ImmunologyImmunology
Nonspecific defense Nonspecific defense
Definition of immunity Definition of immunity (Mechnikov, 1903)(Mechnikov, 1903)
Immunity Immunity is a possibility of organism to is a possibility of organism to remain healthy after agent of disease remain healthy after agent of disease penetrationpenetration
Definition of immunity Definition of immunity (Petrov, (Petrov, 19761976))
Immunity Immunity is a way of organism defense is a way of organism defense against alive agents and substances that against alive agents and substances that are genetically foreign. It realizes by are genetically foreign. It realizes by specific immune system specific immune system
Resistance
For species For individual
Nonspecific (innate)
Specific (acquired)
Barriers and physiological
factors
Cell factors
Chemical factors
Features of nonspecific defense Features of nonspecific defense
The most ancient according to evolution The most ancient according to evolution Act again all of the most foreign antigensAct again all of the most foreign antigens Immediate action (without latent period)Immediate action (without latent period)Specific immune reactions is realized Specific immune reactions is realized
through nonspecific factors through nonspecific factors
The second line of defense The second line of defense
The first line of defense includes any barrier that blocks invasion at the portal of entry.
The second line of defenseThe 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.
The third line of defense The third line of defense
The third line of defense is specific immune factors
(antibodies and T-lymphocytes)
Factors of nonspecific defenseFactors of nonspecific defense Physical and anatomical barriersPhysical and anatomical barriers
Skin (flora and bactericidal chemicals)Skin (flora and bactericidal chemicals) Mucous membrane (flora and bactericidal chemicals)Mucous membrane (flora and bactericidal chemicals)
Chemical defensesChemical defenses Complement Complement Lysozyme Lysozyme Interferons Interferons
Cellular defenses Cellular defenses Phagocytes Phagocytes
Microphages Microphages Macrophages Macrophages
Natural cell-killers Natural cell-killers
Physical and anatomical barriers at the Physical and anatomical barriers at the body’s surface, chemical defense 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
The ciliary defense of the The ciliary defense of the respiratory treerespiratory tree
Cilia
The role of normal flora in human The role of normal flora in human organism organism
Antagonism. Inhibition of growth of potentially Antagonism. Inhibition of growth of potentially pathogenic microorganisms pathogenic microorganisms
Stimulation of the immune system Stimulation of the immune system Producing of essential nutrient as vitamins (K, E, Producing of essential nutrient as vitamins (K, E,
B)B) Normal flora of the digestive tract are essential for Normal flora of the digestive tract are essential for
degrading cellulose degrading cellulose
Cells that take part in immune Cells that take part in immune response response
Cell typeCell type Location in bodyLocation in body Functions Functions GranulosytesGranulosytesBasophilBasophil Basophils in circulation; mast Basophils in circulation; mast
cells present in most tissues cells present in most tissues Release histamine and other Release histamine and other mediators of inflammation mediators of inflammation
EosinophilEosinophil More are in circulation, few in More are in circulation, few in tissuestissues
Participate in inflammatory Participate in inflammatory reactionreaction
NeutrophilsNeutrophils Most in circulation, few in tissuesMost in circulation, few in tissues Phagocytosis and digestion of Phagocytosis and digestion of engulfed materialsengulfed materials
Mononuclear phagocytes Mononuclear phagocytes Monocyte, Monocyte, macrophagemacrophage
MPh present in all tissues and in MPh present in all tissues and in of vessels, monocytes are less of vessels, monocytes are less mature circulation formmature circulation form
Phagocytosis and digestion of Phagocytosis and digestion of engulfed materials, can participate engulfed materials, can participate in killing foreign cells that are not in killing foreign cells that are not engulfedengulfed
Lympho-Lympho-cytescytes
In lymphoid tissues; also in the In lymphoid tissues; also in the circulation circulation
Participate in immunological Participate in immunological responceresponce
Stages of phagocytosisStages of phagocytosis
Activation Activation ChemotaxisChemotaxisAdsorbtion Adsorbtion Ingestion Ingestion Phagolysosome formationPhagolysosome formationDestruction Destruction Excretion Excretion
Opsonization of microbial cell Opsonization of microbial cell surface surface
Immunoglobulin wear
Cell wall
Opsonins
Immunoglobulins
Activated C3b component of complement
Fibrinolysin
Leukotriens
Surfactants
C-reactive protein
Macrophages attacking bacteria Macrophages attacking bacteria and yeastand yeast
Phagocytosis and intracellular Phagocytosis and intracellular digestiondigestion
Mechanisms of destruction of Mechanisms of destruction of microorganisms in phagocytes microorganisms in phagocytes
The oxygen-dependent The oxygen-dependent system system (“respiratory explosion”)(“respiratory explosion”)
The oxygen-The oxygen-independent systemindependent system
Mieloperoxidase Mieloperoxidase
Halogen ionsHalogen ions
Hydrogen peroxideHydrogen peroxide
Superoxide anion (OSuperoxide anion (O22--))
Hydroxyl free radical (OH Hydroxyl free radical (OH --) )
Lysozyme Lysozyme
Lactic acid Lactic acid
Nitric oxid Nitric oxid
Lactoferrin Lactoferrin
Proteases Proteases
Hydrolase Hydrolase
Cationic proteinCationic protein
Types of phagocytosis Types of phagocytosis CompletedCompleted phagocytosis when microorganism is engulfed phagocytosis when microorganism is engulfed
by phagocyte and ingested thereby phagocyte and ingested there UncompletedUncompleted phagocytosis when microorganism is not phagocytosis when microorganism is not
destroyed in phagocyte but can reproduce in it. 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
Uncompleted phagocytosis of Uncompleted phagocytosis of gonococci and meningococcigonococci and meningococci
Effects of macrophages Effects of macrophages
Phagocytosis that lead to distraction and Phagocytosis that lead to distraction and elimination of microorganisms from organism elimination of microorganisms from organism
Secretion of mediators Secretion of mediators Antigen-presentationAntigen-presentation
IFN-
IFN-
Definition of interferonDefinition of interferon
InterferonsInterferons are proteins that cause are proteins that cause nonspecific activities and influent to cell nonspecific activities and influent to cell metabolism, including RNA and protein metabolism, including RNA and protein synthesis. INFs are the most active in cell synthesis. INFs are the most active in cell that organism where they were produced that organism where they were produced
Types of interferons Types of interferons
Alpha interferonAlpha interferon ( (-IFN).-IFN). Produced by Produced by
lymphocytes and macrophageslymphocytes and macrophages Beta interferonBeta interferon ( ( -IFN).-IFN). Produced by Produced by
fibroblasts and epithelial cellsfibroblasts and epithelial cellsGamma interferonGamma interferon ( ( -IFN).-IFN). Produced by T-Produced by T-
lymphocytes 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.
