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?

Rangkaian reaksi 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

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
non-spesifik

Sistem imun
spesifik

Sistem imun
alamiah/natura
l

Sistem imun
Dapatan/acquir
ed

Innate
immunity

Adaptive
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
resistensi

sama saja pada tiap infeksi

Meningkat pada infeksi

berikutnya

Spesifitas

Bereaksi terhadap semua

pathogen

Spesifik untuk pathogen yg

telah menstimulus

Reseptor

Pola molekuler yg terdapat

pada semua pathogen

Struktur pathogen detil,

clonal, dan mengalami
rearrangament

Waktu respon

Menit-jam (cepat); respon

yg pertama timbul

Jam-hari (lambat)

Panjanan

Langsung bereaksi

Perlu pajanan terlebih

dahulu

Memori

Tdk ada

Ada

Non-spesifik

Spesifik

Diskriminasi

Sempurna, karena reseptor

spesifik untuk pola molekul
pathogen

Sangat baik, tapi bisa

gaga penyakit
autoimun, karena
reseptor dibentuk
belakangan

Komponen
humoral

Komplomen, CRP, peptida2

antimikroba dan protein

Ab (Ig)

Komponen seluler

Turanan Myeloid
NK cell

Turunan Lymphoid, 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 selfregulation
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

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

ability to discharge potent biological mediators into
the cellular microenvironment proses degranulation
FcR 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 antibodyproducing 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-cell receptors 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 aortagonadmesonephros (AGM) give rise to
the first progenitor cell (intraembryonik)
Plasenta
Embryonic liver is the first organ 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

Myeloid Progenitor 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

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

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