IMMUNOLOGY

HOST PARASITE INTERACION

Mutalism Komensalism Opportunism Parasitism

Factors that determine the kind and number

availability of oxygen pH of the host site other microorganism availability of nutrien immunological state

Parasites
Extracelluler parasites persist and multiply outside of the host cells Intracelluler parasites
must resist digstion by the host cells

Intracelluler Parasites
Facultative intracelluler
Salmonella species M .tuberculosis Brucella

Obligate intracelluler viruses, rikettsiae and certain protozoa

Diseases - shift in the equilibrium between man and the infecting agent - ability to cause disesase can be termed as pathogen - individual who harbor and shed infectious agent but show no symtoms called carrier

Microorganism cause disesase by

. Competition for metabolits

.production of virulent factors .production of toxins .hypersensitivity .vascular obstruction

Microbial Factors

Adhesive factor Invasive factors Toxin Antiphagocytic factor Antigen variation

Host factors

Genetic Age Socio-economic Immune status

Bacteria

Virus

Fungal

HUMAN BODY

Riketsial

Mycoplasm

Chemical

IMMUNE RESPONSE RECOGNITION ELIMINATION

Autoimmunity

Immunodeffisiency

Hypersensitivity

Foreign Antigent
Enter Human body

Elimination

Elimination

Specific Pathologic

Non-specific

PHASE OF IMMUNE RESPONSE

1. Cognitive phase Binding of foreign Ag to specific reseptor on mature lymphocytes. 2. Activation phase Proliferation & differentiation of lymphocytes 3. Effector phase Elimination of Ag by lymphocytes that have been specifically activated

Humoral Immunity Mediated by molecules in the blood that are reponsible for spesific recognition & elimination of Ag Cell-mediated-immunity (celluler immunity) mediated by T lymphocytes

Lymphoreticular system :
1. Cells : T cells , B cells & subsets of lymphocytes that involved in specific and nonspecific immune response 2. Organ and tissue a. primary : thymus, bonne marrow and equivalen of bursa fabricus b. secondary/perifer : spleen & lymp nodes

SISTIM IMUN

NONSPESIFIK FISIK / MEKANIK Kulit Sel.lendir Silia Batuk Bersin

SPESIFIK SELULER SEL T HUMORAL SEL B

BIOKIMIA

SELULER

BIOKIMIA As.lambung Lisosim Laktoferin As.neuraminik HUMORAL Komplemen Interferon CRP

FAGOSIT monosit makrofag neutrofil eosinofil SEL NULL sel NK sel K SEL MEDIATOR basofil sel mast

antibodi Th Tc Ts

Non-speciic
- Action immediate
- Respnonse is nonspecific

Specific
- Action requires day todevelop - Specific

- Response is not - Response enhance on enhance by repeat repeat unfection infection -Recognition molecule - Clonal selection naturally express in all cells types

Non-specic

Specific

-Complex carbohydrate - Small segments of or lipoprotein that form protein or glicoprothe wall of microbe tein ( B cells) or processed protein (T cell) -Circulating molecules : Complement -Cells : Phagocytes ( macrophages, neutrophils) NK cells

Antibody

Lymphocytes

IMMUNOLOGY

ANTIGEN ANTIBODY IMMUNOGEN ANTIGENICITY IMMUNOGENICITY COMPLEMENT EPITOPE VALENCE ADJUVANS

IMMUNE .SYTEM
Adaptive immunity Cells Humoral mediated -Macrofages -Granulocytes -NK cells -Complement -Other chemicals HCl, lysozym -APC -T cells -B cells -Antibodies -Complement

Innat immunity

TYPES OF ANTIGEN
1. T-dependen Ag require Th cells in order to evoke immune response. 2. T- independen Ag without involvement of T cells - primary response - don t yield immunological memory - don t produce hight affinity Ab - Ig M - e.g : LPS of Gram (-) bact

3. Auto Antigen Ag from a person that initiated immune response in that individual 4. Allo-Ag Ag from different individual of the same spesies ( different genetic make up) 5. Iso-Antigen Like Allo-antigen with identical genetic make up

Immunogenicity depent on
1. Properties of Ag
- foreigness - molecular size - chemical complexity - Solubility - rigidity

2. Host factors
- enzymes of the host - availability of appropriate lymf. Clone - ability of APC

- age - nutritional status - MHC locci

3. Mode of Ag adiminstration
- dose - route - form - scedule

BACTERIAL ANTIGENTS
Flagellar -Antigenic protein ( H-Ag) -protective : Cholera Pilli two form : ordinary pilli & sex pilli -ETEC -N. gonorrhoeae Bacterial somatic Ag a. capsule or slime layer b. O-antigen (LPS outer membrane) Bacterial Toxin : I. Exotoxin II.Endotoxin

