PERAN MIKRONUTRIEN TERHADAP RESPON

IMUN
IMUN PADA
PADA MANUSIA
MANUSIA

Judiono OLEH :
Dr. Judiono, MPS
Email : judi.fkundip@gmail.com
E-Mail. Judi_fkundip@yahoo.co.id

Disampaikan pada Pelatihan Pelayanan Gizi Rumah Sakit

(PGRS) tahun 2019 tanggal 22 Agustus 2019
 BAGAIMANA PERAN GIZI
MIKRO PADA RESPON IMUN?

Peranan gizi → terapi dasar

(bukan terapi pelengkap)

Karbohidrat, Protein, Lemak, Vitamin,

Mineral, dll
LATAR BELAKANG

1. Gizi berhubungan erat dengan sistem

immun manusia.
2. Mikronutrient  (Mineral and Vitamin)
Minerals : Zn, Cu, Cr, Se, Mn, Fe, Co
Vitamin : A, E, C,  carotene
3. Kondisi Stress
4. Kebutuhan mikronutrien untuk respon
imun yang optimal lebih besar dari jumlah
yang dibutuhkan untuk pertumbuhan dan
reproduksi(Harmon,1994; Scaletti,1992)
IMMUNO NUTRIENTS
ZAT GIZI YANG BERPERAN MENINGKATKAN IMMUN TUBUH

Glutamin
Arginin
N-acetylcysteine ( as acystein precursor)
Asam amino rantai cabang
Nukleotida
Asam lemak omega 3 rantai Panjang
Vitamin antioksidan
Mineral (Trace elemen)
Taurin
IMMUNODEFICIENCY
(THYMIC ALYMPHOPLASIA) KELAINAN GENETIC YANG
MENYEBABKAN BAGIAN UTAMA DARI KEKEBALAN TIRUAN
(SEL B DAN T)

AUTOIMMUNE
SUATU PENYAKIT KETIKA SYSTEM KEKEBALAN MENYERANG
KEKEBALAN TUBUH SEL YANG SEHAT

Artitis rheumatoid
Lupus eritmatosus sistemik
Penyakit seliak (reaksi terhadap konsumsi
gluten, protein)
HIV
Mikronutrien
Minerals
Zinc (Zn)
Copper (Co)
Chromium (Cr)
Selenium (Se)

Vitamins (Antioxidants)
Vitamin A, C, E
Carotenoids (beta carotene )
MINERALS
Review

Immune Function and Micronutrient Requirements

Change over the Life Course
Silvia Maggini 1,*, Adeline Pierre 1 and Philip C. Calder
 Zinc

Zinc is component of numerous enzymes

Super oxide dismutase (SOD)
RNA Polymerase
DNA polymerase
Ribonulease
Thymidine kinase
Zinc influences host defence mechanisam via:
• Phagocytic activity
• Cell mediated immunity
• Humoral immunity

Phagocytic activity
Zinc enhances phagocytic activity of
macrophages
and neutrophils (Babior, 1978)

Phagocytic activity through respiratory burst

( McCord & Fridovich,1969 ; Chew, 1996)

Increase release of vasoactive amines by

basophils
 Imunitas yang dimediasi sel;
Meningkatkan kekebalan yang dimediasi sel T
Seng adalah kofaktor untuk hormon timin
thymulin

Thymulin deficiency

Impaired T lymphocyte
proliferation

Impaired T lymphocyte function

Kekebalan humoral:
Meningkatkan produksi
(Bach,1983)
antibodi
 Mekanisme kekebalan tembaga
Aktivitas fagositosis
Neutrofil
Monocyte

Respon Humoral:
Meningkatkan produksi antibodi
Produksi ab menurun pada diet
defisiensi Cu (Gengelbech dan tombak,
1998)
 TEMBAGA (COPPER)

Tembaga adalah komponen dari

Superoxide dismutase (SOD)

Ceruloplasmin.
Memodulasi respons peradangan dengan fagositosis
Copper..

Imunitas yang dimediasi sel

• Terutama melalui T-limfosit (Th, Tc) oleh
produksi sitokin
menghambat replikasi virus
Produksi interlukin
Pematangan sel B
Aktivitas sel NK
Daya tarik taktik kemo

Faktor nekrosis tumor 

Bertindak membunuh sel tumor
itu.
 CHROMIUM

Komponen Glucose Tolerance Factor (GTF).

