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Imunologi

Respon imune

Adaptive
Innate
(Specific)
(Nonspecific) o
2 line of defense
1o line of defense Protects/re-exposure

Cellular Components Humoral Components Cellular Components Humoral Components

Interactions between the two systems


Innate/non Adaptive/
spesifik spesifik
Imunitas Imunitas yang
nonspesifik didapat dengan
yang tidak cara pemaparan
memerlukan antigen pada
kontak dengan penjamu yang
antigen responsif.

First line of Third line of


defense defense
Second line of
defense
biokimia

humoral
Innate Immunity Adaptive Immunity

• No time lag • A lag period

• Not antigen specific • Antigen specific

No memory • Development
of memory
Immune System

Myeloid Cells Lymphoid Cells

Granulocytic Monocytic T cells B cells NK cells

Neutrophils Macrophages Helper cells


Basophils Kupffer cells Suppressor cells Plasma cells
Eosinophils Dendritic cells Cytotoxic cells
DEVELOPMENT OF CELLS OF THE IMMUNE SYSTEM
Bone Marrow

Lymphoblasts

Bone marrow maturation Thymus

Regulator Effector
B lymphocytes T cells T cells

Memory Cells Plasma Cells Helper Supressor Cytotoxic


T Cells T Cells T Cells
Antobodies

HUMORAL RESPONSES CELLULAR RESPONSE


Innate immunity/second line of
defense Celluler Components
Myeloid Cells - Granulocytic Cells
Innate immunity/second line of
defense Celluler Components
Myeloid Cells - Granulocytic Cells
Innate immunity/second line of
defense Celluler Components
Myeloid Cells - Monocytic Cells
Innate immunity/second line of
defense Celluler Components

Lymphoid Cells
Innate immunity/second line of
defense Celluler Components
Interferon

Produce by virus
infected cells,
Enhance the activity
of phagocytes and
NK cells
Inhibit cell growth
Supress tumor
formation

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COMPLEMENT
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 the
surface
Innate immunity/second line of defense
Humoral Components
a. Lysis of bacteria
and some viruses
b. Opsonin
c. Increase in
vascular
permeability
d. Recruitment and
activation of
phagocytic cells
Cytokines
 Mediator yang
dihasilkan oleh
sel dalam reaksi
radang atau
imunologik
Innate immunity/second line of
defense Humoral Components

Biocarta.com
Innate
immunity/
second line of
defense
Humoral
Components
Adaptive immunity /third line of defense
Cellular dan Humoral Components

 Three
important
aspects

1. Specificity
2. Systemic
3. Prossesses
memory
 Cell-Mediated
Immunity (CMI) – T
cells
◦ Fungi, Parasites
◦ Viruses, Some cancer
cells
◦ Foreign tissue
transpalants
 Antibody-Mediated
(Humoral) Immunity
(AMI) – B cells
◦ Antigens dissolved in
body fluids
◦ Extracellular pathogens
 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; # ThTs

 TDH lymphocytes
◦ delayed hypersensitivity
CD4 T cells: Th1 , Th2 classification:
----------------------------------------------------------------------------------------------
CD4 T cells
Th1 cell: cytokines secreted: IL-2, IFN-g, 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- b


“helper” T cells Antibody-mediated
: involved in activating (humoral) immunity

B cells
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CD4 T cells: Th1 , Th2 classification:
Antibodi
• Class variation Total
Ab
IgM
Ab
IgG Ab

– 1o - IgM
– 2o - IgG, IgA or IgE
Ab Titer
1o Ag 2o Ag

Days After Immunization


Perubahan Ab
1o and 2o Responses
Primary and secondary antibody responses to protein
antigens differ qualitatively and quantitatively

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Perubahan Ab
1o and 2o Responses
 Complete antigen
◦ Immunogenecity
◦ reactivity
 Hapten (incomplete antigen)
◦ Not immunogenic
◦ Antigen yang dapat melakukan reaksi spesifik Ag -
Ab, tetapi tidak dapat merangsang pembentukan
antibodi
 Bahan asing (keasingan)
 Ukuran molekul BM > 10,000 ( protein,
nucleoprotein, lipoprotein, glycoprotein,
polysaccharida)
 Kerumitan struktur kimiawi
 Konstitusi genetik
 Metode pemasukan antigen
 Dosis
 Bagian tertentu dari molekul yang terlibat
menimbulkan ikatan antibodi (biasanya
pada permukaan) ; antigen binding site
 Major Histocompatability Complex (MHC) Ag
= human leucocyte-associated 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 MHC class III

