SYSTEM IMMUNE

Dr. dr. Zinatul Hayati, M.Kes., Sp.MK

We all get sick sometimes...but
then we get better.

What happens when we get sick?

Why do we get better?

ANATOMY OF THE IMMUNE
SYSTEM

The immune system is

localized in several
parts of the body
• immune cells
develop in the
primary organs -
bone marrow and
thymus (yellow)
• immune
responses occur
in the secondary
organs (blue)
 PASSIVE IMMUNITY
(IMUNITAS PASIF)

IMMUNITY
ACTIVE IMMUNITY
(IMUNITAS AKTIF)
 PASSIVE IMMUNITY
(IMUNITAS PASIF)

Ketika sistem imun kita berkembang, kita

dilindungi oleh pertahanan imun yang disebut
antibodies. Antibodi tersebut masuk dari
aliran darah maternal melewati plasenta
menuju darah fetus.
Antibodies (Y) are also found
in breast milk.
The antibodies received
through passive immunity
last only several weeks.
CONTOH IMUNITAS PASIF

 Air Susu Ibu (ASI) mengandung antibodi

 Darah fetus mengandung antibodi dari
ibunya
 Anti Tetanus Serum (ATS) mengandung
antibodi antitetanus
 ACTIVE IMMUNITY
(IMUNITAS AKTIF)

Innate Immunity Adaptive Immunity

(Imunitas Non (Imunitas Spesifik)
Spesifik)
Foreign invadersACTIVE
- viruses, bacteria,
IMMUNITY allergens, toxins an
parasites- constantly bombard
(IMUNITAS AKTIF)
our body.

Innate Immunity Adaptive Immunity

- invariant (generalized) - variable (custom)
- early, limited specificity - later, highly specific
- the first line of defense - ‘‘remembers’’ infection
 INNATE IMMUNITY
(IMUNITAS DIDAPAT)

Ketika kita lahir, kita telah memiliki

beberapa mekanisme untuk mencegah
penyakit. Tipe imunitas ini disebut juga
dengan nonspecific immunity (imunitas
nonspesifik).
Innate immunity
consists of:

 Barriers

 Cellular response
• phagocytosis
• inflammatory reaction
• NK (natural killer) and
mast cells

 Soluble factors
 INNATE IMMUNITY
Barriers

 Physical  Chemical

• skin • sweat
• hair • tears
• mucous • saliva
• stomach acid
• urine
 INNATE IMMUNITY
Cellular response

• nonspecific - the same response works

against many pathogens

• this type of response is the same no matter

how often it is triggered

• the types of cells involved are macrophages,

neutrophils, natural killer cells, and mast cells

• a soluble factor, complement, is also involved

 Phagocytic cells include:

Macrophages engulf pathogens and dead

cell remains

Neutrophils release chemicals that kill

nearby bacteria
• pus = neutrophils, tissue cells and dead
pathogens
 Macrophages

 WBCs that ingest bacteria, viruses, dead cells, dust

 most circulate in the blood, lymph and extracellular

fluid

 they are attracted to the site of infection by chemicals

given off by dying cells

 after ingesting a foreign invader, they “wear” pieces

of it called antigens on their cell membrane receptors
– this tells other types of immune system cells what
to look for
 Macrophage and E. coli

©Dennis Kunkel Microscopy, Inc., www.DennisKunkel.com

 Macrophage ingesting yeast

CELLS alive!

This human macrophage, like the neutrophil, is a

professional "phagocyte" or eating cell (phago = "eating",
cyte = "cell"). Here, it envelops cells of a yeast, Candida
albicans. After ingestion, the white cell must kill the
organisms by some means, such as the oxidative burst.
 Neutrophils

 WBCs – are phagocytic, like macrophages

 neutrophils also release toxic chemicals that destroy

everything in the area, including the neutrophils
themselves
 Neutrophil phagocytosing
S. pyogenes, the cause of strep throat

CELLS alive!

Human neutrophils are WBCs that arrive quickly at the

site of a bacterial infection and whose primary function is
to eat and kill bacteria. This neutrophil ingesting
Streptococcus pyogenes was imaged in gray scale with
phase contrast optics and colorized.
 Neutrophil killing yeast

NEUTROPHIL

YEAST 

CELLS alive!

