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

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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

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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.