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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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