Special Practice in Immunology
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1 Special Practice in Immunology Department of Veterinary Microbiology การฝ กพ เศษทางว ทยาภ ม ค มก น (Special Practice in Immunology) เน อหารายว ชา ความร ในเร องชน ดและการใช ว คซ นในเช งส ตวแพทย เทคโนโลย ในการ ผล ตว คซ น และหล กการใช ว คซ นป องก นโรคในส ตว การประย กต ใช ความร ท เก ยวก บว ทยาภ ม ค มก นและการใช ว คซ นในการ ควบค มและป องก นโรคในส ตว กระบวนการและข นตอนในการผล ตและตรวจสอบค ณภาพว คซ นส าหร บ ส ตว ชน ดต างๆ ว ตถ ประสงค ท วไปและ/หร อว ตถ ประสงค เช งพฤต กรรม น ส ตสามารถ เร ยนร ชน ดของว คซ น เทคโนโลย ในการผล ตว คซ น และหล กการใช ว คซ นป องก น โรคในส ตว การประย กต ใช ความร ท เก ยวก บว ทยาภ ม ค มก นและการใช ว คซ นในการ ควบค มและป องก นโรคในส ตว กระบวนการและข นตอนในการผล ตและตรวจสอบค ณภาพว คซ นส าหร บ ส ตว ชน ดต างๆ 1
2 Schedule คร งท ว นท 26, 27 พฤษภาคม :30-18:00 น. 5 ม ถ นายน ม ถ นายน ม ถ นายน ม ถ นายน กรกฎาคม กรกฎาคม กรกฎาคม กรกฎาคม ส งหาคม ส งหาคม ส งหาคม ส งหาคม ก นยายน ก นยายน ก นยายน 2552 ห วข อ ด งาน ณ ศ นย ควบค มค ณภาพช วภ ณฑ และศ นย โรคปากและเท าเป อย กรมปศ ส ตว อ.ปากช อง จ.นครราชส มา Introduction and review: Vaccine and adjuvant Principles of herd immunity Application of serosurveillance for monitoring of herd immunity Application of vaccination for disease prevention and control Factor affecting the vaccine efficacy and vaccine failure Biotechnology derived veterinary vaccines Self-study Midterm Examination (20-24 กรกฎาคม 2552) Overview on vaccine production and quality control ว คซ นเฮโมราจ กเซพต ซ เม ย อห วาต ไก แอนแทรกซ แบลคเลก และ บร เซลโลซ ส ว คซ นกาฬโรคเป ด และว คซ นอห วาต ส กร ว คซ นน วคาสเซ ล หลอดลมอ กเสบต ดต อ ฝ ดาษไก และ ก มโบโร ว คซ นโรคปากและเท าเป อย การทดสอบค ณภาพว คซ น การผล ตและควบค มค ณภาพว คซ น โดยบร ษ ทเอกชน Final examination ผ สอนหล ก* staff SS DN DN DN DN SS SS DLD1 DLD2 DLD3 DLD4 DLD5 TC staffs Final Examination (21 กย. -2 ตค. 2552) การว ดผลการเร ยน การประเม นความร ทางว ชาการ สอบข อเข ยน ปลายภาค 30 % การประเม นการท างานหร อก จกรรมในช นเร ยน 20 % การเข าร วมก จกรรมการด งานนอกสถานท 50 % รวม 100 % 2
3 Immunology for veterinary practitioners Sanipa Suradhat, D.V.M, Ph.D Faculty of Veterinary Science Chulalongkorn University 3
4 Cells of the immune system CD4 + CD8 + Layers of body defenses Invading microorganisms Physical barriers Examples: skin, enzymes, self-cleaning, normal flora Innate immunity Examples: Inflammation, phagocytes Specific/adaptive immunity Examples: antibody production, cell-mediated immunity The 3 general ways by which the animal body defends itself against microbial invasion 4
5 Here s s how we fight the intruders Pathogen attacks Security breached Sentinel cells sending SOS Inflammation Phagocytic cell entering the site APC migration (APC leave the crime scene) Killing and clearing of invaders Pathogen clearance & Tissue repair Effector cells entering the site Activation of adaptive immunity In the lymphoid tissues Immediate action Back up plan Innate & specific immune responses Innate Immunity Response is antigenindependent There is immediate maximal response Not antigen-specific Exposure results in no immunologic memory Specific Immunity Response is antigen-dependent There is a lag time between exposure and maximal response Antigen-specific Exposure results in immunologic memory 5
6 Time course Level of protection Physical barrier Adaptive immunity Innate immunity Minutes Hours Days Time Innate immunity Abbas et al.,
7 Innate immunity and inflammation Adaptive immunity 7
8 Role of innate immunity on T cell activation Signal 0 Signal 1 Signal 2 The APCs: Dendritic cells (DC), Macrophage, B cells Kono and Rock, Nat. Rev. Immunol. 8:
9 Guy, Nat. Rev. Microbiol. 5:
10 Classification of adjuvants according to immunological events Gr. Concept of action Examples Key events A Facilitate Ag uptake, transport and presentation by APCs ISCOMs, Quil A, Alum, Liposomes Ag localization in the lymph node B Depot effect Oil emulsion, Alum, gels, microspheres, non-ionic block copolymers Prolonged Ag presentation C Signal 0 Complement, CpG, LPS, mycobacteria, yeast extracts, ISCOMs? Signaling of PRRs on innate immune cells D Danger signal Oil-emulsion surface active agents, Alum, IFNs, hsps Tissue destruction/stress E Recombinant signal 2 Cytokines, costimulatory molecules APC polarlization, T & B cell help Adapted from Schijns (2000) Properties of adjuvants Guy, Nat. Rev. Microbiol. 5:
