student guidance 2012

8/2/2019 Student Guidance 2012

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BLOCK 3: IMMUNE RESPONSE MODULESemester 2, Academic Year 2011/20121. OverviewImmune response module will be held in second semester within 5 days. It consist ofprincipal of innate immunity and adaptive immunity, and overview of abnormality ofimmune responses and the diseases. This block will use expert lecture, tutorial,discussion and seminar as a learning method. For evaluations we use: scoring ofdiscussion activities, scoring of modul tasks and multiple choice question in the BlockExamination.

2. Learning ObjectivesUpon completion of this module, the student will be able to :

a. explain about principal of Innate Immunity and adaptive immunityb. explain about antigen recognition, processing and presentationc. explain about maturation, activation and regulation of T and B lymphocytesd. explain about effector mechanism of humoral and cellular Immunity

e. explain about immune respons in some kinds of diseases: hypersensitivity,autoimmunity, immune deficiency, and cancer immunology.

f. explain about immunity to cancer, transplantation immunology andvaccination.

3.ModulesPART ONE: BASIC CONCEPTS IN IMMUNOLOGYSubmodul 1. Overview in immunology

a. Function of Immune responseb. Principals of innate immunity and adaptive immunityc. Cells and organ of system immun

Submodul 2. Innate Immunity and Complementa. Recognition of microbes by the innate immune systemb. Components of innate immunity: epithelial barriers, phagocytes, NK cellsc. Role of innate immunity in stimulating adaptive immune responsesd. The Complement system

Submodul 3. Antigen Recognition and Presentation in adaptive immunitya. Antigen capture, processing and presentationb. MHC types and functionc. T cell receptor and immunoglobulin

Submodul 4. Maturation and activation of Lymphocytes &a. Maturation and activation of T Lymphocytes

b. Maturation and activation of B Lymphocytes

Submodul 5. Effector Mechanism of cell mediated immunitya. Types of Cell-Mediated Immunityb. The effector functions of CD4+ and CD8+ T lymphocytesc. How do effector T cells eradicate infections and resistance of pathogenic

microbes.Submodul 6. Effector Mechanism of humoral immunity


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PART TWO: IMMUNE SYSTEM AND DISEASES

Submodul 7. Allergy/Hypersensitivitya. Immediate hypersensitivityb. Antibody mediated hypersensitivityc. Immune complex mediated hypersensitivityd. T cell mediated hypersensitivity

Submodul 8.Immune deficiencya. General features of Immunodeficiencyb. Congenital Immunodeficiencyc. Acquired immunodeficiency and immune response against HIV

Submodul 9. Tolerance & Autoimmmunitya. Types of Immune Toleranceb. Susceptible genes in autoimmunityc. Pathogenesis of Autoimmunityd. Autoimmune diseases

Submodul 10.Immunity to cancer , vaccination & immune transplantationa. Immunity to cancersb. Vaccinationsc. Immune transplantation

4. References:1. Abbas AK, Lichtman AH. Basic Immunology, 2nd ed. Philadelphia, Saunders;

20042. Male D, Brostoff J, Roth DB, Roitt I. Immunology, 7th ed. Philadelphia, Elsevier

Ltd; 20063. Murphy K, Travers P, Walport M. Janeways Immunobiology, 7 th ed. New York,

Garland and Science; 2008


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5. Lecturers/tutors of Immune Response

Department Lecturer/Tutor Code

Dept ofPhysiology

1. DR.Dr. Endang Sri Wahyuni, MS ESW

Dept ofParasitology 2. Dr. Sudjari DTM&H, Msi, SpParK3. DR.Dr.LoekiEnggarfitri, MKes,SpParK4. Agustina Tri Endarti, Ssi, PhD

SDRLK

AT

Dept of ClinicalPathology

5. Prof.DR.Dr. Edi Widjajanto, MS,SpPK6. DR.Dr. KusworiniHandono, M.Kes7. Dr. Maimun Zulhaidah, SpPK8. Dr. Hani Susianti, SpPK

EW

KRMZHN

Dept of

Microbiology

9. Prof.DR.Dr.Sanarto Santoso,

DTM&H, SpMK10. Prof. DR.Dr. Soemarno, SpMK11. Dr. Roekistiningsih, SpMK12.DR.Dra. Sri Winarsih, Apt13.Dr. Aulia, SpM

SN

SMRKSWAU

Dept of Paediatric 14. DR. Dr. Wisnu Barlianto, SpA(K)15. Dr. Irene Ratridewi, SpA16. Dr. Diana Anggarani, SpA, MKes

WNIRDA

Dept of ENT-Head

& Neck

17.Dr. Endang Retnoningsih, SpTHT-

KL (K)18.Dr. Iriana Maharani, SpTHT-KL

ER

IM

Dept ofPulmonology

19. Dr. Yani Jane Sugiri, SpP20.Dr. Iin Nurchozin, SpP

YJSIN

Dept of InternalMedicine

21.Prof.DR.Dr.Handono Kalim, SpPD-KR22.Dr. B.P. Putra Suryana, SpPD-KR23.Dr.Cesarius SinggihWahono, SpPD24.Dr.Niniek Burhan, SpPD-KPTI

25.Dr.Didi Candradikusuma, SpPD

HK

PSCSWNB

DC

Dept ofDermatoveneorology

26.Dr. TaufiqHidayat, SpKK (K)27. Dr. ArifWidiatmoko, SpKK28.Dr. HerwindaBrahmanti, SpKK

THAWHD


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Time Schedule

Class A : R. Amphy FKUB, Class B : R. Biomedic, Class BI: R.4.05

Time Wednesday14-3-12

Thursday15-3-12

Monday19-3-12

Tuesday20-3-12

Wednesday21-3-11

Thursday22-3-2012

07.00-08.00 Self Learning Self Learning Self Learning Self Learning Self Learning Self Learning

08.00-10.00 LECTURE

SubModul 1:Overview ofImmuneresponse

Lecturers: A : EWB : KRKBI: HK

LECTURE

SubModul 4:Maturation andactivation of T &B Lymphocytes

Lecturers: A : ESWB : SDRKBI: SN

LECTURE

SubModul 6:Effectormechanism ofhumoralimmunity &Cytokines

Lecturers: A : SNB : SMKBI: EW

LECTURE

SubModul 8:Immunedeficiency

Lecturers: A : WNB : PSKBI: CSW

10.00-12.00 Small groupdiscussionSubModul1 & 2

20 groups20 tutors

Small groupdiscussionSubModul3 & 4

20 groups20 tutors


20 groups20 tutors


20 groups20tutors

12.00-13.00 Lunch Break Lunch break Lunch break Lunch break Lunch break &Friday praying

13.00-15.00 LECTURESubModul 2:Innate Immunity& Complement

Lecturers:

A : KRB : ESWKBI: SN

LECTURESubModul 3:

AntigenRecognition

Lecturers

A : KRB : SDRKBI: SM

LECTURESubModul 5:Effectormechanism ofcell mediatedimmunity

Lecturers:

A : ESWB : SDRKBI: SM

LECTURESubModul 7:

Allergy/Hypersensitivity

Lecturers:

A : WNB : CSWKBI: HK

LECTURESubModul 9:Tolerance&Autoimmmunity

Lecturers:

A: PSB: HKKBI: CSW

LECTURESubModul 10:Immuneresponse totumors &Vaccination&ImmuneTransplantation

Lecturers:

A: EWB: PSKBI: WN

15.00-16.00 Small groupdiscussionSubModul7 & 8

20 groups20tutors


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SCHEDULE OF SMALL GROUP DISCUSSIONSDay/date Group Room

