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)

 Thymus

Bone

marrow
nodes vessels

Spleen Lymph

Lymphatic

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.

Foreign invaders - viruses, bacteria,DEFENSES an allergens, toxins ACTIVE IMMUNE parasites- constantly bombard our body. (PERTAHANAN IMUN AKTIF)

Innate Immunity
- invariant (generalized) - early, limited specificity - the first line of defense

Adaptive Immunity
- variable (custom) - later, highly specific - 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 hair mucous

sweat tears 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 antibacterial 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.

INNATE IMMUNITY Cellular response

Complement

complement is not a cell but a group of proteins

these proteins circulate in the blood complement plays a role in inflammatory responses of both the innate and adaptive immune responses

INNATE IMMUNITY Cellular response

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 cells 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

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 (contd)
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 (contd)
Fevers have both positive and negative effects on infection and bodily functions POSITIVE

NEGATIVE

indicate a reaction to infection

stimulate phagocytosis slow bacterial growth
increases body temperature beyond the tolerance of some bacteria decreases blood iron levels

extreme heat enzyme denaturation and interruption of normal biochemical reactions > 39 C (103F) is dangerous
> 41C (105F) could be fatal and requires medical attention

Natural killer cells (NK cells)

instead of attacking the invaders, they attack the bodys 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 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

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.

 Your moms 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 cant 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.

RESPONSE

Foreign invaders - viruses, bacteria, allergens, toxins a parasites- ACTIVE IMMUNE DEFENSES constantly bombard our body.

Innate Immunity
- invariant (generalized) - early, limited specificity - the first line of defense
1. 2. 3. 4.

Adaptive Immunity
- variable (custom) - later, highly specific - remembers infection

Barriers - skin, tears Phagocytes - neutrophils, macrophages NK cells and mast cells Complement and other proteins

SITOKIN
A.Definisi Merupakan molekul yang menyerupai hormon yang belerja secara parakrin, berperan dalam sistem imun

Dieksresikan - Limfosit - Mikrofag - Sel Endotel - Sel Glia - Neuron Bersifat parakrin : Sitematik atau lokal

B. 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 dan

b.

Limfokin : polipeptida tapi bukan imunoglobin, oleh sel T aktif dan sel NK
Inter leukin -2 Inter leukin -6 Interferon 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 - I dan IL - I

Efek sistemik IL I rekombinant

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
-Costimulator me produksi IL-2, produksi IFN-, produksi IL-3 -Me proliferasi -Aktivitas cytotoxic chemotaxis

Sel B
-Growth Faktor - Sinergis dgn IL4, IL-6 -Me produksi antibodi chemataxis pendewasaan (maturation

NK sel
-Synergis dgn IL-2 & IFN - Stimulasi tumor lisis -Stimulasi sitokin sintesis

 INTERLEUKIN 2

Disintesis : Sel T CD 4+ > dan sel T CD 8+ < Membantu pembentukan sitokin lain oleh sel T, ex : interferon 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 IFN-, - IFN- (intrferon) TNF (faktor nekrosis tumor) LT (limfotoksin) TGF- (pengalih faktor pertumbuhan) IL-1 (interleukin-1) IL-2 (interleukin-2) IL-3 (interleukin-3) IL-4 (interleukin-4) IL-10 (interleukin-10) GM-CSP (faktor perangsang koloni makrofaggranulosit) M-CSF G-CSF (faktor perangsang kolom granulosit)

Sumber Seluler Utama Fagosit Sel T Fagosit, sel T Sel T Sel T, makrofag Fagosir Sel T Sel T Sel T penolong Sel T penolong Sel T, fagosit, dll Makrofag, dll Set T, fagoset, dll

Efek Biologik Terpilih Antivirus, pirogen Mengaktivasi mononuklir fagosit

Aktivasi sel, demam, kakeksia, antitumor Mengaktivasi antitumor leukosit,

Regulasi pertumbuhan leukosit, angiogenesis Aktivasi kakeksia sel, demam,

Aktivasi dan pertumbuhan sel T Hematopoiesis Isotipe (kelas) menjadi IgE berubah B,

Mengaktivasi sel menghambat sel T

Hematopoiesis granolosit, keturunan monosit Diferensiasi monosit Diferensiasi granulosit menjadi menjadi

INTERFERON (IFN) Protein immunoglobin yang dihasilkan oleh sel T, fibroblast dan beberapa sel lain setelah dirangsang oleh virus / antigen , , 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.

Fungsi

Berikatan dengan antigen Melemahkan struktur biologi antigen hancur

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

Fungsi Struktur Antibodi

Rantai L :

kappa dan lambda Rantai H : gamma, alpha, mu, delta, epsilon

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 110130 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 berbedatdk 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