Imunologi

Early forms of smallpox vaccine---variolation

"The Genius of China: 3000 Years of Science, Discoveries
and Inventions", Simon and Schuster, New York, by Robert
Temple, 1986

Gadis yang terkena cacar dengan sengaja diberi bubuk

yang berasal dari penderita cacar yang tidak parah

1798 Edward Jenner

Reasoning:
Bibit penyakit cacar dari sapi dapat
digunakan untuk
mencegah penyakit cacar manusia

Observation:
Pemerah susu sapi yang
terjangkit penyakit cacar
tidak menderita cacar
parah dan terbebas
cacar manusia

Testing:
Menyuntikkan bibit
Penyakit sapi pada
anak usia 8 th
dan beberapa bulan
kemudian anak
tersebut
tidak terinfeksi
cacar

Sistem Imun
Respon imune

Innate
(Nonspecific)
o
1 line of defense

Cellular Components

Humoral Components

Adaptive
(Specific)
o
2 line of defense
Protects/re-exposure

Cellular Components

Humoral Components

Interactions between the two systems

Sistem Imun

biokimia

humoral

Sistem Imun
Innate/non
spesifik

Adaptive/
spesifik

Imunitas
nonspesifik
yang tidak
memerlukan
kontak dengan
antigen

Imunitas yang
didapat dengan
cara pemaparan
antigen pada
penjamu yang
responsif.

First line of
defense
Second line of
defense

Third line of
defense

Sistem imun

First line of defense : skin and mucous

membranes
Second line of defense : internal
defenses phagocytes, natural killer
cells, inflammation and fever, internal
antimicrobial proteins
Third line of defense : involves the
production of spesific lymphocytes or
antibodies against a specific antigen

Innate immunity/first line of

defense
Anatomical Barriers System or
Cell type
Mechanism
Mechanical
Factors
Organ
Skin

Mucous
Membranes

Squamous
epithelium

Non-ciliated
epithelium (e.g. GI
tract)
Ciliated epithelium
(e.g. respiratory
tract)
Epithelium (e.g.
nasopharynx)

Physical barrier
Desquamation
Peristaltik

Mucociliary
elevator
Flushing action of
tears, saliva,
mucus, urine

Innate immunity/first line of

defense
Anatomical Barriers - Chemical
System or
Component
Mechanism
Factors
Organ
Skin

Sweat

Anti-microbial
fatty acids
HCl (parietal cells) Low pH

Mucous
Membranes

Tears and saliva

Lysozyme and
phospholipase A

Defensins
(respiratory & GI
tract)
Sufactants (lung)

Antimicrobial

Opsonin

Innate immunity/first line of

defense
Anatomical Barriers - Biological
System or
Component
Mechanism
Factors
Organ
Skin and
mucous
membranes

Normal flora

Antimicrobial
substances

Competition for
nutrients and
colonization

Innate immunity /second line of

defense
Cellular Components
Cell

Neutrophils

Functions

Phagocytosis and intracellular

killing

Inflammation and tissue damage

Macrophages Phagocytosis and intracellular
killing
Extracellular killing of infected
or altered self targets
Tissue repair
Basophil

Antigen
Unknow presentation cell

Innate immunity/ /second line

of defense
Cellular Components
Cell

Functions

Eosinophils

Killing of certain parasites

Mast cell

Release of granules
containing histamine and
other active agents
Antigen presenting cell

Dendritic
cell
Natural
Killer

Killing of virus-infected and

tumor cells

Figure 1-4 part 2 of 3

Figure 1-4 part 3 of 3

Figure 1-4 part 1 of 3

Figure 1-6

Inflammation and fever

faal_imun/ikun/2006

19

Innate immunity/ /second line

of defense
Inflammation and fever

Innate immunity/ /second line

of defense Humoral
Components
Component
Interferon

Mechanism

Produce by virus infected cells,

Enhance the activity of phagocytes
and NK cells
Inhibit cell growth

Complement

Supress tumor formation

Lysis of bacteria and some viruses
Opsonin
Increase in vascular permeability

Recruitment and activation of

phagocytic cells
Lactoferrin
Compete with bacteria for iron and
and transferrin Antiviral Activity
Cytokines
Various effects/mediator

faal_imun/ikun/2006

22

Protein yang
meningkatkan
fungsi respon
terhadap
infeksi/inflamasi
Classical pathway
requires an
antibody and
antigen to form a
complex
Alternate pathway
requires certain
polysacharrides on
thr surface
membrane attack
complex (MAC)

cytokines

Mediator yang dihasilkan oleh sel dalam

reaksi radang atau imunologik

Respon imun : interaksi antara limfosit,

monosit, sel radang, sel endotel perlu
mediator agar terjadi kontak antar sel.