(GPPFKUB)Tutor

Wednesday14 March 201210.00 12.00 WIB

A1 R. 2.01 MZ

A2 R. 2.02 DA

A3 R. 2.03 SW

A4 R. 2.04 IM

A5 R. 2.05 WN A6 R. 2.06 IN

A7 R. 2.07 RK

B1 R. 3.01 HD

B2 R. 3.02 YJS

B3 R. 3.03 CSW

B4 R. 3.04 NB

B5 R. 3.05 DC

B6 R. 3.06 TH

B7 R. 3.07 AW

B8 R. 3.08 LK

BI 1 R. 3.09 ESW

BI 2 R. 3.10 AT

BI 3 R. 3.11 PS

BI 4 R. 3.12 SDRBI 5 R. 3.13 AU

Monday

19 March 201210.00 12.00 WIB

A1 R. 2.01 IR

A2 R. 2.02 DA

A3 R. 2.03 ER

A4 R. 2.04 IN

A5 R. 2.05 MZ

A6 R. 2.06 DC

A7 R. 2.07 LK

B1 R. 3.01 HN

B2 R. 3.02 ESW

B3 R. 3.03 SDR

B4 R. 3.04 WN

B5 R. 3.05 AU

B6 R. 3.06 ATB7 R. 3.07 HD

B8 R. 3.08 YJS

BI 1 R. 3.09 CSW

BI 2 R. 3.10 RK

BI 3 R. 3.11 PS

BI 4 R. 3.12 TH

BI 5 R. 3.13 AW

Tuesday20 March 201210.00 12.00 WIB

A1 R. 2.01 HD

A2 R. 2.02 YJS

A3 R. 2.03 AU

A4 R. 2.04 DA

A5 R. 2.05 SDR

A6 R. 2.06 NB

A7 R. 2.07 IRB1 R. 3.01 DA

B2 R. 3.02 IM

B3 R. 3.03 IN

B4 R. 3.04 MZ

B5 R. 3.05 DC

B6 R. 3.06 HN

B7 R. 3.07 TH

B8 R. 3.08 AW

BI 1 R. 3.09 RK


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BI 2 R. 3.10 WN

BI 3 R. 3.11 AT

BI 4 R. 3.12 SW

BI 5 R. 3.13 PSWednesday21 March 201210.00 12.00 WIB

A1 R. 2.01 RK

A2 R. 2.02 WN

A3 R. 2.03 PS

A4 R. 2.04 AU A5 R. 2.05 CSW

A6 R. 2.06 AW

A7 R. 2.07 IN

B1 R. 3.01 IM

B2 R. 3.02 SW

B3 R. 3.03 AT

B4 R. 3.04 SDR

B5 R. 3.05 HN

B6 R. 3.06 TH

B7 R. 3.07 DA

B8 R. 3.08 YJS

BI 1 R. 3.09 NB

BI 2 R. 3.10 MZ

BI 3 R. 3.11 ESWBI 4 R. 3.12 DC

BI 5 R. 3.13 HDThursday22 March 201215.00 16.00 WIB

A1 R. 2.01 PS

A2 R. 2.02 RK

A3 R. 2.03 WN

A4 R. 2.04 AT

A5 R. 2.05 ER

A6 R. 2.06 HD

A7 R. 2.07 DC

B1 R. 3.01 NB

B2 R. 3.02 IN

B3 R. 3.03 AU

B4 R. 3.04 TH

B5 R. 3.05 AWB6 R. 3.06 IR

B7 R. 3.07 ESW

B8 R. 3.08 SW

BI 1 R. 3.09 CSW

BI 2 R. 3.10 SDR

BI 3 R. 3.11 HN

BI 4 R. 3.12 MZ

BI 5 R. 3.13 YJS

PANDUAN UNTUK TUTORIAL

Tutorial (small group discussions) akan diadakan selama 5 hari perkuliahan Respon Imun,mulai dari pukul 10.00 sampai 12.00 WIB, kecuali pada hari Kamis, 23 Maret 2012,tutorial dilakukan pada jam 15.00 16.00 WIB.Semua mahasiswa semester II akan dibagi menjadi 20 kelompok, dan tiap kelompokakan dibimbing oleh satu orang tutor. (Jadwal dan ruangan seperti tertera di atas).


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Tugas Mahasiswa:- Membaca modul (student guidance) dan referensi sebelum jadwal tutorial- Mengerjakan modul tasks secara tertulis (tulisan tangan sendiri) sebelum tutorial

dan ditulis di buku log masing-masing.- Berperan aktif selama diskusi berlangsung dan sesuai dengan topik yang

dibicarakan.- Meminta tandatangan tutor untuk jawaban modul task masing-masing setiapsebelum mulai diskusi kepada tutor.

- Setiap 1 kelompok diskusi, harus mengumpulkan 1 laporan diskusi, palinglambat 1 hari setelah diskusi topik. Dikumpulkan ke Pak Didik, di lantai 3 GPPFKUB.

Tugas tutor:- Membaca teacher guidance- Absensi mahasiswa- Melakukan evaluasi untuk setiap mahasiswa dalam kelompok diskusi tersebut

selama tutorial berjalan.- Mengingatkan waktu sesuai jadwal.- Memberikan arahan bila diskusi menyimpang.- Mengevaluasi dan menandatangani buku log mahasiswa.

Panduan tutorial:- Mahasiswa dan tutor harus siap di ruangan masing-masing sesuai jadwal- Perkenalan diri tutor (bila dirasakan masih diperlukan)- Pemilihan ketua dan sekretaris untuk tiap topic yang dibahas- Diskusi dipimpin oleh ketua kelompok- Pencatatan hasil diskusi dan membuat oringkasan hasil diskusi oleh sekretaris


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SubModul 1

INTRODUCTION TO THE IMMUNE SYSTEM

Deskripsi

Area Kompetensi Area Kompetensi 3 dari Standart Kompetensi DokterIndonesia

Komponen Kompetensi Mengingat dan mengerti tipe respon imun, fase-fase responimun, sel dan jaringan yang terlibat dalam sistem imun

Kemampuan akhir yangdiharapkan

1. Mampu menyebutkan tipe respon imun2. Mampu menjelaskan perbedaan respon imun alami

dan respon imun adaptif3. Mampu menjelaskan fase respon imun adaptif

humoral dan seluler4. Mampu menyebutkan sel-sel dan jaringan yang

terlibat dalam sistem imun

Metoda pembelajaran 1. Belajar mandiri/tugas modul2. Kuliah pakar3. Diskusi kelompok

Waktu Kuliah pakar 50 menit dan diskusi kelompok 50 menit

Tutor 1. Prof, DR, Dr, Handono Kalim, SpPD-KR2. Prof, DR. Dr. Edy Widjayanto, MS, SpPK(K)3. DR.Dr. Kusworini Handono, Mkes, SpPK

Evaluasi Penilaian aktivitas diskusi, penilaian tugas modul, Ujiantertulis (tes MCQ)

Referensi Abbas AK dan Lichtman AH. Basic Immunology, 2 nd ed.Philadelphia, Saunders ; 2004

OverviewFungsi fisiologi sistem imun adalah melindungi individu terhadap infeksi.

Imunitas alami merupakan pertahahan awal, diperantarai oleh sel dan molekul yangselalu ada dan siap mengeliminasi mikroba-mikroba infeksius yang masuk kedalamtubuh. Respon imun adaptif merupakan bentuk imunitas yang distimulasi olehmikroba, mempunyai spesifitas terhadap substansi asing dan memberikan respon yanglebih efektif terhadap setiap paparan mikroba. Limfosit merupakan sel yang berperan

dalam imunitas adaptif dan satu-satunya sel yang mempunyai reseptor yangdidistribusikan secara clonal untuk mengenal antigen.

