1. www.immunology.unideb.hu Downloads Login: student Password: download Downloading immunology lectures, seminars and practices from

2. CELLS AND MOLECULES OF THE IMMUNE SYSTEM

3. WHAT IS THE FUNCTION OF THE IMMUNE SYSTEM? How does it need to function? Is there room for failure? Immunodeficiencies!!! What about speed? What about specificity? What about flexibility? What about functional overlap?

4. Immunitas = exemption, protection Protection from / against what? Self or non-self substances? (What about the useful bacteria living together with us and what about tumors in this modell?) -„Danger model”: (Matzinger P., The danger model: a renewed sense of self. Science. 2002 Apr 12;296(5566):301-5.) -harmful self / harmless self -harmful non-self / harmless non-self factors! DANGER SIGNAL / NO DANGER SIGNAL -obligate pathogen (Mycobacterium tuberculosis) -facultative pathogen (Candida albicans, E. coli) -opportunistic pathogen (Pseudomonas aeruginosa)

5. Smallpox virus was declerad eradicated In 1979 by WHO VACCINATION IS A POWERFUL WEAPON AGAINST PATHOGENS AND PREVENTS EPIDEMICS

6. THE TWO ARMS OF THE IMMUNE SYSTEM Differentiation between harmless and harmful impacts DETECTION OF STRESS AND DANGER SIGNALS INNATE IMMUNITY Differentiation between self and non-self structures Antigen-specific recognition ADAPTIVE IMMUNITY Neutralization and elimination of foreign and harmful structures EXECUTIVE FUNCTIONS COORDINATED AND REGULATED ACTIONS INNATE IMMUNITY - immediate reaction - not antigen-specific - no memory ADAPTIVE IMMUNITY - developes in several days - specific - has memory Humoral immunity Cellular immunity communication

7. The innate and the aquired arm of the immune system works hand-in-hand to eliminate germs

8. Pathogens win the battle in the absence of either the innate or the adaptive arm of immunity

9. INNATE IMMUNE MECHANISMS ESTABLISH A STATE OF INFLAMMATION AT SITES OF INFECTION How do innate cells recognize bacteria and various other pathogens? Is the reaction specific?

10. Recognition of lipopolysaccharide by Toll-like receptor 4 (TLR4)

11. embryo: yolk sac, liver, spleen after birth:red bone marrow - epiphysis of cancellous long bones - flat bones (sternum, ribs, vertebras, hip bone) CONSTANT REGENERATION FAST REGENERATION INTENSE ADAPTATION THE SITES OF IMMUNE CELL PRODUCTION DURING DEVELOPMENT

12. IMMUNOCOMPETENT CELLS DERIVE FROM A COMMON HEMATOPOIETIC STEM CELL (HSC)

13. Plasma cell NK cell Tissue dendritic cell Mast cell Monocyte Macrophage Lymph node dendritic cell Resting lymphocyte FUNCTIONALLY DIFFERENT CELLS OF THE IMMUNE SYSTEM

14. MONOCYTES - origin: pluripotent cells of the bone marrow myeloid progenitors - size: 10-15um - nucleus: bean-shaped - localization: circulation out of circulation: macrophage TISSUE - VENTRICLE MACROPHAGES - phagocytic cells - antigen presenting cells (APC) -main types (based on tissue localization): a)microglia (brain) b)Kuppfer-cells (liver) c)histiocytes (connective tissue) d)osteoclasts (bone) e)alveolar macrophages (lung) - function: in cellular and humoral immun response

15. DENDRITIC CELLS -origin: myeloid or lymphoid progenitors -localization: the immatured dendritic cell migrates from the circulation into the tissues and upon pathogen uptake it differentiates to mature dendritic cell and migrates to the draining lymph nodes - antigen presenting cells (APC) -types : a) myeloid DCs: - Langerhans cells (mucosa, skin) - intersticial DCs (liver, spleen, etc.) b) lymphoid DCs: - thymic DCs - plasmacytoid DCs (pDC) Follicular DCs: stroma cells of the centrum germinativum of lymph nodes

16. BASOPHIL GRANULOCYTES NEUTROPHIL GRANULOCYTES EOSINOPHIL GRANULOCYTES - 0.1 - 1.5% of circulating leukocytes - large granules in the cytoplasm - nucleus with 2 lobes - mast cells, histamin, allergic reactions - high affinity IgE receptors - against parasites - highest number in blood (68% of circulating leukocytes, 99% of circulating granulocytes) - phagocyting cells - does not present in healthy tissues - tissue damage, migration, elimination of pathogens (enzymes, reactive oxygen intermediers) - main participants in acute inflammatory processes - against parasites - 0.1 - 5% of leukocytes - allergic reactions