I. EXOTOXIN
1. Hemolysin : S. aureus , V. cholerae C. tetani , C, septicum 2. Leucocidine : S aureaus 3. Hyaluronidase : S. aureus , Strep. pyogenes C. welchii 4. Colagenase : C. welchii 5. Coagulase : S. aureus

II. ENDOTOXIN
Has several biological properties - induce of fever - elicit early IgM & latter IgG - stimulate endocrine gland - activates complement - induce Swartman reaction - cause release of lasma kinin

ENDOTOXIN
1. Dermonecrotizing agent - schick toxin : C. diphteriae - E- toxin : C.welchhi 2. Cardiotoxic agent - streptolysin-O : S. pyogenes - tetanolysin : C.tetani 3. Deoxyribonuclease - F toxin : C. septicum - sterptodornase : C. botulinum V. cholerae

Mayor cells types involved in immune response

LEUKOCYTES
LYMPHOCYTES PHAGOCYTES AUXILLARY

B T NK Mono- Neutro Eosicells cells cells cyt phil nophil Macrophage

Baso- Mast phil cells

GRANILOCYTES AQUIRED INNATE IMMUNE RESP

Lymphocytes
- Capable of specifically recognizing and disttinguishing different antigenic diterminat - Responsible for adaptive IR

B Cells - Comprise 5 - 10 % - Atibody production - Spcific Ag reseptor : surface Ig - Ag-reseptor complex (CD79) - bind to foreign protein,polysacc, lipoprotein in soluble form

2. Sel B - Pemasakan pada sumsum tulang (bone marrow) - 5-10% total limfosit - dpt membentuk antibodi - dpt mengenal antigen langsung - mempunyai surface immunoglobulin (sIg). - Dpt berfungsi sebagai sel penyaji antigen (APC) - berperan dlm imunitas spesifik

T cells - Small , non granular lymphocytes - Antigen receptor (TCR) - small peptides prosesed by APC - Surface marker : CD4 : Th and CD 8 : CTL

Sel T - pemasakan di timus - 65-80% dr total limfosit - membentuk roset dgn eritrosit domba (sel B tdk) - glikoprotein permukaan (CD) - tdk dpt mengenal antigen langsung - imunitas spesifik - subset : CD4 (Th) dan CD8 (Tc) dan Ts (supresor)

3. Sel null - tdk mempunyai petanda permukaan - mempunyai reseptor C3 dan Fc - 10-15% total limfosit - dapat membunuh sel tumor dan sel yang terinfeksi virus - tdr dari 2 subset : 1. sel K : memerlukan bantuan antibodi untk membusel sasaran 2. sel NK :tdk memerlukan bantu an antibodi

NK cells - subset found in blood & lymphoid tissues - derived from bone marrow - primitive CTLs - possess ability to kill tumor cells & normal infected by virus - express CD2 & low affinity reseptor for IgG called FcKRIII (CD16)

Phagocytic Cells
1. Professional phagocytes : - PMN leukocytes - Monocytes - Macrophages 2. Paraprofessional -Dendritic cells (DC) have selective phagocyte activity 3. Non professional : - fibroblast & ephithelial cells

4. Sel fagosit Fungsi : fagositosis Ag membunuh memproses Ag mempresentasikan Ag ke sel limfosit mempunyai banyak reseptor dipermukaannya

Macrophage function
1. Detection of microbial invasion Opsonic and nonopsonic receptor for microbe and their product 2. Restriction of microbial spread Phagocytosis Granuloma formation Intracelluler killing 3. Recruitment of immune cells Cytokines & inflamatory mediators

4. Accessory cells in lymphocyte activ. -Ag processing & and presentation -Costimulatory molecules : ligand for CD40 L, CD28 and CTLA4 (T cells) -Cytokines 5. Effector cells in CMI -Increase phagocytosis -Increase intracelluler killing -Clearence of apoptotic cells 6. Participation in humoral immunity

Properties of Macrophages 1. Membrane receptor -Scavenger receptor -C receptor -FcK- eceptor -Macrosialine -Cytokines receptor -CD14 (LPS receptor) 2. Production of cytokines -IL-1

- TNF E - IL-12 - IL-10 - IL-4 - FGF 3. Antigent processing and presentation 4. Produce enzymes - colagenase - elastase - lysozymes - lysosomal enzymes

5. Production of bioactive lipid and small radical - Prostaglandin - Platelet activatig factor - reactive oxygen & nitrogen intermediate .

Phagocytosis
1. Microbial recognition - PRRs (pattern recognition reseptor a. membrane bound b. free in plasma - Recognize wide variety of microbial molecules - As reeptors for binding & entry of many intraclluler pathogens

2. Microbial uptake - actin polymerization - engulfment and internalization 3. Phagosomal maturtion - depolymerization of actin - fussion with endosome - final step : fussion with lysosome ---> phagolysosome generating low pH and containig degradative hylases

4. Microbial killing Accomplished by : - low pH of phagosom - limitation of nutrien (iron) - generation of reactive oxygen and nitrogen intermediates - Nramp-1 : removal of iron and divalen cation from phagosom - phox ---> reactive oxygen intermed. - inos ----> reactive nitrogen intermed.

