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KONSEP DASAR IMUNOLOGI 1 Pengampu : Praptiwi H Acuan materi ajar : 1. Pembentukan sel imun 2. Sistem imunitas tubuh 1. PEMBENTUKAN SEL IMUN Imunitas berarti perlindungan terhadap penyakit, dengan pengertian lebih spesifik yaitu penya-kit infeksi.Berbagai jenis sel imun terjadi dari progenitor atau prekursornya. Gambar dibawah memperlihatkan sel-sel imun yang berasal dari sumsum tulang, memroduksi sel induk hematopoietic stem cell yang menghasilkan beragam tipe sel darah, serta elemen lain.

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KONSEP DASAR IMUNOLOGI 1Pengampu : Praptiwi HAcuan materi ajar :1. Pembentukan sel imun2. Sistem imunitas tubuh

1. PEMBENTUKAN SEL IMUNImunitas berarti perlindungan terhadap penyakit, dengan pengertian lebih spesifik yaitu penya-kit infeksi.Berbagai jenis sel imun terjadi dari progenitor atau prekursornya. Gambar dibawah memperlihatkan sel-sel imun yang berasal dari sumsum tulang, memroduksi sel induk hematopoietic stem cell yang menghasilkan beragam tipe sel darah, serta elemen lain.

Sumber : Morgan, 2014.

2. SISTEM IMUNITAS TUBUHSel sel dan molekul molekul yang bertanggungjawab untuk imunitas, membentuk sistem imun. Respon kolektif sel dan molekul tersebut yang terkoordinasi terhadap pengenalan dengan substansi (benda) asing, disebut respon imun. Fungsi fisiologik sistem imun adalah pertahanan melawan mikroba infeksius, bahkan substansi asing non infeksius juga dapat menimbulkan respon imun. Infeksi adalah masuk dan berkembangbiaknya mikroba infeksius (patogen) dalam tubuh. Infeksi pada manusia disebabkan oleh berbagai unsure pathogen dalam lingkungan di sekitar, misalnya bakteri, virus, fungus, protozoa, dan parasit. Infeksi pada orang normal pada umumnya singkat, dan jarang meninggalkan kerusakan yang menetap. Sistem imun memberikan respon dan melindungi tubuh terhadap unsure patogen. Selanjutnya diketahui bahwa mekanisme tubuh untuk melindungi terhadap infeksi dan mengusir substansi asing, pada keadaan tertentu dapat menimbulkan kerusakan jaringan tubuh. Lebih jauh, fenomena imunologik yang sangat beragam dapat dihubungkan satu dengan yang lain melalui penjelasan biokemik dan struktur komponen-komponen yang terlibat dalam sistem imun. Pemeriksaan imunobiologi dan imuno-kimia menjadi penunjang diagnosis, sebagai pedoman dalam memenej penderita. Respon imun sangat bergantung pada kemampuan sistem imun untuk mengenali molekul asing (antigen) dalam patogen potensial, kemudian membangkitkan reaksi yang tepat untuk mengusir sumber antigen. Limfosit sebagai unsur utama sistem imun, akan mengenali antigen, diikuti oleh fase efektor yang melibatkan berbagai ojenis sel.

GambarPerkembangansellimfositberasaldariselinduknya.

Sumber :Biochemistryden Satish, 2014,

GambarLimfosit, an-tibodi,dan antigen.

Sumber : www.shutter-stock.com, 2014.

GambarFungsisel T helper.

Sumber :Grundlagen des

Particularly important was the work ofPaul Ehrlich, who proposed theside-chain theoryto explain the specificity of theantigen-antibody reaction; his contributions to the understanding of humoral immunity were recognized by the award of a Nobel Prize in 1908, which was jointly awarded to the founder of cellular immunology,Elie Metchnikoff.

Gambar Organ organ dalamsistemimun.

Sumber : aids.gov, 2014.

Sumber : virtualmedicalcentre.com, 2014.

Complement system -Wikipedia, 2014.Thecomplement systemhelps or complements the ability of antibodies andphagocyticcells to clearpathogensfrom an organism. It is part of theimmune systemcalled theinnate immune systemthat is not adaptable and does not change over the course of an individual's lifetime. However, it can be recruited and brought into action by theadaptive immune system.The complement system consists of a number of small proteins found in the blood, in general synthesized by theliver, and normally circulating as inactive precursors (pro proteins). When stimulated by one of several triggers,proteasesin the system cleave specific proteins to releasecytokinesand initiate an amplifying cascade of further cleavages. The end result of this activation cascade is massiveamplificationof the response andactivationof the cell-killingmembrane attack complex. Over 30 proteins and protein fragments make up the complement system, includingserum proteins,serosalproteins, andcell membrane receptors. They account for about 5% of the globulin fraction of blood serum and can serve asopsonins.Threebiochemical pathwaysactivate the complement system: theclassical complement pathway, thealternative complement pathway, and thelectin pathway depicted below.

Sumber : Mayer, 2011.

GambarJalurklasik.Antibodi yang berasaldarisel B ((limfosit B)mengikat antigen, sehinggamencegahpatogenmemasukiselinang (host).Sumber :SaidulNaik, 2014.

GambarJalurlectin.

Sumber : classes.midlandstech.edu, 2014.

Gambar Jalur alternatif.

Sumber : immunopaedia.org, 2014.

Lectin pathwaya. Phagocytosis by macrophages induces release of chemicals that stimulate the liver to produce carbohydrate binding proteins (lectins)b. One such lectin, mannose-binding lectin (MBL) binds to mannose on bacterial cells walls and on some viruses.c. MBL opsonizes and activates C2 and C4 to activate C3.d. C3 activation can result in cell lysis, inflammation, and opsonization.e. Complement is deactivated by host-regulatory proteins and water.

