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imunologi
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Learning Objective
• Apa itu sistem imun?• Apa itu imunitas?• Apa itu respon imun?• Apa saja anggota sistem imun?• Bagaimana cara kerja sistem imun?• Bagaimana hubungan sistem imun dengan
mekanisme terjadinya suatu penyakit?
Klasifikasi Imunitas
• Imunitas alami (natural or innate or non-spesific immunity)• Imunitas dapatan (Aquired or adaptive or spesific
immunity)
Komponen imunitas dapat dikelompokkan menjadi: Imunitas humoral: respon imun oleh molekul terlarut
dalam plasma (non-cell response)Imunitas seluler: respon imun oleh sel atau produk sel
(cell mediated imunity)Baik pada innate imunity atau aquired imunity kedua jenis respon imun diatas saling berelaborasi
BARIER FISIK & biokimia
NON SPESIFIK (ALAMIAH) SPESIFIK (DAPATAN)
SISTEM IMUN
HUMORAL HUMORALSELULER SELULER
KulitMukosaSiliaMucus Biokimia:LisozimSekresi sebaseusAsam lambungLaktoferinAs. neuraminik
komplemenAPPMediator asal lipidSitokin
MonunuklearPolimorfonuklearSel NkSel mastBasofilEosinofilSel dendritik
Anti bodi (imunoglobulin) yang dihasilkan oleh sel B:Ig AIg MIg GIg DIg ESitokin
Sel T:Sel Th1Sel Th2Sel T cytotoxic (CD 8)NKT
Komponen Seluler
• The major cellular constituents of both innate and acquired immunity originate in the bone marrow where they differentiate from MHSC:– granulocytes,– lymphocytes, and – APCs
• Granulocytes (Poly Morphonuclear)– Neutrophil• Phagocytic activity of neutrophils surface receptors:• antibody molecules (Fc portion dari Ig G)• complement proteins (C3b component)
– Non phagocytic Eosinophil, bashophil, sel mast • ability to discharge potent biological mediators into the
cellular microenvironment proses degranulation• FcεR on their surfaces• Proses alergi akut yg dimediasi Ig E
Komponen Seluler
• Lymphocytes– B cells, T cells, and NK cells identified based on display of
particular surface molecules– All lymphocytes differentiate from common lymphoid progenitor
in the bone marrow– T cells undergo further maturation and selection in the thymus
for expression of antigen receptors useful in self/nonself discrimination
– B cells continue differentiation into antibody-producing cells in the bone marrow
– T cells and B cells are the heart of specific immune recognition, a property reflecting their clonally specific cell surface receptors for antigen
– NK cell Innate Immunity
Komponen Seluler
• Reseptor Lymphocytes – Clonally expressed: (spesific immunity)• B-cell receptors for antigen (BCR) are membrane
immunoglobulin (Ig) molecules• The T-cell receptor for antigen (TCR) is a heterodimeric
integral membrane molecule
– NK cells are not clonally expressed innate immunity (non-spesific) germline-encoded cellular receptors
Komponen Seluler
• Antigen-presenting cells (APC)– A morphologically and functionally diverse group of cells, all of
which are derived from bone marrow precursors, is specialized for presentation of antigen to lymphocytes, particularly T cells
– Monocytes (present in the peripheral circulation);– Macrophages (solid tissue derivatives of monocytes); cells
resident within– dendritic cells The solid organs of the immune system such
as; And constituents of the reticular endothelial system within other solid organs.
– B lymphocytes that specifically capture antigen by virtue of M Ig receptors can also function efficiently in antigen presentation to T cells.
Komponen Seluler
Innate Immunity
• Main function:– engulf and destroy pathogens, – to trigger proinflammatory responses, and– to help present antigen, thereby priming adaptive immune
responses• Aktivitas;
– Physical barriers to pathogen invasion (such as skin, mucous membranes, cilia, and mucus)
– Biochemical secretion: lisozime, HCl, sebaseus – Inflammatory responses by ‘innate’ immune cells: granulocytes
and macrophages ( phagocytes)– Activation of dendritic cells and natural killer (NK) cells
• Innate imunne system = a relatively non specific • Innate immune system has a great degree of
specificity that enables it to discriminate efficiently between self and foreign entities, including microorganisms and unnecessary self molecules
• Pattern recognition receptors (PRRs), which include the Toll-like receptors (TLRs), NOD-like receptors (NLRs), and the recently described RIG-I-like receptors (RLRs)
Basis of acquired immunity
• The essence of acquired immunity is molecular distinction between self constituents and potential pathogens
• This discrimination is predominantly a responsibility of T lymphocytes
• The vast majority of antigens for T cells: oligopeptides; T cells can also recognize glycolipid
• B cells produce antibody • Antibodies show less preference for recognition of
proteins; antibodies against carbohydrates, nucleic acids, lipids, and simple chemical moieties can be readily produced
Mechanisms of immunologicdiseases
1. Immunologic disease can reflect a failure or deficiency of the immune system – Failure can be congenital (e.g., X-linked agammaglobulinemia) or acquired
(e.g., acquired immunodeficiency syndrome (AIDS))– It can be global (e.g., severe combined immunodeficiency) or quite specific,
involving only a particularcomponent of the immune system (e.g., selective IgA deficiency).
