Sistem Limfatik dan Sistem ImunitasPurwo Sri Rejeki

*Sistem LimfatikSistem Satu Arah: menuju jantungMengembalikan cairan jaringan berlebihMengembalikan protein yang bocorLymph = cairanBila buntu Edema

*Kapiler LimfatikPunya katup mini cairan masuk tidak bisa keluar Menangkap Bakteri dan Virus dihancurkan Menyerap protein, elektrolit dan cairan

*

*Kapiler LimfatikTidak didapatkan di tulang, sumsum tulang, gigi dan SSPMasuk ke lymphatic collecting vesselsLymphatic collecting vesselsMempunyai lapisan seperti pembuluh vaskuler (3 lapis), tapi tipis dan lenturYang superfisial tdp di kulit: bersama vena superfisialYang dalam: di badan dan organ visera, berjalan bersama arteriTekanannya sangat rendahMemberikan gambaran khusus pada lymphangiographyMengalir ke dalam lymph nodes

*Nodus Limfatik: bean shaped organs sepanjang lymphatic collecting vesselsUkiuran: bisa sampai 1 inchClusters of both deep and superficial LNs

*Superficial groups-Cervical-Axillary-InguinalDeep groups-Tracheobronchial-Aortic-IliacDrainage-Superior R 1/4 of body: R lymphatic duct (green) *-The rest: thoracic duct *Lymph Nodes**

*Fibrous capsule sends in dividing trabeculaeAfferent & efferent lymphatic vesselsLymph percolates through lymph sinusesFollicles: masses of lymphoid tissue divided into outer cortex & inner medulla (details in later slides)

*Macrophages on reticular fibers consume pathogens and foreign particles

Usually pathogen free lymph enters lymph trunks

*Lymphatic Trunks

(Semua berpasangan, kecuali yang di intestinal trunk)LumbarIntestinalReceives fatty lymph (chyle) absorbed through lacteals in fingerlike villi of intestinesBroncho-mediastinalSubclavianJugular

*Lymph ducts(variable)Thoracic duct: everyone has

20% also have a right lymphatic duct*20%

*

Sistem Imun Tubuh Leukosit ( sel darah putih )

*Sistem ImunMengenali molekul asing yang spesifik Setiap paparan (patogen yang sama) meningkatkan efektivitasLymphoid organsLymph nodesSpleenThymusTonsilsSmall intestine & appendix aggregated lymphoid nodules

*Imunologi DasarTergantung kemampuan sistem imun untukmembedakan antara self dan non-self moleculesSelf molecules: komponen otubuh yang dapat dibegadakan dari subtans asing oleh sistem imun. Autoimmunity is an immune reaction against self molecules (causes various diseases)Non-self molecules: dikenali sebagai molekul asing One class of non-self molecules are called antigens (short for antibody generators) and are defined as substances that bind to specific immune receptors and elicit an immune response

Jenis Leukosit Granulosit Neutrofil 62,0% Eosinofil 2,3% Basofil 0,4%

Agranulosit

Monocytes 5,3% Lymphocytes 30,0%

Jumlah Leukosit 9000 sel / mm3 darah ( liter) atau 4 11 x 109 / liter

Fungsi Leukosit Menahan atau mengeliminasi sel abnormal, atau benda asing yang berpotensi merusak.

Menahan invasi patogen penyebab penyakitMengidentifikasi & menghancurkan sel kankerMembersihkan sampah tubuh memfagositosis debris/sel-sel mati

Sistem Imun TubuhNon Spesifik SpesifikGranulositMonosit-makrofagLimfosit BLimfosit T

Sistem Imun Non Spesifik Fisik / Mekanik Kulit, selaput lendir, silia, batuk, bersin Biokimia Asam lambung, lisosim, lactoferin, spermin Humoral Komplemen InterferonC-reaktive protein (CRP)Selular FagositNatural killer cell

Sifat Pertahanan Netrofil dan Monosit Makrofag

Marginasi (menepi)

Diapedesis (menembus dinding pori-pori)

Ameboid motion (bergerak seperti amoeba)

Chemotaxis (bergerak mendekati sumber bahan kimia) Kelompok Chemokines, yaitu : * Complement system * Leukotrien * Polipeptida, hasil dari limfosit, mast cell dan basofil Efektif : radius 100 daerah radang

Fagositosis (= endositosis) Selektif dan bersyarat * permukaan partikel harus kasar * tidak dilapisi protein * dapat : Opsonisasi

Gambar sifat leukosit:

Marginasi

Diapedesis

Amoeboid Motion

Chemotaxis Tjitra Wardani , dr., MSBag. I Faal F.K. Unair

Fagositosis NetrofilMakrofagMelekat pada reseptor partikelPseudopaniaMenyatu Vesikel fagosit( fagosome)Pembunuh bakteri (secara oksidatif)

