Pregled imunosnog sustava
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1 Pregled imunosnog sustava L. Sompayrac: How the Immune System Works, 2nd Ed (Lecture 1: An Overview) Sherwood: Human Physiology, 6th Ed (Chapter 12: Body Defences) 1
2 hematologija imunologija većina tipova krvnih stanica su dio imunosnog sustava Imunosti sustav štiti od patogena (bakterije, virusi, paraziti) otklanja istrošene stanice i oštećeno tkivo prepoznaje i uništava abnormalne ili mutirane stanice u tijelu imunosno nadgledanje započinje neprikladne imunosne odgovore koji vode do alergija i autoimunih bolesti 2
3 Imunosni sustav 1. Koža, sluznice 2. Urođena imunost 3. Stečena imunost 3
4 Urođena imunost 4
5 Fagocitoza Urođena imunost Bakterija Prihvaćanje pomoću nespecifičnih receptora Pseudopodiji Spajanje fagosoma s lizosomom Makrofag Ciklus se ponavlja Degranulacija lizosoma i razgradnja bakterija Egzocitoza 5
6 6
7 eritrocit monocit makrofag E. coli 7
8 Leukociti svi imaju jezgru, neki imaju granule u citoplazmi 5-10 x 10 9 /L obrana organizma dijapedeza, ameboidno pokretanje, kemotaksija i fagocitoza Granularni leukociti (granulociti) Agranularni leukociti (agranulociti) Neutrofil µm 50-70% Eozinofil µm 1-5% Bazofil µm 0-1% Monocit µm 1-6% Limfocit 8-10 µm 20-40% Diferencijalna krvna slika 8
9 Koštana srž monocit Pluripotentna hematopoietska matična stanica Mijeloidna matična stanica Limfoidna matična stanica Megakariociti Preteče eritrocita Preteče granulocita Preteče monocita Limfociti u limfatičkom tkivu Trombociti Eritrociti Granulociti Monociti Limfociti Cirkulacija 9
10 kapilara Diapedeza Kemotaksija Infekcija, oštećenje tkiva, mrtve stanice, otpuštanje kem. signala fig ; pg:
11 11
12 12
13 Bacterial invasion or tissue damage Urođena imunost Local arteriolar vasodilation Increased blood delivery to injured tissue Release of histamine by mast cells Increased local capillary permeability Local accumulation of fluid Redness Heat Swelling Pain Upala Glavna funkcija: čišćenje od infektivnih i toksičnih tvari i od tkivnih ostataka Increase in crucial plasma proteins, such as clotting factors, in tissue Increase in phagocytes in tissue Phagocytic secretions Defense against foreign invader; tissue repair Systemic responses, such as fever 13
14 Komplement Urođena imunost Bakterije Razaranje (liza) Fagociti Kemotaksa Bakterije Opsonizacija Poboljšana fagocitoza 14
15 Urođena imunost Virus IFNα IFNβ Zaražena stanica Sustav interferona T H IFNγ Antivirusno stanje u stanici Antigen Limfocit T 15
16 Urođena imunost NK stanice (natural killer cells, stanice ubojice) slične limfocitima nespecifično uništavaju stanice inficirane virusom i stanice tumora način djelovanja sličan citotoksičnim T limfocitima (direktni kontakt s ciljnom stanicom i induciranje apoptoze) ne trebaju sazrijevati mogu djelovati odmah, prije no što specifični i brojniji T limfociti postanu funkcionalni 16
17 Stečena (adaptivna, specifična) imunost 17
18 18
19 Velike boginje - Variola vera (engl. smallpox) Edward Jenner,
20 Antigens Specific antigenbinding sites Fab Light chain Fc Heavy chain Antibody 20
21 21
22 PRINCIP KLONSKE SELEKCIJE 22
23 MODULARNI DIZAJN PROTUTIJELA rearanžmani gena 23
24 24
25 Vezanje protutijela neutralizira (inaktivira) antigen) Neutralizacijom (blokadom mjesta vezivanja) Aglutinacijom čestica Precipitacijom topljivog antigena Aktivacijom komplementa Bakterije Komplement Virus Oštećenje membrane Bakterija Topljivi antigen Strana stanica što potiče što dovodi do Fagocitozu stranog antigena Lizu (razaranje) stanice 25
26 Enhancement of phagocytosis (opsonization) Fc receptor Invading bacterium coated with antibodies specific to it Phagocyte 26
27 Neutralization Invading bacterium Bacterial toxin Antibody neutralizing toxin Antibody specific to toxin 27
28 28
29 stanična imunost humoralna imunost 29
30 Nastanak limfocita Koštana moždina ili fetalna jetra Pluripotentna matična stanica Preteča limfoidne loze Timus limfocit Limfocit B Limfocit T Limfni čvorovi, slezena, krv i limfa 30
31 klonska selekcija i modularni dizajn 31
32 stanica koja prikazuje antigen (APC) T limfocit 32
33 33
34 stanica koja prikazuje antigen (APC) gotovo bilo koja stanica s jezgrom 34
35 Limfatička tkiva i organi Tonzile Timus Limfni čvorovi Peyer-ove ploče Limfne žile Slezena Slijepo crijevo Koštana moždina 35 Design by dr. Zoran Tadić
36 Peyerove ploče u stijenci tankog crijeva 36
37 IMUNOLOŠKO PAMĆENJE memorijske stanice 37
38 38
39 39
40 Macrophages secrete interleukin 1, which enhances B cell proliferation and antibody secretion Interleukin 1 Invading bacteria Macrophage Macrophages process and present bacterial antigen to B and T lymphocyte clones specific to the antigen Antibodies enhance phagocytosis by coating the bacteria and serving as opsonins Antibodies B cell B cell growth factor Plasma cell Helper T cell Activated helper T cell Plasma cells secrete antibodies that bind with the antigenic bacteria Helper T cells secrete B cell growth factor that enhances B cell proliferation and antibody secretion 40
41 1. Virus inficira stanicu 3. Citotoksični T limfocit prepoznaje i veže se na strani, virusni antigen vezan za vlastitu (MHC) molekulu 2. Virusni antigeni se izlažu na površini stanice pomoću MHC molekula 4. Citotoksični T limfocit otpušta kem. tvari (npr. molekule 41 perforina), koje penetriraju u membranu i tvore pore, prije no što virus dospije u jezgru i započne replikaciju
42 IMUNOST Urođena (nespecifična) trenutni maksimalni odgovor nema imunološke memorije nije antigen-specifična prepoznavanje robusnih molekularnih struktura par stotina receptora nepogrešivo prepoznavanje vlastitog i stranog Stečena (specifična) potrebno 3-4 dana za maksimalni odgovor imunološka memorija antigen-specifična prepoznavanje detaljne molekularne strukture receptora pogreške u prepoznavanju vlastitog i stranog 42
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