Imunitas adaptif terdiri dari a) imunitas humoral, dimana antibodi yangdisekresikan akan menetralkan dan membersihkan ekstraseluler mikroba dan toksin,dan b) imunitas yang diperantarai sel, dimana sel limfosit T akan mengeliminasimikroba intraseluler. Respon imunitas adaptif terdiri dari serangkaian fase : pengenalanantigen, oleh limfosit, aktivasi limfosit untuk berproliferasi dan berdeferensiasi menjadi


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sel efektor dan memori, eliminasi mikroba, penurunan respon imun dan terbentuknyasel memori dengan umur panjang

Terdapat beberapa populasi limfosit yang berbeda fungsinya yang dapatdiidentifikasi melalui ekspresi membrane molekulnya. Limfosit B merupakan sel yangmemproduksi antibodi. Limfosit B mengekspresikan antibodi pada membran yang

dapat mengenal antigen dan efektor sel B mensekresikan antibodi yang dapatmenetralisasi dan mengeliminasi antigen. Limfosit T mengenal fragmen peptide antigenprotein yang disajikan pada sel lain. Limfosit T helper akan mengaktifasi sel fagosituntuk merusak mikroba yang ditelannya dan mengaktifasi limfosit B untukmemproduksi antibodi. Limfosit T sitolitik membunuh sel yang terinfeksi mikrobadidalam sitoplasma. Sel penyaji antigen (APC) akan menangkap setiap antigen mikrobayang masuk melalui epithelia, membawa antigen tersebut kedalam organ limfoid danmenyajikannya untuk dikenali oleh limfosit.

Limfosit dan APC berkumpul di organ limfoid perifer, dimana respon imundiawali dan berkembang. Limfosit nave bersirkulasi melalui organ limfoid periferuntuk mencari antigen asing. Limfosit T efektor akan bermigrasi ke tempat infeksidimana mereka berfungsi mengeliminasi infeksi. Limfosit B efektor tetap berada diorgan limfoid dan dalam sumsum tulang dimana mereka akan mensekresi antibodiyang akan masuk ke dalam sirkulasi dan akan mencari serta mengeliminasi mikroba.

Modul tasks:

1. Describe the principal components of innate immunity

2. List the major characteristics of innate and adaptive immunity!

3. Describe the differences between humoral and cellular immunity!

4. Describe the fundamental properties of adaptive immune response!

5. Describe subpopulations of lymphocytes and their functions!

Direction :

The module-tasks should be written, done by the student individually prior the smallgroup discussion. To work with the module, the student may refer to the reference asmentioned above.


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SubModule 2INNATE (NON SPECIFIC) IMMUNITY & THE COMPLEMENT

2.1 INNATE (NON SPECIFIC) IMMUNITYCompetency Area Area of competence 3 of Indonesian Medical Doctor

Competencies StandardCompetencycomponent

To apply the concept and principles of Innate Immunity

Objectives Upon completion of this submodul, student will be ableto:1. Differentiate between innate and adaptive immunity2. Explain the role of the skin, mucous membranes and

normal microbiota in innate immunity (first line ofdefense)

3. Describe the second line of defense

Learning methodes Lecture, tutorial and discussionEquipments Classroom, computer, LCD, screen, flipchart/whiteboard,

spidolsTime Lecture : 2 hrs, discussion: 1.5 hrsLecturer 1. Prof.Dr.dr. Sanarto Santoso, DTM&H, SpMK

2. DR.Dr. Endang Sri Wahyuni, MS3. DR.Dr. Kusworini Handono, M.Kes, SpPK

Evaluation Activity in discussions, tasks modules, MCQ testRefferences 1. Abbas AK, Lichtman AH, Pillai S, 2007. Cellular and

Molecular Immunology, 6th ed. Saunders, Elsevier.

Philadelphia.

2. Tortora GJ, Funke BR, Case CL, 2007. Innate Immunity :Nonspecific Defenses of the Host, in Microbiology anIntroduction, 9th ed. Pearson Benjamin Cummings,SanFransisco.

2.1 Overview: Innate (non specific) Immunity

Our ability to ward off disease caused by microbes or their products and toprotect against environmental agents such as pollen, drugs, foods, chemicals, andanimal hair is called immunity, or resistance. Vulnerability or lack of immunity isreferred to as susceptibility. In general there are two types of immunity : innate andadaptive.

Innate (nonspesific) immunity refers to defenses that are present at birth. Theyare always present and available to provide rapid responses to protect us againstdisease. Innate immunity does not involve specific recognition of a microbe and acts


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against all microbes in the same way. Further, innate immunity does not have a memorycomponent that is, it cannot recall previous contact with a foreign molecule. Amongthe components of innate immunity are the first line of defense (skin and mucousmembranes) and the second line of defense (NK cells and phagocytes, inflammation,fever and antimicrobial substances)

Adaptive (specific) immunity refers to defenses that involve specific recognitionof microbe once it has breached the innate immunity defenses. Unlike innate immunity,adaptive immunity is slower to respond, but it does have a memory component.Adaptive immunity involve lymphocytes called T cells and B cells.

It has recently been learned that the responses of the innate system are activatedby protein receptors in the plasma membranes of defensive cells; these activators arecalled toll-like receptors (TLRs).

Innate immune responses represent immunitys early-warning system and aredesigned to prevent microbes from gaining access into the body and to help eliminatethose that do gain access.

Module Tasks

01.Define the following terms :a. innate immunityb. adaptive immunity

02. Identify physical and chemical factors that prevent microbes from entering thebody through :

a. skinb. digestive tract

03.Describe the role of normal microbiota in innate immunity

04.Describe the process of phagocytosis, and include the stages of adherence andingestion

05.Define inflammation, and list its characteristic

06.Why is inflammation beneficial to the body?

07.How is fever related to innate immunity?

2.1 THE COMPLEMENTCompetency Area Area of competence 3 of Indonesian Medical Doctor


To apply the concept and principles of Complements

Objectives Upon completion of this submodul, student will be ableto:


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1. Describe the way of complement activation.2. Describe about the function of complement.3. Explain the relation between innate immune

response and adaptive immune response throughcomplement system.

4. To know the protection mechanism of host cellstowards destroy effect of complement activation.

Learning methodes Self learning, Expert Lecture, discussionEquipments Classroom, computer, LCD, screen, flipchart/whiteboard,


2. DR.Dr. Endang Sri Wahyuni, MS3. DR.Dr. Kusworini Handono, M.Kes, SpPK

Evaluation Activity in discussions, tasks modules, MCQ testRefferences 1. Abbas AK, Lichtman AH. Basic Immunology, 2nd ed.Philadelphia, Saunders; 2004

2. Male D, Brostoff J, Roth DB, Roitt I. Immunology, 7thed. Philadelphia, Elsevier Ltd; 2006

3. Murphy K, Travers P, Walport M. JanewaysImmunobiology, 7th ed. New York, Garland andScience; 2008

2.2OVERVIEW: THE COMPLEMENT

Complement was discovered many years ago as a heat labile component of

normal plasma that augments the opsonization of bacteria by antibodies and allow some

antibodies to kill bacteria. This activity was said to complement the antibacterial

activity of antibody, hence the name is complement.

Complement is the other major effector mechanisms of humoral immunity and

also an important effector mechanism of innate immunity. Complement is a system of

serum and cell surface proteins that interact with one another and with other molecules

of the immune system to generate important effectors of innate and adaptive immune

responses. The complement system is made up of a large number of distinct plasma

protein; one is activated directly by antigen-bound antibody to trigger a cascade of


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SubModul 3

ANTIGEN CAPTURE AND PRESENTATION TO LYMPHOCYTE

Description

Competency Area Area of competence 3 of Indonesian Medical DoctorCompetencies Standard

Competency component Understand the concept of antigen recognition by T and Blymphocytes, antigen processing by the APC, structure andfunction of MHC and APC in antigen presenting cells.

Objectives 1.Able to explain the antigen recognized by T and Blymphocytes

2.Able to explain the antigens are processed and presentedby APC

3.Able to mention the type of MHC molecule and explainthe function of MHC molecule

Learning Methods 1. Self learning/modul task2. Lecture3. Small group discussion

Equipments Classroom, computer, LCD, screen, flipchart/whiteboard,spidols

Time Lecture: 2 hours, discussiion: 2hours.