Alternative pathway1. Aktivasi C3, memerlukanFaktor B dankation Mg2+2. amplifikasiloopoleh C3. 3. pengendalian loop amplifikasi4. stabilisasi C convertaseolehpermukaanaktivator (protektor).

GambarOpsonisasibakteri.

Sumber : pathmicro.med.sc.edu, 2014.

DaftarPustakaAbbas AK, Lichtman AH, Pillai Shiv. Cellular and Molecular Immunology 7th ed. Philadelphia: Elsevier Saunders, 2012; pp 1-14.aids.gov. Organs of the immune system, 2014.classes.midlandstech.edu. Lectin complement pathway, 2014.Immunopaedia. Org. Alternative complement pathway, 2014.Mayer G. Complement. Immunology Chapter two. Microbiology and Immunology on-line. University of South California, 2011. Morgan ME. Theibdimmunologist.com. Immune cell generation, 2014.SaidulNaik. appsgroup.blogspot.com, 2014.SitiBoedinaKresno. Imunologi: Diagnosis danProsedurLaboratoriumedisike 4. Jakarta: BalaiPenerbitFakultasKedokteranUniversitas Indonesia, 2001; hal 1-13.virtualmedicalcentre.com, Immune system, 2014.Wikipedia. Immunity, 2014.

Signs of Allah in Our Immune System Islamcan.com, 2014.Every day, a war is fought in the innermost parts of your body unperceived by you. On the one side are viruses and bacteria that aim to intrude into your body and take it under control and on the other are the immunity cells that protect the body against these enemies.

First, the soldiers who swallow and neutralize the enemy soldiers (phagocytes) arrive at the battleground. However, sometimes the fight is tougher than these soldiers can handle. On such occasions, other soldiers (macrophages) are summoned up. Their involvement causes alarm in the target area and other soldiers (helper T cells) are also called to battle.

These soldiers are very familiar with the local populace. They quickly distinguish their own army from that of the enemy. They immediately activate the soldiers assigned to weapon production (B cells). These soldiers have extraordinary abilities. Although they never see the enemy, they can produce weapons which will render the enemy ineffectual. In addition, they carry the weapons they produce as far as they should be taken. During this journey, they succeed in the difficult task of not causing any harm either to themselves or to their allies. Later, the striker teams cut in (killer T cells). These discharge the poisonous material they carry on themselves at the most vital spot of the enemy. In case of victory, another group of soldiers arrives at the battleground (suppressor T cells) and sends all the warriors back to their camp. The soldiers who arrive at the battleground last (memory cells) record all relevant information about the enemy, so that it can be used in the event of a similar invasion in the future.The excellent army discussed above is the immune system in the human body. Everything explained above is done by microscopic cells unobservable to the naked eye.

How many people are aware that they have such an organized, disciplined and perfect army inside their bodies? While one is unaware of all that is going on, the cells in one's body make strenuous efforts to save one from an illness that may even bring about one's death(12 04 2014)

KONSEP DASAR IMUNOLOGI 2Pengampu :Praptiwi HAcuanmateriajar :1. Sel(limfosit) B, sel (limfosit) T, danreseptor - reseptornya2. Mayor Histocompatibility Complex MHC).

1.SEL B, SEL T, DAN RESEPTOR RESEPTORNYASel B - merupakansel yang bertanggungjawabataspembentukanImunoglobulin (Ig), - 5 15% daribesaranlimfositdalamsirkulasidarah; Jenis: sIg, pre-B, sel B memori,dll.

Gambarkerjasamasel B- dansel T.Bacteria, the Invader diusirkeluar, sebelum orang yang terinfeksi merasakan gejalanya.Sumber :www.nobelpprize.org, 2014.

GambarAcquired (Adaptive) Immunity:a. sel B, jenissertaproduk-nya : plasma danIg.b. Sel T, jenisdanresponter- hadap antigen.

Sumber : Nature Reviews,2014.

.Gambar Sel B, sel T, dan reseptor2nya.

Sumber :en.wikipedia.org, 2014.

+ Gambar Jenis imunitas Acquired (Adaptive) dan Gambar Kelas limfosit.

2. MAJOR HISTOCOMPATIBILITY COMPLEX (MHC).Major HCadalahsuatukelompokmolekulpermukaansel yang dikodeolehkeluarga gen besar, danterdapatpadasemua vertebrata. Molekul MHC memediasiinteraksi leukosit2selimundenganleukosit lain atau sel2tubuh. MHC menentukankemungkinanpenggabungandonor untuktransplantasi organ, jugakemudahanseseoranguntukterpengaruholehpenyakitautoimmunemelaluiimunisasicrossreacting.Padamanusia, MHC jugadisebuthuman leuko-cyte antigen(HLA). Dari 3 kelas MHC yang diketemukan,padaumumnyafokusdiberikanpadakelas I dan II.

MHC (HLA) kelas I memediasi kerusakan sel host yang terinfeksi atau yang ganas,melalui interaksi dengan molekul CD8 pada permukaan sel T sitotoksik. Contoh pada Gambar : Molecules of HIV.

Sumber : www.mcld.co.uk,2014.

By interacting with CD4molecules on surfaces ofhelper T cells, MHC class II mediates establishment ofspecific immunity(also called acquired immunity or adaptive immunity). Sumber : mol.bio14masters. masters.grkraj.org,2014.

