Patologi Sistem Imun

By Sawiji Amani
Mobile phone: 081 328 028333
E-mail: sawijiamani@gmail.com

Basic Sciences Department

Muhammadiyah Gombong University
Central Java Indonesia
 Why are we sick?
 “Enemies” in the environment in the form of
microbes and chemicals are constantly
attacking our bodies, disrupting homeostasis.

 Sometimes immune system homeostasis is

disrupted on its own

1 2

it may over-react to
 it may react to self
antigens such as 3 proteins as with
with allergies autoimmune disease
it may under-react as
with human
immunodeficiency virus
infection (HIV)
2
 1. Over-Reaksi Thd antigen
•Sistem imun bereaksi dg antigen (allergens) yang tak
menyebabkan reaksi pada byk org– mis. Tepung sari

Pollen grains Mast cell

 Antibodi IgE berikatan dg alergen menyebabkan sel mast

menghasilkan produk kimia yang disebut histamin yg
menimbulkan gejala :
 runny nose and itchy, watery eyes, with repeated exposure
resulting in a more rapid onset of symptoms
Pengobatan
 antihistamines are given to counteract the histamines
 shots containing low doses of an allergen can help a person to
become desensitized to that specific antigen 3
 2. Reaksi Thd Diri Sendiri
Occurs when the immune system sees “self” antigens
as “nonself”

 Berhub dg faktor genetik, agen infeksi, jenis kelamin

dan umur

 Respon autoimmune akibatkan kerusakan jaringan

 Some damage occurs in only one or a few organs, in other
cases it may be body-wide (systemic)

 ~ 3.5 % manusia menderita penyakit autoimmune

 Rata-rata wanita 2.7 X drpd pria

 Sbgn besar tak diketahui sebabnya/obatnya- terapi

hanya untuk mengontrol gejala
4
Why does the immune system attack the body that
it’s supposed to protect?

 Kegagalan mengenali sel sebagai “self”

 Pada rheumatic fever, antigen streptococcus antigen sangat
mirip dengan protein pada katub jantung, shg badan KELIRU
mengidentifikasi jantung sbg benda asing

 Sel tampak sbg BENDA ASING shg diserang dan

dihancurkan
 Hanya beberapa sel/organ tertentu (organ-specific) – mis.,
multiple sclerosis, juvenile diabetes, rheumatic fever
 Mungkinsystemic - mis., systemic lupus erythematosus,
rheumatoid arthritis

5
 Penyakit Otoimun
 Sistem Imun menghasilkan antibodi yang
menyerang sel tubuh sendiri (otoantibodi)
Akibat :
- berupa kerusakan organ yang abnormal, mis :
diabetes otoimun
- Deposisi kompleks antigen antibodi (rheumatoid
artritis)
Terapi dg obat penekan sistem imun
- Kortison (menekan lekosit) & imuran
(menghambat pembelahan sel B dan T)
Lebih sering terkena pada wanita
Examples of autoimmune diseases

 Organ-specific

 Multiple Sclerosis

 Juvenile Diabetes

 Systemic

 Systemic Lupus
Erythematosus

 Rheumatoid arthritis

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Penyakit Auto Imun
 1. Rheumatic Fever
 usually occurs between 1-5 wks after a strep infection
 the Streptococcus antigen is almost identical to a protein
present in heart muscle
 untreated strep infections may result in the production of antibodies
that destroy not only the strep bacteria but also heart tissue

9
Hyperthyroidism karena
autoimmune (TSH ditiru
oleh autoantibodi

2. Grave’s Disease
 3. Chronic thyroiditis
(Hashimoto's disease)
 Hypothyroidism
karena
autoimmune
(autoantibodies
serang dan
hancurkan sel
follikuler) Inflamasi
lambat kelenjar
tiroid yang menuju
hipotiroidisme
 Biasa pada wanita
usia pertengahan .
4. Rheumatoid artritis
 Rheumatoid Arthritis (RA)
 chronic systemic autoimmune disease
- anti-self antibodies that react with the constant regions of
other antibodies (rheumatoid factor)
 onset of disease occurs most often between the ages
of 25-55
 women are 3 times more likely to develop this than men
 symptoms include weakness, fatigue, and joint pain
 infections, hormones and genetic factors may be
involved