Lecturer 1. DR. Dr. Kusworini Handono, Mkes, SpPK2. dr. Sudjari, DTM&H., MSi.,Sp.ParK3. Prof. DR.Dr. Soemarno, SpMK

Evaluation Activity in discussions, modul tasks, MCQ test

References 1. Abbas AK dan Lichtman AH. Basic Immunology, 2nd ed. Philadelphia, Saunders ; 20042. Male D, Brostoff J, Roth DB, Roitt I. Immunology, 7th

ed. Philadelphia, Elsevier Ltd; 2006

1. Overview

Adaptive immune response is began when antigen receptor on the cell surface oflymphocytes recognize antigens. T and B lymphocytes have a different way ofintroduction to the types of antigens. Antigen receptor on B lymphocytes were called

immunoglobulin receptor, it can recognize various macromolecules (proteins,polysaccharides, lipids and nucleic acids) or small molecules are soluble or attached tothe cell surface. On the other hand, T lymphocytes can only recognize peptide fragmentor protein antigen if that fragment is presented by special molecules that exist on thesurface of host cells.

Induction of immune responses to antigens of microbial protein is dependent onspecial mechanisms that capture and present in those antigens, then they are specificallyrecognized by T lymphocytes. Microbes and parasites antigen that enter to the body


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through epithelial cells will be captured by professional Antigen Presenting Cells (APC),especially by dendritic cells in epithelial tissue, then that antigen is transported tolymph node or it will be captured by APC in lymph node or spleen. Protein frommicrobial antigens are processed by APC and presented to nave T cells circulatingthrough lymphoid organs.

Proteins is captured by the APC from extracellular environment will bedegraded by using proteolytic enzymes which exist in the vesicles of APC. The peptideswill be bound with MHC class II molecules. Next, this peptide is bound with MHC classII molecule`s cleft. This peptide will be recognized by CD4+ T cells. We know that CD4+T cells are specific for peptides derived from extracellular proteins.

The protein is produced by microbes or parasites in the cytoplasm of infectedcells would be degraded by enzyme protease and followed by bound in cleft of newMHC class I molecules. MHC class I molecules that carry on these peptides will berecognized by CD8+. Those cytolytic CD8+ T lymphocytes are specific for peptidebinding to MHC class I which derive from cytosolic protein.

The role of MHC molecules for present antigens that T cells will only recognizeprotein antigens which bind with cell surface molecules, and specific types of T cells(helper or cytolytic) that will responses to types of microbes or parasites. Thosemicroorganisms will be attacked by T cells

Microbes or parasites will activate APC to express a membrane protein (costimulator) and secrete cytokines that provide signals and together with antigen joint tostimulate T cells.

B lymphocytes recognize antigen protein and non protein in original form. Stillunknown whether there is a specific mechanism of antigen presentation is required toinduce B cells response.

Module Task .

1. If antigens enter to the body through the skin, antigen will be concentrated.Which organs are concentrated? What kind of cell is involved in the process ofantigen capture?

2. What is the difference between the antigens presented by MHC molecules ofclass I and class II

3. What isthe difference between antigen recognition by T cells, and antigenrecognition by B cells?


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SubModule 4

LYMPHOCYTE MATURATION & ACTIVATION4.1 Lymphocyte MaturationCompetency Area Area of competence 3 of Indonesian Medical Doctor


To apply the concept and principles of T lymphocyte and Blymphocyte maturation

Objectives Upon completion of this submodul, student will be ableto:

1. To know the sequence event begining from theforming of somatic receptor genes recombination toreceptor gene expression

2. Understand about the steps of B lymphositematuration

3. Understand about the steps of T lymphocytematuration

4. To know how is the selection process of lymphocytematuration


spidolsTime Lecture : 2 hrs, discussion: 1.5 hrsLecturer 1. DR.Dr. Endang Sri Wahyuni, MS

2. Dr. Sudjari DTM&H, SpParK3. Prof.DR.Dr.Sanarto Santoso,DTM&H, SpMK

Evaluation Activity in discussions, modul tasks, MCQ testRefferences 1. Abbas AK, Lichtman AH. Basic Immunology, 2nd ed.

Philadelphia, Saunders; 20042. Male D, Brostoff J, Roth DB, Roitt I. Immunology, 7th ed.

Philadelphia, Elsevier Ltd; 20063. Murphy K, Travers P, Walport M. Janeways

Immunobiology, 7th ed. New York, Garland and Science;2008

4.1 Overview : Lymphocyte maturation

A: The maturation of lymphocytes from bone marrow stem cells consist of three types of

processes: proliferation of immatute cells, expression of antigen receptor genes, and


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4.2 Lymphocyte Activation


Competency

component

To apply the concept and principles of T and B lymphocyte

activation, and immune respons regulation

Objectives Upon completion of this submodul, student will be able to:1. Describe about T lymphocyte activation2. Describe the sequence of T lymphocyte activation3. Describe about B lymphocyte activation4. Describe the sequence of B lymphocyte activation5. Explain the mechanism of immune system regulation


spidolsTime Lecture : 2 hrs, discussion: 1.5 hrsLecturer 1. DR.Dr. Endang Sri Wahyuni, MS

2. Dr. Sudjari DTM&H, SpParK3. Prof.DR.Dr.Sanarto Santoso,DTM&H, SpMK

Evaluation Activity in discussions, modul tasks, MCQ testRefferences 1.Abbas AK, Lichtman AH. Basic Immunology, 2nd ed.

Philadelphia, Saunders; 20042.Male D, Brostoff J, Roth DB, Roitt I. Immunology, 7th ed.

Philadelphia, Elsevier Ltd; 20063.Murphy K, Travers P, Walport M. JanewaysImmunobiology, 7th ed. New York, Garland and Science;2008

6.2. Overview: Lymphocyte Activation

Cell-mediated immunity, the arm of the adaptive immune system that combatsintracellular microbes, which may be microbes that are ingested by phagocytes and live

within these cells or microbes thet infect non phatogenicytic cells.The responses of T lymphocytes consist of sequential phases: recocnition of cell-associsted microbes by naive T cells, expansion of the antigen-specific clones byproliferation, and differentiation of some of the progeny into effector cells and memorycells.APCs exposed to microbes or to cytokines produced as part of the innate immunereactions to microbes express costimulators that are recognized by receptors on T cellsand deliver necessary second signals for T cell activation.


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In response to antigen recognition and costimulation, T cells secrete cytokines, some ofwhich induce proliferation of the antigen-stimulated T cells and others mediate theeffector functions of T cells.Humoral immunity is mediated by antibodies, which neutralize and help to eliminateextracellular microbes and their toxins.

Humoral immune respons are initiated by the recoqnition of antigen by spesificimmunoglobulin, (Ig) receptors of naive B cells. The binding of antigen-Ig reseptors ofspecific B cells, and biochemical signals are delivered to the inside of the B cells by Ig-associated signaling proteins with the second signal for B cell activation induce B cellclonal expansionThe components of immune system regulation are antibody to the specific antigen,idiotype epitope (idiotope) antibody, and regulator T cells.

Module task :

1. Draw the scheme about the sequence of T lymphocyte activation!

2. What is the role of costimulator in T cells activation?3. Mention the molecules that are involved in CD4+T cell activation (molecules

that expressed by APC and T cell).

4. Explain about the steps of CD8+T cell activation

5. What is memory T cell?

6. Explain about the steps of B lymphocyte activation by CD4+Tcell!


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SubModule 5

EFFECTOR MECHANISM IN CELLULAR IMMUNE RESPONSECompetency Area Area of competence 3 of Indonesian Medical Doctor

Competencies Standard

Competencycomponent

To apply the concept and principles of effector mechanism incellular immune response

Objectives Upon completion of this submodul, student will be ableto:1. Describe the types of Cell-Mediated Immunity and the

migration of effector T lymphocytes to sites of infection

2. Describe the effector functions of CD4+ and CD8+ T

lymphocytes

3. Explain how do effector T cells eradicate infections and

resistance of pathogenic microbes.

Learning methods Self learning, Expert Lecture, discussionEquipments Classroom, computer, LCD, screen, flipchart/whiteboard,

spidolsTime Lecture : 2 hrs, discussion: 1.5 hrsLecturer 1. Prof. DR.Dr. Soemarno, SpMK

2. Dr. Sudjari DTM&H, Msi, SpParK3. DR.Dr. Endang Sri Wahyuni, MS

Evaluation Activity in discussions, modul tasks, MCQ testRefferences 1. Abbas AK, Lichtman AH. Basic Immunology, 2nd ed.

