Antibody in the treatment of immune complex diseases

Imperial Users onl

The role of immunoregulatory cells in healthy and sick African children.

Doctoral Degree. University of KwaZulu-Natal, Durban.Abstract available in PDF.Papers from thesis on page iii

Désordres immunitaires induits par des concentrations subtoxiques de méthyl-mercure sur les lymphocytes T murins

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal

Loss and recovery of Humoral Immunity to Influenza Virus following Malaria Infection

The mechanisms of maintenance of humoral immunity to infectious pathogens, particularly the contributions of memory B cells and long-lived plasma cells in maintaining specific serum antibody titres, are not well understood. Furthermore, it is not clear whether sequential heterologous humoral immune responses and disease pathology can result in the dysregulation and loss of previously acquired antibody-mediated immune responses to unrelated antigens. Here, depletion of memory B cells using anti-hCD20 monoclonal antibodies in hCD20 transgenic mice was used to dissect the role of memory B cells and long-lived plasma cells in maintaining long-term serum antibodies after intranasal Influenza A infection. Next, an experimental model of sequential infections with Influenza A/PR/8/34 and Plasmodium chabaudi chabaudi (AS) was set up, with a 15-20 week interval between the infections, in order to investigate whether sequential infection with P. chabaudi would affect pre-established humoral immunity to Influenza A. This study demonstrates that memory B cells are essential for the maintenance of long-lived serum Ab titres to Influenza A, as depletion of memory B cells results in the eventual loss of long-lived plasma cells and serum antibodies. Sequential infection with P. chabaudi results in the loss of pre-established serum antibodies to Influenza A by inducing the loss of long-lived plasma cells in an FcγRI,II,III-dependent manner, and this renders mice susceptible to secondary infection with Influenza A. However, this loss of pre-established humoral immunity is temporary, as serum antibodies do eventually return to normal levels. These findings demonstrate a mechanism shared by memory B cells and long-lived plasma cells which ensures that serum antibodies are maintained for long periods of time in the face of continuous generation and incorporation of new specificities throughout the lifetime of the host. A more complete understanding of the parameters that affect the longevity of immunological memory and how heterologous infections influence this will be vital in our understanding of the effect of continuous exposure to infectious pathogens on the efficacy and longevity of previously established immune memory

Health-seeking behaviour for childhood illnesses in urban South Africa

In urban South Africa there has been increasing child morbidity and mortality as a result of HIV/AIDS; a paucity of data on health-seeking behaviour for childhood illnesses; high reported use of traditional medicine and general patient dissatisfaction with free public health services. This study therefore aims to investigate the main factors influencing choice of health care provider for Black children under 6 years of age in Johannesburg and Soweto, using both qualitative and quantitative methods. In-depth interviews with caregivers (n = 5), providers of traditional (n = 6) and Western (n=6) health care, as well as 5 focus groups with caregivers, provide insight into different health care beliefs and practices. An utilisation-based survey was conducted with 206 Black caregivers of children under 6 years of age from 1 public clinic in Soweto (n = 50), 2 private clinics (50 caregivers in total) in Johannesburg, 2 public hospitals (53 caregivers in total) from Johannesburg and Soweto and 2 traditional healers (53 caregivers in total) from Johannesburg and Orange Farm, an informal settlement on the outskirts of Johannesburg. The facilities where interviews took place in this study were purposively selected. Caregiver beliefs were found to be at the heart of the decision-making process. These beliefs are shaped by the caregiver's world-view, religion, family (particularly grandmothers of the child and caregiver), social networks and previous experiences. Beliefs were also found to affect the caregiver's perceptions of the child and the illness. Findings suggest that the caregiver will be limited in her decision-making by her age and accumulated knowledge, her socio-economic status as well as the availability of support and social networks. These in turn affect the degree to which distance and cost are barriers to health care-seeking. Characteristics of the provider, experiences in the past, as well as the outcome of the treatment, were all found to interact with the afore-mentioned factors to shape current patterns of resort, as well as future decisions made. When a child was unwell, caregivers usually gave home treatments first, particularly for diarrhoea, vomiting, fever, constipation and crying. Although the use of over-the-counter (OTC) medicines in this study varied according to the illness being treated, overall the higher socio-economic status (SES) respondents were more likely to use OTC medicines and less likely than other groups to use home treatments. Home treatments as well as OTC medicines were not always used appropriately. Nearly three-quarters of caregivers had given or would give traditional medicine to their child if the need arose, although this varied by education levels and SES. The most wellknown African childhood illnesses were inyoni and ibala, which in the South African world-view Western medicine is not able to treat. In general, private sector care (primary and higher) was perceived to be better than public sector care because of more thorough examinations, stronger medicines, enough medicines and generous prescriptions, no queues, friendly staff who listen and are attentive, the availability of a doctor, high-tech equipment, cleanliness and the food provided. Although the public hospitals suffer from similar problems to those found at PHC clinics, compared with the primary health care facilities they were generally thought to be better-stocked with medicines and more accessible in terms of opening hours, performing better physical examinations, having more doctors and high-tech equipment, and staff were believed to be more attentive than their PHC counterparts. Results from this study highlight the need for community and household integrated management of childhood illnesses {IMCI) which has remained underdeveloped in South Africa. In particular, this should involve understanding the symptoms that mothers themselves recognise as significant and incorporating these into health education messages, as well as educating caregivers (mothers, grandmothers and relatives) about the safe, timely and appropriate use of enemas, home treatments, over-the-counter medicines and traditional medicines. Furthermore, these results underline the need to improve patient and provider communication as well as patient care in public services, the need to include traditional healers in the community component of IMCI, as well as training Western health care providers about health-seeking behaviour in the context of the local belief system. In order to improve the future health and well-being of millions of children in South Africa, understanding the determinants of health-seeking behaviour is essential for ensuring that effective strategies are put in place and that changes are implemented where they are needed most.EThOS - Electronic Theses Online ServiceGBUnited Kingdo