Beberapa pengertianAntibodi dikelompokkan dalam berbagai CDs sesuai dengan antigen permukaan yang dide-teksinya. Sekitar tahun 2001, terdapat 166 jenis CD antigen. Setiap jenis sel dan setiap stadi-um maturasi mengekspresikan CD spesifik atau kombinasi spesifik CD yang relevan, contoh: ekspresi CD3 untuk limfosit, CD14 untuk monosit, dst.CD = clusters of differentiation antigen = clusters designation =adalah antigen permukaan, me-nunjukkan korelasi dengan stadium deferensiasi. Interleukinsare a group ofcytokines(secretedproteinsandsignaling molecules) that were first seen to be expressed bywhite blood cells(leukocytes).The function of theimmune systemdepends in a large part oninterleukins, andraredeficiencies of a number of them have been described, all featuringautoimmune diseasesorimmune deficiency. The majority of interleukins are synthesized by helper CD4T lymphocytes, as well as through monocytes,macrophages, andendothelialcells. Theypromote the development and differentiation of T andB lymphocytes, andhematopoieticcells.

Gambar Crystallographic structure of human interleukin 1B.Sumber :enWikipedia.org, 2014.

Bacaan sumberAbbas AK, Lichtman AH, Pillai Shiv. Cellular and Molecular Immunology 7th ed. Philadelphia: Elsevier Saunders, 2012; pp 1-14.enWikipedia.org. Interleukin, 2014. SitiBoedinaKresno. Imunologi: Diagnosis danProsedurLaboratoriumedisike 4. Jakarta: Balai Penerbit Fakultas Kedokteran Universitas Indonesia, 2001; hal 1-13.www.mcld.co.uk,2014.www.mcld.co.uk. Molecule of HIV, 2014.www.mol.bio14masters. masters.grkraj.org, MHC class II, 2014.

RENUNGANThey said, "Glory be to You!We have no knowledge except what You have taught us.You are the All-Knowing, the All-Wise."(Qur'an, 2:32)

Kajianalergologidanimunologiberasaldaridunia Islam.Muhammad ibn ZakaryaRzi(Rhazes) telahbertanggungjawabpadapenemuan "asthmaberalergi", dan adalah doctor pertama diketahui telah menulis rencana-rencana padaalergidansistemimun. DalamSense of Smelling, dia menjelaskan kemunculanrhinitisselepas membau sekuntum mawarsewaktuMusimBunga. DalamRencana pada Alasan Mengapa Abou Zayd Balkhi Menderita Rhinitis apabila Membau Mawar pada Musim Bunga, diamembincangkan rhinitis bermusim, yang adalahsamadengan asthmaberalergiataudemam hay. Al-Raziadalah orang yang pertamauntukmenyedaribahawademamadalahsuatumekanismepertahan yang asli, carabadanmelawanpenyakit.

