THE 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 Spleen Lymph nodes Lymphatic vessels

Host Defense Mechanisms

Nonspecific Immunity
barriers inflammatory response

Specific Immunity
Passive Active
humoral cell-mediated

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.

aders -ACTIVE viruses, bacteria, allergens IMMUNE DEFENSES onstantly bombard our body.

RESPONSE

(PERTAHANAN IMUN AKTIF)

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

INNATE IMMUNITY

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
skin hair mucous Chemical 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.

Antigen Presenting Cell (APC)

Merupakan suatu sel yang menampilkan kompleks antigen asing & MCH pada permukaannya sehingga mudah dihancurkan oleh limfosit.

Fungsi utama APC

1. Menangkap & memproses Ag, kemudian menampilkannya kepada limfosit T. 2. Memberikan sinyal untuk proliferasi & diferensiasi limfosit.

Ikatan Ag dengan MHC

Jenis-jenis APC
Terdapat 3 jenis utama APC: 1. Makrofag 2. Limfosit 3. Sel Dendrit

MAKROFAG
Mengekspresikan MHC-II pada level rendah Ekspresi MHC-II diinduksi oleh bakteri dan sitokin Aktif tehadap antigen ektraseluler Penampilan protein antigen berupa MHC-II Lokasi terdapat pada jaringan limpa, jaringan ikat, da rongga tubuh.

Limfosit B
Ekspresi MHC-II diinduksi tergantung aktivasi Antigen ekstraseluler berikatan dengan reseptor Ig-G spesifik Penampilan melalui MHC-II Lokasi terdapat pada jaringan limfoid dan darah.

Sel Dendrit
Selalu mengekspresikan MHC-II Aktif terhadap antigen ekstraseluler & intraseluler Penampilan melalui MHC-I & MHCII Lokasi terdapat pada jaringan limfoid, jaringan ikat , dan epitel.

INFLAMASI
Mekanisme imun terdepan terhadap trauma atau invasi mikroba Meliputi aktivitas berbagai tipe Sel Inflamasi dan Mediator

Peningkatan permeabilitas kapiler Peningkatan pasokan darah fagositosis

Pencetus :
Trauma Infeksi Alergi Bahan-bahan kimia Autoimun Benda-benda asing lainnya

SEL INFLAMASI

Poli morpho Nuklear Leucocytes (netrofil, eosinofil, basofil) Sel Endotel Sel Mast Makrofag (monosit, dan limfosit)

MEDIATOR
Produk sel inflamasi (histamin, Prostaglandin, Leukotrien, Interleukin, Oksigen radikal bebas, dan Oksidan lain (nitric okside, kloramin, asam hipoklorus). Secara langsung berperan dalam proses inflamasi dan dapat menimbulkan kerusakan jaringan

MEDIATOR

Histamin

Meningkatkan permeabilitas kapiler

Udem dan merah

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 menjadi sel plasma dan menghasilkan antibodi spesifik

Struktur Antibodi
4 rantai polipeptida 2 rantai H , 2 rantai L (dihubungkan dengan ikatan disulfida)
Rantai L : kappa dan Lambda Rantai H : gamma, alpha, mu, delta, epsilon

 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

 Fab sebagai tempat pengikatan antigen Fc terlibat dalam transfer plasental, pengikatan komplemen, perlekatan berbagai sel, dan aktivitas biologik lainnya

Kelas Antibodi (Imunoglobulin)

IgM IgG IgA IgE IgD

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 Fungsi : mengikat komplemen

IgD

Belum jelas Mungkin berfungsi sbg perangsang reseptor Ag BM 150.000 Reseptor pd permukaan limfosit

IgE
Terdpt di permukaan membran plasma basofil & mast sel pd jar.connectivus Berperan dlm hipersensitivitas & melawan parasit,ex:worm BM = 190.000 Fungsi : antibodi reaginik, antibodi homositropik