IL 1 17, IFN , TNF, TGF

Origin of Immune Cells

Biocarta.com

Adaptive immunity /third line of

defense
Cellular dan Humoral
Three important aspects
Components
Specificity
Systemic
Prossesses memory

Adaptive immunity /third line of

defense
Cellular
danImmunity
Humoral
Cell-Mediated
(CMI) T cells
Fungi
Components
Parasites
Viruses
Some cancer cells
Foreign tissue transpalants

Antibody-Mediated (Humoral) Immunity

(AMI) B cells
Antigens dissolved in body fluids
Extracellular pathogens

Immunity and the Immune Response System

Antigen

Complete antigen
Immunogenecity
reactivity

Hapten (incomplete antigen)

Not immunogenic
Antigen yang dapat melakukan reaksi

spesifik Ag - Ab, tetapi tidak dapat

merangsang pembentukan antibodi

Faktor yang mempengaruhi

Immunogenicity; Imunogen

Bahan asing (keasingan)

Ukuran molekul BM > 10,000 ( protein,
nucleoprotein, lipoprotein, glycoprotein,
polysaccharida)
Kerumitan struktur kimiawi
Konstitusi genetik
Metode pemasukan antigen
Dosis

Epitop/antigenic
determinants

Bagian tertentu dari molekul yang terlibat

menimbulkan ikatan antibodi (biasanya
pada permukaan) ; antigen binding site

Self-antigens : MHC
Proteins

Major Histocompatability Complex

(MHC) Ag = human leucocyteassociated antigen (HLA)
Kompleks aloantigen pada permukaan
sel manusia = Kode yg terikat pd

permukaan membran sel; khas pd

setiap individu

MHC

(Major Histocompatibility Complex)

MHC class I

MHC class II

HLA-A
HLA-B
HLA-C

HLA-DP
HLA-DQ
HLA-DR
Expressed to
cell surface

Responsible to
endogenous antigen

Responsible to
exogenous antigen

MHC class III

Released into
body solution
Predicted to be involved
in complement
activities

Adaptive immunity /third line of

defense
Cellular dan Humoral
Components

Antigen presenting cells

(APCs)

Dendritic cells
Langerhans cells
Macrophages
B cells

B cells (AMI)

Antibodi/Ig Subclass
Comparison

Fungsi Efektor Antibodi

A

Abbas.A, Basic
Immunology, 2 ed, 2004
38

Primary and secondary antibody responses to protein

antigens differ qualitatively and quantitatively

39

Sistem Imun
Imunitas Pasif

Imunitas Aktif

Diperankan oleh antibodi atau

limfosit yang telah dibentuk
sebelumnya didalam tubuh
penjamu

Diinduksi setelah kontak dengan

antigen. Kontak dapat berupa :
infeksi klinis atau sub-klinis,
imunisasi antigen atau
transplantasi sel asing

Keuntungan : tersedianya
antibodi dalam jumlah banyak
secara cepat

Keuntungan: imunitas jangka

panjang (memori kontak)

Kerugiannya: jangka waktu aksi

antibodi pendek dan reaksi
hipersensitivitas

Kerugian: onset imunitas lambat

dan membutuhkan kontak
dengan antigen lebih lama atau
kontak ulangan

Infection dan Immunity

infection

immunity

Disease =

Bolus of infection x virulence

immunity

T cells (CMI)

Th lymphocytes (CD4, T4)

T.helper immune respon yang awal

Tc lymphocytes (CD8, T8)

