Bohomolets Microbiology Lecture #9

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