X-ray shows severe arthritis

affecting the joints and
limiting mobility
Radang parah pada banyak sendi membentuk pannus
yang menyebabkan kerusakan cartilago dan sendi. Tak
dapat disembuhkan dan menyebabkan kecacatan pada 1-2
% populasi dunia .
Sitokin : molekul sinyal utama pada peradangan ; terlibat
dlm patogenesis RA:
Vasculitis dg sel radang monosit / makrofag,limfosit T-
&, netrofil khas ditemukan di jaringan yg terinfeksi
 5. Multiple Sklerosis
 Penyakit autoimmun pada sistem saraf pusat.
 Ssitem imun merusak selubung myelin pada
akson dg proses "demyelinasasi." – kerusakan
sel saraf
 Sel T (lekosit untuk pertahanan tubuh) masuk ke
otak (N=tak bisa).
 Sel CD4+ helper (sel T tipe khusus) menyerang
selubung myelin ( "myelin sheath").
 Sel T multiplikasi di otak dan menghasilkan
sitokin – aktivitas sistem imun meningkat–
banyak sel imun masuk, termasuk "makrofag –
peningkatan radang dan kerusakan saraf.
 Kerusakan saraf dapat dilihat dalam pmx MRI
(magnetic resonance imaging) scan otak -- "lesi"
(titik putih) .
 Multiple Sclerosis (MS)
 chronic organ-specific disease - may be mild or severe
 involves the destruction of the myelin sheath that covers cells of
the spinal cord and brain
 affects ~ 1 in 1600 people
 60% of the cases occur in women
 symptoms include weakness, tremors or paralysis of one
or more extremities, numbness, decreased memory and
attention span and may disappear and recur over time
 infections, hormones and genetic factors may be involved

Magnetic resonance image of

brain of patient with chronic form
of multiple sclerosis, showing
characteristic lesions of MS
(white spots)

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 Akibat dari demyelinanasi (kerusakan lapisan
myelin yang membungkus akson pada otak dan
medulla spinalis)
 Myelin : menyebabkan sinyal saraf
ditransmisikan dg cepat
 Kerusakan saraf parah - transection – terjadi
jika akson terpotong
 Timbul “hubungan buruk" antara otak dan
tubuh.Gejala yang terjadi tergantung saraf mana
yang rusak dan berbeda tiap penderita.
 6. Systemic Lupus Erythematosus (SLE)
 a chronic systemic autoimmune disease
 Complexes of anti-self antibodies and antigen deposit in, and
cause damage to, tissue
 1 million sufferers in the U.S.
 Strikes women nine times more often than men
 symptoms may include butterfly-shaped rash on face,
fatigue, headaches
 triggered by environmental effects in persons who
are genetically susceptible

Damaged kidney (left) caused by

Butterfly rash of lupus immunoglobulin deposits (right)
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 7. Juvenile Diabetes
 also known as Type I diabetes or insulin-dependent
 beta-cells in the pancreas produce little or no insulin.
 usually occurs before the age of 30
 occurs in 1 in 7000 children each year
 incidence decreases after the age of 20
 symptoms include increased thirst and urination,
weight loss, nausea, fatigue
 cause is linked to genetic, viral, and autoimmune
factors

Normal Diabetic
pancreas pancreas

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 Treatments for autoimmune diseases
 current treatments are based on easing disease
symptoms
 anti-inflammatory drugs to reduce the inflammatory
response
 cytotoxic drugs to kill immune cells
 treatments that block interaction of immune cells – e.g.,
bind to cytokines, block second signals
 replacement of necessary chemical – e.g., injections of
insulin for diabetes
 changes in diet
 exercise

 in the future
 gene therapy
 vaccines to turn off the autoimmune response
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 3. Under-reaksi thd antigen
Immunodeficiencies
 occur when some part of the immune system is
defective or missing
 T cells, B cells, phagocytes, or complement

 these deficiencies are grouped as:

 primary: inherited or congenital
 severe combined immunodeficiency

(SCID)
 secondary: acquired
 HIV infection
 chemotherapy, malnutrition, trauma (burns), tumors, David Vetter 1972-
 microbial immunosuppression (malaria), 1984, the original
bubble boy
 other diseases (diabetes), or aging. 26
Acquired immunodeficiency syndrome (AIDS)
• first identified in 1981
• caused by the human immunodeficiency virus (HIV) and is spread by
contact with body fluids
• infects CD4+ (helper) T cells, which decrease in number
• decreased numbers of CD4+ T cells lead to increased susceptibility to
opportunistic infections.
• treatments include drugs that inhibit the activity of HIV proteins,
thereby preventing production of the virus