= Pengoksidir :

Superoxide radikal (O2)

Hidrogenperoxida (H2O2)

Hidroxyl radikal (OH) Llsosom Berisi : Enzim proteolitik Lipase Lisosim Myeloperoksidase (mpo) Diproduksi oleh : Membran fagosom PeroxisomeH2O2 + C1hypochlorite

kerusakan jaringan Memproduksi - Histamine - Bradikinine - Serotonine - Prostaglandin Hasil suatu sistem komplemen Hasil reaksi sistem koagulasi darah Lymphokinesterjadi perubahan jaringanbakteri trauma panasbahan kimiaKeradangan

Vasodilatasi pembuluh darah lokalPermeabilitas kapiler meningkatPenjendalan cairan interstitialMigrasi granulosit dan monositPembengkakan sel jaringanPerubahan jaringan keradangan tanda tanda kardinal keradangan yaitu Dolor (nyeri), Calor (panas), Rubor (kemerahan), Tumor (bengkak) dan Functio laesa (gangguan fungsi)

The first line of defense Respon Netrofil Makrofag terhadap keradangan The second line of defenseAksi fagositosMobil makrofag(dilepas)

Inflamasi Neutrofilia 15.000-25.000/1KapilerMembranProduk radangMarginasiDiapedesiskemotaksisThe third line Of defense IIIBone Marrow Stem cellsMonositBloodmokrofagIIIThe fourth line of defense GranulakositMonosit3 4 hrProd : 50 x NIV

Eosinofil 1 3 % sel darah putih Fagosit lemah Mencegah infeksi tertentu Jumlah eosinofil meningkat pada

major basic protein (MBP) dan menghancurkan alergen

untuk membunuh larvainfeksi parasit reaksi alergi

enzim hidrolitik (lisosim) chemotactic factor

oksigen reaktif untuk detoksifikasi

Basofil

0,5 % sel darah putih

Serupa dengan mast cell (sel besar dalam kapiler-kapiler)

Mengeluarkan :

Heparin

Histamin

Bradikinin

Serotonin

Slow reacting substance (SRS

Enzym lisosim

dikeluarkan selama terjadi keradangan

Sistem Imun SpesifikACQUIRED IMMUNITYHumoral Immunity Cell-mediated Immunity

B-cell immunity T-cell immunity Antibodi Activated Lymphocytes

Antigen Adalah bahan yang mampu bereaksi dengan antibodi yang diproduksi atas rangsangan imunogen

Imunogen Adalah setiap bahan yang dapat menimbulkan respons imun spesifik baik respons seluler maupun humoral (protein besar dengan BM 100.000) Hapten determinan antigen dengan BM kecil Untuk menjadi antigen harus terikat oleh molekul besar (carrier)AntibodiAdalah imunoglobulin (Ig) yang merupakan gol. Protein yang dibentuk oleh sel plasma, yang berasal dari proliferasi sel B akibat adanya kontak dengan antigen.

*Lymphocytesthe primary cells of the lymphoid systemRespond to:Invading organismsAbnormal body cells, such as virus-infected cells or cancer cellsForeign proteins such as the toxins released by some bacteriaTypes of lymphocytesT cells (thymus-dependent)B cells (bone marrow-derived)NK cells (natural killer)

*T Cells80% of circulating lymphocytesSome of the types:Cytotoxic T cells: attack foreign cells or body cells infected by viruses (cell-mediated immunity)Regulatory T cells: Helper T cells and suppressor T cells (control activation and activity of B cells)Memory T cells: produced by the division of activated T cells following exposure to a particular antigen (remain on reserve, to be reactivated following later exposure to the same antigen)

*B Cells10-15% of circulating lymphocytesCan differentiate into plasmocytes (plasma cells) when stimulated by exposure to an antigenPlasma cells produce antibodies: soluble proteins which react with antigens, also known as immunoglobulins (Igs)Humoral immunity, or antibody-mediated immunityMemory B cells: produced by the division of activated B cells following exposure to a particular antigen (remain on reserve, to be reactivated following later exposure to the same antigen)

*NK Cells5-10% of circulating lymphocytesAttack foreign cells, normal cels infected with viruses, cancer cells that appear in normal tissuesKnown as immunologic surveillance

Antigen Kontak II

AntigenKontak ITerbentuk klon limfositSel memori

Respons sekunder spesifik(lebih cepat dan intensif) Dihancurkan sel imunProliferasi klon limfosit

