Suzy Maria

POSITION
Medical Staff of Allergy and Clinical Immunology Divison,
Internal Medicine Department,
RSUPN Dr. Cipto Mangunkusumo / Universitas Indonesia

Vice Secretary of Indonesian Society of Allergy and Immunology

Secretary of Indonesian Association of Physician in AIDS Care

EDUCATION

• 2021 – present MSc in Rheumatology

University of South Wales, UK
• 2020 Allergy Immunology consultant
Faculty of Medicine of Universitas Indonesia
• 2015 Internist
Faculty of Medicine of Universitas Indonesia
• 2009 Medical Doctor
Faculty of Medicine of Universitas Indonesia
PATHOPHYSIOLOGY OF
AUTOIMMUNITY AND
IMMUNODEFICIENCY

Suzy Maria, Alvina Widhani, Evy Yunihastuti

Allergy and Clinical Immunology Division, Internal
Medicine Department
Cipto Mangunkusumo General Hospital/ Faculty of
Medicine of Universitas Indonesia

16 May 2023
 Immune System

Immune system is responsible Antigen is a piece of protein

to protect the body from that is recognized by the body
foreign objects that are as a foreign objects which will
harmful to the body trigger an immune response

Immune system has the

Normally, immune system will
capability to recognize our own
not react to our own cells (self
cells (self) and foreign cells
tolerance)
(non-self)
• Normally, immune system will not react to its own
cell (self tolerance)

SELF VS NON-
SELF

http://ib.bioninja.com.au
 A BALANCED IMMUNE SYSTEM

INTERNAL THREAT EXTERNAL THREAT

Autoimmune disease Allergic Reaction

Immune Over-reaction

BALANCED IMMUNE SYSTEM = OPTIMAL EFFECTIVENESS

Immune Under-reaction

Cancer Infection
TYPES OF IMMUNE SYSTEM
DYSFUNCTIONS
1. Hypersensitivity
• Excessive reaction towards harmless substance
• Example: allergy
2. Autoimmunity
• Immune system fails to recognize our own cells as “self”
and will attack our own cells and organs
3. Immunodeficiency
• Immune system has reduced capabilities to fight
infection or virtually nonexistent
 Immune
System
Dysfunctions

http://ib.bioninja.com.au
AUTOIMMUNE
DISEASES
 WHAT IS AUTOIMMUNE DISEASES?

• Cells of the immune system attack self-molecules (self-antigen)

• It can be systemic or organ-specific

• Systemic
The auto-immunity is directed against an antigen that is present at many different sites and can
include involvement of several organs
• Organ specific
The auto-immunity is directed against a component of one particular type of organ (e.g.
thyroid, beta cell of the pancreas, etc)
OH NOO
I’M YOUR FRIEND !!
• Both – can get overlap

http://www.ucl.ac.uk/~zchabg4/autoimmune.htm
HOW AUTOIMMUNE DISEASES DEVELOP??
Genetic
>>multigenic
hormone(estrogen, testosteron,
Susceptibility can be inherited
or acquired
Failure of self-tolerance
COMPLEX INTERACTION
Environmental
(Infection, Drug,
UV , smoking, Adjuvant, Microbiome
prolactin, vitamin D))
Activation of self reactive
lymphocyte Failure of self-tolerance

heritable changes in gene activity that

Epigenetic are not caused by changes in the
changes DNA sequence

↑self antigen
Break of tolerance
PROCESS OF AUTOIMMUNE DISEASE

Initiating Event Genetic susceptibility

Failure of self tolerance

Immune system reactivity

Autoimmunity

Severe inflammation, organ

damage/failure, and cycle of disease

Irie J, et al. Keio J Med 2005;54:121-6.

 AND
CENTRAL

TOLERANCE
PERIPHERAL

Abbas et al. Cellular and Molecular Immunology, 10th ed.

 GENETIC RISK
FACTOR

Richard-Miceli et al. Genome Med 2012;4:6.

 INFECTION AND AUTOIMMUNITY

Sfriso et al. J Leukoc Biol 2010;87: 385–95.

 Smoking and
autoimmunity

HAREL-MEIR ET AL. 2007;3(12):707-15.

WHY WOMEN GET AFFECTED
MORE THAN MEN?

• Women undergo sweeping hormonal

changes several times during their
lifetime, puberty, pregnancy, and
menopause
• These interactions between the
hormonal and immune systems
modulate the susceptibility of
women to autoimmune diseases.

Desai et al. Front Endocrinol 2019;10:265.

