HUMAN

IMMUNOLOGY
dr. May Valzon, MSc
INTRODUKSI
 Apa itu imunitas?
 Resistensi terhadap suatu penyakit (terutama infeksi)
 Apa itu sistem imun?
 Gabungan sel, molekul, jaringan, dan organ yang
berperan dalam imunitas
 Apa itu respon imun?
 Rangkaianreaksi yang dikoordinasi oleh anggota sistem
imun untuk melawan pathogen
 Apa saja anggota sistem imun?
 Sel, molekul, jaringan, dan organ
 Bagaimana cara kerja sistem imun?
 Bagaimana hubungan sistem imun dengan mekanisme
terjadinya suatu penyakit?
All the cellular elements of the blood, including
leukocytes are the monocytes, the dendritic cells,
and the neutrophils, eosinophils, and basophils
arise from pluripotent hematopoietic stem cells in
the bone marrow
KOMPONEN SISTEM IMUN
 Barier fisik  Kulit, mukosa, silia,
mekanisme batuk, bersin
 Barrier biokimia  lisozim, sebum, asam
lambung, laktoferin, asam neuraminik
 Humoral (Non-cell Response)  molekul
terlarut dalam darah: Komplemen, APP,
Sitokin, Ig
 Seluler (Cell Response)  Fagosit, sel NK, Sel
Mast, Basofil, Eosinofil, Sel Dendritik, Sel T,
Sel B
KLASIFIKASI SISTEM IMUN