Themajorhistocompatibilitycomplex(MHC) is a set of cell surface molecules encoded by a largegene familyin allvertebrates. MHC molecules mediate interactions ofleukocytes, also calledwhite blood cells(WBCs), which areimmune cells, with other leukocytes or body cells. MHC determines compatibility of donors fororgan transplantas well as one's susceptibility to anautoimmune diseasevia crossreacting immunization. In humans, MHC is also calledhuman leukocyte antigen(HLA).Proteinmoleculeseither of the host's ownphenotypeor of other biologic entitiesare continually synthesized and degraded in acell. Occurring on the cell surface, each MHC molecule displays a molecular fraction, calledepitope, of a protein.[1]The presented antigen can be eitherselfornonself. On the cell membrane, the MHC population in its entirety is like a meter indicating the balance of proteins within the cell.The MHC gene family is divided into three subgroups:class I,class IIand class III. Diversity ofantigen presentation, mediated by MHC classes I and II, is attained in at least three ways: (1) an organism's MHC repertoire ispolygenic(via multiple, interacting genes); (2) MHC expression iscodominant(from both sets of inheritedalleles); (3) MHCgene variantsare highlypolymorphic(diversely varying from organism to organism within aspecies).[2]Discovery of MHC loci[edit]MHC genes were first identified in inbred mice strains.Clarence Littletransplanted tumors across differing strains and found rejection of transplanted tumors according to strains of host versus donor.[3]George Snellselectively bred two mouse strains, attained a new strain nearly identical to one of the progenitor strains, but differing crucially inhistocompatibilitythat is, tissue compatibility upon transplantationand thereupon identified an MHClocus.[4]For this work, Snell was awarded the 1980Nobel Prize in Physiology or Medicine.MHC in immunity[edit]Of the three MHC classes identified, human attention commonly focuses on classes I and II. By interacting withCD4molecules on surfaces ofhelper T cells, MHC class II mediates establishment ofspecific immunity(also called acquired immunity or adaptive immunity). By interacting withCD8molecules on surfaces ofCytotoxic T cells, MHC class I mediates destruction of infected or malignant host cells, the aspect of specific immunity termedcellular immunity. (The other arm of specific immunity ishumoral immunity, whose relation to MHC is more indirect.)Lymphocytes[edit]As a lineage ofleukocytes,lymphocytesreside in peripherallymphoid tissues, includinglymphoid folliclesandlymph nodes, and includeB cells,T cells, andnatural killer cells(NK cells).B cells, which actspecifically, secrete antibody molecules but do not bind MHC. T cells, which actspecifically, as well as NK cells, which actinnately, interact with MHC. When MHC class I expression is low, as is typically the case with abnormal cell function, NK cells triggerprogrammed cell deathof the cell. NK cell thus help prevent progress ofcancerouscells by contributing totumor surveillance.MHC class II[edit]MHC class II can be conditionally expressed by all cell types, but normally occurs only on professionalantigen-presenting cells(APCs):macrophages,B cells, and especiallydendritic cells(DCs). An APC uptakes anantigen, performsantigen processing, and returns a molecular fraction of ita fraction termedepitopeto the APC's surface, coupled within an MHC class II molecule mediatingantigen presentationby displaying this epitope. On the cell's surface, the epitope can contact itscognate, that is, matching, molecular region on immunologic structures recognizing that epitope. That molecular region whichdockstothat is,bindsor injargonligatesthe epitope is theparatope.On surfaces ofhelper T cellsareCD4receptors as well asT cell receptors(TCRs). When anaivehelper T cell's CD4 molecule docks to an APC's MHC class II molecule, its TCR can meet and be imprinted by theepitopecoupled within the MHC class II. This eventprimesthe naive helper T cell. According to the local milieu, that is, the balance ofcytokinessecreted by APCs in the microenvironment, the naive helper T cell (Th0)polarizesinto either amemoryTh cell or aneffectorTh cell ofphenotypeeither type 1 (Th1), type 2 (Th2), type 17 (Th17), or regulatory/suppressor (Treg), as so far identified, the Th cell'sterminal differentiation.MHC class II thus mediates immunization toor, if APCs polarize Th0cells principally to Tregcells,immune toleranceofanantigen. The polarization during primary exposure to anantigenis key in determining a numberchronic diseases, such asinflammatory bowel diseasesandasthma, by skewing the immune response that memory Th cells coordinate when their memory recall is triggered upon secondary exposure to similar antigens. (B cells express MHC class II to present antigen to Th0, but when theirB cell receptorsbind matchingepitopes, which interactions are not mediated by MHC, theseactivated B cellssecrete solubleimmunoglobulins:antibodymolecules mediatinghumoral immunity.)MHC class I[edit]MHC class I occurs on allnucleatedcellsin essence all cells butred blood cellsand presents epitopes to killer T cells, also calledcytotoxic T lymphocytes(CTLs). A CTL expressesCD8receptors, in addition toT cell receptors(TCRs). When a CTL's CD8 receptor docks to a MHC class I molecule, if the CTL's TCR fits the epitope within the MHC class I molecule, the CTL triggers the cell to undergoprogrammed cell deathbyapoptosis. Thus, MHC class I helps mediatecellular immunity, a primary means to addressintracellular pathogens, such avirusesand somebacteria, including bacterialL forms, bacterialgenusMycoplasma, and bacterial genusRickettsia.MHC genes[edit]MHC gene families are found in allvertebrates, though they vary widely. Inhumansthe MHC region occurs on chromosome 6, between the flankinggenetic markersMOG and COL11A2 (from 6p22.1 to 6p21.3 ~29Mb to 33Mb on the hg19 assembly), and contains 140 genes spanning 3.6 megabase pairs(3.6 Mb or 3 600 000 bases).[5]About half have known immune functions.The same markers in the gray short-tailedopossum(Monodelphisdomestica), amarsupial, span 3.95 Mb yielding 114 genes, 87 shared with humans.[6]Marsupial MHCgenotypicvariation lies betweeneutherian mammalsandbirdstaken as minimal MHC encodingbut is closer in organization to that of nonmammals, and MHC class I genes of marsupials have amplified within the class II region, yielding a unique class I/II region.[6]Class III function very differently from class I and class II, but itslocusoccurs between the other two classesonchromosome 6in humansand are frequently discussed together.ClassEncodingExpression

I(1) peptide-binding proteins, which select short sequences of amino acids forantigen presentation, as well as (2) molecules aidingantigen-processing(such asTAPandTapasin).One chain, called , whose ligands are theCD8receptorborne notably bycytotoxic T cellsand inhibitory receptors borne byNK cells.

II(1) peptide-binding proteins and (2) proteins assisting antigen loading onto MHC class II's peptide-binding proteins (such asMHC II DM,MHC II DQ,MHC II DR, andMHC II DP).Two chains, called & , whose ligands are theCD4receptors borne byhelper T cells.

IIIOther immune proteins, outside antigen processing and presentation, such as components of thecomplement cascade(e.g.,C2,C4,factor B), thecytokinesof immune signaling (e.g.,TNF-), andheat shock proteinsbuffering cells from stresses.Various.

MHC proteins[edit]MHC proteins haveimmunoglobulin-like structure.

MHC class I protein moleculeClass I[edit]Main article:MHC class IMHC I occurs as an chain composed of three domains1, 2, 3. The 1 rests upon a unit of the non-MHC molecule2 microglobulin(encoded on human chromosome 15). The 3 subunit is transmembrane, anchoring the MHC class I molecule to the cell membrane. The peptide being presented is held by the floor of thepeptide-binding groove, in the central region of the 1/2heterodimer(a molecule composed of two nonidentical subunits). The genetically encoded and expressed sequence of amino acids, the sequence ofresidues, of the peptide-binding groove's floor determines which particular peptide residues it binds.[7]

