Lecture 01_The roles of immune response, the composition of the immune system PDF

The role of immune response, the composition of the immune system Dr. Krisztina Szarka  Important info regarding the semester Teaching institute: One Health Institute Head of Institute: Dr. Gábor Kardos, associate professor ([email protected]) Academic adviso...

The role of immune response, the composition of the immune system Dr. Krisztina Szarka  Important info regarding the semester Teaching institute: One Health Institute Head of Institute: Dr. Gábor Kardos, associate professor ([email protected]) Academic advisor: Dr. Krisztina Szarka, associate professor ([email protected]) Lecture materials are available on the institute's e-learning platform The attendance at the 50% of lectures are compulsory. The attendance at the lectures is registered through the e-learning system, using a QR code. This takes at the beginning (within 5 minutes) and at the end of the lectures. Students who leave during class cannot return to the classroom, so their participation is invalid. To accept presence, you need to scan BOTH QR codes. Presentation of medical certificate is needed within 5 working days after the absence. Exams are performed under controlled conditions in computer rooms.  Topics of the lectures Week Date Title Lecturer 1. 10th Sep The role of immune response, the composition of the immune system Dr. Krisztina Szarka 2. 17th Sep Properties of natural immunity and its cellular components, its mode of action Marcell Gulyás 3. 24th Sep The complement system, acute phase reaction Dr. Dalma Papp 4. 1st Oct MHC molecules and antigen presentation Lilla Buzgó 5. 8th Oct The B- and T-cell receptors, clonal selection Dóra Boros-Pál 6. 15th Oct B-lymphocytes and antibody production; the structure and function of antibodies Lilla Buzgó 7. 22nd Oct Types of T-cells, effector functions Dr. Dalma Papp 8. 29th Oct Connection of natural immunity to adaptive immunity Dr. Dalma Papp 9. 5th Nov Immune tolerance, hypersensitivity and autoimmune reactions Marcell Gulyás Properties of immune response against extra-and intracellular pathogens, the immune 10. 12th Nov response as a selection pressure Dr. Krisztina Szarka 11. 19th Nov Immunology of pregnancy. Transplantation and tumour immunology, immune therapy Dóra Boros-Pál 12. 26th Nov Immune memory and immunization Dóra Boros-Pál 13. 3rd Dec Immunoserological methods I Dr. Krisztina Szarka 14. 10th Dec Immunoserological methods II Dr. Krisztina Szarka  Science of immunology Latin origin – immune (free, acquitted) The discipline dealing with the functioning of the immune system – medical, veterinary and biological sciences. Immune system – aimed at maintaining the integrity of the body; protection against various foreign substances, their detection → protection against diseases (infections, tumours). All aspects of the immune system and immune defences − diversity, specificity, memory, self and non-self recognition − structure and function − diseases of the immune system; improper functioning – immunopathology, autoimmunity, allergies, cancers, immunodeficiency states − blood banks – transfusion − transplantation − Immunization − immunopharmacology Immunity Immunochemistry Immunobiology  Science of immunology Classic immunology – relationship between the body systems, the pathogens and immunity Immunological mechanisms effektor function memory function cellular immune response humoral immune response chapter 2: Innate immunity and different ways Biological-physiological regulation  History of immunology 430 BC - Thucydides, historian; Athenian plague epidemic – those who survived previous epidemics did not fall ill again while caring for the diseased individuals Smallpox epidemics Eastern societies (China, Ottoman Empire) from the 9th century – variolation 1718 Lady Mary Wortley Montague – application of variolation 1798 – Jenner – use of cowpox to protect against smallpox; Vaccination is widespread worldwide  History of immunology Development of microbiology G. Fracastoro (1478/49-1553) live contagious substance – contagium vivum (1546) J. Tyndall (1820-1893) A. van Leeuwenhoek (1632-1723) 1875-77 discovery of heat-resistant bacterial 1676 Royal Society of London spores ~300x magnification microscope new method for the decontamination