhanced viral clearance and protection following challenge. Thus, vaccination strategies promoting TRM may convey enhanced protection from disease compared to those relying on circulating responses. The factors governing TRM generation, however, are unclear and whether individuals most susceptible to infection, such as the very young, generate functional TRM is not known. This body of work investigates the nature of T cell responses and TRM establishment following influenza vaccination and infection in early life and adulthood. We have identified distinct capacities of commercially available inactivated influenza virus (IIV) and live-attenuated influenza virus (LAIV) vaccines to elicit protective responses with IIV inducing strain-specific neutralizing antibodies and LAIV generating lung-localized, virus-specific TRM capable of providing heterosubtypic protection upon viral challenge. We have further found that infants generate robust primary T cell responses following influenza infection or LAIV vaccination comparable to adults. However, mice infected or vaccinated in infancy fail to efficiently generate TRM and are less protected from subsequent infection in adulthood. We have identified enhanced expression of T-bet, known to promote effector differentiation while limiting memory T cell establishment, by primary infant effectors and further demonstrate that heterozygous infants expressing reduced T-bet generate lung TRM comparable to adults. Together, these findings have implications in influenza vaccine design, highlighting differing mechanisms of protection between IIV and LAIV, establishing TRM as a correlate of vaccine-mediated protection to influenza, as well as identifying cell-intrinsic dysregulation of a transcriptional pathway early in life necessary for effective lung TRM generation.

The purpose of this research was to determine the relationship of the slime layer antigen(s) to the "101" or LPS antigens and to attempt to evaluate the role of antibodies against the latter in protection against experimental infections in mice with the homologous strain of Pseudomonas aeruginosa. Results from agglutination tests, chromatographic separations, passive protection tests, and characterizations of the antigens by gel double diffusion do not support the concept that LPS is a necessary portion of the immunogenic material. The immunogenicity of LPS can be attributed to co-purification of residual amounts of slime layer antigens on the washed cells from which LPS was extracted.

The pathogenesis of autism has proven difficult to characterize. However, in many recent studies, it is suggested that the onset of this disorder is the result of multiple etiological factors, which include genetic, immunologic, and viral elements. Possible immunological influences found in subpopulations of patients with autism include decreased lymphocyte responsiveness, reduced natural killer cell activity, abnormal response to rubella vaccine, abnormal immune response to brain tissue, and decreased plasma levels of the fourth component of complement(C4). These aberrations and others imply a possible autoimmune mechanism in some cases for the development of autism. C4 deficiencies have been found in subjects with established autoimmune disorders, such as systemic lupus erythematosus and chronic active hepatitis, in recent investigations. There is also evidence that the major histocompatibility genes play an intimate role in autoimmune processes. Therefore, in knowing that the C4 genes are closely linked to the major histocompatibility genes, this study determined and analyzed the human leukocyte antigen profile of autistic patients, their siblings, and parents. In this study, it was found that the C4B complement null allele occurred in autistic patients at nearly twice the frequency compared to normals. However, the C4A complement null allele frequency was not found to be significantly altered. Several extended haplotypes were represented within the patients studied. However, the extended haplotype B44- SC30-DR4 was the only one found at a significantly increased frequency. Further investigations are needed to better understand the significance of these findings.

Ph.d.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 4 uppsatser.

Thesis (M.D.)--University of Adelaide, Dept. of Paediatrics, 1991. / Includes bibliographical references (leaves 287-310).

Thesis (Ph. D.)--Cornell University, August, 1995. / Vita. Includes bibliographical references (leaves 155-205).

Thesis (Ph. D.)--University of Nevada, Reno, 2002. / Includes bibliographical references. Online version available on the World Wide Web.