T.cytotoxic - responsible for cellular

immunity

Ts lymphocytes
T.suppressor - menurunkan immune

respon; # ThTs

TDH lymphocytes
delayed hypersensitivity

CD4 T cells: Th1 , Th2 classification:

---------------------------------------------------------------------------------------------CD4 T cells
Th1 cell: cytokines secreted: IL-2, IFN-, IL-12
inflammatory T cells
: involved in activating
Macrophages
Cell-mediated
immunity
NK cells
(effector mechanisms
are cellular)
CD8 T cells
B cells
Th2 cell: cytokines secreted: IL-4, IL-5, IL-6, IL-10, TGF-
helper T cells
Antibody-mediated
: involved in activating
(humoral) immunity
B cells
4

43

Ag

IMMUNE RESPONSE
IL-12/1L-1

IL-6
IL-4
Th-2

CTL

MHC-I

IL-2, IFN-

APC

MHC-II

IL-5

B-lymph

IL-16
TNF-, IFN-

Abnormal cell

FAST
IL-2

Th-1

IFN-

Memory cell
NK cell

Activated NK cell
Lysis cell

CYTOKINE

Abnormal cell

FC-R

HIPERSENSITIVITAS

respon imunitas yang berlebihan atau

tidak sesuai.
menimbulkan manifestasi klinik dan
patologik yang sangat heterogen
kontak yang kedua dengan antigen
spesifik (alergen)

REAKSI HIPERSENSITIVITAS
Gell & Combs
TIPE 1
anaphylactic reaction
TIPE 2
cytotoxic reaction
TIPE 3
Immune complex reaction
TIPE 4
Delayed hypersensitivity reaction

HIPERSENSITIVITAS
Reaksi Tipe I, II, III terjadi karena:
interaksi antigen-antibodi
reaksi humoral
reaksi tipe segera (immediate)
Reaksi Tipe IV terjadi karena:
interaksi antigen-reseptor limfosit T
reaksi selular
reaksi tipe lambat (delayed)

Contoh immediate hypersensittivity: type I

ANAPHYLAXIS
Respons anafilaktik yang mengancam jiwa
akibat sensitisasi oleh alergen spesifik yang
dalam hitungan menit dapat diikuti oleh
kegagalan napas, edema larings dan spasme
bronkhus, kolaps pembuluh darah atau
renjatan, manifestasi gastrointestinal
(nausea, vomiting, nyeri abdomen, diare)
serta manifestasi kulit (pruritis, urtikaria,
angioedema) (Austen, 2005)

Clinical manifestations of immediate hypersensitivity reactions

CLINICAL SYNDROME

CLINICAL AND PATHOLOGIC

MANIFESTATIONS

Allergic rhinitis, sinusitis (hay

fever)

Increased mucus
secretion,;inflammation of upper
airways, sinuses

Food allergies

Increased peristalsis due to contraction

of intestinal muscles

Bronchial asthma

Bronchial hyper-responsiveness
caused by smooth muscle contraction;
inflammation and tissue injuery caused
by late hase reaction

Anaphylaxis (may be caused by

drugs, bee sting, food)

Fall in blood pressure (shock) caused

by vascular dilatation; airway
obstruction due to laryngeal edema

Treatment of immediate hypersensitivity reactions

SYNDROME

THERAPY

MECHANISM OF ACTION

Anaphylaxis

Epinephrine

Causes vascular smooth

muscle contraction; increase
cardiac output (to counter
shock); inhibits further mast cell
degradation

Bronchial asthma

Corticosteroids
Phosphodiesterase
inhibitors

Reduce inflammation
Relax bronchial smooth
muscles

Most allergic
disease

Desensitization
(repeated
administration of low
doses of allergens)
Anti-IgE antibody (in
clinical trials)
Antihistamines

Unknown; may inhibit IgE

production and increase
production of other Ig isotypes;
may induce T cell tolerance
Neutralized and eliminate IgE

Cromolyn

Block actions of histamines on

vessels and smooth muscles
Inhibits mast cell degranulation

TIPE ANAPHYLACTIC (TIPE I)

Rasa gatal dimulai telinga dan kulit

kepala
Angioedema, sesak napas, urtikaria,
lemah, tekanan darah menurun, shock
Kematian akibat gagal pernapasan/
respiratory failure
Anapylactic shock sering pada orang
dengan atopik alergy (predisposisi
familial/genetik)

