DEFINITION AND PROPERTIES OF ANTIGEN IMMUNOLOGICAL DEFINITION Any chemical structure

1. DEFINITION AND PROPERTIES OF ANTIGEN IMMUNOLOGICAL DEFINITION Any chemical structure Soluble or corpuscle Simple or complex Originated from the body or comes from outside Genetically self or non-self Natural or artificial

2. DEFINITIONS • ANTIGEN(Ag) - any substance, which is recognizedby the mature immune system of a given organism • ANTIGENICITY– capability of an antigen to bind specifically with certain product of the adaptive immunity: TCR or BCR/antibody, • immunogenicity - capability of an antigen to induce an (adaptive) immune response, • tolerogenicity - capability to induce immunological tolerance, specific immune non-responsiveness

3. FACTORS INFLUENCING IMMUNOGENICITY I. • Foreignness • Size • Genetics • Species • Individual • Age • Dose • Route subcutaneous > intravenous > oral / intranasalNot true for live vaccines (i.e. oral polio vaccine)

4. FACTORS INFLUENCING IMMUNOGENICITY II. • Adjuvant (vaccination) • substances that enhance an immune response to an antigen(aluminum salts, LPS, Freund’s adjuvant, TLR ligands) • complex effects • depot effect – slowerbiodegradation,prolonged antigen intake by antigen presenting cells • activation of innate immunity • Physical status • corpuscle (cell, colloid) or soluble • denatured or native • Degradability • antigen presentation by APC

5. ANTIGENIC DETERMINANT (=EPITOPE) part of the antigen which isrecognized by a defined immunoglobulin(BCR / antibody) or by T cell receptor

6. Ig (antibody) BCR (mIg)

7. TYPES (STRUCTURE) OF ANTIGEN DETERMINANTS linear determinant conformational determinant (TCR, BCR, Ig) (BCR, Ig) conformational determinant Ab2 Ab1 surface/accessible determinants cleveage denaturation hidden/revealed determinant new/neoantigen determinant conformational/linear determinant

8. B cell epitope T cell epitope recognized by T cells • proteins mainly (8-23 amino acids) • requires processing by APC recognized by B cells • proteins polysaccharides lipids DNA steroids etc. (many artificial molecules) • cell or matrix associated or soluble

9. ANTIGEN RECOGNITION ≠ CELL ACTIVATION

10. ANTIGEN RECOGNITION BY NAIVE T CELLS REQUIRES PRESENTATION VIA MHC MOLECULES Recognition/ No activation Recognition/ Activation

11. SUPERANTIGENS Fever Microbial proteins that bind to and activate all the T cells that express a particular set or family of TCR molecules resulting in a polyclonal activation. Interaction is not via the peptide binding cleft of MHC molecule. Hypotension Rash Desquamation

12. superantigen conventional antigen polyclonal T cell response 1:4 - 1:10 SUPERANTIGENS Microbial proteins that bind to and activate all the T cells in an individual that express a particular set or family of TCR molecules monoclonal/oligoclonal T cell response 1:104 - 1:105 activated T cells 1010 / 1011 107 – 108 / 1011

13. SUPERANTIGENS .

14. MHCII T cell +peptide 1 B cell CD4 TCR 2 cytokines T CELL-DEPENDENT BCELL ACTIVATION Polysacharides are not presented!

15. B CELL ACTIVATION WITHOUT THE HELP OF T CELLS T-INDEPENDENT ANTIGEN TI-1 T-INDEPENDENT ANTIGEN TI-2 B cell Simultaneous activation of BCR and other receptors on B cells (i.e. LPS binding protein /CD14) induces the B cells to proliferate and differentiate Strong crosslinking of BCR by repetitive polysaccharide or protein epitopes B CELL ACTIVATION (extra activation signal) (extensive receptor-aggregation)

16. B CELL ACTIVATION WITHOUT THE HELP OF T CELLS

17. Microorganisms have several different cell surface epitopes

18. COMPLEX ANTIGENS CONSIST OF THE CARRIER AND MULTIPLE EPITOPES (=ANTIGEN DETERMINANTS) HAPTEN substance that is non-immunogenic but which can react with the products of a specific immune response. Haptens are small molecules which could never induce an immune response when administered by themselves but which can when coupled to a carrier molecule. Free haptens, however, can react with products of the immune response after such products have been elicited. Haptens have the property of antigenicity but not immunogenicity. Haptenic/antigen determinant (epitope) part of the antigen which are recognized by a defined immunoglobulin (B cell receptor or antibody) or by T cell receptor Carrierpart of the antigen directly not involved in connection with the defined Ig/BCR or TCR These terms can only be used to describe the interaction of particular antigenic determinant and single immunoglobulin or T cell receptor