Philadelphia, Saunders; 20042. Male D, Brostoff J, Roth DB, Roitt I. Immunology, 7th

ed. Philadelphia, Elsevier Ltd; 20063. Murphy K, Travers P, Walport M. Janeways

Immunobiology, 7th ed. New York, Garland andScience; 2008

Overview: Effector Mechanism In Cellular Immune Response

Cell mediated immunity is the arm of adaptive immunity that eradicatesinfections by intracellular microbes. Cell-mediated immune reactions are of two types :CD4+ T cells activate macrophages to kill ingested microbes that are able to survive inthe vesicles of phagocytes, and CD8+ CTLs kill cells harboring microbes in theircytoplasm, thus eliminating reservoirs of infections

Effector T cells are generated in peripheral lymphoid organs, mainly lymphnodes draining sites of microbes entry, by the activation of nave T lymphocytes. Theeffector T cells are able to migrate to any site of infection.


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The migration of effector T cells is controlled by adhesion molecules, which areinduced on these cells after activation and bind to their ligands, which are induced onendothelial cells by microbes and by cytokines produced during innate immuneresponses to microbes. The migration of T cells is independent of antigen, but cells thatrecognize microbial antigens in tissues are retained at these sites.

Effector cells of the Th1 subset of CD4+

T cells recognize the antigens of microbesthat have been ingested by macrophages. These T cells express CD40 ligand and secrete

IFN-, which function cooperatively to activate macrophages. Th17 cells are recentlyrecognize subset of CD4 effector T cells. They induce local epithelial and stromal cells toproduce chemokines that recruit neutrophil to sites of infection early in the adaptiveimmune respons and they may enhance leucocyte recruitment and inflammation.The remaining subset of effector T cells are the regulatory T cells (T reg cells), aheterogeneous class of cells that suppress cell activity and help prevent thedevelopment of auroimmunity during immune reponses.

Activated macrophages produce substances, including reactive oxygenintermediates, nitric oxide, and lysosomal enzymes, that kill ingested microbes.Macrophages also produce cytokines that induce inflammation and other cytokines thatpromote fibrosis and tissue repair.

Effector CD4+ T cells of the Th2 subset stimulate eosinophilic inflammation andinhibit macrophage activation. Eosinophils are important in host defense againsthelminthic parasites. The balance between activation of Th1 and Th2 cell determines theoutcomes of many infections, with Th1 cells promoting and Th2 cells suppressingdefense against intracellular microbes. Th2 have more role in humoral immunity,because they can stimulate B cells to produce antibodies.

CD8+ T cells differentiate into CTLs that kill infected cells, mainly by inducingDNA fragmentation and apoptosis. CD4+ and CD8+ T cells often function cooperativelyto eradicate intracellular infections.

Many pathogenic microbes have evolved mechanisms to resist cell mediated

immunity. These mechanism include inhibiting phagolysosome fusion escaping fromthe vesicles of phagocytes, inhibiting the assembly of class 1 MHC-peptide complexesand producing inhibitory cytokines or decoy cytokine receptors

Module Task

1. How the effector T lymphocyte migrates to the sites of infections ?

2. Explain the effector function of CD4+ T lymphocytes

3. Explain the effector function of CD8+ T lymphocytes

4. What are some of the mechanisms by which intracellular microbes resist the

effector mechanisms of cell-mediated immunity ?5. A much more recently subset of CD4 effector T cells are the Th17 and T reg

describe briefly the function of these subset .


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Submodul 6:EFFECTOR MECHANISM IN HUMORAL IMMUNE RESPONSE& CYTOKINES


Competencycomponent

To apply the concept and principles of effector mechanism in

humoral immune response and cytokines

Objectives Upon completion of this submodul, student will be ableto:1.Describe the type of receptors in cells which contribute

in effector of humoral immunity2.Describe the function of effector of humoral immunity

in combating microbes3.Define cytokines and describe its nomenclature

4.Describe the general properties of cytokines and itsreceptor

5.Describe cytokines that mediate and regulate innateimmunity

6.Describe cytokines that mediate and regulate adaptiveimmunity

7.Describe cytokines that stimulate hematopoiesis



2. Prof.DR.Dr. Edi Widjajanto, MS,SpPK3. Prof. DR.Dr. Soemarno, SpMK


Philadelphia, Saunders; 20042.Male D, Brostoff J, Roth DB, Roitt I. Immunology, 7 th ed.

Philadelphia, Elsevier Ltd; 20063.Murphy K, Travers P, Walport M. Janeways

Immunobiology, 7th ed. New York, Garland and Science;2008


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6.1 OVERVIEW: EFFECTOR MECHANISM IN HUMORAL IMMUNE

RESPONSE

Humoral immunity is conducted by antibodies, which have physiologic function

in defense against extracellular microbes and microbial toxin. This type of immunitycontrast with cell-mediated immunity, the other effector arm of adaptive immunesystem which is mediated by T lymphocytes and function to eradicate microbes thatinfect and live within hoost cells.

The types of microorganism that are combated by humoral immunity areextracellular bacteria, fungi and even obligate intracellular microbes such as viruseswhich are the targets of antibodies before enter host cells or when they are released frominfected cells. The main function of antibodies to neutralize and eliminate pathogen andmicrobial toxin.

Antibodies are produced by B lymphocytes as plasma cells in the primary andsecondary lymphoid organs, but the antibodies perform their effector function at site

distant from their production sites.The antibodies that mediate protective immunitymay be derived from short-live or long-live antibody-producing plasma cells followingthe activation of nave or memory B cells.

Many of the effector function of antibodies are mediated by the heavy chainconstant regions of Ig molecules, and different of Ig heavy chain isotypes serve distincteffector fuction. Even though, all these function are triggered by binding of antigen tothe variable region of antibodies.

Leukocytes Fc receptors promote the phagocytosis of opsonized particles anddeliver signals that stimulate the microbicidal activities of leukocytes. Binding ofopsonized particles to phagocytes receptor, particularly FcyR I, will activate phagocytes.

MODULE TASKS1. What the difference between innate and adaptive of humoral immunity

effector2. Explain the mechanisms of adaptive humoral immunity effector toward

Staphylococcus aureus when they enter body through injury.

6.2 Overview: CYTOKINES

Cytokines are proteins secreted by the cells of innate and adaptive immunity thatmediate many functions of these cells. Cytokines are produced in response to microbesand other antigens, and different cytokines stimulate diverse responses of cells involved

in immunity and inflammation. Cytokines mediate their actions by binding with highaffinity to receptors, which belong to a limited number of structural families. Thecytokines that mediate innate immunity are produced mainly by activated macrophageand include TNF and IL-1 that mediate acute inflammatory reactions to microbes; IL-12and IL-18 stimulate production of the macrophage-activating cytokine IFN-. Thecytokines that mediate and regulate adaptive immune responses are produced mainlyby antigen-stimulated T lymphocytes, and they include IL-2 a T cell growth factor; IL-4stimulates IgE production and the development of TH2 cells from nave helper T cells; IL-


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5 activates eosinophyl. In the activation phase of adaptive immune responses,cytokines stimulate the growth and differentiation of lymphocytes, and in the effectorphases of innate and adaptive immunity, they activate different effector cells toeliminate microbes and other antigens. Cytokines also stimulate the development ofhematopoietic cells. In clinical medicine, cytokines are important as therapeutic agents

and as targets for specific antagonists in numerous immune and inflammatory diseases.