17. MAST CELLS - origin: pluripotent cells of the bone marrow myeloid progenitors - localization: absent from circulation differentiate in tissues especially around small vessels - function: - upon activation they regulate the permeability of the vessels with their secreted molecules - native and adaptive immunity - allergic reactions (cell surface Fc  RI receptors) - main types: a) mucosal b) connective tissue

18. COMMON LYMPHOID PROGENITOR CELLS B lymphocyteT lymphocyte (Bursa fabricii) (thymus) maturation: begins in bone marrow continues in bone marrow continues in thymus differentiation: peripheral tissues plasma cells effector T cells - cytotoxic T cell - helper T cell antigen recognition without MHC molecules only via cell surface MHC molecules

19. origin: pluripotent cells of the bone marrow lymphoid progenitors maturation: bursa equivalent tissues (embrionic liver, later bone marrow) -localization: takes 5-10% of the circulating lymphocytes; migrate from the bone marrow to the secondary lymphatic organs thorugh the circulation - antigen presenting cells (APC) - activation: with antigens, via interaction with macrophages or T lymphocytes, lymphokines, cytokines - upon activation they differentiate to plasma cells or memory B cells B LYMPHOCYTES PLASMA CELLS -function: - antibody production - humoral immun response

20. - origin: pluripotent cells of the bone marrow lymphoid progenitors - maturation: thymus - localization: in the thymus the thymocytes mature into immunocompetent T cells and they enter to the peripheral (secunder) lymphoid organs as TCR expressing T lymphocytes - antigen recognition only via MHC molecules on the surface of APCs -types: - T helper (CD4+) - T cytotoxic (CD8+) - T regulator (suppressor) T LYMPHOCYTES

21. NK CELLS (natural killer) - origin: pluripotent cells of the bone marrow lymphoid progenitors - 5-10% in circulation - bigger than lymphocytes - several granules in their cytoplasm - has no antigen binding receptors („null cells”) - participants of native immunity

22. Professional phagocytic cells macrophages neutrophyl granulocytes dendrtitic cells the phagocytosed cells or molecules may modify the functions of the cell phagocytosis followed by enzymatic degradation Professional antigen presenting cells macrophages B lymphocytes dendritic cells they express MHC II molecules the protein degradation products (peptides) can be presented to T lymphocytes by MHC molecules

23. WHITE BLOOD CELLS IN THE SMEAR OF HUMAN PERIPHERAL BLOOD LYMPHOCYTE LYMPHOCYTE MONOCYTE neutrophil granulocyte basophil granulocyte neutrophil granulocyte eosinophil granulocyte

24. DISTRIBUTION OF BLOOD CELLS AND LYMPHOCYTE SUBTYPES PercentageCell number/L WHITE BLOOD CELLS leukocytes 4.8 – 10.8 x 10 9 neutrophil granulocytes 40 – 741.9 – 8 x 10 9 eosinophil granulocytes 0.1 – 50.01 – 0.6 x 10 9 basophil granulocytes 0.l – 1.50.01 – 0.2 x 10 9 lymphocytes 19 – 410.9 – 4.4 x 10 9 monocytes 3.4 – 90.16 – 0.9 x 10 9 RED BLOOD CELLS erythrocytes 4.2 – 6.1 x 10 12 PLATELETS thrombocytes 150-400 x 10 9

25. LYMPHOID ORGANS Primer lymphoid organs: bone marrow thymus Secunder lymphoid organs: lymph node spleen tonsils MALT (Mucosal-Associated Lymphoid Tissue) –GALT (Gut-Associated Lymphoid Tissue) –BALT (Bronchus-Associated Lymphoid Tissue)

26. MOLECULES OF THE IMMUNE SYSTEM Cell surface molecules: markers (CD) receptors (BCR, TCR, MHCI, MHCII, PRR, cytokine, etc.) costimulatory molecules adhesion molecules (integrins, selectins, mucins, etc.) Soluble molecules: cytokines antibodies complements metabolites

27. RECOGNITION OF PATHOGENS BY THE INNATE ARM OF THE IMMUNE SYSTEM

28. THE MAIN TYPES OF CELL SURFACE MOLECULES PARTICIPATING IN ANTIGEN RECOGNITION AND THE INTERACTION BETWEEN DENDRITIC CELLS AND T CELLS

29. SOLUBLE MOLECULES In plasma and other fluids plasma:90% H 2 O 10% dry material:90% organic material 10% inorganic material organic material: carbohydrate (glucose) lipid (cholesterol, triglyceride, phospholipid, lecithin, fat) protein (globulin, albumin, fibrinogen) glycoprotein hormon (gonadotropin, erythropoietin, thrombopoietin) amino acids vitamins inorganic material:minerals in ionic, water-soluble forms BIOACTIVE MOLECULES, THEY INFLUENCE THE ACTIVITY AND FUNCTION OF THE IMMUNE SYSTEM

30. cytokines chemokines interleukines monokines limphokines Nomenclature is based mainly on the producing cell type