*Humoral vs Cell mediatedCell-mediated immunity - direct attack by activated T cells (react with foreign antigens on the surface of other host cells)

Antibody-mediated (humoral) immunity attack by circulating antibodies, also called immunoglobins (Igs), released by the plasma cells derived from activated B cellshumor from old-fashioned word for stuff in the blood, like good humors and bad humors

These two systems interact with each other

Gambar: Cell-mediated immunity dan Humoral immunity

RECOGNITION ACTIVATION EFFECTOR PHASE PHASE

Respon Imun Humoral

Gambar Imonuglobulin

ANTIBODI Ig G (75%), Ig A, Ig M, Ig E, Ig DDirect attackagglutinationprecipitationneutralizationlysisagglutinationActivation of the Complement System(C1-9, B, D)lysisopsonization & phagocytosis neutralizationMekanisme KerjaChemotaxisActivation of mast cell-basophilsInflamatory effects

Respons Imun SelulerMerupakan fungsi limfosit TT-helperT-sitotoksikThd antigen yang terdpt pdpermukaan makrofagAntigen pada antigen dalam makrofagMenginduksi limfositProduksi : limfokin Langsung Menghasilkan : interferon Menghancurkan Mikroorganisme/antigenMencegah penyebaran Mikroorganisme

Prinsip Imunisasi Immunisasi (Imunitas spesifik) Alamiah Buatan Pasif Antibodi (mel plasenta, kolostrum )Pasif Antitoksin AntibodiAktif Infeksi: virus, bakteriAktif Toksoid vaksinasi

*B LymphocytesThe receptor for antigens is an antibody on B cell surfaceB lymphocytes can respond to millions of foreign antigensThis capability exists before exposure to any antigensEach lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufactureA B cell identifies pathogens when antibodies on its surface bind to a specific foreign antigenThis antigen/antibody complex is taken up by the B cell and processed by proteolysis into peptides (small pieces)As the activated B cell then begins to divide (clonal expansion), its offspring secrete millions of copies of the antibody that recognizes this antigenThese antibodies circulate in blood plasma and lymph, bind to pathogens expressing the antigen and mark them for destruction by complement activation or for uptake and destruction by phagocytesAntibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cellsAb

*The needsTo be able to attack cells which have been infectedT cells target alien cells they reject transplanted organs, destroy our own cells that have been infected, and kill some cancer cells: these are all treated as foreign because they have altered (antigenic) proteins on their surfacesTo be able to take care of small extracellular antigens such as bacteria which multiply outside cells, the toxins they make, etc.Antibodies made by plasma cells (differentiated B lymphocytes) bind to antigens on bacteria, marking them for destruction by macrophages

*Development of lymphocytesOriginate in bone marrow from lymphoid stem cellsB cells stay in bone marrow, hence B cellsT cells mature in thymus, hence T cells

These divide rapidly into familiesEach has surface receptors able to recognize one unique type of antigen=immunocompetence

*

*Lymphoid Organs

Lymph nodesSpleenThymusTonsilsSmall intestine & appendix aggregated lymphoid nodules

*Lymphoid TissueSpecialized connectivetissue with vast quantitiesof lymphocytesLymphocytes become activatedMemoryMacrophages & dentritic cells alsoClusters of lymphoid nodules or follicles

*ThymusProminent in newborns, almost disappears by old ageFunction: T lymphocyte maturation (immunocompetence)Has no follicles because no B cells

*Lymph NodesLymphatic and immune systems intersectMasses of lymphoid tissue between lymph sinuses (see next slide)Some of antigens leak out of lymph into lymphoid tissueAntigens destroyed and B and T lymphocytes are activated: memory (aiding long-term immunity)

*Follicles: masses of lymphoid tissue divided into outer cortex & inner medullaAll follicles and most B cells: outer cortexDeeper cortex: T cells, especially helper T cellsMedullary cords: T & B lymphocytes and plasma cells

*

*lymphangiogram

*SpleenLargest lymphoid tissue; is in LUQ posterior to stomachFunctionsRemoval of blood-borne antigens: white pulpRemoval & destruction of aged or defective blood cells: red pulpStores plateletsIn fetus: site of hematopoiesisSusceptible to injury; splenectomy increases risk of bacterial infection

*Spleen

*Palatine (usual tonsillitis)Lingual (tongue)Pharyngeal (adenoids)TubalTonsils***Simplest lymphoid tissue: swellings of mucosa, form a circleCrypts get infected in childhood

*

*Aggregated lymphoid nodules (Peyers Patches)About 40 follicles, 1 cm wideDistal small intestine (ileum)AppendixParts of the intestine are so densely packed with MALT (mucosa-associated lymphoid tissue) that they are considered lymphoid organs