Sei sulla pagina 1di 22

Imunosenessencekuliah wm

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

11
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

12
Immunosenescence - facts

13
Evidence for Decline in Immune Function with Aging

Aged Individuals have:


1) Increased incidence of INFECTIONS:
For example: pneumonia, influenza, tuberculosis,
meningitis, urinary tract infections

2) Increased incidence of AUTOIMMUNE DISEASE:


For example: rheumatoid arthritis, lupus, hepatitis,
thyroiditis (graves-hyper/hashimotos-hypo), multiple
sclerosis
(Predisposition toward these diseases is related to Human
Leukocyte Antigens HLA genes)
Evidence for Decline in Immune Function with Aging

Aged Individuals have:

3) Increased CANCER INCIDENCE:


For Example: prostate, breast, lung, throat/neck/head,
stomach/colon/bladder, skin, leukemia,
pancreatic

4) TOLERANCE to organ transplants:


Kidneys, skin, bone marrow, heart (valves), liver,
pancreas, lungs
Table 15-2: Some Aging Related Effects
on B-Cells

• Decreased number of circulating and peripheral


blood B cells
• Alteration in B-cell repertoire (diversity)
• Decreased generation of primary and secondary
memory B cells
• General decline in lymphoproliferative capacity
Table 15-14: Some Aging-Related Effects on T-cells
•General decline in cell mediated immunological function
•T-cell population is hyporesponsive
•Decrease responsiveness in T-cell repertoire (i.e. diversity of
CD8+ T-cells)
•Decline in new T-cell production
•Increase in proportion of memory and activated T-cells while
naïve T-cells decrease
•Diminished functional capacity of naïve T-cells (decreased
proliferation, survival, and IL-2 production)
•Senescent T-cells accumulate due to defects in apoptosis
•Increased proportion of thymocytes with immature
phenotype
•Shift in lymphocyte population from T-cells to NK/T cells
(cell expressing both T-cell receptor and NK cell receptors)
Table 15-13 Aging-Related Shifts in Antibodies
General decrease in humoral responsiveness:
Decline in high affinity protective antibody production

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

General decline in cell function

Good correlation between mortality risk and NK cell number

Increased in proportion of cells with high NK activity (i.e. CD16+, CD57-)

Progressive increase in percentage of NK cells

Impairment of cytotoxic capacity per NK cell

Increase in NK cells having surface molecule CD56


dim subset
Table 15-10 Some Aging-Related Shifts in Cytokines
•Increased proinflammatory cytokines IL-1, IL-6,
TNF-
•Increased cytokine production imbalance
•Decreased IL-2 production
•Increased production of IL-8, which can recruit
macrophages and may lead to pulmonary
inflammation
•Increase in dysfunctional IL-8
•Decreased secretion of IFN- (interferon)
•Altered cytokine responsiveness of NK cells, which
have decreased functional abilities
•Increased levels of IL-10 and IL-12 upregulated by
Antigen Processing Cells
Table 15-9 Hallmarks of Immunosenescence
Atrophy of the thymus:
decreased size
decreased cellularity (fewer thymocytes and epithelial cells)
morphologic disorganization

Decline in the production of new cells from the bone marrow

Decline in the number of cells exported by the thymus gland

Decline in responsiveness to vaccines

Reduction in formation and reactivity of germinal center nodules in


lymph nodes where B-cells proliferate

Decreased immune surveillance by T lymphocytes and NK cells