Human Immunology

dr. May Valzon

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?

The human immune response

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 vs Aquired Immunity

Apakah keduanya saling berhubungan atau bekerja sendiri-sendiri?

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

Clonal basis of immunological memory

• Bagaimana bisa terbentuk immunological memory?

Antigen Presentation

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

Organization of theimmune system

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

Thymus

MALT

Organisasi Sistem Imun

Sistem imun terdiri dari:

2. Movable cells or molecule Cells from bone marrow, blood and

lymphatics Molekul dari sel

1. Organs Organ Lymphoid spleen, thymus, and the lymph nodes