One way that neutrophils kill is by producing an anti-

bacterial compound called “superoxide anion“, a
process called oxidative burst. Here, an amoeboid
human neutrophil senses, moves toward and ingests
an ovoid yeast. In the next two panels, oxidation can
be seen by using a dye, and is colorized here.
 Natural killer cells (NK cells)

 instead of attacking the invaders, they attack the

body’s own cells that have become infected by
viruses

 they also attack potential cancer cells, often before

they form tumors

 they bind to cells using an antibody “bridge”, then kill

it by secreting a chemical (perforin) that makes holes
in the cell membrane of the target cell. With enough
holes, the cell will die, because water rushing inside
the cell will induce osmotic swelling, and an influx of
calcium may trigger apoptosis.
 Mast cells

 are found in tissues like the skin, near blood vessels.

 are activated after antigen binds to a specific type of

antibody called IgE that is attached to receptors on the
mast cell.

 activated mast cells release substances that contribute

to inflammation, such as histamine.

 mast cells are important in allergic responses but are

also part of the innate immune response, helping to
protect from infection.
 INNATE IMMUNITY
Cellular response

Inflammatory response

• chemical and cell response to injury or localized infection

• eliminates the source of infection
• promotes wound healing

Step 1. Circulation to the site increases  tissue warm,

red and swollen

Step 2. WBCs leak into tissues  phagocytes engulf

and destroy bacteria
 INNATE IMMUNITY
Cellular response

Inflammatory response (cont’d)

The release of histamine and prostaglandin causes

local vessel dilation resulting in:
– more WBCs to site
– increased blood flow  redness and warmth
– increased capillary permeability
– phagocytes move out of vessels into
intracellular fluid (ICF)
– edema (swelling) due to fluids seeping from
capillaries
 INNATE IMMUNITY
Cellular response

Inflammatory response (cont’d)

Fevers have both positive and negative effects on
infection and bodily functions
POSITIVE
 indicate a reaction to
infection
 stimulate phagocytosis
 slow bacterial growth
• increases body temperature
beyond the tolerance of
some bacteria
• decreases blood iron levels
NEGATIVE
 extreme heat  enzyme
denaturation and
interruption of normal
biochemical reactions
> 39° C (103°F) is dangerous
> 41°C (105°F) could be fatal
and requires medical
attention
 INNATE IMMUNITY –
Soluble factors

 Interferon
• a chemical (cytokine) produced by virus-infected
cells that contributes to their death by apoptosis

 Acute phase proteins

• proteins in the plasma that increase during
infection and inflammation
• can be used diagnostically to give an indication of
acute inflammation
 INNATE IMMUNITY
Soluble factors
Complement

 complement is not a cell but a group of proteins

 these proteins circulate in the blood
• help to recruit phagocytes to site of inflammation and
activate them
• bind to receptors on phagocytes, helping to remove agent of
infection
• form pores in the invader or infected cell’s membrane (like
the NKs do)
• activate mast cells to release histamine and other factors
 complement plays a role in inflammatory responses
of both the innate and adaptive immune responses
 Apoptosis or cell death

CELLS alive!
Human neutrophils released into the blood "commit
suicide“ after only 1 day. A neutrophil (left) undergoes
apoptosis, a series of changes including violent
membrane blebbing and fragmentation of DNA.
Apoptotic cells break into smaller pieces called apoptotic
bodies that other body cells recognize and eat.
 Adaptive Immunity
(Imunitas Spesifik)

Immunitas Humoral Immunitas Seluler

Sel B Sel T

Sel Plasma Sel Memory

Subset Sel T
(Th, Ts, Tc)
Antibodi
• Your mom’s antibodies were effective for
just a short time at birth, but your innate
immune system can be activated quickly.
It is always your first line of defense
during an infection, but it can’t always
eliminate the germ.
• When this happens, your body initiates a
focused attack against the specific
pathogen that is causing the infection.
This attack may lead to long-term
protection against that pathogen.
• This type of immunity is called adaptive
immunity, the customized second line of
defense.
 SITOKIN
Merupakan molekul yang menyerupai
hormon yang belerja secara parakrin,
berperan dalam sistem imun