MHC class II protein moleculeClassical MHC moleculespresent epitopes to theTCRsof CD8+ T lymphocytes.Nonclassicalmolecules(MHC class IB) exhibit limited polymorphism, expression patterns, and presented antigens; this group is subdivided into a group encoded within MHC loci (e.g., HLA-E, -F, -G) as well as those not (e.g.,stress ligandssuch as ULBPs, Rae1, H60); the antigen/ligand for many of these molecules remain unknown, but they can interact with each of CD8+ T cells, NKT cells, and NK cells.Class II[edit]Main article:MHC class IIMHC class two is formed of two chains, and , each having two domains1 and 2 and 1 and 2each chain having a transmembrane domain, 2 and 2, respectively, anchoring the MHC class II molecule to the cell membrane.[8]The peptide-binding groove is formed of the heterodimer of 1 and 1.MHC class II molecules in humans have five to six isotypes.Classic moleculespresent peptides to CD4+ lymphocytes.Nonclassic molecules, accessories, with intracellular functions, are not exposed on cell membranes, but in internal membranes inlysosomes, normally loading the antigenic peptides onto classic MHC class II molecules.Class III[edit]Class III molecules have physiologic roles unlike classes I and class II, but are encoded between them in the short arm of human chromosome 6. Class III molecules include several secreted proteins with immune functions: components of thecomplement system(such as C2, C4, and B factor),cytokines(such asTNF-, LTA, LTB), andheat shock proteins(hsp).Antigen processing and presentation[edit]

MHC class I pathway: Proteins in thecytosolare degraded by theproteasome, liberating peptides internalized byTAPchannel in theendoplasmic reticulum, there associating with MHC-I molecules freshly synthesized. MHC-I/peptide complexes enterGolgi apparatus, areglycosylated, enter secratory vesicles, fuse with thecell membrane, and externalize on the cell membrane interacting with T lymphocytes.Peptides are processed and presented by two classical pathways: InMHC class IIphagocytessuch asmacrophagesand immaturedendritic cellsuptake entities byphagocytosisintophagosomesthoughB cellsexhibit the more generalendocytosisintoendosomeswhich fuse withlysosomeswhose acidic enzymes cleave the uptaken protein into many different peptides. Viaphysicochemical dynamicsin molecular interaction with the particular MHC class II variants borne by the host, encoded in the host's genome, a particular peptide exhibitsimmunodominanceand loads onto MHC class II molecules. These are trafficked to and externalized on the cell surface.[9] InMHC class Iany nucleated cell normally presents cytosolic peptides, mostlyselfpeptides derived from protein turnover and defective ribosomal products. During viral infection, intracellular microorganism infection, or cancerous transformation, such proteins degraded in theproteosomeare as well loaded onto MHC class I molecules and displayed on the cell surface. T lymphocytes can detect a peptide displayed at 0.1%-1% of the MHC molecules.Table 2.Characteristics of the antigen processing pathways

CharacteristicMHC-I pathwayMHC-II pathway

Composition of the stable peptide-MHC complexPolymorphic chain and 2 microglobulin, peptide bound to chainPolymorphic chains and , peptide binds to both

Types ofantigen presenting cells(APC)All nucleated cellsDendritic cells, mononuclear phagocytes,B lymphocytes, some endothelial cells, epithelium ofthymus

T lymphocytes able to respondCytotoxic T lymphocytes(CD8+)Helper T lymphocytes(CD4+)

Origin of antigenic proteinscytosolicproteins (mostly synthetized by the cell; may also enter from the extracellular medium viaphagosomes)Proteins present inendosomesorlysosomes(mostly internalized from extracellular medium)

Enzymes responsible for peptide generationCytosolicproteasomeProteasesfrom endosomes and lysosomes (for instance,cathepsin)

Location of loading the peptide on the MHC moleculeEndoplasmic reticulumSpecialized vesicular compartment

Molecules implicated in transporting the peptides and loading them on the MHC moleculesTAP(transporter associated with antigen processing)DM, invariant chain