Module Tasks1. Define cytokines and describe its nomenclature2. Describe briefly the general properties of cytokines


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Sub Module 7HYPERSENSITIVITY

Competency area Area of competence 3 of Indonesian Medical Doctor

Competencies StandardCompetency component To apply the concept and principles of Hypersensitivity

Objectives 1. Understand the mechanism effector of immediatehypersensitivity

2. Understand the mechanism effector of antibodymediated hypersensitivity

3. Understand the mechanism effector of immunecomplex mediated hypersensitivity

4. Understand the mechanism effector of T cellmediated hypersensitivity

Learning methods Self learning, Expert lecture, Discussion

Equipment Classroom, computer, LCD, screen,flipchart/whiteboard, spidols

Time Lecture : 2 hours, discussion : 1,5 hours

Lecture 1. DR. Dr. Wisnu Barlianto, SpA(K)2. dr. C. Singgih Wahono, SpPD3. Prof. DR. Dr. Handono Kalim, SpPD-KR

Evaluation Activity in discussions, modul task, MCQ test

References 1. Abbas AK, Lichtman AH. Basic ImmunologyFunction and Disorders of the Immune system, 3th ,Philadelphia, Saunders Elsevier, 2009. Page : 205

2222. Decker JM. Immunology Tutorials. August 2003,

http://microvet.arozona.edu/Courses/MIC419/Tutorials/Allergy.html

3. Abbas AK, Lichtman AH, Pillai S. Cellular andMolecular Immunology . 6th Int ed. PhiladelphiaSaunders Elsevier 2007 : 419-462

Overview

Immune responses that cause tissue injury are called hypersensitivity reactions,

and the diseases caused by these reactions are called hypersensitivity diseases or

immune-mediated inflammatory diseases

Hypersensitivity reactions may arise from uncontrolled or abnormal responses to

foreign antigens or autoimmune responses against self antigens


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Hypersensitivity reactions are classified according to the mechanism of tissue

injury

Immediate hypersensitivity (type I, commonly called allergy) is caused by the

production of IgE antibody against environmental antigens or drugs *allergens),

sensitization of mast cells by the IgE, and degranulation of these mast cells on

subsequent encounter with the allergen

The clinical and pathologic manifestation of immediate hypersensitivity are due

to the actions of mediators secreted by the mast cells. These include amines,

which dilate vessels and contract smooth muscles; arachidonic acid metabolities,

which also contract muscles; and cytokines, which induce inflammation, the

hallmark of the late phase reaction. Treatment of allergies is designed to inhibit

the production of and antagonize the actions of mediators and to counteract their

effects on end organs

Antibodies against cell and tissue antigens may cause tissue injury and disease

(type II hypersensitivity). IgM and IgG antibodies promote the phagocytosis of

cells to which they bind, induce inflammation by complement and Fc receptor-

mediated leukocyte recruitment, and may interfere with the functions of cells by

binding to essential molecules and receptors

Antibodies may bind to circulating antigens to form immune complexes, which

deposit in vessels and cause tissue injury (type III hypersensitivity). Injury is due

mainly to leukocyte recruitment and inflammation

T-cell mediated diseases (type IV hypersensitivity) caused by TH1-mediated

delayed-type hypersensitivity reactions or TH17-mediated inflammatory

reactions, or by killing of host cells by CD8+ CTLs.


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Module task

1. Explain the mechanism of immunopathologic, tissue injury and diseases cause by

various type hypersensitivity reaction !

2. Explain the sequence of events in a typical immediate hypersensitivity reaction !


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Sub Modul 7HIPERSENSITIVITAS

Area kompetensi Area kompetensi 3 dari standart Kompetensi KedokteranIndonesia

Komponen Kompetensi Mengingat dan mengerti konsep dan prinsip-prinsiphipersensitivitas

Kemampuan akhiryang diharapkan

1. Mengerti mekanisme kejadian hipersensitivitas tipe cepat2. Mengerti mekanisme kejadian hipersensitivitas yang

diperantarai oleh antibodi3. Mengerti mekanisme kejadian hipersensitivitas yang

diperantarai oleh kompleks imun4. Mengerti mekanisme kejadian hipersensitivitas yang

diperantarai oleh sel T

Metode belajar Belajar sendiri/tugas modul, kuliah pakar, diskusi kelompok

Sarana Ruang kelas, komputer, LCD, layar, lembar balik, papan putih,

spidolWaktu Kuliah pakar 2 jam, diskusi kelompok 1,5 jam

Tutor 1. DR. Dr. Wisnu Barlianto, SpA(K)2. dr. C. Singgih Wahono, SpPD3. Prof. DR. Dr. Handono Kalim, SpPD-KR

Evaluasi Aktivitas dalam diskusi kelompok, keaktifan dalam diskusikelompok, mengerjakan tugas modul dan tes pilihan ganda(MCQ test)

Daftar pustaka 1. Abbas AK, Lichtman AH. Basic Immunology Function andDisorders of the Immune system, 3th ed , Philadelphia,

Saunders Elsevier, 2009. Pages : 205 2222. Decker JM. Immunology Tutorials. August 2003,

http://microvet.arozona.edu/Courses/MIC419/Tutorials/Allergy.html

3. Abbas AK, Lichtman AH, Pillai S. Cellular and MolecularImmunology . 6th Int ed. Philadelphia Saunders Elsevier 2007: 419-462

Ringkasan

Respon imun yang menyebabkan kerusakan jaringan disebut reaksi

hipersensitivitas, dan penyakit yang disebabkan oleh reaksi tadi disebut

penyakit hipersensitivitas atau penyakit keradangan akibat proses imun

Reaksi hipersensitivitas mungkin berasal dari respon yang tidak terkontrol atau

abnormal terhadap antigen asing atau respon autoimun terhadap antigen self


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Reaksi hipersensitifitas diklasifikasikan berdasarkan mekanisme kerusakan

jaringan

Hipersensitivitas tipe cepat (tipe I, umumnya disebut alergi) disebabkan oleh

produksi antibody IgE melawan antigen lingkungan atau obat (allergen),

sensitisasi sel mast oleh IgE, dan degranulasi sel mast pada paparan ulang

alergen

Mekanisme klinik dan patologi hipersensitivitas tipe cepat disebabkan oleh kerja

mediator yang diproduksi / di sekresi oleh sel mast. Disini termasuk vaso aktif

amin yang menyebabkan delatasi pembuluh darah dan kontraksi otot polos;

metabolit asam arakidonat yang juga menyebabkan kontraksi otot; serta sitokin

yang merangsang keradangan, merupakan tanda dari reaksi fase lambat.

Pengobatan alergi dirancang untuk menghambat produksi dan melawan kerja

mediator dan meniadakan efeknya pada organ sasaran.

Antibodi melawan sel dan anti jaringan mungkin menyebabkan kerusakan

jaringan dan penyakit (hipersensitivitas tipe II). Antibodi IgM dan IgG

memungkinkan fagositosis dari sel yang diikatnya, merangsang keradangan

akibat serbukan lekosit yang diperantarai oleh komplemen dan reseptor Fc, dan

mungkin berpengaruh pada fungsi dari sel yang terikat pada molekul utama dan

reseptor

Antibodi mengikat antigen dalam sirkulasi dan membentuk kompleks imun

yang mengumpul di pembuluh darah dan menyebabkan kerusakan jaringan

(hipersensitivitas tipe III), kerusakan ini terutama disebabkan oleh serbukan

lekosit dan proses keradangan

Penyakit yang diperantarai sel T (hipersensitivitas tipe IV) disebabkan oleh

reaksi hipersensitivitas tipe lambat yang diperantarai TH1 atau reaksi

keradangan yang diperantarai TH17 atau kematian sel host oleh CD8+ CTLs

(limfosit sitotoksik)

TUGAS MODUL:

1. Jelaskan mekanisme imuno - patologi dan mekanisme kerusakan jaringan serta

penyakit yang disebabkan oleh berbagai macam reaksi hipersensitivitas

2. Jelaskan tahapan yang khas terjadi pada reaksi hipersensitivitas tipe cepat ?


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Sub Modul 8:

IMMUNODEFICIENCY


Competencycomponent

To apply the concept and principles of Immunodeficiency

Objectives Upon completion of this submodul, student will be ableto:1. Describe the general features of Immunodeficiency2. Describe about congenital immunodeficiency3. Explain the mechanism of acquired immunodeficiency

and immune response against HIV


spidols

Time Lecture : 2 hrs, discussion: 1 hrsLecturer 1. DR. Dr. Wisnu Barlianto, SpA(K)

2. dr. C. Singgih Wahono, SpPD3. Dr. B.P. Putra Suryana, SpPD-KR


Philadelphia, Saunders; 2004

2.Abbas AK, Lichtman AH, Pillai S. Cellular and MolecularImmunology. 6th Int ed. Philadelphia ; Saunders Elsevier2007 : 419 462

OVERVIEW: IMMUNO DEFICIENCY

A. INTRODUCTION

Integrity of the immune system is essential for defense against infectious organism and

their toxic product. Therefore, it is very important for the survival of all individuals.