19. Antibody response generated against a hapten-carrier conjugate carrier + hapten antibodies carrier specific hapten specific carrier +hapten specific

20. ACUTE INFLAMMATION AND ACUTE-PHASE RESPONSE

21. THE INFLAMMATORY RESPONSE

22. ACUTE INFLAMMATION • Acute inflammation is a rapid response to an injurious agent that servesto deliver mediators of host defense—leukocytes and plasma proteins—to the site of injury. • Vascular phase • Vasoconstrictionvasodilation • Increased permeability  edema, leakage of plasma proteins (acute phase proteins, antibodies) • Cellular phase • Migration of leukocites from the circulation to the site of inflammation

24. CAUSES LEADING TO ACUTE INFLAMMATORY REACTIONS: • Infections (pathogenic microbes and microbial toxins) • Trauma (blunt and penetrating) • Physical and chemical agents (thermal injury e.g. burns or frostbite; irradiation; some environmental chemicals) • Foreign bodies (splinters, dirt, sutures) • Immune reactions (hypersensitivity and autoimmune reactions)

25. The classic symptoms of inflammation: redness (rubor) - vasodilation, swelling (tumor) - edema, heat (calor) – increased perfusion, pain (dolor) – factors stimulating nociceptors, loss of function (functio laesa)

27. CHEMICAL MEDIATORS OF INFLAMMATION I. • Vasodilation • Prostaglandins (PG..), nitric oxide (NO) • Increased vascular permeability • vasoactive amines (histamine, serotonin), C3a and C5a, bradykinin, leukotrienes (LT..), PAF • Chemotaxic leukocyte activation • C3a, C5a, LTB4, chemokines

28. CHEMICAL MEDIATORS OF INFLAMMATION II. • Fever • IL-1, IL-6, TNF, prostaglandins • Pain • prostaglandins, bradykinin • Tissue damage • neutrophil and macrophage products • lysosomal enzymes • oxygen radicals • nitric oxide (NO)

29. MIGRATION OF NEUTROPHILS FROM BLOOD TO INFLAMMED TISSUE

30. MIGRATION OF NEUTROPHILS

31. Neutrophil Transendothelial Migration (Diapedesis)

32. ENDOTHELIAL ADHESION MOLECULES DURING INFLAMMATION

33. PUS Pus is a whitish-yellow, yellow, or yellow-brown exudate produced by vertebrates during inflammatory pyogenic bacterial infections. Pus consists of a thin, protein-rich fluid, known as liquor puris, and dead cells.

34. CONSEQUENCES OF MACROPHAGE ACTIVATION SYNTHESIS OF CYTOKINES

35. ACUTE-PHASE REACTION proinflammatory cytokines hypothalamic control of body temperature increased ‚set-point’ value fever

36. ACUTE PHASE REACTION IL-6 Complement Liver C-reactive protein (CRP) Mannose binding lectin/protein MBL/MBP Fibrinogen Serum amyloid protein (SAP) UNDER THE INFLUENCE OF IL-6 THE LIVER PRODUCES A BUNCH OF ACUTE-PHASE PROTEINS

37. ACUTE-PHASE RESPONSE

38. RESOLUTION OF ACUTE INFLAMMATION

39. SEPTIC SHOCK Triggering factors: • systemic infection (bacteraemia) • microbial cell wall products and/or toxins released from the pathogens Result: Systemic activation of neutrophilsandmacrophages  High level of cytokine (TNF-alpha) production: „cytokine storm”  Excessive inflammatory response

40. SEPTIC SHOCK The key molecule of the process: TNF-alpha TNF-alpha and other inflammatory cytokines DIC capillar permeability blood pressure high fever multiorgan failure disseminated intravascular coagulation Therapy: anti-TNF-alpha antibody

41. DICDisseminatedIntravascularCoagulation • pathologic activation of thrombotic process • distress of thrombotic process, bleeding • other causes: snake bite, septic abortion, acute obstetric complications, malignant tumors, leukemias

42. DIC: Disseminated Intravascular Coagulation