Kul Blok Imun 1 2012
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Transcript of Kul Blok Imun 1 2012
Imunologi
Respon imune
Innate(Nonspecific)
1o line of defense
Adaptive(Specific)
2o line of defenseProtects/re-exposure
Cellular Components Humoral Components Cellular Components Humoral Components
Interactions between the two systemsInteractions between the two systems
Innate/non spesifik
Adaptive/spesifik
Imunitas nonspesifik yang tidak memerlukan kontak dengan antigen
First line of defenseSecond line of defense
Imunitas yang didapat dengan cara pemaparan antigen pada penjamu yang responsif.
Third line of defense
humoral
biokimia
Innate Immunity Adaptive Immunity
No memory
• No time lag
• Not antigen specific
• A lag period
• Antigen specific
• Development
of memory
Immune System
Myeloid Cells Lymphoid Cells
Granulocytic Monocytic T cells B cells
NeutrophilsBasophils
Eosinophils
MacrophagesKupffer cells
Dendritic cells
Helper cellsSuppressor cellsCytotoxic cells
Plasma cells
NK 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
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
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 complexAlternate pathway – requires certain polysacharrides on the surface
Innate immunity/second line of defense Humoral Components
a. Lysis of bacteria and some viruses
b. Opsoninc. Increase in
vascular permeability
d. Recruitment and activation of phagocytic cells
Cytokines Mediator yang
dihasilkan oleh sel dalam reaksi radang atau imunologik
Biocarta.com
Innate immunity/second line of defense Humoral Components
Innate immunity/second line of defense Humoral Components
Adaptive immunity /third line of defenseCellular dan Humoral Components
Three important aspects
1. Specificity
2. Systemic3. Prossess
es 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; # ThTs
TDH lymphocytes ◦ delayed hypersensitivity
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CD4 T cells: Th1 , Th2 classification:CD4 T cells: Th1 , Th2 classification:----------------------------------------------------------------------------------------------
CD4 T cellsTh1 cell: cytokines secreted: IL-2, IFN-, IL-12
“inflammatory” T cells: involved in activating
Macrophages
NK cells
CD8 T cells
B cells
Th2 cell: cytokines secreted: IL-4, IL-5, IL-6, IL-10, TGF- “helper” T cells: involved in activating
B cells
Cell-mediatedimmunity(effector mechanismsare cellular)
Antibody-mediated(humoral) immunity
4
CD4 T cells: Th1 , Th2 classification:CD4 T cells: Th1 , Th2 classification:
Antibodi
• Class variation– 1o - IgM
– 2o - IgG, IgA or IgE 1o Ag 2o Ag
Total Ab
IgM Ab
IgG Ab
D a y s A f t e r I m m u n i z a t i o n
A b
T i
t e
r
Perubahan Ab 1o and 2o Responses
33
Primary and secondary antibody responses to protein antigens differ qualitatively and quantitatively
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
MHCMHC(Major Histocompatibility Complex)(Major Histocompatibility Complex)
MHC class IMHC class I MHC class IIMHC class II MHC class IIIMHC class III
HLA-AHLA-AHLA-BHLA-BHLA-CHLA-C
HLA-DPHLA-DPHLA-DQHLA-DQHLA-DRHLA-DR
Expressed to cell surface
Responsible to endogenous antigen
Responsible to exogenous antigen
Released into body solution
Predicted to be involved in complement
activities
Dendritic cells
Langerhan’scells
Macrophages B cells
IMMUNE RESPONSEIMMUNE RESPONSE
IMMUNE RESPONSEIMMUNE RESPONSE
adaptive immunity
IMMUNE RESPONSEIMMUNE RESPONSE
Hours Days
Time after infection
Complement
6 12 1 3 5
NK cells
Phagocytes
Epithelialbarriers
Microbe
T lymphocytes
B lymphocytes Antibodies
Effector T cells
Adaptive immunityInnate immunity
0
Innate and adaptive immunity
IMMUNE RESPONSEIMMUNE RESPONSE
IMMUNE RESPONSEIMMUNE RESPONSE
IMMUNE RESPONSEIMMUNE RESPONSE
49
Fungsi Efektor Antibodi
Abbas.A, Basic Immunology, 2 ed, 2004
AIMMUNE RESPONSEIMMUNE RESPONSE
IMMUNE RESPONSEIMMUNE RESPONSE
AgIMMUNE RESPONSEIMMUNE RESPONSE
IL-12/1L-1
FAST
TNF-β, IFN-γ
IL-2, IFN-γ
IL-16
Th-2
IL-4
IL-6
IL-5
Abnormal cell
IFN-γTh-1
IL-2
NK cell
Activated NK cellLysis cell
CYTOKINE
Abnormal cell
FC-R
CTL B-lymph
Memory cell
MHC-I MHC-IIAPC
infection immunity
Bolus of infection x virulenceimmunity
Disease =
respon imunitas yang berlebihan atau tidak sesuai.
menimbulkan manifestasi klinik dan patologik yang sangat heterogen
kontak yang kedua dengan antigen spesifik (alergen)
Gell & CombsGell & Combs
TIPE 1 ‘anaphylactic reaction’
TIPE 2TIPE 2‘‘cytotoxic reaction’cytotoxic reaction’
TIPE 3TIPE 3‘‘Immune complex reaction’Immune complex reaction’
TIPE 4TIPE 4‘‘Delayed hypersensitivity reaction’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)
Contoh immediate hypersensittivity: type IContoh immediate hypersensittivity: type I
ANAPHYLAXISANAPHYLAXIS
• 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 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
Clinical manifestations 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
CorticosteroidsPhosphodiesterase inhibitors
Reduce inflammationRelax bronchial smooth muscles
Most allergic disease
“Desensitization” (repeated administration of low doses of allergens)
Anti-IgE antibody (in clinical trials)
Antihistamines Cromolyn
Unknown; may inhibit IgE production and increase production of other Ig isotypes; may induce T cell tolerance
Neutralized and eliminate IgE
Block actions of histamines on vessels and smooth muscles
Inhibits mast cell degranulation
Treatment of immediate hypersensitivity reactionsTreatment of immediate hypersensitivity reactions
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
Reaksi IgM / IgG dengan Ag yang berikatan pada sel aktivasi komplemen (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
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.
Yang termasuk tipe III : Arthus reaction Serum sickness Immune-complex disease
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 Granulomatous hypersensitivity
reaction.