Sistem imun Sistem imun

non-spesifik spesifik

Sistem imun Sistem imun

alamiah/natural Dapatan/acquired

Innate Adaptive
immunity immunity

Klasifikasi hanya dimaksudkan untuk mempermudah dalam

memahami saja  kedua sistem imun tersebut faktanya saling
bekerjasama
PERBEDAAN IMUNITAS NON-
SPESIFIK & SPESIFIK
Non-spesifik Spesifik
Kemampuan sama saja pada tiap Meningkat pada infeksi
resistensi infeksi berikutnya
Spesifitas Bereaksi terhadap Spesifik untuk pathogen
semua pathogen yg telah menstimulus
Reseptor Pola molekuler yg Struktur pathogen detil,
terdapat pada semua clonal, dan mengalami
pathogen rearrangament
Waktu respon Menit-jam (cepat); Jam-hari (lambat)
respon yg pertama
timbul
Panjanan Langsung bereaksi Perlu pajanan terlebih
dahulu
Memori Tdk ada Ada
 Non-spesifik Spesifik
Diskriminasi Sempurna, karena Sangat baik, tapi bisa
reseptor spesifik untuk gaga  penyakit
pola molekul pathogen autoimun, karena
reseptor dibentuk
belakangan
Komponen Komplomen, CRP, Ab (Ig)
humoral peptida2 antimikroba dan
protein
Komponen Turanan Myeloid Turunan Lymphoid,
seluler NK cell kec. NK cell
MEKANISME KERJA SISTEM
IMUN
 Immunological recognition
 Pengenalan Ag oleh reseptor permukaan
 Immune effector functions
 Penghancuran pathogen
 Fagositosis dan opsonisasi
 Immune regulation
 Kemampuan sistem imun untuk melakukan self-
regulation
 Kegagalan  Alergi & Autoimunitas
 Immunological memory
 Mencegah infeksi ulang
 Hanya dilakukan oleh imunitas adaptif
IMUNITAS NON-SPESIFIK
(INNATE IMUNITY)
 Barrier Fisik & Kimia
 Pertahanan pertama terhadap pathogen
 Barier fisik  kulit & mukosa, cilia
 Barier kimia  lisozim, asam lambung, dll
 Innate imunity  bentuk kuno sistem imun
 Reaksi pertama yg muncul setelah barier fisik
dan kimia terlewati
 Anggota:
 Imunitas Humoral
 Imuitas seluler
Phagocytic innate immunity Non-Phagocytic innate
SEL DENDRITIK
KOMPONEN HUMORAL INNATE
IMMUNITY
 Molekul larut: lokal atau dari sirkulasi
 Lokal: defensin, katelisidin, IFN
 Sirkulasi: komplemen dan Protein fase aktiv
KOMPLEMEN
 Sekumpulan protein larut dalam plasma yg
dihasilkan oleh hepatosit
 Dapat diaktifkan secara langsung oleh pathogen
 Komplemen yang teraktifkan  kaskade
komplemen (reaksi yang bertingkat-tingkat)
 Komplemen aktif bertindak sbg opsonin 
opsonisasi
 Opsonisasi  meningkatkan fagositosis,
kemotaktik, dan lisis pathogen
 Membentuk MAC (Mebrane Attack Complex) 
melubangi membran sel bakteri
INNATE IMMUNITY
 Physical barriers to pathogen invasion (such as
skin, mucous membranes, cilia, and mucus)
 Inflammatory responses by ‘innate’ immune
cells: granulocytes and macrophages
 Activation of dendritic cells and natural killer
(NK) cells
 a relatively nonspecific immune system
 Main function:
 engulf and destroy pathogens,
 to trigger proinflammatory responses, and
 to help present antigen, thereby priming adaptive
immune responses
 Innate immune system has a great degree of
specificity that enables it to discriminate
efficiently bbetween 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)
KOMPONEN SELULER
 The major cellular constituents of both
innate and acquired immunity originate in
the bone marrow where they differentiate
from multipotential hematopoietic stem cells
(MHSC) along several pathways to become:
 granulocytes,
 lymphocytes, and
 APCs
GRANULOCYTES
 Neutrophil
 Phagocytic activity of neutrophils  surface
receptors:
 antibody molecules (Fc portion dari Ig G)
 complement proteins (C3b component)
 Non phagocytic  Eosinophil, bashophil, sel
mast
 abilityto discharge potent biological mediators
into the cellular microenvironment  proses
degranulation
 FcεR on their surfaces
 Proses alergi akut yg dimediasi Ig E
LYMPHOCYTES
 B cells, T cells, and NK cells  identified based
on display of particular surface molecules
 All lymphocytes differentiate from common
lymphoid stem cells 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
RESEPTOR LYMPHOCYTES
 Clonally expressed: (spesific immunity)
 B-cellreceptors for antigen (BCR) are membrane
immunoglobulin (mIg) molecules
 The T-cell receptor for antigen (TCR) is a
heterodimeric integral membrane molecule
 NK cells  are not clonally expressed 
innate immunity (non-spesific)
ANTIGEN-PRESENTING CELLS
(APC)
 A morphologically and functionally diverse group of cells,
all of whichv 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
 the solid organs of the immune system such as dendritic cells;
 And constituents of the reticular endothelial system within
other solid organs.
 B lymphocytes that specifically capture antigen by virtue of
mIg receptors can also function efficiently in antigen
presentation to T cells.
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?
MECHANISMS OF IMMUNOLOGIC
DISEASES
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 transformation
3. Dysregulation of an essentially intact immune system 
The acute allergic diseases
4. Ambiguity in this discrimination can lead to autoimmune
tissue damage
5. 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
ORGANIZATION OF THE
IMMUNE 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
HEMATOPOIESIS
AND LYMPHOPOIESIS
 Pluripotent hematopoietic stem cells:
 Lhyphoid progenitor:
 B cell progenitor
 T cell progenitor
 Nk cell progenitor
 MyeloidProgenitor  CFU GEMM (colony
forming unit - granulocytic,erythroid,
monocytic–dendritic, and megakaryocytic:
CHARACTERISTICS OF HEMATOPOIETIC
STEM 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
 Secondarylymphoid organs are sites where
mature lymphocytes reside and where immune
responses are generated.
 Primary Lymphoid Organs
 Bonemarrow
 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
ORGANISASI SISTEM IMUN
Sistem imun terdiri dari:
1. Organs  Organ Lymphoid
 spleen,
 thymus, and
 the lymph nodes

2. Movable cells or molecule

 Cells from bone marrow, blood and
lymphatics
 Molekul dari sel
INNATE IMMUNITY: LINI
PERTAHANAN PERTAMA

 Perbedaan kontras  Receptor  germline

 Adaptif  receptor  somatic cell gene
rearrangement