THE IMMUNE

REGULATION
AND RISK OF
ALLERGY
ZAKIUDIN MUNASIR
Outline
Immune system

• Non-specific first line defence

• Non-specific innate immunity
• Specific adaptive immunity (cellular vs
humoral immunity)

Immune regulation
• Immune regulation in the gut: A bridge to
systemic immunity

Immune disorders
• Hyperimmune disorders
• Hypoimmune disorders

Carbohydrates: immuno-nutrition
breakthrough
 What factors that affect development of optimal immune system in early life?

• In its development, the immune system early in life goes through rapid and radical change.
• Host, environmental and microbial factors, determine the growth and maturation of the peripheral Trends Immunol;
immune system and subsequent immune developments early in life. 2015, 36 (11):684-96
 GENETIC FACTOR ENVIRONMENT FACTOR

AGE • Allergens
• Cytokine dysregulation • Infections
• Pollutant

ALLERGIC DISEASES

Gern JE, Lemanske Jr RF. Immunol Allergy North Amer 1999; 19:233-52.
Immune Regulation Utrecht University

Th1/Th2 Paradigm
Resistance to intracellular
infections Resistance to
extracellular infections
Anti-cancer
Tolerance
Delayed type hypersensitivity
reactions
Th1/Th17 Th0 Th2

APC
T-cell mediated autoimmunity
Allergy
Graft rejection Antibody-mediated autoimmunity
 Th 1

Th 2
T reg
Natural Imbalance Utrecht University

Pregnancy and neonates

• Th2 directed immune system: cytokines down regulate cellular-immunity (Th1) > no
rejection of the fetus and or mother tissues

Th 1 Th 2
CD 69+ CD 94+
IL 2 IL 4
TNF α Recurrent Normal IL 5
TNF δ Failure Miscarriages Pregnancies IL 10

After birth

• Development of their own “healthy” Th1/ Th2 balanced immune system

Allergic Inflammation: Sensitization in Utero

T cell responses ~ 22 weeks

Cord T cell responses at birth

• mite ~ 47 %
• egg, milk ~ 75 %
• less IFN and more IL 4 & 10

IgE at birth

• milk, wheat, egg

? transplacental protein,
peptide, cytokines
Gut Microbes. 2012; 3(1): 4–14.
IMPACT C-SECTION DELIVERY MODE ON CHILD’S
IMMUNE DEVELOPMENT
Compounds with immunological
properties in human milk Utrecht University

Oligosaccharides

Field J Nutr 2005

Beneficial Microbes 2010;1(4):367-82
Med Sci (Basel). 2018; 6(3): 56
Acta Pædiatrica 2011,100:1518–
1522
 Caesarean delivery, LGA, and low 5-
minute Apgar score increased the risk
Key of food allergy.
Messages Inversely, very preterm birth was
associated with lower risk of later
food allergy.

J Allergy Clin Immunol Volume 142, Number 5

J Allergy Clin Immunol. 2009 Nov; 124(5): 1031–8.e1-4.
 A retrospective cohort study of
Caesarean Section 8,953 children aged 3-10
Delivery and the Risk of years. Children diagnosed with
Allergic Disorders in allergic rhinoconjunctivitis
Childhood
H Renz-Polster, MR David, AS Buist, WM Vollmer, EA (AR), asthma, atopic dermatitis
O'Connor, EA Frazier, MA Wall (AD), or food allergies were
identified.

Clin Exp Allergy 2005 Nov;35(11):1466-72

 The risk of being diagnosed with AR
was significantly higher in the children
born by C-section than in those
delivered vaginally: adjusted odds ratio
Results (OR)=1.37%, 95% confidence interval
(CI)=1.14-1.63.
 We identified 26 studies on delivery by c-section and
one or more of the six allergic outcomes. C-section was
associated with an increased summary:
◦ OR of food allergy/food atopy (OR 1.32, 95% CI 1.12–1.55;
Impact of C- six studies)

section on
◦ Allergic rhinitis (OR 1.23, 95% CI 1.12–1.35; seven studies)
◦ Asthma (OR 1.18, 95% CI 1.05–1.32; 13 studies)
Allergic ◦ Hospitalization for asthma (OR 1.21, 95% CI 1.12–1.31;

Outcomes
seven studies)

No association with inhalant atopy (OR 1.06, 95% CI

0.82–1.38; four studies) and eczema/atopic dermatitis
(OR 1.03, 95% CI 0.98–1.09; six studies).
Age-Related
Allergy
Prevalence
Atopic March
Nutrients. 2018;10(10):1541.
 Primary elective caesarean section (CS) should be
avoided, otherwise should be performed after 39
gestational weeks.
Maternal complications, as uterine rupture and placenta
previa/increta, increase with the number of previous
Key Notes CSs.
The impact on the neonate mainly comprises
respiratory morbidity, altered gut colonization, divergent
immune system development with increased risk for
allergies, asthma, type 1 diabetes mellitus and possible
epigenetic changes, implicated in diseases occurring
later in life.

Acta Pædiatrica 2011,100:1518–1522

 How to optimize immune system development in early life?

J Allergy Clin Immunol 2013;131:23-30

 How to optimize immune system
Fig 2 development in early life?

Renz H, et al. J Allergy Clin Immunol 2017;140:24-40.)

Journal of Allergy and Clinical Immunology 2017 140, 1-12DOI: (10.1016/j.jaci.2017.05.010)
Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions
 In view of the fact that deliveries by CS
continue to increase in both developed
and developing countries, often in the
absence of obstetrical complications or
serious maternal conditions, the need
for evidence-based counselling about
CONCLUSIONS risks and benefits for mothers and their
offspring seems to be nowadays
imperative.
THANK YOU