HLA-A HLA-DP Released into


HLA-B HLA-DQ body solution
HLA-C HLA-DR
Predicted to be involved
Expressed to in complement activities
cell surface
Responsible to Responsible to
endogenous antigen exogenous antigen
 Dendritic
cells
 Langerhan’s
cells
 Macrophages
 B cells
IMMUNE RESPONSE
IMMUNE RESPONSE
IMMUNE RESPONSE

adaptive
immunity
IMMUNE RESPONSE
Innate and adaptive immunity
Microbe
Innate immunity Adaptive immunity

B lymphocytes Antibodies
Epithelial
barriers

T lymphocytes
Phagocytes Effector T cells

Complement NK cells

Hours Days
0 6 12 1 3 5
Time after infection
IMMUNE RESPONSE
IMMUNE RESPONSE
IMMUNE RESPONSE
A

Fungsi Efektor
Antibodi

Abbas.A, Basic
Immunology, 2 ed, 2004
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IMMUNE RESPONSE
Ag
IMMUNE RESPONSE
IL-12/1L-1 IL-6
IL-4
Th-2

IL-2, IFN-γ IL-5


CTL MHC-I B-lymph
MHC-II
APC
IL-16
TNF-β, IFN-γ

Abnormal cell FAST


Th-1
IL-2 IFN-γ

Memory cell

NK cell

FC-R
Activated NK cell
Lysis cell
CYTOKINE

Abnormal cell
infection immunity

Bolus of infection x virulence


Disease =
immunity
 respon imunitas yang berlebihan atau tidak
sesuai.
 menimbulkan manifestasi klinik dan
patologik yang sangat heterogen
 kontak yang kedua dengan antigen spesifik
(alergen)
Gell & Combs
TIPE 1
‘anaphylactic reaction’
TIPE 2
‘cytotoxic reaction’
TIPE 3
‘Immune complex reaction’
TIPE 4
‘Delayed hypersensitivity reaction’
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)
CAUSES MECHANISM PATHOPHYSIOLOGY
Antigen Increased
Ingestants Blood
Food Capillary dilation Volume
Drugs Release of
Pollens Allergen chemical
Dusts interacts mediators :
with Histamine Increased Exudation of
Molds Cell, fluid protein
IgE on mast cell SRS-A Capillary
Kinins permebiality
Injectants
Drugs Prostaglandins Pressure of
Stings exudate
Vaccines
Serum
Nerve
irritation

Constriction
of smooth
muscle

Type I hypersensitivity reaction


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MANIFESTATIONS CLINICAL EXAMPLES

Respiratory tract
Respiratory tract
1. Upper
1. Upper “sinus
“sinus headache”
headache”
Allergic rhinitis
itching of
itching of eyes
eyes
tearing, sneezing,
tearing, sneezing,
watery nasal
watery nasal discharge,
discharge,
itching of
itching of nose,
nose,
throat irritation
irritation Conjunctivitis
throat
2. Lungs
2. Lungs wheezing,
wheezing, dyspnea,
dyspnea,
dry cough,
dry cough, tightness
tightness in
in chest
chest

Asthma
Gastrointestinal
Glossitis, cardiospasm
Nausea, vomitting
Irritable bowel Food allergies
Diarrhea, pruritus ani

Skin Atopic dermatitis


Urticaria, pruritus,
Angioedema, weeping erthematosus vesico-papular lessions Urticaria