Defect in one or more components of the immune system is generally called

immunodeficiency. This group of diseases is classified into two groups i.e. congenitalimmunodeficiencies and acquired immunodeficiencies.

B. GENERAL FEATURES

Many types of immunodeficiencies have been identified, and the clinical significances

can be summarized as follows :


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Increased susceptibility to infection is the principle consequence of

immunodeficiency. Deficient humoral immunity usually results in increased

susceptibility to infection by pyogenic bacteria. Defect in cell-mediated immunity

lead to infection by viruses and other intracellular microbes.

Increased susceptibility to certain types of cancer. Many of these cancers appears to

be caused by oncogenic viruses

Clinically and pathologically heterogeneous because different diseases involve

different components of the immune system.

Increased incidence of autoimmunity

C. CONGENITAL (PRIMARY) IMMUNODEFICIENCIES

Congenital immunodeficiencies are genetic defects that result in an increased

susceptibility to infection, frequently manifested in infancy and childhood.

The primary abnormality may be in components of the innate immune system, at

different stage of lymphocyte maturation, or in the responses of mature lymphocyte toantigenic, consist of:

Defects in innate immunity

Severe combined immunodeficiencies

Antibody deficiencies

Defects in T lymphocyte activation and function

Multisystem disorder with immunodeficiencies

Therapeutic approaches for congenital immunodeficiencies are passive immunization

and bone marrow transplantation.

D. ACQUIRED (SECONDARY) IMMUNODEFICIENCIESAcquired immunodeficiencies are often developed because of abnormalities that are not

genetic but acquired during life. The causes of acquired immunodeficiencies are :

Complication from malnutrition, neoplasm, or infection

Iatrogenic immunosuppression (immunosuppressive drugs etc)

Human Immunodeficiency Virus (HIV) infection

E. HIV AND AIDS

Acquired immunodeficiency syndrome (AIDS) is a disease caused by infection with HIV

and is characterized by profound immunosuppression, opportunistic infection,

malignant tumors, wasting and CNS degeneration. HIV infects a variety of cells of the

immune system, including CD4+ helper T cells, macrophages, and dendritic cells.

HIV structure and genes

HIV particles consist of two identical strands of RNA packed within a core viral proteins

and surrounded by a phospholipid bilayer envelope derived from the host cell

membrane. The envelope glycoprotein gp120 and gp41 are required for infection of cells.

Pathogenesis of HIV infection and AIDS


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HIV disease begins with acute infection, and advances to chronic progressive infection

of peripheral lymphoid tissues. Dissemination of the virus, viremia, and the

development of host immune responses happened during the transition from acute

phase to a chronic phase of infection. Lymph nodes and the spleen are sites of

continuous HIV replication and cell destruction.

Mechanism of immunodeficiency caused by HIV

Death of CD4+ is caused by the production of virus in infected cells (direct cytophatic

effect) is a major cause of the decline the numbers of these cells, and lead to

immunodeficiency state.

Immune responses to HIV

The early response to HIV infection is similar in many ways to the immune response to

other virus, but the responses fail to eradicate all viruses (provide limited protection).

MODUL TASKS

1. How is the mechanism cellular and humoral immune response in protectingindividuals from infection?

2. How is the pathogenesis of HIV infect and its replication in T lymphocyte?

3. Why individual immune responses to HIV infection provide very limitedprotection?


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Sub Modul 9:IMMUNOLOGIC TOLERANCE AND AUTOIMMUNITY


Competencycomponent

To apply the concept and principles of Immunologictolerance and autoimmunity

Objectives Upon completion of this submodul, student will be ableto:e. Explain about Immunologic tolerance: Central and

Peripheral Tolerance, T and B cells Tolerancef. Explain how self tolerance might be brokeng. Mention about the role of susceptible genes in

autoimmunityh. Describe the role of infections in autoimmunity

Learning methods Lecture, tutorial and discussionEquipments Classroom, computer, LCD, screen, flipchart/whiteboard,

spidolsTime Lecture : 2 hrs, discussion: 1.5 hrsLecturer 1. Prof.DR.Dr.Handono Kalim,SpPD-KR

2. Dr. B.P. Putra Suryana, SpPD-KR3. Dr. C. Singgih Wahono, SpPD

Evaluation Activity in discussions, modul tasks, MCQ testSuggested Refferences 1. Abbas AK, Lichtman AH. Basic Immunology, 2nd ed.

Philadelphia, Saunders; 2004

2. Male D, Brostoff J, Roth DB, Roitt I. Immunology, 7th ed.Philadelphia, Elsevier Ltd; 2006

3. Murphy K, Travers P, Walport M. JanewaysImmunobiology, 7th ed. New York, Garland and Science;2008

OVERVIEW: IMMUNOLOGIC TOLERANCE & AUTOIMMUNITY

Immunologic tolerance is specific unresponsiveness to an antigen induced by

exposure of lymphocytes to that antigen, it means that our immune system is inable to

make an immune response to that antigen. Normally, all individuals are tolerant of

(unresponsive to) their own (self) antigens. These mechanisms are responsible for one of

the cardinal features of the immune system, namely, its ability to discriminate between

self and nonself (usually microbial) antigens. If these mechanisms fail, the immune


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system may attack the individual's own cells and tissues. Such reactions are called

autoimmunity, and the diseases they cause are called autoimmune diseases.

Central tolerance (negative selection) is induced by the death of immature

lymphocytes that encounter self antigens in the generative lymphoid organs (bone

marrow and thymus). Peripheral tolerance results from the recognition of self antigens

by mature lymphocytes in peripheral tissues.

Central tolerance (negative selection) of T cells is the result of high-affinity

recognition of self antigens in the thymus, which tend to be widely disseminated self

antigens. Central tolerance may eliminate the potentially most dangerous T cells, which

express high affinity receptors for disseminated self antigens. This process of central

tolerance affects self-reactive CD4+ T cells and CD8+ T cells, which recognize self

peptides (antigens) displayed by class II MHC and class I MHC molecules, respectively.

Peripheral tolerance of T cells is induced when mature T cells recognize self

antigens in peripheral tissues, leading to functional inactivation (anergy) or death, or

when the self-reactive lymphocytes are suppressed by regulatory T cells (immune

supression). Anergy (functional inactivation) results from the recognition of antigens

without costimulators (second signals) or when T cells use inhibitory receptors to

recognize costimulators. Deletion (death by apoptosis) occurs when T cells repeatedly

encounter self antigens.

In lymphocytes, central tolerance is induced when immature lymphocytes

interact strongly with self antigens in the bone marrow, the cells are either killed

(negative selection) or they change their receptor specificity (receptor editing). While

peripheral tolerance is induced when mature lymphocytes that encounter high

concentrations of self antigens in peripheral lymphoid tissues and do not receive T cell

help (because helper T cells are absent or tolerant), become anergic and cannot again

respond to that self antigen

Autoimmune diseases result from a failure of self-tolerance. This is cause by an

adaptive immune response against self antigen. Multiple factors contribute to

autoimmunity, including immunologic abnormalities, susceptibility genes (especially

HLA genes), and environmental triggers such as infections.


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Multiple genes predispose to autoimmune diseases, the most important of these

being MHC (HLA) genes. Particular MHC alleles may contribute to the development of

autoimmunity because they are inefficient at displaying self antigens, leading to

defective negative selection of T cells, or because peptide antigens presented by these

MHC alleles may fail to stimulate regulatory T cells. There are some other genes that

have role in autoimmunity such as: complement, Fas and FasL, AIRE.

