11 - vaccines 2 Flashcards
surface polysaccharides have many different combinations
these different combinations are immunologically distinct and very specific
cross reactivity between different polysaccharides?
little or none
use of polysaccharides in immunity
antibdies can be generates against polysaccharides so they are exploited as vaccines
streptococcus pneumoniae causes
pneumonia
meningitis
bacteremia
both local and systemic infection
mortality and morbidity of strep pneumoniae
leading cause of mortality in very young and elderly
biggest cause of death for under 5s
major problems in vaccine development against strep pneumoniae
1- different strains have different serotypes
2 - needs strong immune system
problem:
1- different strains have different serotypes
solution?
different strep pneumon bacteria have diff combinations of polysaccs on their surface
this allows infection of those who have already made antibdies against previous strains
only produce vaccines against serotypes most liekly to cause disease in humans
by isolating polysaccs from strains
problem:
2 - needs strong immune system for vaccine
solution?
immune systems of the very young are too immature and the elderly too ineffective to recognise and respond effectively to polysacc vaccine
polysaccharides are processed via different pathways to proteins
chemical coupling –> glycoconjugate vaccine
link polysaccharide to protein carrier
polysaccharide processing pathways
different to proteins
interact directly with B cells to cause clonal B cell proliferation
T cell inderpendent
- no production of cytokines by CD4 cells
- no activation of accessory T cells, no antigen presentaion
why does polysacc only immune response look immature
lots of IgM produced
very little IgG
no immune memory
only sufficient for those with a fully functioning immune system
chemical coupling
link polysaccharide vaccine to protein carrier
converts polysacc to look like protein antigen
creates glycoconjugate vaccine
e..g diptheria toxin
t cell acitvation by glycoconjugate vaccine
- glycoconjugate is internalised into endosome of B cell where it is processed into small peptide and sugar fragments
- MHC II presentation of glycan-peptide to a/B receptor of CD4+ T cells
- T cell activated
- cytokine production, B cell maturation, memory B cell
example glycoconjugate vaccine
PCV7
very effective in under 2s
live attenuated vaccines
disabled living microbe
able to enter cytosol and replicate
antigens can then be presented to MHC I immune pathway and stimulate response - activate CD8 T cells
why are CD8 T cells critical for clearing infections in many diseases
many diseases have pathogens that grow and infect within the host cell
immune system needs to eliminate the infected cells