Worldwide HIV infection,

1999

HIV virus particle

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 Hypersensitivity
 Klasifikasi : Gell & Coombs
Type I: Immediate hypersensitivity
- onset within minutes of antigen challenge
- examples are allergies to molds, insect bites
Type II: Cytotoxic hypersensitivity
- onset within minutes or a few hours of antigen challenge
- examples are adult hemolytic anemia and drug allergies
Type III: Immune complex-mediated hypersensitivity
- onset usually within 2-6 hours
- examples include serum sickness and systemic lupus
erythematosus
Type IV: Delayed Hypersensitivity
- inflammation by 2-6 hours; peaks by 24-48 hours
- examples include poison ivy and chronic asthma

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Type I hypersensitivity – sensitization to an
inhaled allergen or bee sting

cytokines

 

Mast
cell

Antigens (red dots) from inhaled pollen are ingested and presented by
macrophages to T cells. Activated T cells produce cytokines leading to
the production of IgE, which binds to receptors on mast cells and causes
the release of histamine, which is responsible for allergy symptoms.
Onset is usually within minutes of contact with antigen. 29
 I. Anafilaksik
( Atopy, Allergy )

Antigen ( Allergen ) : protein, polypeptida,

polisakarida, asam nukleat
Alergen Umum :
debu rumah (tungau), tepung sari,serpihan
kulit binatang, mikroorganisma, serum
protein hewan, antibiotika ( penicillin,
streptomycin ), racun serangga
 Mekanisme Hypersensitivitas Tipe 1
Kulit, Sal. Napas, Sal.cerna, Mata

Ag Body B-cell IgE- Ab

Chemical mediators Mast cell

- Histamine Ag
- Serotonin
- etc.
Spasmogen :
- Histamine - Kontraksi otot
polos Bronkus
- Prostaglandin
- Leukotriene-C4 -Edema Mukosa
- Leukotriene-D4 - Sekresi Mucus
 Organ Target
Otot polos Kontraksi
Kapiler Dilatasi
Kelenjar mukosa Peningkatan sekresi
Contoh penyakit
- Asma Bronchiale
- Rhinitis lergika
- Urticaria
- Syok anafilaksik
- Alergi makanan
- Eksim
- Hay fever
 Laboratory Testing
1. Skin test ( Prick test )

2. Prausnitz-Kustner ( PK ) test

Allergenic serum Normal skin ( human )

allergen
Wheal & Flare
3. Passive cutaneous anaphylaxis ( PCA ) test
Allergic i.d Normal skin (G.P)
serum i.v allergen
24 h. +
Evan blue
Blue skin
4. Histamine determination
5. IgE lavel - RIA
6. Eosinophil count = 10-20 %
 Treatment & Prevention
1.Allergen avoidance
- Environmental control
2. IgE removement
2.1 Hyposensitization ( Desensitization )

Allergen i.d Blocking IgG

Type II hypersensitivity – immune-mediated
destruction of red blood cells

Drug (p=penicillin)
modified red blood cells
 induce the production of
antibodies, because the
bound drug makes them
look foreign to the
immune system. When
these antibodies are
bound to them, the red
blood cells are more
susceptible to lysis or
phagocytosis. Onset is
dependent on the
presence of specific
antibodies.
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 Type II Sitotoksik/sitolitik
Antigen - Red blood cell
- White blood cell
- Platelet
- Tissue
Antibody - IgG, IgM
Complement = + , -
Mekanisme Hipersensitivitas Tipe II