WHAT AFFECTS THE COURSE OF DISEASE

Smoking Hormone Age

Sun Infection Vitamin D

Exposure

Microbiome Stress
NEW THEORY: AUTOIMMUNITY AND
GASTROINTESTINAL TRACT
• Microbiome is bacteria, virus, fungus and parasite that resides in
human body
• Intestinal surface is our largest body contact with outside world
(surface area of 200 m2)
• Gut also possess large amount of immune cells
• There are 1x1013 microorganisms in our gut, the two most
dominant are Bacteroidetes and Firmicutes
• Difference in commensal bacteria in the gut will cause everyone to
response differently to similar environmental challenge/trigger

Campbel. Autoimmune Dis 2014;2014:152428.

Sorini et al. Am J Clin Exp Immunol 2013;2(2):156-71.
FACTORS AFFECTING MICROBIOME?
• Directly after birth, human gut will be colonized by microbe
• Age of gestation, methods of delivery, breast milk or milk formula, etc
• Diet
• Low in fat and high in complex carbohydrate vs high fat and high sugar
• Probiotic
• Antibiotic
• Intestinal infection
IMMUNODEFICIENCY
Introduction
• Quantitative and/or functional changes in the different mechanisms involved in both the
innate and the adaptive immune response
• Can be primary or secondary
• Primary immunodeficiency (PID)  genetic
• result from intrinsic defects in immune cells, including T cells (humoral and
cellular immunity), complement components, and phagocytes.
• Secondary immunodeficiency  acquired
• Maybe caused by medical treatment (immunosuppressive drugs, chemotherapy,
radiation), systemic disorders (infections, malnutrition, diabetes), prolonged
serious illness
• Associated with or predispose to complications, such as infections, autoimmune
disorders, and cancer
Roles of immune system components
innate immunity defense against
• humoral - complement • bacteria, some viruses
• cellular - phagocytes, NK cells • bacteria, fungi

adaptive immunity
• extracelullar bacteria
• humoral - antibodies
• Viruses

• intracelullar bacteria
• cellular - T lymphocytes
• viruses, fungi
Genomic vs phenotype of
primary immunodeficiency

Shields et al. Medicine 2017;45(10):597-604)

 Defects of
immune
response in
PID

Shields et al. Medicine 2017;45(10):597-604)

The site(s) of infection provides a clue to possible associated
immune defect

Site of infection Immune defect

Otitis media B cell deficiency
Sinusitis B cell deficiency
Pneumonia B cell deficiency
Meningitis B cell deficiency
Chronic diarrhoea B cell or T cell deficiency
Gingivitis Neutrophil/phagocyte defect
Skin infections Neutrophil/phagocyte defect
Organ abscesses Neutrophil/phagocyte defect
The infective organism suggests the immune defect

Organism Immune defect

Viruses (CMV, Herpes, T cell
Varicella)
Fungi
Candida T cell
Aspergillus T cell or phagocyte
Parasites
Giardia lamblia B cell
Pneumocystis carinii T cell
Toxoplasma Gondii T cell
Bacteria
Mycobacteria T cell
Encapsulated organisms B cell or complement
Low-virulence organisms Neutrophil/phagocyte
In thinking about immunodeficiency, the key word is
“unusual”
• An unusual frequency (Recurrent)
• An unusual duration (Persistent)
• An unusual/uncommon organism
• An unusual severity of a “usual” infection
• An unusual complication
• Shared by family members (others in your family have
or have had a similar susceptibility to infection)

These should prompt suspicion of an immunodeficiency.

 Although
Non-infective recurrent
features infections
associated are the hallmark
with immunodeficiency of an
syndromes
underlying immunodeficiency, they may not be the
presenting manifestation.
• Autoimmune phenomena e.g. • Malignancies e.g.
SLE lymphoreticular
• Allergy • Poor or delayed wound healing
• Anaemia • Vitiligo
• Thrombocytopenia • Eczema
• Diarrhoea, Malabsorption, • Recurrent aphthous ulcers
Lactose intolerance, Celiac
disease
Acquired imunodeficiencies
Infectious malnutrition INFECTION
disease: HIV

Environmental
stress Adaptive &
innate IMMUNODEFI
Age extremes: old CIENCY
age IMMUNITY

Surgery & trauma,

splenectomy

Immunosuppresive TUMOR
Genetic and
drugs *
metabolic disease
*20 mg or more per day of prednisone, 14 days or longer
NOT aerosols, alternate day, short courses, topical
Chinen J, Shearer.WT. Secondary immunodeficiency. J Allergy Clin Immunol 2010; 125: S195-202 , Epidemiology and Prevention of Vaccine-
Preventable Diseases. National Center for Immunization and Respiratory Diseases. CDC. Revised April 2009.
Abbas et al. Cellular and Molecular Immunology, 10th ed.