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Basics of Immunity

Basics of Immunity. Assoc. Prof. Edyta Mądry MD.PhD Department of Physiology Poznań University of Medical Sciences. Innate defense. The innate immune response is the first line of defense against invading microorganisms.

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Basics of Immunity

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  1. Basics of Immunity Assoc. Prof. Edyta Mądry MD.PhD Department of Physiology Poznań University of Medical Sciences

  2. Innate defense The innate immune response is the first line of defense against invading microorganisms. This system is not specific for a given pathogen, but can aid in the induction of cell-mediated immunity (antibody and specific killer cells).

  3. Nonspecific Body Defenses 1. Physical Barriers -Mechanical (skin, mucus, cilia in respiratory tract, sebum, cerumen ( earwax) ) 2. Chemical Barriers (low pH – stomach, vagina, genito-urinary tract, sweat/ high pH –small intestinal juice 3.Others: vomiting, diarrhea, sneezing, coughing

  4. Nonspecific Defenses • Phagocytes (eg. macrophages) • Complement • Fever • Inflammation • NK cells • Lysozyme • Interferons

  5. Innate defense

  6. Lysozyme Lysozyme protects us from the ever-present danger of bacterial infection. It is a small enzyme that attacks the cell walls of bacteria. Lysozyme breaks the carbohydrate chains of bacterial walls, destroying their structural integrity. The bacteria burst under their own internal pressure. • tears • mucus • blood • salive • urine

  7. IFN-alpha-is made by almost all type of cell infected with virus( fibroblsts are the principal source of INFα) INFα recently is used in treatment:AIDS,hair cell leucemia, hepatitis B and hepatitis C IFN-beta treats autoimmune disease: multiple sclerosis. INF-gamma-produced by activated T-lymphocytes and NK cells.Currently is used to treat chronic granulomatous disease and rare hereditary disease of blood Interferons Interferon alpha

  8. Interferons

  9. Inflammation • Bodies response to tissue injury • Classic signs • Heat • Redness • Swelling • Pain • Impairment of function

  10. Skin Blood

  11. Tissue Damaged

  12. Histamine Released

  13. Plasma Leaks Out Capillary More Permeable

  14. Antibodies Leaks Out Capillary More Permeable

  15. WBCs Leave by Diapedesis Capillary More Permeable

  16. Wall of Fibrin Forms

  17. Pus Forms

  18. Complement

  19. Complement- Membrane Attack Complex Aftercleavage by the C5 convertase, C5b islooselymembrane associated. Additionalinteractionwith C6 and C7 leads to theformation of a complexthatcan insert itselfinto a cell's lipid bylayer. When C8 associates, thecomplexiscapable of initiating lysis, but furtherassoicationwith C9 isrequired for fullMAC (membraneattackcomplex) generation. Fourmolecules of C9 conferfulllyticactivity, but as many as 15 canassociate to make largerpores. Theanimationbelowdemonstrateshowthisporeformation works.

  20. Complement- Activation by a Pathogen An invadingbacteriainitiatesthecomplementresponse. The C3bBb3b complexisthe C5a convertase; an enzymethatisable to cleave C5 to C5a and C5b.

  21. Complement A critical byproduct of complement fixation is the C5a peptide. This small protein has a large number of functions and its receptor is expressed in many different cell types. Since it is an enzyme, the C5 convertase complex continually cleaves C5 to C5a, increasing a concentration gradient. The concentration of C5a is highest near the area of production, decreasing farther from this region. This gradient can lead to the chemotactic migration of immune effector cells including macrophages, which can then kill bacteria and initiate an immune response.

  22. Complement-macrophage migration to C5a After the C5 convertase cleaves C5 to C5a and C5b, the C5a protein diffuses away from the production area to set up a concentration gradient. Different cell types including macrophages, neutrophils and mast cells can recognize this gradient and "crawl" toward the area of activation. .