Phox : phagocyte NADPH oxydase

phox

O2
NADPH

O 2NADPH+ H2O2 + OH* + H2 O ClHOCl- + OH* MPO antibacterial

O2 H2 O 2

LPS IL-1F TNFE IFN-K

INOS

Deaminasi oxydative L-arginin

NO + H2O2 peroxynitrit

NO + Thiol groups nitrosothiol

5. Production of soluble mediator - signal & recruit other cells to the side of infect. . Stimulate adaptive immune resp. 6. Antigen presentation - Histocompatibility molecule(HLA) - HLA-I --> CD8 cells - HLA-II --> CD4 cellsa - Costimulatory molecules

Ag
MJ HLA-I

IL-1 HLA-II CD4 IL-4 , IL-12 BCGF, BCPF, BCDF IFN-K ADCC Th1 Th2

CD8

B Ab P NK
IL-2

Exogenous antigen processing: MHC class II peptide presentation

microbe

CD 4

phagosom lysosom

golgi phagolysosom Phox Inos Nram-1

"

RE

EF

Endogenous antigen processing: MHC class I peptide presentation

viral

CD 8

golgi proteasom

RE TAP

T cells
CD40L CD28

CTLA4

TCR

Ag-HLA CD40 B7-1

APC

B7-2

COMPLEMENT SYSTEM
- Heat labil protein - Inactive - After being activated : some protein act as enzymes, while Lysis of foreign cells: other as substrat. - pathogenic microorgsnism - enhancement of phagocytosis - inflamation of host tissue - stimulation of chemotactic

- Regulated by several soluble and cellmembrane-assoiated protein 1. Limit or stop complemen activ 2. Prevent abnomal or constitutiv activation in the absent of microbe and antibodies 3. Prevent formation of the MAC on self tissue and excessive generation of inflamatory mediators

Overviewe of Complement
- Synthesized : hepatosytes , blood moncytes , epithelial cells of GE tract and tissue macophages -Four mayor functions : 1. opsonization 2. target cytolysis 3. inflamation 4. immune complex clearence

ACTIVATION OF COMPLEMENT
1. Classic pathway - IgG (IgG1, IgG2, IgG3) & IgM , DNA retrovirus , mycoplasma , protein-A , heparin , CRP , MBP , Tripsin 2. Alternative pathway - Not require formation Ag- Ab complex. - IgA , IgE , cobra venon , LPS gram(-)

1. Classic pathway
a. Binding C1 on Fc region of Ag-Ab b Poduction of C3 convertase ( C4b2b) c. Production of C5 convertase ( C4b2b3b) d. Production of MAC ( C5b 678). C5b67 insert itself into membrane of target cells. C8 bind to the complex ( C5b678) forming smal pore in the membrane. Finally C9 poymerize araound the C5b678 ---> hole---> lysis of target cells.

C3a Ag-Ab C1 C4b2b C4a C4 C4b C2b C2 C2a C9

Target cell lysis

C3 C3b

C4b2b3b C6 C5b6 C7 MAC C8 C5b

C5

C5a

Alternative pathwy
-Not require specific Ab for initiation -Does not utilize C1 , C4 & C2 activ. -Utilize at least 3 serum protein : 1. Factor B 2. Factor D 3. Factor P (properdine)

Microbial surface
Ba

C3a C3 C3b C3bB C3bBb

B
C3 C3a C3b C3bBb

D P

C3 convertase
C3bBb3b

As C5 convert.

Additional role of complement fragment - C3a , C4a and C5a are anaphylatoxin. - C5a : - chemotaxis - increases production of reactive oxygen intermediates - increase adhesiveness - C3B : - opsonin - enhance phagocytosis - elimination immune complex circulating in the blood

Regulation of Complement cascades 1. Regulation of classical pathway a. C1INH- inhibit C1 activation - halting initiation of clasical pathway. - in the blood C1 is bound to C1INH - C1INH deficiency cause --> hereditary angiodema

b. protein that interfere with C3 & C5 C4bp &DAF (decay accelerating (factor) ---> inhibit formation and dissociation C3 convert ---> cofactor for Factor-1mediated ted cleavage of C3b & C4b

MCP (CD 46) : mediated inactivation C4b. 2. Regulation of alternative pathway a. inhibit binding B to C3b : Factor-H b. inhibit formation C3 convertase alternative pathway (C3bBb) : Factor-1 (mediated proteolysis C3b)

3. Regulation of MAC formation a. CD59 also called MIRL (membrane inhibitor of reactive lysis) and HRF (homologous restriction factor) also called C8bp.--> block binding C9 to C8--> preventing MAC formation b. S-protein (vitronectin) : bind to C5b-7 complex --> prevent membrane insertion of the MAC bp : binding protein