Tipe Sitolitik Rbc lysis

+C
Antibody + Red cell Ab- Rbc
-C
Tipe Sitotoksik Rbc lysis by
RE system
 Contoh Penyakit
1. Hemolytic transfusion reaction
Blood group A Blood group B
Blood group B Blood group A
2. Hemolytic disease of the new born(HDN)
( Erythroblastosis fetalis )
- Rh incompatibility disease
- ABO incompatibility disease
3. `Anemia hemolitik autoimmu
a. Warm-reactive autoantibodi
- Anti-Rh
- Autoimmune antibodies
- SLE : - Anti-nucleus
- Anti-Rbc etc.
b. Cold-reactive autoantibodi
- Cold hemagglutinins
c. Reaksi obat
4. Goodpasture’s Syndrome
Ab membrana basalis glomerulus
Rheumatic heart disease
Ab mioendocardium
5. Myasthenia gravis
Ab reseptor asetilkoolin
 Type III hypersensitivity – immune complex
formation and deposition
Immune complexes Inflammation and
Immune complexes activate complement
of antigen (red dots) edema occur, and
(green dots- C3a, C4a, organ is damaged
and antibody form in and C5a), and mast cells
target organ (yellow cell) degranulate.

In sensitized individuals, allergen (antigen) combined with antibody

leads to the formation of immune complexes, which activate
complement and the inflammatory response. The location of the
inflammation depends on the location of the antigen - inhaled, under
skin, systemic. Onset is usually within 2-6 hours. 54
Tipe III Kompleks Imun/Arthus
-penimbunan komplek antigen-antibodi
dalam jaringan/pembuluh darah
Tipe IV Hipersensitivitas Tipe Lambat
-terjadi > 24 jam stlh terpapar
antigen, krn respon sel T yg
tersensitisasi makrofag yang yg
diaktifkan merusak jaringan, mis :
dermatitis kontak
Tipe IV Hipersensitivitas Tipe Lambat
-terjadi > 24 jam stlh terpapar antigen, krn
respon sel T yg tersensitisasi makrofag
yang yg diaktifkan merusak jaringan, mis :
dermatitis kontak
Type IV hypersensitivity – delayed-type or contact
T cells (blue cells)
that recognize
Antigen (red dots) antigen are Inflammatory
are processed by activated and response causes
local APCs release cytokines tissue injury.

Antigen is presented by APCs to antigen-specific memory T cells

that become activated and produce chemicals that cause
inflammatory cells to move into the area, leading to tissue injury.
Inflammation by 2-6 hours; peaks by 24-48 hours.
57
 Transplantasi
 Sistem Imun dapat meghasilkan Antibodi
melawan Benda Asing menyebabkan
reaksi penolakan terhadap organ yang
ditransplantasi, transfusi darah dan skin
graft
 Solusi : pilih organ yang cocok dan
penekanan sistem imun dg
- radiasi dg sinar X
- obat : kortikosteroid
 Exercise and stress

 exercise has been shown to boost the immune response

 moderate exercise increases the immune response in all age
groups
 intensive exercise can stress the immune system

 lack of sleep and exhaustion decrease immune function

 psychological stress has also been found to decrease

immune function

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 Diet

 a well-balanced diet is essential for good immune

system health
 fats are very important in the production of WBCs, cytokines
and natural killer cells
 selenium, zinc, and copper are required in small amounts,
which you get if you eat a balanced diet
 vitamin E has been shown to boost antibody production in
the elderly
 vitamin B6 aids in antibody synthesis

 but mega-dosing can be harmful, too!

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 Environment
Exposure to certain things in their environment may
activate the immune systems of some people

 Chemicals  Viruses
 dioxin

 pesticides

 solvents

 Bacteria
 Sunlight

 Medication  Food

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 Gender and the immune system

 women respond to antigens more strongly than men

 estrogen may affect the development or function of

immune cells

 may explain why more women develop autoimmune

diseases

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Re-Educating the Immune System

 Tujuan mengajarkan kembali sistem imun dg

menghentikan sel T otoreaktif yang merusak
 Injeksi limfoit normalyang sesuai dg tipe HLA
(Hetero Lymphocyte Antigen), sesuai dg tipe
donmor SEmakin sesuai, tingkat kesembuhan
semakin besar
 Limfosit normal menghancurkan sel T yang
empunyai "self" antigen pada pwermukaannya
dan mencegah mis-education pada sel T baru,
shg tidak menjadikan jaringan tubuyh sendiri
sebagai benda asing.

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