TIPE ANAPHYLACTIC (TIPE I)

Pengobatan dan pencegahan :

Menghentikan aksi mediator dengan

mempertahankan jalan nafas,
memberikan ventilasi buatan dan
mempertahankan fungsi jantung

Injeksi adrenalin 1 : 1000, sebanyak 0,1

0,3 ml i.c, kortikosteroid, antihistamin

Pencegahan : tes kulit dan menghindari

alergen

Reaksi IgM / IgG dengan Ag yang berikatan pada sel aktivasi

komplemen (jalur klasik) fagositosis & lisis sel sasaran (ADCC /
Antibody dependent cellular cytotoxicity)

TYPE CYTOTOXIC (TIPE II)

Diperani oleh IgG dan IgM

Antigen pada dinding sel, dapat berupa
hapten
Antibodi spesifik terikat pada antigen
Kadang-kadang mengikat komplemen
Sel mengalami lisis

TYPE CYTOTOXIC (TIPE II)

Yang termasuk tipe II :
Reaksi transfusi
Rhesus incompatibility
Transplantasi organ
Auto reaksi

HYPERSENSITIVITY TIPE III

Immune complex reaction.

Diperani oleh IgG dan IgM

Reaksi imun terbentuk antigen

antibodi kompleks pada dinding
pembuluh darah dan cairan lainnya
reaksi inflamasi

TYPE COMPLEX MEDIATED

HYPERSENSITIVITY (TIPE III)

Antigen
Non-Self antigens ; infeksi virus

(hepatitis B), bakteri (streptococcus dan

staphylococcus), jamur ( Aspergillus),
protozoa (malaria), dan protein asing
(serum).
Self antigens : DNA, RNA, cytoplasm,
dan jaringan.

TYPE COMPLEX MEDIATED

HYPERSENSITIVITY (TIPE III)

Kompleks imun pada keadaan

normal segera disingkirkan secara
efektif oleh jaringan retikuloendotel,
ada kalanya menyebabkan reaksi
hipersensitifitas

TYPE COMPLEX MEDIATED

HYPERSENSITIVITY (TIPE III)

Kontak salah satu antigen terjadi

reaksi antigenantibody kompleks
dan Ig yang berperan IgG atau IgM.

Macrophage tidak mampu

menghancurkan kompleks imun -->
pembuluh darah, menembus dinding
pembuluh darah diginjal dan jantung.

TYPE COMPLEX MEDIATED

HYPERSENSITIVITY (TIPE III)
Yang termasuk tipe III :

Arthus reaction

Serum sickness

Immune-complex disease

HYPERSENSITIVITY
TIPE IV

Synonym: cell-mediated
hypersensitivity reaction, delayed
hypersensitivity reaction.
Yang berperan T cell (CD4TH1),
makrophag

DELAYED TYPE
HYPERSENSITIVITY (TIPE IV)

Kontak awal; antigen Macrophages

T sel (CD4-T sel) T memori sel.
Kontak kedua; antigen T sel memori
perubahan bentuk lymphoblasts dan
T sel memori (CD4TH1-T lymphocytes)
delayed immunity effector cells.
pelepasan macrophage cytokines:
MAF ( macrophage-activating faktor)
MCF ( faktor macrophage-chemotactic);
MIF ( migration-inhibitory faktor)
MFF ( macrophage faktor peleburan)

DELAYED TYPE
HYPERSENSITIVITY (TIPE IV)

CD8-T sel cytotoxic dan

macrophages menghancurkan sel
target dengan mekanisme
Apoptosis
Proteolysis

DELAYED TYPE
HYPERSENSITIVITY (TIPE IV)

Reaksi tipe IV pada umumnya timbul

lebih dari 12 jam
Pembentukan antibodi diperlukan
adanya sensitisasi yang lama kirakira 14 hari

DELAYED TYPE
HYPERSENSITIVITY (TIPE IV)
Yang termasuk tipe IV
Contact allergy
Tuberculin reaction
Granulomatous hypersensitivity
reaction.