11 Principle mechanisms of innate and adaptive immunity Abbas & Lichtman, 2004 Clonal selection theory Abbas & Lichtman,
12 Adaptive (acquired) immunity Humoral immunity Cell-mediated immunity Abbas et al.,
13 Essential feature of adaptive immunity Foreign material (antigen) Antigen presenting cells Antigen-specific B cells Antigen-specific T cells Memory cell Antibody producing cell Effector T cell Memory cell Humoral Immunity Cell-mediated immunity Antigen elimination Type of immune responses depends on the nature of the antigen. Dead/extracellular Pathogens Living/intracellular pathogens Exogenous Antigen MHC II Endogenous Antigen MHC I B cell activation Th activation CTL activation Ab production Macrophage & NK activation Pathogen/cell elimination 13
14 Abbas & Lichtman, 2004 Th dichotomy Factors influence on the Th development? costimulatory molecule, type of APC (DC), Ag, dose, cytokines, environment, etc. CTL, NK Mast cells 14
15 Role of regulatory DC in counter regulation Early phase Late phase Th1 Immune Activation DCreg (IL-10) Inflammation Immunopathology IL-10, TGF-β Treg Th2 Immune Activation DCreg (IL-10) Adapted from Yazdanbakhsh et al Science. 296: Diversification of CD4 T cell lineages Weaver at al., Immunity. 24:
16 Regulatory network Th1/Th2 Effector cells Pathogen expansion Microbe induced pathology Persistent infection Pathogen elimination Immunopathology Adapted from Belkaid and Rouse Nature Immunology. 6: Phase of immune response 16
17 Antibody (or effector) Memory How long did the anti-rabies immunity last? 17
18 Although there is a rapid decline in the titers of serum neutralizing antibodies, an anamnestic protective response against the rabies challenge persists. Duration Of Immunity Minimum Duration of vaccinal Immunity (DOI) DOI is dependent on the persistence of memory B and T cells the persistence of long-lived plasma cells Revaccination does not appear necessary to maintain the memory cells and long live plasma cells. Schultz, Vet. Microbiol. 117:
19 Human CMI half-life = 8-15 yrs Persisting antigen drives continuous proliferation and terminal differentiation of all T cells. High numbers of effector cells are maintained for some time and mediate effective protection from a challenge. Terminal differentiation, however, prevents the generation of TCM. The term memory cells should be avoided in this case, as stimulation is ongoing. Upon antigen removal, effector cells disappear and memory T cells do not develop. Lanzavecchia and Sullusto, Cur. Opin. Immunol :
20 How can we activate a protective immunity? Knowing pathogens Where are they? How do they cause damages? Knowing protective immunity What level of protection?.infection or disease What kind of immunity do I want, CMI, Antibody? What kind of vaccine should I use? Immunogenicity, potency, safety Knowing host How immunocompetent is the host? What about maternal antibody? Maternal immunity and induction of immune responses Antibody titer 160 Protected by Susceptible Responsive maternal antibody to infection to vaccination Protective antibody level 80 Interfering antibody level 10 Age 20
21 - AGE - Breed - MDA - nutritional/psychological status - Concurrent infections - Immunosippressive Tx. etc. VACCINE HOST HEALTH PATHOGENS ENVIRONMENTS Type of immunization procedures Immunization Active immunity Passive immunity Artificial immunization Natural infection Artificial - hyperimmune serum Colostral antibodies Living organisms Non-living vaccines Fully virulent Modified live Heterologous Culture attenuated -distemper Recombinant organisms - vaccinia/rabies Genetically attenuated - pseudorabies Killed whole organisms -bacterins Isolated antigens Cloned antigens - FeLV Toxoids Synthetic antigens DNA vaccine Adapted from Tizards,
22 Vaccine failure Vaccination failure Correct administration Incorrect administration Animal responds Inappropriate route of administration Animal fails to respond Death of live vaccine Administered to passively protected animal Too late, animal already infected Wrong strain of organism used Non- protective antigen Prior passive immunization Animal immuno- suppressed Biological variation Inadequate vaccine Tizard,
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