T lymphocyte recognition restrictions[edit]Main article:MHC restrictionIn their development in thethymus, T lymphocytes are selected to recognize MHC molecules of the host but not recognize other self antigens. Following selection each T lymphocyte shows dual specificity: The T cell receptor (TCR) recognizesselfMHC but onlynon-selfantigens.MHC restriction occurs during lymphocyte development in the thymus through a process known as positive selection. T cells that do not receive a positive survival signal mediated mainly by thymic epithelial cells presentingselfpeptides bound to MHC molecules to their TCR undergoapoptosis. Positive selection ensures that mature T cells can functionally recognize MHC molecules in the periphery (i.e. elsewhere in the body).The TCRs of T lymphocytes recognise onlysequential epitopes, also calledlinear epitopes, of only peptides and only if coupled within an MHC molecule. (Antibody molecules secreted byactivated B cells, on the other hand, ligate diverse epitopespeptide,lipid,carbohydrate, andnucleic acidand recognizeconformational epitopes, which have3Dstructure.)MHC in sexual mate selection[edit]Main article:Major Histocompatibility Complex and Sexual SelectionSee also:Interpersonal compatibilityMHC molecules enable immune system surveillance of the population of protein molecules in a host cell, and greater MHC diversity permits greater diversity ofantigen presentation. In 1976 Yamazakiet aldemonstrated preference by male mice for females of different MHC. Similar results have been obtained withfish[10]andbirds(e.g.,black-throated blue warblers).[11]Some data find lower rates ofearly pregnancy lossin human couples of dissimilar MHC genes.[12]It has been proposed that MHC is related to mate choice in some human populations, a theory that has found support by studies by Ober and colleagues in 1997,[13]as well as by Chaix and colleagues in 2008.[14]However, the latter findings have been controversial.[15]If it exists, the phenomena might be mediated byolfaction, as MHC phenotype appears strongly involved in the strength and pleasantness of perceived odour of compounds fromsweat. Fatty acidesterssuch asmethyl undecanoate,methyl decanoate,methyl nonanoate,methyl octanoateandmethyl hexanoateshow strong connection to MHC.[16]In 1995Claus Wedekindfound that in a group of female college students who smelled T-shirts worn by male students for two nights (without deodorant, cologne, or scented soaps), by far most women chose shirts worn by men of dissimilar MHCs, a preference reversed if the women were on oral contraceptives.[17]Results of a 2002 experiment likewise suggest HLA-associated odors influence odor preference and may mediate social cues.[18]In 2005 in a group of 58 subjects, women were more indecisive when presented with MHCs alike their own,[19]although without oral contraceptives, the women showed no particular preference.[20]There are no studies on the extent to which odor preference determines mate selection (or vice versa).MHC evolutionary diversity[edit]Mostmammalshave MHC variants similar to those of humans, who bear greatallelic diversity, especially among the nine classical genesseemingly due largely togene duplicationthough human MHC regions have manypseudogenes. The most diverse loci, namely HLA-A, HLA-B, and HLA-DRB1, have roughly 1000, 1600, and 870 known alleles, respectively. Many HLA alleles are ancient, sometimes of greaterhomologyto a chimpanzee MHC alleles than to some other human alleles of the same gene.MHC allelic diversity has challengedevolutionary biologistsfor explanation. Most positbalancing selection(seepolymorphism (biology)), which is anynatural selectionprocess whereby no single allele is absolutely most fit, such asfrequency-dependent selectionandheterozygote advantage. Recent models suggest that a high number of alleles is implausible via heterozygote advantage alone.[citation needed]Pathogenic co-evolution, a counter-hypothesis, posits that common alleles are under greatest pathogenic pressure, driving positive selection of uncommon allelesmoving targets, so to say, for pathogens. As pathogenic pressure on the previously common alleles decreases, their frequency in the population stabilizes, and remain circulating in a large population. Despite great MHC polymorphism at the population level, an individual bears at most 18 MHC I or II alleles.Relatively low MHC diversity has been observed in thecheetah(Acinonyxjubatus),[21]Eurasian beaver(Castor fiber),[22]andgiant panda(Ailuropodamelanoleuca).[23]In 2007 low MHC diversity was attributed a role in disease susceptibility in theTasmanian devil(Sarcophilusharrisii), native to the isolated island ofTasmania, such that an antigen of a transmissible tumor, involved indevil facial tumour disease, appears to be recognized as aself antigen.[24]To offsetinbreeding, efforts to sustain genetic diversity in populations of endangered species and of captive animals have been suggested.MHC in transplant rejection[edit]In a transplant procedure, as of an organ orstem cells, MHC molecules act themselves asantigensand can provoke immune response in the recipientthus transplant rejection. MHC molecules were identified and named after their role intransplantrejection between mice of different strains, though it took over 20 years to clarify MHC's role in presenting peptide antigens tocytotoxic T lymphocytes(CTLs).[25]Each human cell expresses six MHC class I alleles (one HLA-A, -B, and -C allele from each parent) and six to eight MHC class 2 alleles (one HLA-DP and -DQ, and one or two HLA-DR from each parent, and combinations of these). The MHC variation in the human population is high, at least 350 alleles for HLA-A genes, 620 alleles for HLA-B, 400 alleles for DR, and 90 alleles for DQ. Any two individuals not identical twins express differing MHC molecules. All MHC molecules can mediate transplant rejection, but HLA-C and HLA-DP, showing low polymorphism, seem least important.[clarification needed]When maturing in thethymus,T lymphocytesare selected for their T cell receptors (TCR) incapacity to recognizeself antigens. Yet T lymphocytes can react against the donor MHC'speptide-binding groove, the variable region of MHC holding the presented antigen'sepitopefor recognition by TCR, the matchingparatope. T lymphocytes of the recipient take the incompatible peptide-binding groove asnonself antigen. The T lymphocytes' recognition of the foreign MHC as self isallorecognition.[clarification needed]Transplant rejection has two types known as mediated by MHC (HLA): Hyperacute rejectionoccurs when, before the trasplantation, the recipient has preformed anti-HLA antibodies, perhaps by previous blood transfusions (donor tissue that includes lymphocytes expressing HLA molecules), by anti-HLA generated during pregnancy (directed at the father's HLA displayed by the fetus), or by previous transplantation; Acute humoral rejection and chronic disfunctionoccurs when the recipient's anti-HLA antibodies form directed at HLA molecules present onendothelial cellsof the transplanted tissue.In either situation, immunity is directed at the transplanted organ, sustaining lesions. Across-reaction testbetween potential donor cells and recipient serum seeks to detect presence of preformed anti-HLA antibodies in the potential recipient that recognize donor HLA molecules, so as to prevent hyperacute rejection. In normal circumstances, compatibility between HLA-A, -B, and -DR molecules is assessed. The higher the number of incompatibilities, the lower the five-year survival rate. Global databases of donor information enhance the search for compatible donors.HLA biology[edit]

