The document discusses nonspecific defense mechanisms, which provide immediate protection against pathogens as the first line of defense. It describes various physical and chemical barriers that block pathogen entry like the skin and mucous membranes. It also outlines cellular defenses such as phagocytes that engulf and destroy pathogens. Additionally, it examines soluble factors like complement proteins, lysozyme, and interferons that directly kill microbes or enhance immune responses.

1. Immunology Nonspecific defense

2. Definition of immunity (Mechnikov, 1903) Immunity is a possibility of organism to remain healthy after agent of disease penetration

3. Definition of immunity (Petrov, 1976 ) Immunity is a way of organism defense against alive agents and substances that are genetically foreign. It realizes by specific immune system

4. Resistance For species For individual Nonspecific (innate) Specific (acquired) Barriers and physiological factors Cell factors Chemical factors

5. Features of nonspecific defense The most ancient according to evolution Act again all of the most foreign antigens Immediate action (without latent period) Specific immune reactions is realized through nonspecific factors

6. The second line of defense The first line of defense includes any barrier that blocks invasion at the portal of entry.

7. The second line of defense The second line of defense is a slightly more internalized system of protective cells and fluids that includes inflammation and phagocytosis .

8. The third line of defense The third line of defense is specific immune factors ( antibodies and T-lymphocytes )

9. Factors of nonspecific defense Physical and anatomical barriers Skin (flora and bactericidal chemicals) Mucous membrane (flora and bactericidal chemicals) Chemical defenses Complement Lysozyme Interferons Cellular defenses Phagocytes Microphages Macrophages Natural cell-killers

10. Physical and anatomical barriers at the body’s surface, chemical defense Mechanical barrier of intact skin Excretion function of organism Ciliated epithelium Sneeze, coughing Lysozyme in tears and saliva High lactic acid of sweat Skin’s acidic pH and fatty acid Hydrochloric acid in the stomach Intestine’s digestive juices

11. The ciliary defense of the respiratory tree Cilia

12. The role of normal flora in human organism Antagonism. Inhibition of growth of potentially pathogenic microorganisms Stimulation of the immune system Producing of essential nutrient as vitamins (K, E, B) Normal flora of the digestive tract are essential for degrading cellulose

13. Cells that take part in immune response Participate in immunological responce In lymphoid tissues; also in the circulation Lympho-cytes Phagocytosis and digestion of engulfed materials, can participate in killing foreign cells that are not engulfed MPh present in all tissues and in of vessels, monocytes are less mature circulation form Monocyte, macrophage Mononuclear phagocytes Phagocytosis and digestion of engulfed materials Most in circulation, few in tissues Neutrophils Participate in inflammatory reaction More are in circulation, few in tissues Eosinophil Release histamine and other mediators of inflammation Basophils in circulation; mast cells present in most tissues Basophil Granulosytes Functions Location in body Cell type

14. Stages of phagocytosis Activation Chemotaxis Adsorbtion Ingestion Phagolysosome formation Destruction Excretion

15. Opsonization of microbial cell surface Immunoglobulin wear Cell wall Opsonins Immunoglobulins Activated C3b component of complement Fibrinolysin Leukotriens Surfactants C-reactive protein

16. Macrophages attacking bacteria and yeast

17. Phagocytosis and intracellular digestion

18. Mechanisms of destruction of microorganisms in phagocytes Lysozyme Lactic acid Nitric oxid Lactoferrin Proteases Hydrolase Cationic protein Mieloperoxidase Halogen ions Hydrogen peroxide Superoxide anion (O 2 - ) Hydroxyl free radical (OH - ) The oxygen-independent system The oxygen-dependent system (“respiratory explosion”)

19. Types of phagocytosis Completed phagocytosis when microorganism is engulfed by phagocyte and ingested there Uncompleted phagocytosis when microorganism is not destroyed in phagocyte but can reproduce in it. Mechanisms of interference with destruction microorganisms in phagocyte: Capsule ( Streptococcus pneumoniae ) Protective proteins on bacterium surface ( Streptococcus pyogenes ) Coagulase production ( Staphylococcus aureus ) Rickettsia can escape the phagosome before it fuses with lisosome Mycobacterium tuberculosis changes the phagosome surface and thereby prevent it from fusing with the lysosome

20. Uncompleted phagocytosis of gonococci and meningococci

21. Effects of macrophages Phagocytosis that lead to distraction and elimination of microorganisms from organism Secretion of mediators Antigen-presentation IFN-  IFN- 

22. Definition of interferon Interferons are proteins that cause nonspecific activities and influent to cell metabolism, including RNA and protein synthesis. INFs are the most active in cell that organism where they were produced

23. Types of interferons Alpha interferon (  -IFN). Produced by lymphocytes and macrophages Beta interferon (  -IFN). Produced by fibroblasts and epithelial cells Gamma interferon (  -IFN). Produced by T-lymphocytes IFNs are a family of inducible glycoproteins produced by eukaryotic cells in response to viral infections and other microbial pathogens that reproduce within host cells.

24. Antiviral action of interferon 1. The binding of a virus to the receptors of an infected cell sends a signal into the cell nucleus that activates the genes coding for interferon. 2. Interferon is synthesized and secreted into the extracellular spaces . 3. IFN enters into uninfected cell and activates gene complex that code for another protein 4. This synthesized protein interfered with the multiplication of viruses.

25. Characteristic of human interferons + + + Activation of natural killer cells ++ - - Macrophage activation + +++ +++ Antiviral activity 20-25 kD 16-26 kD 16-26 kD Molecular mass - + + Resistance to рН 2,0 1 1 More then 20 Quantity of variants Antigens, mitogens Viruses, interferonogens Viruses, interferonogens Inductor γ - interferon β - interferon α - interferon Features

26. Effects of interferons Antiviral Antibacterial Against inflammation Antitumoral Immunomodulation (changing of immune response) Enhancing of macrophage activity

27. Pathways of complement activation. Inductors of activation Classical pathway Antigen-antibody complex (antibodies: IgM, IgG) Alternative pathway LPS of Gram-negative bacteria (lipid A) Teichoic acid of Gram-positive bacteria Fungal cell wall carbohydrates Viral envelope

28. The complement cascade. Classical scheme of activation

29. Electron micrograph of a cell reveals multiple puncture sites Puncture sites Enzyme complex

30. Complement proteins C5 C6 C7 C8 C9 Membrane attack components (common to both pathways) C1 C4 C2 C3 Properdin Factor D Factor D Factor C3b Mg Classical (initial portion) Rapid and efficient Alternative or properdin (initiatial portion) Slower and less efficient Components Pathway

31. Effects of complement activation Opsonization Cell lysis Inflammatory response Chemoattraction

32. Some important nonspecific antimicrobial factors Cell lysis, opsonization and chemotaxis Produced by macrophages, lymphocytes, and liver hepatocytes Complement system Interferes with the multiplication of viruses and bacteria; immune regulation Leukocytes and tissue cells Interferon Kills a variety of microorganisms; important within neutrophils Leukocytes, saliva, and other Peroxidase Attacks cytoplasmic membrane; active against Gram-positive bacteria Serum, leukocytes Beta-lysin Destroys bacterial cell walls Most body fluids; also within phagocytes Lysozyme Effects Source Factor