Infections predispose to autoimmunity, by induce a local innate immune

response, and this may lead to increased expression of costimulators and cytokines by

tissue APCs. As a result, these activated tissue APCs may be able to stimulate self-

reactive T cells that encounter self antigens in the tissue (break T cell anergy). The

second mechanism is by cross-reactions between microbial and self antigens (molecular

mimicry). Infections may also injure tissues and release antigens that are normally

sequestered from the immune system.

Modul Tasks

1. What is immunologic tolerance? What is the function of immunologic tolerance

for our body?

2. How is central tolerance induced in T lymphocytes?

3. How is peripheral tolerance induced in T lymphocytes?

4. How may MHC genes play a role in the development of autoimmune diseases?

5. How can autoimmunity be developed? Mention some risk factors for

autoimmunity?

6. Mention some diseases that include in organ specific autoimmune diseases


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Sub Modul 10:

IMMUNE TRANSPLANTATION

TUMOR IMMUNOLOGY

VACCINATION


Competencycomponent

To apply the concept and principles of Immunodeficiency

Objectives Upon completion of this submodul, student will be ableto:1. Describe the definition of graft, recipient, donor2. Explain about graft rejection

3. Understand and explain about immune surveillance4. Explain about innate immunity and adaptive immunityagainst cancer

5. Describe about types of human vaccine6. Describe about primary and secondary antibody response


spidolsTime Lecture : 2 hrs, discussion: 1 hrsLecturer 1. Prof.DR.Dr. Edi Widjajanto, MS,

SpPK

2. Dr. Wisnu Barlianto, SpA3. Dr. B.P. Putra Suryana, SpPD-KR

Evaluation Activity in discussions, modul tasks, MCQ testRefferences Abbas AK, Lichtman AH. Basic Immunology, 2nd ed.

Philadelphia, Saunders; 2004Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular

Immunology. 6th Int ed. Philadelphia ; Saunders Elsevier2007 : 419 462

12.1 Overview: TRANSPLANTATION IMMUNOLOGY

Transplantation is the process of taking cells, tissues, or organs, called a graft,

from one individual and placing them into a (usually) different individual. The

individual who provides the graft is called the donor, and the individual who receives


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the graft is called either the recipient or the host. If the graft is placed into its normal

anatomic location, the procedure is called orthotopic transplantation; if the graft is

placed in a different site, the procedure is called heterotopic transplantation.

Transfusion refers to the transfer of circulating blood cells or plasma from one

individual to another. In clinical practice, transplantation is used to overcome a

functional or anatomic deficit in the recipient. This approach to treatment of human

diseases has increased steadily during the past 40 years, and transplantation of kidneys,

hearts, lungs, livers, pancreata, and bone marrow is widely used today. More than

30,000 kidney, heart, lung, liver, and pancreas transplantations are currently performed

in the United States each year. In addition, transplantation of many other organs or cells

is now being attempted.

A major factor limiting the success of transplantation is the immune response

of the recipient to the donor tissue. This problem was first appreciated when attempts

to replace damaged skin on burn patients with skin from unrelated donors proved to be

uniformly unsuccessful. During a matter of 1 to 2 weeks, the transplanted skin would

undergo necrosis and fall off. The failure of the grafts led Peter Medawar and many

other investigators to study skin transplantation in animal models. These experiments

established that the failure of skin grafting was caused by an inflammatory reaction

called rejection. Several lines of experimental evidence indicated that rejection is caused

by an adaptive immune response

Graft transplanted between two genetically identical or syngeneic individuals is

called a syngeneic graft. A graft transplanted between two genetically different

individuals of the same species is called an allogeneic graft (or allograft). A graft

transplanted between individuals of different species is called a xenogeneic graft (or

xenograft). The molecules that are recognized as foreign on allografts are called

alloantigens, and those on xenografts are called xenoantigens. The lymphocytes and

antibodies that react with alloantigens or xenoantigens are described as being

alloreactive or xenoreactive, respectively.

Alloantigens elicit both cell-mediated and humoral immune responses.Recognition of transplanted cells as self or foreign is determined by polymorphic

genes that are inherited from both parents and are expressed codominantly. Major


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histocompatibility complex (MHC) molecules are responsible for almost all strong

(rapid) rejection reactions.

Allogeneic MHC molecules are presented for recognition by the T cells of a graft

recipient in two fundamentally different ways. The first way, called direct presentation,

and the second way, called indirect presentation.

For historical reasons, graft rejection is classified on the basis of histopathologic

features or the time course of rejection after transplantation rather than on the basis of

immune effector mechanisms. Based on the experience of renal transplantation, the

histopathologic patterns are called hyperacute, acute, and chronic.

The strategies used in clinical practice and in experimental models to avoid or

delay rejection are general immunosuppression and minimizing the strength of the

specific allogeneic reaction. An important goal in transplantation is to induce donor-specific tolerance, which would allow grafts to survive without nonspecific

immunosuppression.

Module task

1. Explain two ways that T cells recognize allogeneic MHC!

2. Explain the type of graft rejection!

12.2 Overview: Tumor Immunology

Some tumor elicit specific immune responses that suppresses or modify their growth. A

partially functioning immune system can lead to the outgrowth of tumors, suggesting

that the immune system does play an important role in suppressing development.

Tumors evade or suppress the immune system in a number of ways, and regulatory T

cells have received much attention in this area. Monoclonal antibodies have been

successfully developed for tumor immunotherapy in several cases, including anti-CD20

for B-cell lymphoma, and anti-VEGF antibodies in colorectal cancer. Attempts are also

being made to develop vaccines incorporating peptides designed to generate effective

cytotoxic and helper T-cell responses. The efficiency of dendritic cells in presenting


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tumor antigens has been improved by pulsing the individuals dendritic cells in vitro

with modified tumor cells or tumor antigens and then replacing them in the body. This

approach has been extended in animal experiments to the transfection of tumor cells

with genes encoding co-stimulatory molecules or cytokines that attract and activate

dendritic cells. The possibility of the near eradication of cervical cancer has been brought

a step closer by the development of an effective vaccine against specific strains of the

cancer-causing human papilloma virus.

Module Task

1. How do tumors evade the immune response?

12.3 Overview: Vaccination

The greatest triumphs of modern immunology have come from vaccination, which haseradicated or virtually eliminated several human diseases. It is the single most

successful manipulation of the immune system so far, because it takes advantage of the

immune systems natural specificity and inducibility. Nevertheless, there are many

important infectious diseases for which there is still no effective vaccine. The most

effective vaccines are based on attenuated live microorganism, but these carry some risk

and are potentially lethal to immunosuppressed or immunodeficient individuals. Better

techniques for developing live-attenuated vaccines, or vaccines that incorporate both

immunogenic components and protective antigens of pathogens, are therefore being

sought. Most current viral vaccine are based on live attenuated virus, but many bacterial

vaccines are based on components of the microorganism, including components of the

toxins that it produces. Protective responses to carbohydrate antigens can be enhanced

by conjugation to a protein. Vaccines based on peptide epitopes are still at an

experimental stage and have the problem that the peptide is likely to be specific for

particular variants of the MHC molecules to which they must bind, as well as being only

very weakly immunogenic. A vaccines immunogenicity often depends on adjuvants

that can help, directly or indirectly, to activate antigen-presenting cells that are

necessary for the initiation of immune responses. Adjuvant activate these cells by

engaging the innate immune system and providing ligands for Toll-like and other

receptors on antigen-presenting cells. The development of oral vaccines is particularly


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important for stimulating immunity to the many pathogens that enter through the

mucosa. Cytokines have been used experimentally as adjuvants to boost the

immunogenicity of vaccines or to bias the immune response along a specific path.

Module tasks

1. Explain the differences between primary and secondary antibody responses!

2. Explain the Immunization schedule for children < 1 year in Indonesia!

3. What is an adjuvant and how does it work?

student guidance 2012

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