Codominant expression of HLA genes.Main article:Human leukocyte antigenHuman MHC class I and II are also calledhuman leukocyte antigen(HLA). To clarify the usage, some of the biomedical literature uses HLA to refer specifically to the HLA protein molecules and reserves MHC for the region of the genome that encodes for this molecule, but this is not a consistent convention.The most intensely studied HLA genes are the nine so-called classical MHC genes:HLA-A,HLA-B,HLA-C,HLA-DPA1,HLA-DPB1,HLA-DQA1,HLA-DQB1,HLA-DRA, andHLA-DRB1. In humans, the MHC is divided into three regions: classes I, II, and III. The A, B and C genes belong to MHC class I, whereas the six D genes belong to class II.MHC genes are expressed in codominant fashion.[8]This means that thealleles(variants) inherited from both progenitors are expressed in equivalent way: As there are 3 Class-I genes, named in humans HLA-A, HLA-B and HLA-C, and as each person inherits a set of genes from each progenitor, that means that any cell in an individual can express 6 different types of MHC-I molecules (see figure). In the Class-II locus, each person inherits a pair of HLA-DP genes (DPA1 and DPB1, which encode and chains), a couple of genes HLA-DQ (DQA1 and DQB1, for and chains), one gene HLA-DR (DRA1) and one or more genes HLA-DR (DRB1 and DRB3, -4 or -5). That means that oneheterozygousindividual can inherit 6 or 8 functioning Class-II alleles, three or more from each progenitor. The role of DQA2, DQB2 is not verified. The DRB2, DRB6, DRB7, DRB8 and DRB9 are pseudogenes.The set of alleles that is present in each chromosome is called MHChaplotype. In humans, each HLA allele is named with a number. For instance, for a given individual, his haplotype might be HLA-A2, HLA-B5, HLA-DR3, etc... Each heterozygous individual will have two MHC haplotypes, one in each chromosome (one of paternal origin and the other of maternal origin).The MHC genes are highly polymorphic; this means that there are many different alleles in the different individuals inside a population. The polymorphism is so high that in a mixed population (non-endogamic) there are not two individuals with exactly the same set of MHC genes and molecules, with the exception ofidentical twins.The polymorphic regions in each allele are located in the region for peptide contact, which is going to be displayed to the lymphocyte. For this reason, the contact region for each allele of MHC molecule is highly variable, as the polymorphic residues of the MHC will create specific clefts in which only certain types of residues of the peptide can enter. This imposes a very specific link between the MHC molecule and the peptide, and it implies that each MHC variant will be able to bind specifically only those peptides that are able to properly enter in the cleft of the MHC molecule, which is variable for each allele. In this way, the MHC molecules have a broad specificity, because they can bind many, but not all types of possible peptides. This is an essential characteristic of MHC molecules: In a given individual, it is enough to have a few different molecules to be able to display a high variety of peptides.On the other hand, inside a population, the presence of many different alleles ensures there will always be an individual with a specific MHC molecule able to load the correct peptide to recognize a specific microbe. The evolution of the MHC polymorphism ensures that a population will not succumb to a new pathogen or a mutated one, because at least some individuals will be able to develop an adequate immune response to win over the pathogen. The variations in the MHC molecules (responsible for the polymorphism) are the result of the inheritance of different MHC molecules, and they are not induced byrecombination, as it is the case for the antigenreceptors.Because of the high levels ofallelicdiversity found within its genes, MHC has also attracted the attention of manyevolutionarybiologists.[citation needed]References[edit]1. Jump up^Kimball's BiologyHistocompatibility Molecules2. Jump up^Janeway CA Jr, Travers P, Walport M,et al,Immunobiology: The Immune System in Health and Disease, 5thedn (New York: Garland Science, 2001),"The major histocompatibility complex and its functions".3. Jump up^Little CC 1941, "The genetics of tumor transplantation", pp 279309, inBiology of the Laboratory Mouse, ed by Snell GD, New York: Dover.4. Jump up^Snell GD & Higgins GF 1951, "Alleles at the histocompatibility-2 locus in the mouse as determined by tumor transplantation",Genetics36:3063105. Jump up^MHC Sequencing Consortium (1999). "Complete sequence and gene map of a human major histocompatibility complex".Nature401(6756): 921923.doi:10.1038/44853.PMID10553908.6. ^Jump up to:abBelov K, Deakin JE, Papenfuss AT, Baker ML, Melman SD, Siddle HV, Gouin N, Goode DL, Sargeant TJ, Robinson MD, Wakefield MJ, Mahony S, Cross JG, Benos PV, Samollow PB, Speed TP, Graves JA, Miller RD (March 2006)."Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex".PLoS Biol.4(3): e46.doi:10.1371/journal.pbio.0040046.PMC1351924.PMID16435885.7. Jump up^Toh H, Savoie CJ, Kamikawaji N, Muta S, Sasazuki T, Kuhara S (October 2000). "Changes at the floor of the peptide-binding groove induce a strong preference for proline at position 3 of the bound peptide: molecular dynamics simulations of HLA-A*0217".Biopolymers54(5): 31827.doi:

This page was last modified on 14 April 2014 at 00:17.Etc

SOAL UJIAN AKHIR BLOK VIMUNOLOGIPengampu : Praptiwi H

Skenario 1 Dua orang ibu berdebat mengenai anak-anak mereka yang senang bermain di pekarangan sebelah rumah. Lokasi tersebut berdekatan dengan Tempat Pembuangan Sampah sementara di lingkungan RT setempat. Ibu I tidak setuju, berbeda dengan ibu ke II.

1.1. Ibu I tidak setuju, dengan dasar pemikiran sebagai berikut a. Sampah merupakan sumber patogen, yang akan menyebar terbawa oleh angin, semut, lalat, dan vektor lain menempel ke tubuh anak, menyebabkan anak sakit b. bau sampah yang busuk mengganggu pernafasan anak c. anak mudah sakit, berhubung daya tahannya masih lemah d. sumsum tulang anak yang membentuk semua sel imun, belum bisa mengimbangi kuantitas patogen sampah e. kelompok sel imun yang aktif mengenali patogen dengan memorinya, belum terbentuk pada anak.

1.2. Ibu II setuju, dengan dasar a. anak yang terlalu bersih akan mudah menderita sakit b. sebagian kekebalan akan terbentuk, bila tubuh bertemu dengan patogen c. sampah bisa bermanfaat untuk kesuburan tanaman, selanjutnya manusia d. kegembiraan bermain pada masa kanak-kanak akan berpengaruh baik pada perkembangan fisik dan mentalnya e. aktivitas fisik / bermain pada waktu masih kecil, membina kebiasaan hidup yang baik.

