09 - March 13, 2013.docx

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University of Toronto St. George
Cell and Systems Biology
Gray- Owen

MIJ485 – Immunity and Age Limited by the fact that must do tests in animal models – always imperfect Cannot test vaccines on humans without testing in mice or other animal models – so if the latter is unsuccessful, a potentially successful human vaccine may never reach the population Childhood vaccine – some vaccines may have no effect in adults but protective in children Very specific reasons why certain vaccines work differently in children vs adults – immune responses differ young vs older – the young and the old are more susceptible to an infection – WHY? In the young, immune system is not yet mature; in the elderly, ability to produce new cells, functional and structural changes, very different challenge as seen a life time’s worth of antigens and pathogens, many of which are pathogens they are still infected with. Neonatal vaccination Most vaccines are not introduced until after birth – birth is optimal time to vaccinize children - exposure, contact – ideal vaccine would be one dose and administered early in life because they are exposed to contact with health care system them – ALSO some infections happen early on Neonatal immunity – somewhat biased away from response against mother-derived antigens/proteins when in womb but soon after birth too – increase susceptibility of pathogens – problem with classical definitions – most of the B cell response immunity – can get response when immunize newborn – most of response is not to make anybody as to make memory cells – early on, baby has maternal antibodies and later on, do that alone – if frequent exposure to pathogen, want to build up memory B cells Not a good antibody response – it has elicited a memory response – boost this later on – Getting vaccines for younger children – one dose – focus on adjuvant Maternal antibody can inactivate or suppress response to vaccine – problem! Immunize mother – if half-life is similar, more antibody given to child at time of birth, protection for a longer time – Amount of antibody decreased in immunized mothers – at four weeks, similar levels of antibody regardless of whether mother was immunized or not Pup making the antibodies in the non-immunizd mother whereas in immunized mothers, at 4 weeks, mostly maternal anitobides Let pups grow until maternal antibodies gone – boost with antigen again – the pups from immunized mice have antibody response – the immune response is relying on mother at young age and develop memory response Immunize mother idea Vaccine interference? Titers before and after immunization – no response to vaccine appears but depends on comparison to BASELINE Immunosenescene? As people age, less immune response Effect of age known from flu, other vaccines Attributed to? Antibody repertoire is not gremline encoded – so even identical twins have different responses Response to red virus – some are the same Both have protective effect against antigen – if exposed to another virus later on, different outcome in disease and in Original antigenic sin – if to an epitope that is not protective, body sees it and expands memory population to this non-protective epitope – OAS – if immune system has seen it before, will focus on this – Immunize different animals with antigen – in developing vaccines, not an all ornothing – a vaccine can hopefully make things better but some will get different outcomes of disease and some cases Heterologous immunity – cross reactive epitopes between two different viruses or bacteria Heterotypic immunity – epitopes preserved on diverse strains of a single virus M1 protein – when get infected again, strong resonse against virus but may be not protective – not protective epitope – so when think about making live recombinant flu virus or bacterial vaccines, the pathogens themselves are trying to subvert the immune response – by removing epitope from M1 protein and infecting with life vaccine strain – get more braod immune response Outer member vesicle blebs – over 95% - if remove prions from strains, get more braod immune response against other antigens – by removal, increase your ability to generate heterotypic immunity Immunodominant – antigen or protein expressed by pathogen – what tends to happen is: immunize with protein and a large part of antibody response will be against one or few variant epitopes Can get immune response to other peptides, but DO NOT WANT this Characteristics of the peptide important; whether the epitope similar to human self antigens Stage of infection – have immune response against something early – Glycosylation – immune response puts down – if put sugar right in the middle, two epitopes go through the roof
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