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OPTIMIZING IMMUNE

DEVELOPMENT for protection


against infection & allergy

WISTIANI
UKK Alergi & Imunologi
IKATAN DOKTER ANAK INDONESIA
30 Juli 2017
Dr. Wistiani, SpA(K), MSi Med
Kepala Divisi Alergi-Imunologi
Departemen Ilmu Kesehatan Anak RSUP Dr. Kariadi/FK UNDIP

Tempat/tgl lahir : Wisconsin, AS/6 Juli 1962


Alamat : Pandana Merdeka R-27 Ngalian Semarang
Alamat e mail : wistiani@yahoo.com
Pendidikan :
S1 : FK Undip 1989
S2 : FK Undip-Nijmegen Radboud Medical Center Netherlands
S3 : FK Undip (dalam studi)
Karya ilmiah:
1. Syndromic Mental Retardation: Diagnosis and Molecular Screening
2. Faktor Risiko Alergi Pada Anak: Studi di RSUP Dr. Kariadi Semarang
3. Karakteristik Klinis Penderita Lupus Eritematosus Sistemik Pada Anak di RSUP Dr. Kariadi Semarang
4. Hubungan Antara Kadar Leptin dan Seng Serum Dengan Atopi Pada Anak Dengan Obesitas
5. Risbiniptekdok : Pengaruh Suplementasi Seng (Zn) Terhadap Respon Imun Penderita Obes
6. Perbedaan Kadar Hepatocyte Growth Factor Plasma Pada Awal Sepsis Dengan Dan Tanpa Disfungsi Hepar
7. Kolerasi Antara Kadar Fosinofil Sekret Hidung dan Darah Tepi Pada Anak Dengan Rinitis Alergika
8. Hubungan Antara Fungsi Fagositosis Netrofil pada Sindroma Nefrotik Resisten Steroid Dengan Sindroma Nefrotik Sensitif
Steroid
9. Pengaruh Kecacingan Terhadap Jumlah Eosinofil Darah Pada Anak Usia 6 10 Tahun
10. Medica Hospitalia : Correlations Between Serum Lepine, Zinc, and IgE in Obesity
11. APAPARI : Effect of Zinc Supplementation on Cytokines Profile of Atopy
OUTLINE

Immune system development in early life


Optimal immune system definition, how to achieve it
The benefit of optimal immune system for long term health
The role of optimal immune system/immunity in development of
allergy and infection
The association of immune system and gut microbiota growth in
early life
Nutrition plays important role in immune system development
What nutrition can do related to management of allergy and
infection
Nutrition management for allergy (prevention and management),
IDAI algorithm
1. Immune system development in early life
Maturation starts early in fetal life
B lymphocytes develop in liver at 9 weeks gestation, present
in spleen at 12 weeks
T lymphocytes at 14 weeks gestation (Thelper, Tsuppressor)

Newborn:
Acquired IgG transplacenter at adult levels
Small amounts of IgM
IgA synthesis at 2-3 weeks postnatal
Poor antibody response following immunization
susceptibility to viral infection

Hayward AR. Birth Defects Orig Artic Ser


1983
First 1000 days of life
Contributes to the quality of future life (health & disease)
-9 -24 bulan
Effectiveness
Penyakit

Kesehatan

Lahir Dewasa
Pertumbuhan & metabolisme Stunting
Kualitas
Pematangan sal cerna Alergi
hidup
Perkembangan otak dan saraf Obesity
Pematangan imunitas Penyakit Jantung
Pengenalan rasa dini Diabetes
Penurunan fungsi kognitif
The impact of breastmilk in the development of infants immune
system

a. Transfer of b. sIgA antibody


microbiotas
Present in secretion such as saliva,
breastmilk
Provides localized defense of mucous
membranes by cross-linking and
neutralization of antigens
Presence in breastmilk confers
passive immunity on nursing infant

Human breastmilk contains numerous protective factors against infectious disease developing infant
immune system
Premature discontinuation of breastfeeding may predispose to chronic disease in later life (allergy,
autoimmune)
It helps to shape infant mucosal gi tract immunity
Factors shaping neonatal microbiome

Window of opportunity to microbial modulation


HUMAN BREASTMILK

Evidence based medicine:


First 3 mo of exclusive breastfeeding will protects children against allergic rhinitis
(Mimouni BA, et al. Acta Paedtr 2002;91)

Breastfeeding facilitates immunological tolerance so decrease future risk of autoimmune


diseases (Hanson LA, et al. Pediatr Int 2002;44)

Infants who are breastfed showed larger thymus glands thus it has direct effect on T
lymphocytes development (Hasselbalch H, et al. Acta Paediatr 1996;85)

It antibodies confer defence aginst every disease the mother has ever been exposed to
provide a dynamic maternal immune protection nurtured transmitted to the suckling
infants

Colustrum contains macrophages, neutrophils that engulf microbial pathogens

Human breastmilk is source of cellular, humoral, either innate and


adaptive immunity
Immune System

Activation (Pro- Tolerance (Anti-


Inflammation) inflammation)

Pathogenic Bacteria Commensal bacteria

Virusses Food antigens

Parasites Environmental antigens


How to achieve optimal immune response?

BALANCING IMMUNE RESPON


Failure resulting in immunodeficency states
Overstimulation resulting in hypersensitivity or allergy
Unable to recognize self and non-self will lead to autoimmunity diseases or
chronic inflammatory states

Factors influencing immune system balance are:


Nutrition
Stress
Age :

Immune system changes throughout life


Elderly: progressive dysregulation, decreased cell-mediated immunity, less
antibody response
Susceptibility to infection
Degenerative diseases
3. The benefit of optimal immune system for
long term health

Concept of immunological surveillance of cancer:

1. Primary immunodeficiency patients are prone to cancer development


2. Organ transplant recipients who are treated with immunosuppressive drugs are also
prone to cancer development
3. Hiv-infected person lead to elevated risk of cancer
4. The quantity and quality of the immune cell infiltrate found in human primary tumors
represent an independent risk factor for survival
5. Cancer cell harbor mutations
6. Cancer cells selectively accumulate mutations to evade immune destructions
7. Lymphocyte able to recognize and eliminate stressed premalignant cells
8. Strategy to treat cancer: potentiating the naturally immune response through
blockade of the immune checkpoint molecules
Therapeutic approaches for cancer

Role of NK cells

Candeias SM, Gaipl US. DOI 10.2174/1871520615666150824153523


Prevention of infection through manipulating of immune
system

Schematic graph of the different arms of the immune response to influenza over the lifetime of an
individual

Simon AK, et al. Proc. R. Soc. B


2015;282
VACCINATION: an apporach for infection diseases
prevention

Principles of vaccination:
1. Goal: to provide protective immunity by inducing a memory response
2. The antibodies are effective primarily against extracellular organisms and their products
3. Cell-mediated immunity is important in preventing intracellular bacterial or viral and fungal
infection goal: eradication of disease
NEW APPROACH: New vaccine strategies for the immunotherapy
and prevention of cancer
Old approach (non-surgical) on cancer therapy:

Targeting on rapidly dividing cells (radio- or


chemotherapy) impact on normal cells
How to prevent harming normal cells?
Basicly cancer cells are derived from the host
(normal self antigen)

The new approach are:


targeting on antigens that clearly mark the cancer
cells as different from host cells by focusing on MHC
antigens to detect foreign or abnormal proteins
made inside the cell
Berzofsky JA, et al. J Clin Invest 2004;113
4. The role of optimal immune system/immunity in development of allergy and
infection

Exposure Sensitization Activation

Treatment
Allergy trace Primary prevention: Re-exposure with
-Allergen
card -Exclusive the same allergen
identification
breastfeeding
- Hydrolyzed
- Avoid cigarette Secondary
formula, AAF, Soya
smoke prevention
- Immunotherapy
- If BF (-) partially
hydrolized formula
Identification of allergen
Avoidance
Pediatr Allergy Imunol 2008;19
5. The association of immune system & gut microbiota
growth in early life

Long-lasting effects of early-life interactions Microbial therapeutics throughout the


between the microbiome and the gut immune course of disease
system Tamburini S, et al. Nature Medicine 2016;22(7)
Lactic acid bacteria (probiotic),
vitamins enhance phagocytic
activity and NK cells. Minerals,
etc increase Tcell and B cell
response, leads to balance
immunity