of heat- examination of water, tooth scrapes, semen sensitive fluids (tyndallisation) L. Spalanzani (1729-1799) 1768 – Micro-organisms must not arise R. Koch (1822-1895) spontaneously either 1876 – examination of anthrax bacillus T. Schwann (1810-1882) 1877 – development of simple staining 1836 – The basic unit of living is the cell 1881 – development of cultivation techniques R. Virchow (1821-1902) solid media – application of agar-agar (W. 1855 – all cells originate from the other one Hesse/1882) L. Pasteur (1822-1895) development of cultivation vessels (J. Petri/1887) 1854 – role of microbes in the fermentation and 1881 – identification of the rabies causative agent the spoilage - pasteurisation 1882 – isolation of the causative agent of TB 1861 – denial of spontaneous generation 1883 – isolation of cholera bacillus 1862 – infectious origin of some diseases development of aseptic techniques  History of immunology Louis Pasteur (1822-1895) 1879 – fowl cholera (Pasteurella multocida) – propagation – injection to chickens, disease development long-term cultivation – attenuation → no disease development ‚Aging’ of the culture leads to a decrease in virulence Use of attenuated strains – protection against disease Vaccine name – "vacca" = cow Anthrax vaccine (medium containing K- bichromate; 42-43 C) – Bacillus anthracis (1881) Rabies vaccine – attenuation by rabbit breeding (1885 – Joseph Meister, 13x vaccination)  History of immunology Robert Koch (1822-1895) 1884 – Koch-postulates – relation between the pathogens and caused diseases Hypersensitivity reaction as a consequence of TB  History of immunology E. von Behring (1854-1917) & S. Kitasato (1852-1931) 1890 – description of bacterial exotoxins and testing of antitoxic immunity (E. Roux and A. Yersin – diphtheria toxin) immunization of guinea pigs with heat- treated diphtheria toxin protective substances have been detected in the blood of guinea pigs; by inoculating them into an infected animal, the animal's recovery can be achieved – antitoxin & serum therapy, for which immunization of large animals can be achieved (1901 - von Behring Nobel Prize)  History of immunology Paul Ehrlich (1854-1915) 1877 – recognition of mast cell recognition 1882 – development of acid-fast staining from 1892 – role of antibodies in immunity, medical use of diphtheria antitoxin 1900 – specific antibody formation 1912 – Salvarsan (compound 606) is developed – an arsenic-containing compound for the treatment of syphilis In the following decades, the active components present in the serum of immunized animals were detected in animal experiments: antitoxins precipitin agglutinin Elvin Kabat (1914-2000) Gamma-globulin in the serum Antibodies They are present in the different body fluids – humoral immunity  History of immunology I.I. Mecsnyikov (1845-1916) discovery of natural immunity 1883 - the concept of cellular immunity 1884 – phagocytic cells - recognition of phagocytosis (macrophages)  History of immunology M. W. Chase (1905-2004) 1940s, Rockefeller University discovery of cellular immunity – investigation of the role of white blood cells as important components of the immune system in addition to antibodies → B and T cells transmissible immunity – white blood cells from immunized guinea-pigs 1850s – lymphocytes (humoral and cellular immunity)  History of immunology B. Glick (1927-2009) 1955 – testing of chickens → two types of lymphocytes T-lymphocytes – thymus – cellular immunity B-lymphocytes – bursa of Fabricius – humoral immunity J. Bordet (1870-1961) immune reaction to non-pathogenic substances (e.g. red blood cells from different species) complement system (1886)  History of immunology K. Landsteiner (1868-1943) Inoculation of animals with different organic materials → production of antibodies → bind specifically to chemical materials Human ABO blood group system (A, B, AB és 0) - Nobel-prize 1930 Other RBC antigens – M, N, P and Rh-factor Safe form of blood transfusion Identification of the causative agent of poliomyelitis; vaccine development Identification of the causative agent of syphilis Study of haptens – small changes in their structure affect the induction of antibody production  History of immunology Theories explaining antigen-antibody binding − antibodies – unlimited variability – reactogenicity even with previously unrecognized antigens − high specificity – recognition of very similar antigens as different 1. Selectivity theory – P. Ehrlich (1900) Receptor specificity is established before exposure to the antigen and the antigen "selects" the appropriate receptor; the specificity of receptors is predetermined; Revised in the 1960s 2. Instructional theory – F. Beinl & F Haurowitz (1930’s and 1940’s) Given antigen – template; the antibody wraps around the template and forms a complementary configuration  History of immunology Theories explaining antigen-antibody binding – clonal selection (N. Jerne, D. Talmage, M. Burnet; 1959) Membrane receptors on lymphocytes – antigen specific even prior to antigen exposure Antigen binding to specific receptor – cell activation Cell proliferation – the proliferation of a particular clone; identical immunological specificity  History of immunology 1906 C. von Pirquet – concept of allergy 1938 J. Marrack - antigen-antibody binding hypothesis 1942 J. Freund & K. McDermott – research on adjuvants 1949 M. Burnet & F. Fenner – immunotolerance hypothesis 1957 A. Isaacs & J. Lindemann – discovery of interferon 1962 R. Porter et al. – description of the structure of antibodies 1962 J. Miller and his working group - the role of thymus in cellular immunity 1962 N. Warner et al. – differences between cellular and humoral immune responses 1968 A. Davis et al. – T- and B-cells work together in immune function 1974 R. Zinkernagel & P. Doherty – MHC restriction description 1985 S. Tonegawa, L. Hood et al – identification of immunoglobulin genes 1987 L. Hood et al., - identification of genes for T-cell receptors since 1985 - identification of cells for immune response  Basic definitions − Tasks of the immune system – recognition of pathogens/dangerous structures → their destruction and neutralization − Pathogen-associated molecular pattern (PAMP) Gram-negative bacteria – LPS viruses with double-stranded RNA genome − Danger-associated molecular pattern (DAMP) injuries, abnormal processes → abnormal molecules − Pattern-recognition receptors (PRRs) − Antigen – specifically recognized by certain cells of the immune system Molecules of pathogens Abnormal own antigens immunogenic antigens tolerogenic antigens − Antigen receptors − Extracellular pathogens – direct attack by pathogens that have entered the body − Intracellular pathogens – destruction of infected own cells; tumor cells  Roles of immune system and its composition − Immune cells anywhere in the body In other tissues, e.g. epithelial tissue Grouped in immune tissues (mucous membranes or islets in the skin) Organized into immune organs – lymphoid organs − Primary/central lymphoid organs formation of white blood cells − Secondary/peripheral lymphoid organs first exposure of immune cells, B- and T- lymphocytes to the antigen - specific (adaptive) immune response providing the tissue environment necessary for activation, division, differentiation of lymphocytes  Primary lymphatic organs − Bone spongy matter – red bone marrow → site for blood cell formation – white blood cells (leukocytes − Hematopoietic stem cells → differentiation into specialized cell types, immunocompetent cells under the influence of cytokines − Development paths – precursors myeloid - macrophages, dendritic cells, mast cells, granulocytes lymphoid - B cells, T cells, NK cells − Primary lymphatic organs red bone marrow thymus formation and development of lymphocytes T-lymphocytes complete their development in the thymus there is no active – immunogenic – immune response, only the body's own antigens can meet the body's own antigens – its own, harmless antigens – tolerance – tolerogenic immunity on the periphery own antigens do not trigger an immune response  Bursa of Fabricius – primary lymphatic organ of birds, on the dorsal side of the cloaca, site of B-lymphocytes maturation Red bone marrow - spongy matter of bones, hematopoietic stem cells Thymus - flat, two-lobed organ behind the sternum - lobes separated by septums (connective tissue) - cortex – immature T cells (thymocytes) - medulla – few thymocytes; thymosin hormone production of immunocompetent T- cells - infancy and childhood; later atrophies, its place is occupied by adipose tissue  Secondary lymphatic organs − activation