2. Malignant transformation3. Dysregulation of an essentially intact immune system The acute
allergic diseases4. Ambiguity in this discrimination can lead to autoimmune tissue
damage5. Disease is disease development as a result of physiologic rather than
pathologic function
Antigen-binding molecules
• Sets of molecules are responsible for the specificity of acquired immune responses by virtue of their capacity to bind foreign antigen
• Dapat berupa: Ig, TCR, and MHC molecules• The exquisite specificity of Ig and TCR
molecules for antigen is achievedby a mechanism of genetic recombination that is unique to Ig and TCR genes
Major histocompatibility complex (MHC)
• The most important difference between the nature of the binding groove of MHC molecules and those of Ig and TCR is that the former does not represent a consequence of gene rearrangement.
• MHC molecules are of two basic types: class I and class II
Perbedaan Nonspesifk
Resistensi Tidak berubah oleh infeksi Membaik oleh infeksi berulang
Komponel sel Fagosit sel NK, monosit/makrofag, neutrofil, basofil, sel mast, eosinofil, sel dendritik
Th, Tc, sel B
Molekul yang penting Lisozim, sitokin, komplomen, APP Lisozim, CRP, kolektin
Antibodi, sitokin
Waktu respon Menit/jam (selalu siap) Hari-minggu (lambat)
Pajanan Tidak perlu Harus ada pajanan sebelumnya
Diversitas Jumlah reseptor terbatas Reseptor bervariasi, jumlah banyak, terbentuk oleh rekomibinasi genetik dari gen reseptor
Respons memori Tidak ada Memori menetap, respon lebih cepat dan lebih baik
Immune Cell Development
• Ontogeny of the cells of the immune system– Bln 1 embryogenesis white blood cell progenitors at yolk
sac erythropoietic islands (ekstra embryonik)– Area aorta–gonad–mesonephros (AGM) give rise to the
first progenitor cell (intraembryonik)– Plasenta – Embryonic liver is the first organ β be populated by these
progenitor stem cells– The elements of the skeleton are formed between the
second and fourt months of gestation– Transisi dari Liver Bone marrow lengkap pd Bln VI
• The first progenitor cells derived from hematopoietic stem cells (HSC) are colony-forming cells that can differentiate into granulocytes, erythrocytes, monocytes, megakaryocytes, and lymphocytes.
• The elements• of the skeleton are formed between the second and
fourth• months of gestation.• The transition from liver to• bone marrow is completed in the sixth month of gestation
• Pluripotent hematopoietic stem cells:– Lhyphoid progenitor:• B cell progenitor• T cell progenitor• Nk cell progenitor
– Myeloid Progenitor CFU GEMM (colony forming unit - granulocytic,erythroid, monocytic–dendritic, and megakaryocytic:
Hematopoiesisand Lymphopoiesis
Characteristics of hematopoieticstem cells
• Memiliki marker• CD = Class of Differetiation • CD 34 primitive precursor (blast)• CD20 sel plasma• CD 33 myeloid• CD 4 T helper• CD 8 T cytotoxic
Organ Lymphoid
• Organ Lymphoid Primer– The primary lymphoid organs are sites where
lymphocytes differentiate from stem cells and proliferate and mature into effector cells.
• Organ Lymphoid Sekunder– Secondary lymphoid organs are sites where
mature lymphocytes reside and where immune responses are generated.
• Primary Lymphoid Organs– Bone marrow– Thymus
• Secondary Lymphoid Organs – systemic immune system: Spleen & lymph nodes– The mucosal immune system mucosa-associated
lymphoreticular tissue (MALT): GALT, BALT, female reproductive tract MALT
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