Modulation of cells immune


function by food-derived
substances
6. Nutrition plays important role in immune system
development
The benefit of nutritional intervention which prevent or delay
onset of allergy:

Limited to infants with high risk of allergy


Maternal dietary restrictions during pregnancy not scientificaly
supported
Restrictions of diet during lactation not scientificaly supported
Breastfeeding at least for 4 months will delays the occurrence of
atopic dermatitis, CMA
High-risk infant who are not exclusively breastfed for 4-6 mo
onset of AD will be delayed by the use of hydrolyzed formulas
Delaying the timing introduction of complimentary foods beyond 4-
6 mo prevents the occurrence of AD little evidence
SHAPING IMMUNITY THROUGH NUTRITION
New paradigm:

Environmental modifiers in allergic disease


Prescott S, Nowak-Wegrzyn. Ann Nutr Metab 2011
PROMOTING TOLERANCE IN EARLY LIFE

Tsuji NM, Kosaka A. Oral tolerance : intestinal homeostasis and antigen-specific regulatory T cells. Trends in Immunology, vol 29 No. 11, 2008
Role of foods on immune function modulation

Foods are able to modulate immune functions (innate or


acquired immunity)
Improvement of immune functions by foods can
normalize the state of allergic or cancer patients
Or reduce the risk of diseases in healthy individuals or at
risk of atopy
Studies involving animal and human subjects

YOU ARE WHAT YOU EAT


Modulation of
Immune
Function by
Foods
The benefit of Fatty Acids

Omega-3 Fatty Acids


Polyunsaturated fatty acids (PUFA)
Eicosapentaenoid acid (EPA)
Docosahexaenoid acid (DHA)
It benefit in decreasing production of inflammatory cytokines
Increase response by white blood cells to control
inflammation
Decrease in clotting problems, cholesterol and tryclycerides

Ratio of Omega-3 to Omega-6


The optimum ratio of omega-3 : omega-6 is 1 : 4
Achieved by supplementation fish or fish oil
Evidence based medicine of nutrition on immunity

The benefit of GOS/FOS

The mixture of prebiotic oligosaccharides (scGOS/lcFOS) has similar


to breast milk positive impact on the factors of local digestive immunity
system in formula-fed infants
It may reduce the risk of allergy and infection in children aged up to 18
months of life compared to baby formula-fed infants without gos/fos*

Significant effect of a dietary mixture of GOS/FOS on the incidence of


atopic dermatitis at 6 months of age
Further study need to be performed to know the mechanism
The studied prebiotic mixture reduces the incidence of atopic dermatitis
in infants at risk, whcih proves the concept of the immune modulating
capacity of prebiotics#

*Ivakhnendo OS, Nyankovskyy SL. Pediatrica Polska


2013
#Moro G, et al. Arch Dis Child 2006
Indonesian Guideline for CMPA management
Exclusively breastfed infants:
Continue breastfeeding
Maternal avoidance of cows milk protein, calcium
supplementation
Formula fed infants:
Mild-moderate: extensively hydrolyzed formula
Severe: amino acid formula
Soy formula can be used in infants more than 6 months of age if
there is tolerability/cost/availability issue of eHF/AAF

IDAI, 2010
Protein Hydrolysates: Different
Types
Prevention

intact protein pHF eHF Amino acids


Treatment

Allergenicity
Role of iron supplementation
on health and disease
8. Nutrition management for allergy (prevention and management), IDAI
algorithm
TATALAKSANA ALERGI
SUSU SAPI PADA BAYI
DENGAN ASI
TATALAKSANA ALERGI
SUSU SAPI PADA BAYI
DENGAN SUSU
FORMULA
CONCLUSION
Effective nutritional interventions in the immune system
may find value not only in therapeutic approach but also in
the prophylactic treatment of subjects with risk of immune
dysfunction
The evolution of the immune system in individual possibly
reflects the central role of individu in the survival from
pathogen
Micronutrients and other food components are play role in
the development of immune system
Issues of pro/pre/synbiotics role on immune system still
need further studies to confirmed the mechanisms on
shaping human immune system
THANK YOU

wistiani@yahoo.com