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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 CLINICAL AND PATHOLOGIC
SYNDROME MANIFESTATIONS
Allergic rhinitis, Increased mucus
sinusitis (hay fever) 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 Fall in blood pressure (shock) caused


caused by drugs, by vascular dilatation; airway
bee sting, food) 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 Corticosteroids Reduce inflammation
asthma Phosphodiestera Relax bronchial smooth muscles
se inhibitors
Most allergic “Desensitization Unknown; may inhibit IgE production
disease ” (repeated and increase production of other Ig
administration isotypes; may induce T cell tolerance
of low doses of Neutralized and eliminate IgE
allergens)
Anti-IgE Block actions of histamines on vessels
antibody (in and smooth muscles
clinical trials)
Inhibits mast cell degranulation
Antihistamines
Cromolyn
 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)
 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
Skin test for allergy

Ragweed

Control negative (saline)


Control positve (histamine)
Reaksi IgM / IgG dengan Ag yang berikatan pada sel  aktivasi
complement (jalur klasik)  fagositosis & lisis sel sasaran (ADCC /
Antibody dependent cellular cytotoxicity)
• Diperani oleh IgG dan IgM
• Antigen pada dinding sel, dapat berupa hapten
• Antibodi spesifik terikat pada antigen
• Kadang-kadang mengikat komplemen
• Sel mengalami lisis
Yang termasuk tipe II :
 Reaksi transfusi
 Rhesus incompatibility
 Transplantasi organ
 Auto reaksi
 Hashimoto thyroiditis
CAUSES MECHANISM PATHOPHYSIOLOGY CLINICAL
EXAMPLES
Antigen
Reaction of IgG or Erytrhrocyte Hemolytic
Antigen IgM antobody with hemolysis anemia
Transfusion
interacts antigen on cell
reaction
with body
cell i.e :
Erythroblastosis Agranulocytosis Susceptability
• Erythrocyte Activates
fetalis to infections
• Leucocyte complement
• Platelet
Drugs
• Vascular Thrombocytopenia Purpura
endothelium
Autoantibodies
Vasculitis Vesicular
Unknown purpura

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 Immune complex reaction.
 Diperani oleh IgG dan IgM
 Reaksi imun terbentuk antigen–antibodi
kompleks pada dinding pembuluh darah dan
cairan lainnya  reaksi inflamasi
 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.
 Kompleks imun pada keadaan normal
segera disingkirkan secara efektif oleh
jaringan retikuloendotel, ada kalanya
menyebabkan reaksi hipersensitifitas
 Macrophage tidak mampu menghancurkan
kompleks imun  pembuluh darah,
menembus dinding pembuluh darah
diginjal dan jantung.
Termasuk tipe III
 Systemic lupus
erythematous (SLE)
 Erythema nodusum
 Rheumatoid arthritis
 Polyarteritis nodosa
 Arthus reaction
 Serum sickness
CAUSES MECHANISM PATHOPHYSIOLOGY CLINICAL
EXAMPLES
Antigen
Glomerulo-
Autoantibodies Antigen and Deposits on vessel walls Tissue nephritis
Drugs antibody form or basement membrane destruction Vasculitis
Serum an immune
Chemicals complex Inflammation Arthus reaction
Foreign antigen
Bacteria Rheumatoid
Virus diseases
Serum sickness

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 Synonym: cell-mediated hypersensitivity
reaction, delayed hypersensitivity reaction.
 Yang berperan T cell (CD4–TH1), makrophag
 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 (CD4–TH1-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)
 CD8-T sel cytotoxic dan macrophages
menghancurkan sel target dengan
mekanisme
◦ Apoptosis
◦ Proteolysis
 Reaksi tipe IV pada umumnya timbul lebih
dari 12 jam
 Pembentukan antibodi diperlukan adanya
sensitisasi yang lama kira-kira 14 hari
Yang termasuk tipe IV
 Contact allergy
 Tuberculin reaction (mantoux tes)
 Granulomatous hypersensitivity reaction.
CAUSES MECHANISM PATHOPHYSIOLOGY CLINICAL
EXAMPLES

Antigen
Release of : Contact
Lymphokines dermatitis
Tuberculin Sensitized Injury and
Migration inhibition Graft vs host
Poison Ivy Lymphocyte destruction of
factor reactions
Chemical reacts with target organ
Interferon Viral infection
Fungi antigen
Killer cells Autoallergic
Transplanted
Transfer factor disease
organs
Virus

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