Antiviral action of interferon 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.
Characteristic of human interferons Characteristic of human interferons
Features Features αα--interferon interferon β β - - interferoninterferon γ γ - - interferoninterferon
Inductor Inductor Viruses, Viruses, interferonogensinterferonogens
Viruses, Viruses, interferonogensinterferonogens
Antigens, Antigens, mitogens mitogens
Quantity of variants Quantity of variants More then 20More then 20 11 11
Resistance toResistance to рН 2,0 рН 2,0 ++ ++ --
Molecular mass Molecular mass 16-26 16-26 kDkD 16-26 16-26 kDkD 20-25 20-25 kDkD
Antiviral activity Antiviral activity ++++++ ++++++ ++
Macrophage Macrophage activation activation
-- -- ++++
Activation of natural Activation of natural killer cellskiller cells
++ ++ ++
Effects of interferons Effects of interferons
Antiviral Antiviral Antibacterial Antibacterial Against inflammation Against inflammation Antitumoral Antitumoral Immunomodulation (changing of immune Immunomodulation (changing of immune
response)response)Enhancing of macrophage activity Enhancing of macrophage activity
Pathways of complement activation.Pathways of complement activation. Inductors of activationInductors of activation
Classical pathwayClassical pathway
Antigen-antibody Antigen-antibody complexcomplex
(antibodies: IgM, IgG)(antibodies: IgM, IgG)
Alternative pathwayAlternative pathway
LPS of Gram-negative LPS of Gram-negative bacteria (lipid A)bacteria (lipid A)
Teichoic acid of Gram-Teichoic acid of Gram-positive bacteriapositive bacteria
Fungal cell wall Fungal cell wall carbohydratescarbohydrates
Viral envelope Viral envelope
The complement cascade. The complement cascade. Classical scheme of activation Classical scheme of activation
Electron micrograph of a cell Electron micrograph of a cell reveals multiple puncture sitesreveals multiple puncture sites
Puncture sites
Enzyme complex
Complement proteinsComplement proteins
Pathway Pathway Components Components
Classical (initial portion)Classical (initial portion)
Rapid and efficientRapid and efficient
Alternative or properdin Alternative or properdin (initiatial portion)(initiatial portion)
Slower and less efficientSlower and less efficient
C1C1
C4C4
C2C2
C3C3
Properdin Properdin
Factor DFactor D
Factor DFactor D
Factor C3bFactor C3b
MgMg
C5
C6
C7
C8
C9
Membrane attack components (common to both pathways)
Effects of complement activationEffects of complement activation
Opsonization
Cell lysis
Inflammatory response
Chemoattraction
Some important nonspecific Some important nonspecific antimicrobial factorsantimicrobial factors
Factor Factor Source Source Effects Effects Lysozyme Lysozyme Most body fluids; also Most body fluids; also
within phagocyteswithin phagocytesDestroys bacterial cell wallsDestroys bacterial cell walls
Beta-lysinBeta-lysin Serum, leukocytesSerum, leukocytes Attacks cytoplasmic membrane; Attacks cytoplasmic membrane; active against Gram-positive bacteriaactive against Gram-positive bacteria
Peroxidase Peroxidase Leukocytes, saliva, Leukocytes, saliva, and other and other
Kills a variety of microorganisms; Kills a variety of microorganisms; important within neutrophilsimportant within neutrophils
Interferon Interferon Leukocytes and Leukocytes and tissue cellstissue cells
Interferes with the multiplication of Interferes with the multiplication of viruses and bacteria; immune viruses and bacteria; immune regulationregulation
Complement Complement systemsystem
Produced by Produced by macrophages, macrophages, lymphocytes, and lymphocytes, and liver hepatocytesliver hepatocytes
Cell lysis, opsonization and Cell lysis, opsonization and chemotaxischemotaxis