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.