IMMUNOSENESCEN

CE IN ELDERLY
Grasia Maria Santos
11-148

Dokter Pembimbing:
dr. Hildebrand Hanoch, SpPD
KEPANITERAAN KLINIK
ILMU KEDOKTERAN PENYAKIT DALAM
Periode 25 Juli 2016 s/d 1 Oktober 2016

Immunosenescence:
ageing of the immune
system
Melinda Suchard, BSc, MBBCh, FCPath(SA)Clin,MMED(Clin),DTM&H

Nutrition, diet, and

immunosenescence
Monica Maijo, Sarah J. Clements, Kamal Ivory, Claudio Nicoletti

Immunologic Changes
in Frail Older Adults
George C. Wang,M.D., PhD, and Vincenzo Casolaro, M.D., PhD

IMMUNOSENESCENCE
Senescence is used to describe programmed
biological ageing, such as discoloration and death
of autumn leaves.
The term given to changes observed in the
immune system of elderly individuals.
Elderly individuals are predisposed to have more
severe symptoms from certain infections and not
having an effective immune respons to
vaccination.

AGEING OF THE
IMMUNE SYSTEM

Immunosenescence affects both innate and adaptive

immunity

Neutrophils
Neutrophils in
in ageing
ageing

Monocytes
Monocytes and
and macrophages
macrophages in
in ageing
ageing

Neutrophils numbers remain

unchanged
Their functionality is
decreased

Monocyte numbers in elderly

similar compared to younger
individuals
Decreased macrophage
precursor in bone marrow
Antigen presentation
decreased

Chemotaxis
Phagoxytosis
Apoptosis

NK
NK in
in ageing
ageing
Neutrophils numbers remain
unchanged
Cytokine and chemokine
production decreased

T-Cell senescence and the ageing

immune system
The immune system can be targeted by several
environment
Lymphocyte numbers can rapidly reduced by some
agents
Then what is our bodys response?

Lymphocyte restored by the homeostatic expansion

of surviving clones and the new generation of nave
clones from lympho-poietic tissues
With advancing age, the contribution of
lymphopoiesis become less prominent

 The ageing of immune system is associated with decline

in immunity against infections
Among the factors involved, cytokines and mediators
produced by immune system most prominently IL-6 and
TNF-a
Produced repeatedly can be accounted
inflammation

Chronic

Cardiovascular disease, autoimmune disease, RA, cancer,

dementia
While these changes may suggest a hyperactive,
uncontrolled state of ageing immune system, they
ultimately originate from a progressive immune defect.

WHAT IS THE
UNDERLYING CAUSE
OF THESE DEFECTS?

Thymus Involution
T-cells develop and mature in thymus
Thymus is simply no longer needed
during adult life because T cells are
long-lived.

Generated during childhood before thymic

involution

Thymus is a disposable soma, and it

involution with age represents
conservation and redirection of energy.

 Thymic athropy dramatically reduced

numbers of emigrant in chronologic
ageing-> nave T-Cells decreased and
memory T-Cells increased
Thymic function gradually starts to
decrease from the first year of life.
The true thymic epithelial space begins to
involutes shortly after birth and decreases
~ 3%/yr through middle age (3545)
years of age and continues to decrease
~1%/yr throughout the rest of life.
Major shrinking replaced with fat

 The balance of nave to memory T-Cells shifts with

age.
Normally: antigen exposure coverts nave T-Cells
into memory T Cells, but in elderly this function is
not implemented.
Approximately 50% of T-Cells are nave in young
adult, whereas most T-Cells are memory T-Cells in
elderly
Results:
Results: Decreasing
Decreasing capacity
capacity to
to respond
respond to
to novel
novel antigen
antigen

Thymus
Involution

Cortex

Repertoire of lymphocytes shift with aging

(membrane components shift)

Effect of CMV infection on immune

function in the elderly?
Viral infection normally cleared by CD8+ virusspecific T cells
Up to 50% CD8+ T cells in elderly reported to be
CMV-specific : may lead to impaired
responsiveness to other viral infections in elderly
people
Impaired leading to poorer cell-mediated responses against
pathogens like influenza.

In elderly, fewer CMV+ CD8+ T cells secreted

IFN compared with cells from younger people

Chronic inflammation leads to

Frailty?
Data from CHS showed that frail older adults, compared
with non-frail ones, have elevated levels of CRP
It has been shown that persistent CMV Infection is
associated with higher fraction of these terminally
differentiated, senescent CD8+ T Cells
The cell exhibit other sign of senescent, including
shortened telomeres and low proliferative response to
mitogens, remarkably resistent to apoptosis.
It has been discovered, the relationship between serum
anti-CMV antibody concentration and prevalent frailty.

DIETARY
INFLUENCE

Dietary influence on the aged immune response

Lifestyle factors can influence the ability to

mount effective immune responses
Nutritional status and dietary:
Micronutrients
Vitamin E
Zinc
Carotenoids
Probiotics
Prebiotics
Polyphenols

Nutrients
Micro

Vitamin E

Can enhance T-Cell functions

Dose: 200IU/d of dl-a-tocopherol

Zinc

Its deficiency leads to reduced immune cell

proliferation, specific reduction in NK activity &
neutrophil function
Dose: 45mg/d

Carotenoid
s

Bactericidal activity increased

High dose (30-60mg/d): increased T-Helper
function
Fruit and vegetable (2-5portions) improved the
responses of Pneumovax II vaccination

Prebiotics

Galacto-oligosaccharide (B-GOS) 5w
NK and phagocytic activity increased, TNF-a, IL-1,
IL-6 decreased
Fructo-oligosaccharide (FOS) 12w
Enhance immune function in frail elderly-> IL-6
and TNF-a decreased

Probiotics

PMN cell phagocytic activity increased

Adm of Bifidobacterium lactis (3x1011CFUs/d)-6w

Polyphenol

Increased production of protective IgA and IgG,

Conclusions
Immunosenescence changes affect both
innate and adaptive immune cells
populations and function
Immunosenescence affects the response to
vaccines. Vaccine-induced antibody
responses wane rapidly in the elderly
Prevalent frailty and the risk of frailty
increased in elderly with high titers of CMV
IgG and IL-6 plasma conc.
Changes in nutrition and lifestyle can be
affective at preventing age-related illness
and possibly immunosenesce

You can live to be a

hundred
if you give up all the things that
make you want to live to be a
hundred
Woody Allen