Dieksresikan Oleh:
- Limfosit
- Mikrofag
- Sel Endotel
- Sel Glia
- Neuron

Bersifat parakrin : Sitematik atau lokal

Sifat Dan Cara Kerja

 Dapat larut dari respon pertahanan,

baik pesifik maupun non pesifik.
 Menyerupai hormon dalam hal
efeknya.
 Diperantarai oleh reseptor
Simbols : IL, INTERLEUKIN; IFN, interferon; TNF, tissue
necrossis faktor
C. Jenis-Jenis Sitokin

a. Monokin : oleh makrofag dan monosit

 Interleukin I
 Faktor nekrosis tumor
 Interferon α dan β
b. Limfokin : polipeptida tapi bukan imunoglobin,
oleh sel T aktif dan sel NK
 Inter leukin -2
 Inter leukin -6
 Interferon γ
 Limfotoksin
Sitokin yang tersusun atas asam amino
dinamakan interleukin

INTERLEUKIN I
- Oleh fogosit monokleus aktif
- Distimulasi oleh lipopolisakarida sel CD4
- Fungsi : pada peradangan dan TNF
- Terdiri : IL - Iα dan IL - Iβ
Efek sistemik

 Efek SSP : - Demam

- ↑ gelombang lambat saat tidur
- Anoreksia

 Efek metabolik : - ↑ sintesis protein hati

- ↑ sekresi natrium
- ↑ kadar seng dan besi plasma
- ↓ sitokrum P450
- Asidosis laktat
 Efek hematologik
• ↑ nekrofil dalam sirkulasi
• Me ↓ limfosit dalam sirkulasi
• Pe ↑ sekresi faktor perangsang koloni
• Pe ↑ tahanan nonspesifik

 Efek dinding pembuluh darah

• Pe ↑ daya lekat leukosit
• Pe ↑ sintesis prostaglandin
• Pe ↑ pelepasan faktor pengaktifan
trombosit
• Hipertensi.
Skema Efek IL- I pada sistem IMUN

IL - 1

Sel T Sel B NK sel

-Costimulator me↑ -Growth Faktor -Synergis dgn IL-2
produksi IL-2, - Sinergis dgn IL- & IFN γ
produksi IFN-γ, 4, IL-6 - Stimulasi tumor
produksi IL-3 -Me ↑ produksi lisis
-Me ↑ proliferasi antibodi -Stimulasi sitokin
-Aktivitas cytotoxic chemataxis sintesis
chemotaxis pendewasaan
(maturation
 INTERLEUKIN 2
• Disintesis : Sel T CD 4+ > dan sel T CD 8+
<
• Membantu pembentukan sitokin lain oleh
sel T, ex : interferon γ dan limfotoksin
 INTERLEUKIN 3
• Sejenis limfokin 20 KD
• Disintesis oleh sel T CD 4+
• Sebagai stimulasi koloni
• Membantu proliferasi sel mast dan
granulasi lisfanin
• Membantu pembentukan koloni-koloni sel
eritroid, nicloid
 INTERLEUKIN 4
• Sitokin 20 KD
• Fungsi :
» Faktor Pertumbuhan
» Pertukaran sintesis Ig E
» Pertumbuhan sel mast dan pengaktifan
makrofag

 INTERLEUKIN 5
• Sel T CD4+ dan sel mast aktif
• Fungsi
» Membantu pertumbuhan sel B dan Sel yang
menghasilkan Ig A
 INTERLEUKIN 6
• Oleh sel endotelium

 INTERLEUKIN 8
• Oleh monosit, makrofagi, fibroblas, sel
endotelium

 INTERLEUKIN 10
• Oleh sel T CD4+, CD8+, Monosit,
Makrofag, Sel B aktif
 Nama Sumber Seluler Utama Efek Biologik Terpilih
IFN-α, -β Fagosit Antivirus, pirogen
IFN-δ (intrferon) Sel T Mengaktivasi fagosit
mononuklir
TNF (faktor nekrosis tumor) Fagosit, sel T Aktivasi sel, demam,
kakeksia, antitumor
LT (limfotoksin) Sel T Mengaktivasi leukosit,
antitumor
TGF- β (pengalih faktor pertumbuhan) Sel T, makrofag Regulasi pertumbuhan
leukosit, angiogenesis
IL-1 (interleukin-1) Fagosir Aktivasi sel, demam,
kakeksia
IL-2 (interleukin-2) Sel T Aktivasi dan pertumbuhan
sel T
IL-3 (interleukin-3) Sel T Hematopoiesis
IL-4 (interleukin-4) Sel T penolong Isotipe (kelas) berubah
menjadi IgE
IL-10 (interleukin-10) Sel T penolong Mengaktivasi sel B,
menghambat sel T
GM-CSP (faktor perangsang koloni – makrofag- Sel T, fagosit, dll Hematopoiesis granolosit,
granulosit) keturunan monosit
M-CSF Makrofag, dll Diferensiasi menjadi
monosit
G-CSF (faktor perangsang kolom granulosit) Set T, fagoset, dll Diferensiasi menjadi
granulosit
INTERFERON (IFN)

