Overview
• Aging
• Immunosenescence
• Causes
• Factors Associated
• Models
• Proposed Model
• Other Applications
• Conclusions and Future Work
2
Immunosenescence
• Progressive changes in the IS that decreases
the individual’s capacity to produce effective
immune responses
• Decay of immunocompetence in the elderly
• Loss of functionality
3
• Sistem imunologi berasal dari stem sel
hematopoitic.
• Dikenal :
– Sel B
– Sel T.
• Berkembang ke perifer: Thimus, Limpa, Kel
getahbening.
• Berkembang menjadi bentuk yang lain.
• Menghasikan:
• Sel Pembunuh Alamiah (NKC)
• Citokin
• Khemokin
• SISTEM
• Imun permulaan (innate)
• Imun Penyesuaian (adaptive)
Sistem Humoral pada usia lanjut:
1. Berkurang produksi dari B limposit
untuk jangka lama. Oleh karena faktor intrinsik
dan defek lingkungan mikro.
2. Hilangnya kemampuan dan penguraian
imunologi. Mengganggu pusat pembentukan
germinasi.
Impak proses penuaan pada sel B
• Multifacet
– Berkurangnya produksi dari sum2 tulang
– Defek pada penyebarannya
– Pengurangan produkasi sampai ¼ atau 1/5
– Kadar didalam darah relatif normal
– Kadar dari B sel telah saturated dan sukar bereaksi
– Berkurangnya pembantu stimulan dari signal2
yang ada.
– Berkurangnya kemampuan dan titer respons
Gangguan pada T sel
• Berkurangnya ukuran thimus atau atropi
karena penuaan.
• Keratinisasi dari sel epithelial thimus (TEC)
• Terjadi negatif ganda dari pembentukan CD4,
CD8 dan lainnya.
Immunosenescence – some causes
• Lifelong antigenic stress
• Filling of the immunological space
• Accumulation of effector T and memory
cells
• Reduction of naïve T cells
• Deterioration of clonotypical immunity
• Up-regulation of the innate IS
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Immunosenescence – some factors
associated
• Decrease in responsiveness to vaccination
• CMV seropositivity
• Increase of autoantibody frequency
• Reactive oxygen species (ROS) causes damages to
cellular components over time
• Chronic inflammation
• Reduced capacity to recover from stress-induced
modifications
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Immunosenescence - facts
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Evidence for Decline in Immune Function with Aging
Increased auto-antibodies:
Organ specific and non-organ specific
antibodies directed to self
Increased serum levels of IgG (i.e. IgG1 and IgG3) and IgA; IgM levels remain
unchanged
Table 15-16 Influence of Aging on Macrophages
and Granulocytes
General functional impairment of macrophages and granulocytes
GM-CSF is unable to activate granulocytes from elderly subjects
(e.g.: superoxide production and cytotoxic abilities)
Polymorphonuclear neutrophils appear to possess higher levels of
surface markers CD15 and CD11b and lesser vesicles containing
CD69 which lead to the impairment observed to destroy a bacteria
In elderly subjects the monocyte phenotype shifts (i.e. expansion of
CD14dim and CD16 bright subpopulations which have features in
common with mature tissue macrophages)
Macrophages of aged mice may produce less IFN-, less nitric
oxide synthetase, and hydrogen peroxide.
Table 15-15 Aging-Related Changes in Natural Killer (NK) Cells