• Meningkatkan aktivitas insulin (Cheng dan Mowat, 1999)
Memfasilitasi interaksi antara insulin dan reseptor insulin
dalam jaringan target.
• Mengurangi tingkat kortisol dalam stres.
Cont.. In stress

Increased cortisol
in blood

Antagonist the
insulin action

Prevents glucose uptake

by insulin receptor

Prevent entry of glucose

to vital tissue

Immune system
under stress.
(Orth,1992)
VITAMINS
SAYURAN, BUAH SEGAR & IKAN
Sumber :Francesco Pecora, Federica Persico, Alberto Argentiero, Cosimo Neglia and Susanna Esposito. 2020 Review
The Role of Micronutrients in Support of the Immune Response against Viral Infections, Nutrients 2020, 12, 3198;
doi:10.3390/nu12103198
 Vitamins

• Bertindak sebagai antioksidan alami

• Termasuk Beta karoten dan vitamin A, Vitamin
E, Vitamin C
• Lindungi jaringan dari kerusakan yang
disebabkan oleh radikal bebas.
• Radikal bebas adalah,
• Dihasilkan dalam metabolisme seluler normal
• Bereaksi dengan enzim, DNA dan kerusakan
jaringan
• Radikal bebas yang umum adalah super oksida,
hidrogen peroksida, radikal hidroksil, radikal
asam lemak
Review

Immune Function and Micronutrient Requirements

Change over the Life Course
Silvia Maggini 1,*, Adeline Pierre 1 and Philip C. Calder
THF ; Tetrahidrofolat
THFA ; Asam Tetrahidrofolat
PmGA ; Asam ptepteloilmonoglutamat
PABA ; Para - Aminobenzoat dan Asam Glutamat
SAM ; S-AdenosilMetionin
SAH ; S-AdenosilHomomsistein
MS ; Metionin Sistein
 Antioxidant system of mammalian cells
Component Location Nutrient Function
involved
Superoxide Cytosol Cu,Zn,Mn An enzyme that converts
dismutase super oxide to hydrogen
peroxide
Glutathione Cytosol Se An enzyme that converts
peroxidase hydrogen peroxide to
water
Catalase Cytosol Fe An enzyme that converts
hydrogen peroxide to
water
Alpha tocopherol Membrane Vit E Break fatty acid
peroxidation chain
reaction
Carotene Membrane Carotene Prevents initiation of fatty
acid peroxidation chain
reactions
Smith et al.,1984
Role of antioxidant on immunity

Miller and Slebodzinska, 1993

 Vitamin E and Selenium
Vitamin E
• Vit E mengurangi radikal bebas lemak berbahaya.

• Meningkatkan aktivitas fagositik neutrofil,

• makrofag dan sel NK. (Miller, 1993)
• Antioksidan utama dalam darah.

Selenium
• Peran biokimia melalui glutathione peroksida
• Meningkatkan fungsi neutrofil
Gambar Peran asam retinoat dan 1,25 (oH) 2VD3 dalam homing limfosit spesifik jaringan.
a | Asam retinoat yang diproduksi oleh jaringan limfoid terkait usus (GALT) -residen sel dendritik dan mungkin oleh sel lain, seperti sel epitel
usus, secara potensial menginduksi ekspresi reseptor usus 47-integrin dan CC-chemokine receptor 9 (CCR9) dengan mengaktifkan sel CD4 +
dan CD8 + T. Asam retinoat juga menghalangi induksi reseptor pelacak kulit oleh sel T, termasuk CCR4

Sumber : J. Rodrigo Mora, Makoto Iwata, Ulrich H. von Andrian. 2008. Vitamin effects on the immune system: vitamins A and D take
centre stage. Nature Reviews Immunology volume 8, pages685–698 (2008)
Sumber :
Marwa K. Ibrahim,a Mara Zambruni, Christopher L. Melby,d Peter C. Melby. 2021. Impact of Childhood Malnutrition
on Host Defense and Infection. Clinical Microbiology Reviews. October 2017 Volume 30 Issue 4
Cont…

Vitamin E and Selenium

• Peran biokimia melalui glutathione

peroksida
• Meningkatkan fungsi neutrofil

• Sapi ditekan immuno ketika konsentrasi

plasma vitamin E dan Se rendah (Grasso et
al., 1990)
PRINSIP HOMEOSTASIS → STABIL, DINAMIS, DAN SEIMBANG
Milk and plasma levels of vitamin E in healthy and
mastitis cows

Milk Plasma

n=75

Aroshi etal, 1986

• Supplementation of Vit E (1500 IU) and Se (0.3ppm) increases plasma
concentration of vitamin E and reduce incidence of mastitis
(Smith,1986)

Plasma concentration alpha tocoferol

 Beta carotene

• Bertindak sbg antioksidan

Beta karoten:
• Meningkatkan aktivitas fagositik enzim
neutrofil-myloperoxidase
• Meningkatkan aktivitas fagositosis makrofag -
peroksidase.
• Meningkatkan toksisitas limfosit
 Respiratory burst

Neutrophil
H20

Bacteria GSHpx
H202
Bacteria
SOD

NADPH OXIDASE 2O2 2O-2

2 e-
NADPH NADP+

Chew,1996
 SKEMA PENGARUH STRES OKSIDATIF (ROS)
YANG BERAKIBAT PROGRESIFITAS ATEROSKLEROSIS

ROS
 Agep
 AOPP
 Homosistein

Makrofag
Merusak APOPTOSIS Merusak IKB
Gliko Protein & Nephrin ENDOTEL
↑ NFKB

Albuminuri ↑ Sitokin Pro Inflamasi

(TNF-, IL-1, IL-6)

ATEROSKLEROSIS

STROKE KORONER PGK

(Bambang P; INASH, 2013)
Arterio Sklerosis and Pluq

Inhibit

Antioksidan inhibits LDL oksidation (free radicals).