 Protein immunoglobin yang dihasilkan oleh

sel T, fibroblast dan beberapa sel lain
setelah dirangsang oleh virus / antigen
 α, β, γ
 Fungsi : menjaga dan meningkatkan
keupayaan makrofolog dalam memusnahkan
sel tumor, virus dan bakteri
Gambar menunjukkan beberapa bahan yang bisa mempengaruhi penghasilan IFN
Gambar menunjukkan berbagai kesan TNF
D. Reseptor Sitokin
ANTIBODI
 suatu protein imunoglobulin yang
dihasilkan oleh limfosit B, bereaksi
secara khusus dengan antigen yang
merangsang produksinya.

 Berikatan dengan antigen

 Melemahkan struktur biologi antigen
Mekanisme Pembentukan Antibodi

 Antigen Processing
Makrofag memfagosit bakteri. Antigen
hancur mjd rantai peptida pendek. Muncul
dan menempel pd MHC II. Hal yg sama
terjadi pada sel B
 Stimulasi Sel B oleh sel T helper

 Produksi Antibodi
sel B yg dirangsang mengalami proliferasi,
maturasi dan diferensiasi sel plasma
antibodi spesifik
Fungsi Struktur Antibodi

 Struktur Antibodi
• 4 rantai polipeptida
• 2 rantai H dan 2 rantai
L
• dihubungkan dgn ikatan
disulfida
 Fab sebagai tempat
pengikatan antigen
 Fc terlibat dalam
transfer plasental,
pengikatan
komplemen,
perlekatan berbagai
sel, dan aktivitas
biologik lainnya
 Rantai H tdd:
1 domain variabel (VH)
3 atau lebih domain
konstan (CH)
 Rantai L tdd :
1 domain variabel (VL)
1 domain Konstan (CL)
 Panjang tiap domain
110-130 asam amino
 Domain variabel:
pengikatan antigen

 Domain konstan :
menentukan
mekanisme
penghancuran
antigen, jg
menentukan jenis Ig
Kelas Ig
Ada lima:
 IgG,
 IgA,
 IgM,
 IgD,
 IgE
 IgG
 Satu2nya terdapat di plasenta
 Paling banyak
 Terdiri atas 2 rantai L & 2 rantai H,
diikat oleh ikatan disulfida
 Ada 4 subkelas :
IgG1(66%),IgG2(23%),IgG3(7%),IgG4(
4%
 BM = 150.000
 Reseptor pd PMN , limfosit, monosit
 Fi biologis : mengikat komplemen,
melewati plasenta, antibodi
heterositotropik
 IgA
 15-20% Ig
 Tdpt di: darah,trac.mukosa di usus,ASI, airmata,
saliva
 Ada 2 subkelas: IgA1(90%),IgA2(10%)
 IgA2 berbeda……tdk diikat oleh ikatan disulfida tapi
dengan ikt nonkovalen
 BM = 170.000 atau 400.000
 Reseptor pd : PMN, limfosit, monosit
 Fi : Antibodi sekteroris
IgM
 Terdapat di serum,kdg di secretory
 Disebut juga Ab natural
 IgM mrpkn Ig yang pertama kali
muncul jk ada serangan dr luar
 BM = 900.000
 Reseptor pd : limfosit
 Fi : mengikat komplemen
IgD
 Belum jelas
 Mungkin berfungsi sbg perangsang
reseptor Ag
 BM 150.000
 Reseptor pd permukaan limfosit
IgE
 Trdpt: permukaan membran plasma
basofil & mast sel pd jar.connectivus
 Berperan dlm hipersensitivitas &
melawan parasit,ex:worm
 BM = 190.000
 Fi : antibodi reaginik, antibodi
homositropik