Pembimbing :Dr. Hildebrand Hannoch Victor

Watupongoh, Sp.PD

Disusun Oleh :Advenny Elisabeth

1161050151

LOW IMMUNE RESPONSES IN

GERIATRIC

Defined as a progressive functional decline, or a gradual deterioration of

physiological function with age, including a decrease in fecundity or

the intrinsic, inevitable, and irreversible age-related process of loss

of viability and increase in vulnerability

AGING

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)

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

Aged Individuals Have :

Normal aging is marked by

dysregulated immune

function or immunosenesc

ence

One of the biggest threats

to reaching reproductive

age was infectious diseases

Aging is also characterized by elevated

systemic inflamation

Strong immune responses early

in life were essential for

human survival

Older adults tend to be more

susceptible to acquiring infectious

diseases, have worse outcomes

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Aging Endocrine Function

Brain Function

Cardiovascular Health

Muscles and

Bones problemsOxidative

Stress

Glucose Disregulatio

n

IMMUNOSENESCENCE

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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

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Immunosenescence ome causes

•Lifelong antigenic stress•Accumulation of effector T and memory cells•Filling of the immunological space •Reduction of naïve T cells•Deterioration of clonotypical immunity•Up-regulation of the innate IS

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Immunosenescence e factors associated

•Mitochondrial damage causing tissues disfunction•Micronutrient inadequacy accelerates aging because of metabolic malfunctioning•The number of telomeres is proportional to life expetancy. They avoid DNA damage•DCs reactivity to self antigens – risk of triggering autoimmune diseases

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Immunosenescence me 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 acts

Function of Immune System is PROTECTION against:

1. Bacteria2. Virus3. Fungus/ multicellular parasites4. Cancer5. Toxins

Tissues and Organs Important for Immune Function

• Cells derived from stem cells: liver, bone marrow

• Cells are stored, multiply, interact, and mature in: thymus, spleen, lymph nodes,

blood• Transport: lymphatic vessels

Accessory Organs• Appendix, tonsils, intestines

Bacterial Infection

Macrophage

Bacteria

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

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)

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

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

Major Diseases Associated with Aging in Immune Function

Increased tumor incidence and cancer

Increased incidence of infectious diseases caused by:E. ColiStreptococcus pneumoniaMycobacterium tuberculosisPseudomonas aeruginosaHerpes virusGastroenteritis, bronchitis, and influenza

Reappearance of latent viral infection

Autoimmune diseases and inflammatory reactions:ArthritisDiabetesOsteoporosis

Dementia

Hallmarks of ImmunosenescenceAtrophy 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

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Questions?