Guntur, 2007
 Terjadi saat infeksi
bakteri intraseluler

Sel NK
Makrofag Limfosit
IFN- Fagositosi
IL-12 Th1 s
γ
terinduksi Limfosit Makrofag
TCD8+

Killing
Bacteria
 Pengaruh
Pengaruh ROS
ROS terhadap
terhadap endotel
endotel
ROS
Endothelial Stressor

Expression
TNFα IL1β IL6 TGFβ1

Necrosis
Apoptosis Plaque HCRP Fibrosis

Atherosclerosis

Renal Cerebral
Coronary - Stroke
Failure
Heart Disease - Dementia
Bambang p, 2010 - Parkinson
Apoptosis
Apoptosis
Lack of adequate macronutrients or selected micronutrients, especially zinc, selenium, iron, and the antioxidant vitamins,
can lead to clinically significant immune deficiency and infections in children. Undernutrition in critical periods of gestation
and neonatal maturation and during weaning impairs the development and differentiation of a normal immune system.
Infections are both more frequent and more often become chronic in the malnourished child. Recent identification of
genetic mechanisms is revealing critical pathways in the gastrointestinal immune response. New studies show that the
development of tolerance, control of inflammation, and response to normal mucosal flora are interrelated and linked to
specific immune mechanisms. Nutrients act as antioxidants and as cofactors at the level of cytokine regulation. Protein
calorie malnutrition and zinc deficiency activate the hypothalamicpituitary-adrenal axis. Increased circulating levels of
glucocorticoids cause thymic atrophy and affect hematopoiesis. Chronic undernutrition and micronutrient deficiency
compromise cytokine response and affect immune cell trafficking. The combination of chronic undernutrition and infection
further weakens the immune response, leading to altered immune cell populations and a generalized increase in
inflammatory mediators. Obesity caused by excess nutrition or excess storage of fats relative to energy expenditure is a
form of malnutrition that is increasingly seen in children. Leptin is emerging as a cytokine-like immune regulator that has
complex effects in both overnutrition and in the inflammatory response in malnutrition. Because the immune system is
immature at birth, malnutrition in childhood might have long-term effects on health. (J Allergy Clin Immunol 2005;115:1119-
28.)
Abstract: As humans age, the risk and severity of infections vary in line with immune competence according to how the immune
system develops, matures, and declines. Several factors influence the immune system and its competence, including nutrition. A
bidirectional relationship among nutrition, infection and immunity exists: changes in one component affect the others. For example,
distinct immune features present during each life stage may affect the type, prevalence, and severity of infections, while poor nutrition
can compromise immune function and increase infection risk. Various micronutrients are essential for immunocompetence,
particularly vitamins A, C, D, E, B2, B6, and B12, folic acid, iron, selenium, and zinc. Micronutrient deficiencies are a recognized
global public health issue, and poor nutritional status predisposes to certain infections. Immune function may be improved by
restoring deficient micronutrients to recommended levels, thereby increasing resistance to infection and supporting faster recovery
when infected. Diet alone may be insufficient and tailored micronutrient supplementation based on specific age-related needs
necessary. This review looks at immune considerations specific to each life stage, the consequent risk of infection, micronutrient
requirements and deficiencies exhibited over the life course, and the available evidence regarding the effects of micronutrient
supplementation on immune function and infection.

Keywords: adults; age-related immunity; deficiency; elderly; immunosenescence; infants; infection;

micronutrients; older people
 KESIMPULAN
Immuno nutrients adl zat gizi yang berperan meningkatkan immun
tubuh Glutamin Arginin, N-acetylcysteine ( as acystein precursor),
Asam amino rantai cabang, Nukleotida, Asam lemak omega 3 rantai
Panjang, Vitamin antioksidan, Mineral (Trace elemen), Taurin
Immunodeficiency (thymic alymphoplasia) kelainan genetic yang
menyebabkan bagian utama dari kekebalan tiruan (sel B dan T)
Autoimmune adalah suatu penyakit ketika system kekebalan
menyerang kekebalan tubuh sel yang sehat
Zinc and copper meningkat kekebalan sel & humoral mediated
immunity
Chromium menstemulir respon immun pada keadaan stress
Vitamin E and Se, Zn, Mn menstimulir kekebalan melawan infeksi
intra mammary infection
Beta carotene meningkatkan baik pada kekebalan humoral dan
selular, bias juga sebagai antioxidan.
 SEKIAN
SEMOGA BERMANFAAT