Skenario 2 Seorang pekerja bangunan mengalami kecapaian yang sangat, sesudah selesai proyek ge-dung 3 lantai tempat ia bekerja. Timbul rasa sakit bila menelan, serta terasa ada benjolan keras di bawah mandibula. Badan terasa demam, panas dingin selama 2 hari, sebelum ia ke dokter. Obat yang dibeli di toko obat tidak bisa menyembuhkan, berbeda dengan biasanya. Pemeriksaan oleh dokter mengharuskan ia membeli berbagai obat yang cukup mahal.

2.1. Apakah yang menyebabkan timbulnya rasa sakit pada pekerja bangunan tersebut ? a. rasa capai yang berkepanjangan melemahkan fisik, sehingga mudah sakit b. kemungkinan kurang gizi karena kerja berat, sehingga mudah sakit c. radang saluran nafas kronik karena terpapar debu saat bekerja d. daya tahan tubuh menurun karena kerja berat dalam waktu panjang. Serangan patogen yang menginfeksi tubuh tidak tertanggulangi oleh imunitas tubuh e. gedung yang dalam proses dibangun merupakan tumpukan sampah material, menjadi sarang penyakit.

2.2. Mengapa obat yang dibeli di toko obat tidak bisa menyembuhkan, berbeda dengan ketika ia sakit sebelumnya ? a. obat mahal lebih mujarab dibanding yang murah b. tubuh sudah kebal dengan obat yang biasa dimakan c. tubuh yang kecapaian memudahkan patogen-patogen berkembang biak, sehingga ketika jatuh sakit, diperlukan obat yang lebih tepat d. jenis penyakit menentukan jenis obatnya e. obat dari toko obat terlalu umum dan ringan.

Skenario 3 Seorang pensiunan Kepala Desa mengeluhkan berbagai penyakit yang silih berganti diderita semenjak ia pensiun. Dokter yang memeriksa memperingatkan kemungkinan bahaya serangan jenis- jenis virus baru.3.1. Mengapa setelah ia sempat beristirahat, justru sering menderita penyakit ? a. peningkatan usia akan menurunkan daya tahan tubuh terhadap penyakit, antara lain dengan mengecilnya timus, pemroduksi sel-sel imun b. kecapaian dalam waktu lama sebagai Kades baru terasa sesudah pensiun c. penyakit menumpuk pada masa tua d. post power syndrome memicu timbulnya bermacam-macam gejala / sakit e. kegiatan yang berat ketika masih aktif bekerja, secara pelahan menurunkan daya tahan tubuh setelah tidak aktif lagi.

3.2. Bagaimana pengaturan cara hidup sehat yang sebaiknya dilakukan ? a. banyak istirahat, berfikir positif, olahraga ringan dan rutin b. berangsur-angsur kerja ringan, agar tubuh beradaptasi terhadap perubahan aktivitas. c. makan teratur dan cukup, zat gizi lengkap dan seimbang, olahraga dan istirahat cukup d. mengurangi stress karena banyak menganggur, dengan cukup rekreasi e. menjauhkan diri dari para penderita penyakit menular karena virus.

Skenario 4 Seorang pemuda setelah didiagnosis menderita HIV-AIDS, ingin memperoleh penjelasan tentang pertahanan tubuh yang perlu diaktifkan untuk melawan penyakitnya. Dari internet diperoleh pengetahuan tentang pentingnya sumsum tulang untuk perlindungan terhadap semua penyakit. Temannya, mahasiswa FK, mengatakan pentingnya protein dalam sistem kekebalan bawaan. Cukup banyak jenis sel dan molekul, dan mereka bekerjasama dalam sistem imun. 4.1. Adakah kaitan antara sumsum tulang dengan sel-sel imun ? a. sumsum tulang membuat sel induk hematopoietic, sumber kekebalan bawaan b. sumsum tulang menghasilkan sel-sel imun c. sumsum tulang memetabolisasi protein dengan hasil akhir sel-sel imun d. sumsum tulang memroduksi sel induk pembuat sel darah. Banyak sel imun berasal dari sel darah putih. e. sumsum tulang merupakan sumber lemak dan protein, penyusun struktur sel imun.

4.2. Bagian dari sistem kekebalan bawaan yang terdiri dari banyak macam protein, yaitu , menambah kemampuan antibodi dan sel faga untuk melawan / membersihkan patogen dari tubuh seseorang. a. sel T-helperb. sel dendritikc. sitokin d. sel Be. sistem komplemen.

4.3. Kerjasama antara limfosit B dan sel T terlihat dalam proses a. pelahapan bakteri oleh makrofag, bersama-sama dengan sel B dan sel T b. pengusiran bakteri, aktivasi sel B oleh sel T helper c. pengikatan antigen - antibodi d. pembentukan reseptor-reseptor di permukaan sel imun e. proliferasi dan diferensiasi sel T.

4.4. Kelompok molekul pada permukaan sel yang memediasi interaksi antara leukosit sel imun dengan leukosit sel lain, dengan hasil disebut a. rusaknya salah satu leukosit; cluster of differentiation b. ekspresi CD spesifik; monosit c. kemungkinan terjadi penyakit autoimmune; imunisasi cross reaction d. peptida bakteri keluar dari sel; aktivasi makrofag e. kerusakan sel inang yang ganas / terinfeksi; major histocompatibility complex kelas 1.

Kunci jawaban1.1.a 1.2.b 2.1.d 2.2.c 3.1.a 3.2.c 4.1.d 4.2.e 4.3.b 4.4.e.