of the adaptive immune response − naive lymphocytes – move to the secondary lymphatic organs, where they recognize the specific antigen, they are activated and differentiate → functioning/effektor immune cells − blood – carriage of nutrients and oxygen to the tissues and cells → given components of the plasm are filtered into the tissues → metabolites from tissue cells, foreign antigens originating from different damages from the environment, microbes → antigen exposure (passive carriage of antigens) − lymphatic capillaries - they begin in tissues as closed-ended, glove finger-like pouches – this is where the intertissue fluid (lymph) collects – Transport of antigens with lymph to lymph nodes - filtration - larger lymphatic vessels − lymph nodes clusters in areas e.g. neck, armpits, abdomen or lumbar region B and T cell zones - lymphocytes can meet antigens here - appropriate receptors → recognition → intensive division of specific lymphocytes → the number of lymphocytes specific to a given antigen is multiplied non-specific lymphocytes that do not recognize the given antigen do not divide, leave the secondary immune organ and can be transferred to other secondary immune organs/immune tissues through lymphatic and blood circulation if they do not encounter a recognizable antigen within a few days/weeks, they die by apoptosis cortex – B-lymphocytes, macrophages, follicular dendritic cells paracortex – T-lymphocytes, interdigitizing (connecting) dendritic cells medulla – plasma cells  Secondary lymphatic organs − active transport of antigens – phagocytic cells (dendritic cells) to lymph nodes → presentation to T lymphocytes − spread of lymphocytes also through blood vessels – they enter the lymph node through the specially structured walls of blood vessels of lymph nodes, leaving it through the excretory lymphatic vessels; through the large collecting lymphatic vessels, they return to the venous circulation near the junction of the large veins of the right and left shoulder- neck region, and then they can reach secondary lymphatic organs/lymphatic tissues again − naïve lymphocytes cannot migrate to the site where pathogens enter, into the skin or mucous membranes, but if they have already encountered the antigen in secondary lymphatic organs or tissues and activated in the process, they can reach many other tissues as effector lymphocytes − various cells and circulating fluid can be exchanged between blood and lymphatic vessels in this way → the lymphatic system can effectively detect pathogens  Secondary lymphatic organs − Spleen flattened elongated organ in the left upper abdomen has no direct connection with lymphatic circulation Screening of blood – collection site of white blood cells – the immune system can come into contact with antigens in the blood − Lymphoid tissue clusters skin, mucus membranes - MALT (Mucosal- Associated Lymphoid Tissue) gastrointestinal tract – Peyer’s patches, appendix, GALT (Gut-Associated Lymphoid Tissue) airways – tonsils, adenoids, BALT (Bronchial/Tracheal Associated Lymphoid Tissue).  Secondary lymphatic organs/lymphatic tissues Primary lymphatic organs - e.g. the spleen, various lymph nodes, lymphatic tissues - bone marrow and thymus attached to the skin or mucous - this is where the cells of membranes of the intestine and the immune system are respiratory organs formed - sites of development of - tolerogenic response immunogenic immune response (tolerance) (mainly primary sites of adaptive response) - lymphocyte activation and differentiation into effector cells  Natural vs. acquired immunity NATURAL immune response or CONSTITUTIVE defence mechanisms - non-pathogen-specific – BUT specific to conservative molecular patterns present in all microorganisms - they do not require prior exposure to the pathogen to function - without latency, they are immediately effective - cellular and humoral components - no immune memory and long-term immunity ADAPTIVE immune response or SPECIFIC defence mechanisms - pathogen (Ag-) specific - prior exposure to the pathogen is necessary for their functioning; - effective after a certain latency period (primary immune response) - they are activated after antigen presentation - cellular and humoral components - immune memory and long-term immunity THANK YOU FOR YOUR ATTENTION!