  23. Complement -Tissue specific cell migration Aftermigrating to thearea of C5a production, themacrophagescanthenphagocytizetheoffendingmicroorganism. Atthat point, thecellmust make a choice. "Do I stay and findsomemoregoodies to eat?" OR "Do I move out of thisarea, become a professionalantigenpresentingcell(dendriticcell), and go to a locallymphnode?”

  24. Complement

  25. Lymphatic System Capillaries

  26. Functions of Lymphatic System • Drain fluid from around cells • Absorb fat from intestines • Circulate lymph • Filter lymph • Immunity

  27. Thoracic Duct Right Lymphatic Duct Lymphatic System

  28. Lymphatic organs -Lymph Nodes • Filter lymph • Microorganisms • Cancer cells • Lymphocytes • Monocytes

  29. Lymphatic organs - Thymus • Programs some lymphocytes to develop into T-cells

  30. Lymphatic organs -Spleen • Filters blood • Worn out RBC • Bacteria • Lymphocytes • Monocytes

  31. Lymphatic organs - Bone Marrow T Cells B Cells

  32. Lymphatic organs – GALT70% of human lymphocytes is localized in GALT

  33. Binding sites Antigenic determinants Antibodies are made by B cells; basic unit : 2 identical light chains; 2 identical heavy chains; stabilized and linked by disulfide bonds-form a Y-shaped molecule Each chain has constant and variable region; Agbinds to variable region on each arm. Light chains exist in 2 forms: kappa and lambda Heavy chains exist in 5 forms: alpha, gamma, delta, epsilon and mu. Fc of the haevy chains can bind complement and receptors on macrophages,monocytes, neutrophils and natural killer cells Light chain Hinge region Variable portion Disulfide bonds RCB Constant portion Carbohydrate Antigen A Heavy chain FcBinding site Antibody A Antigen-antibody complex (agglutinated RBC)

  34. IgG • The major immunoglobulin in normal blood (9-14 g/L), • 4 types, monomers • Can cross the epithelium and placenta, are secreted with mother’s milk • It contributes immunity against many kinds of pathogens, including bacteria, viruses, and fungi. • Distributed evenly between the blood and extravascular fluids. • After IgG1, IgG3 bind thebacteriatheyinitiatetheclassicalpathway of complementreaction • include anti-Rh antibodies

  35. IgM • primary importancein bacterial defense • initiate the classical pathway of complement activation • pentamer –consist of 5 monomers • can NOT cross the epithelium • always produce as 1st • antibodies of ABO system are IgM immunoglobulins.

  36. Ig M – ALWAYS 1st,IgG indicates old infection (" Gfor Grandmother")

  37. IgA • Provides „mucosal immunity” • found in various secretions, such as mucus (respiratory and digestive tract),blood,saliva, milk ( COLOSTRUM !).tears, and fluids secreted into the genitourinary and digestivetracts. • IgA antibodies provide defense against pathogens that contact the body surface or are ingested or inhaled. • Monomer or dimer or trimar ( we discuss DIMERIC Ig A) • IgA does NOT activate the complement-has NOT properties to kill bacteria Function • They prevent bacteria to adhere to mucosa, they neutralize viruses and toxines

  38. IgE • 0.3x10-3 g/L (1000x more in people with allergy) • rarely are foundas free circulating antibodies but commonly are found on the surface of basophils and mast cellls of connective tissue (bind by Fc) • When engaged by an antigen, IgE stimulate basophils and mast cells to release histamine that mediate the allergic response. • important role in defense against parasites (worms) • are produced in tonsills, lymph nodes, mucosa of GI tract. • are involved directly in diseases characterized by hypersensitivity ( eg.asthma, hay fever)

  39. IgD • monomer • present on the plasma membranes of many circulating B-lymphocytes • Involved in differentiation and development of plasma cells and memory cells from B-lymphocytes.

  40. AQUIRED vs. INNATE IMMUNITY 3 maincharacteristicsthatdifferaquired and innateimmunity: 1.MEMORY2. SPECIFISITY3. TIME DEPENANCE

  41. What we had on the board

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