Lecture 5 Infectious process. Non-specific host defence. Immunity. Immune system. - презентация

1 Lecture 5 Infectious process. Non-specific host defence. Immunity. Immune system.

2 Lecture 5 Infectious process. Non-specific host defence. Immunity. Immune system.

3 What Is Infection? Our environment is full of microorganisms (microscopic organisms) referred to as microbes (bacteria, fungi, protozoa and viruses). Microbes that are capable of causing disease (ie., pathogenic) are called pathogens/the infectious or causative agent. The interaction between the pathogen microorganism, the environment and the host is defined as infectious disease process. If a pathogen invades the body and the conditions are favorable for it to multiply and cause injurious effects or disease, the resulting condition is called an infection.

4 Infectious process The process may be thought of as a circular chain with six links. The following story illustrates the chain.

5 Horton & Parker: Informed Infection Control Practice I. Chain of Infection

6 Horton & Parker: Informed Infection Control Practice I. Chain of Infection

7 I. Microorganisms Normal Flora Normal Flora Pathogens Pathogens Opportunistic Pathogens Opportunistic Pathogens Brady; Paramedic Care Principles & Practice

8 Types of microbes causing infectious disease Type Branch Cellular? Genome Nuclear Example (Kingdom) membrane? Metazoan Eucarya yes DNA yes Ascaris parasites (Animalia) lumbricoides Protozoan Eucarya yes DNA yes Plasmodium parasites (Protista) falciparum Fungi/ Eucarya yes DNA yes Candida yeasts (Fungi) albicans Bacteria Eubacteria yes DNA no Streptococcus (not Archaea) pyogenes Viruses no DNA/RNA no Herpes simplex Prions no no genes no BSE (Mad Cow Disease)

9 Phylogenetic Classification of Bacteria Oxford Textbook of Medicine

10 Phylogenetic Classification of Viruses Oxford Textbook of Medicine

11 Mabbott & MacPherson, Nat Rev Microbiol 2006 Prions

12 Two basic types of pathogens - exogenous pathogen - aggressive pathogen, requires acquired immunity for host defense - opportunistic (endogenous) pathogen - becomes a pathogen when host is compromised damage to epithelium introduction of bacteria to sites where they are not normal flora - linked to presence of foreign body, catheters, biofilms disruption of normal flora by antibiotics suppression of immune system by drugs insufficient host defenses due to infection

13 Horton & Parker: Informed Infection Control Practice II. Chain of Infection

14 A host that carries a pathogen without injury to itself and serves as a source of infection for other host organisms. Reservoir of infection – ecological niche where the infectious agent survives and multiplies ex. person, animal, arthropod, soil, or substance (asymptomatic infective carriers) Reservoirs

15 Humans {hepatitis} Other Vertebrates {antrax, pesta} Birds & Bats {chlamidia, leptospirosis} soil, or substance {tetania} NOT vectors Reservoirs, examples

16 Horton & Parker: Informed Infection Control Practice III. Chain of Infection

17 Portal of exit Portal of exit - the route by which the disease agent may escape from the human or animal reservoir. While many disease agents have only one portal of exit, others may leave by various portals. The portals most commonly associated with human and animal diseases are: Respiratory Genitourinary Gastrointestinal Skin Superficial lesions Percutaneous Transplacental

18 Respiratory:

19 the route of many disease agents that cause respiratory illnesses such as common cold, influenza, and tuberculosis. the route used by many childhood vaccine-preventable diseases (measles, mumps, rubella, pertussis, Haemophilus influenzae type b (Hib) and pneumococcal disease). the most important portal, but the most difficult to control.

20 Genitourinary:

21 This portal of exit is the route of sexually transmitted diseases, including syphilis, gonorrhea, chlamydia, HIV. Schistosomiasis, a parasitic disease and leptospirosis, a bacterial infection, are both spread through urine released into the environment.

22 Gastrointestinal:

23 Examples include: Hepatitis A Salmonella, including typhoid Shigella Cholera Giardia Campylobacter In general, enteric diseases may be controlled through good hygiene, proper food preparation and sanitary sewage disposal.

24 Skin:

25 Skin may serve as a portal of exit through superficial lesions or through percutaneous penetration. Superficial skin lesions that produce infectious discharges are found in smallpox, varicella (chickenpox), syphilis, and impetigo. Percutaneous exit occurs through mosquito bites (malaria, West Nile virus) or through the use of needles (hepatitis B and C, HIV).

26 Transplacental:

27 This portal of exit from mother to fetus is important in the transmission of: rubella, HIV, syphilis, and cytomegalovirus (the most common infectious cause of developmental disabilities). It is, fortunately, not a factor for most diseases.

28 Some Pathogens that cross the Placenta

29 Horton & Parker: Informed Infection Control Practice IV. Chain of Infection

30 Mode/means of transmission A mode of transmission is necessary to bridge the gap between the portal of exit from the reservoir and the portal of entry into the host. The two basic modes are: direct indirect

31 Direct transmission occurs more or less immediately. Many diseases are transmitted by direct contact with human, animal or environmental reservoir. Ex. sexually transmitted diseases and enteric diseases such as shigella, giardia and campylobacter. Ex. contact with soil - mycotic (fungal) diseases. Droplet spread is also considered direct transmission. Infectious aerosols produced by coughing or sneezing can transmit infection directly to susceptible people up to 2 m.

32 Indirect transmission May occur through: 1. animate or 2. inanimate mechanisms. Animate mechanisms involve vectors. Ex. flies may transmit infectious agents such as shigella in a purely mechanical way, by walking on feces and then on food. Ex. mosquitoes, ticks or fleas may serve as reservoirs for the growth and multiplication of agents in malaria or Lyme disease.

33 Arthropod Vectors Pathogen - Vector Viruses (Arbovirus) - Mosquitoes Bacteria (Yersinia) - Fleas Bacteria (Borrelia) - Ticks Rickettsias (R. prowazeki) - Lice, ticks Protozoa (Plasmodium) - Mosquitoes Protozoa (Trypanozoma) -Tsetse flies Helminths (Onchocerca) - Simulium flies

34 Inanimate mechanisms: involve environmental vehicles, including objects, food, water, milk, or biological products. Ex. Food - salmonella infections. Water - cholera outbreaks. Surgical instruments and implanted medical devices - staphylococcal infections.

35 Modes of Disease Transmission

36 Horton & Parker: Informed Infection Control Practice V. Chain of Infection

37 Portal of entry The portal of entry into the host is usually the same as the portal of exit from the reservoir. In some diseases, however, the exit and entry portals may differ. Ex.: staphylococcal bacteria may escape from one persons respiratory tract to infect another persons skin lesion. If that person is a foodhandler, the staphylococcal bacteria may escape from the infected skin lesion, contaminate food where it can incubate, and cause food poisoning in people eating the food.

38 Horton & Parker: Informed Infection Control Practice VI. Chain of Infection

39 Susceptible Host The last essential component in the chain of infection is the susceptible host. A person who cannot resist a microorganism invading the body, multiplying, and resulting in infection. Susceptibility is affected by: Genetic factors Non-specific defence Specific acquired immunity

40 Genetic factors The role of genetic factors in susceptibility to infectious diseases is not yet well understood. Genes do seem to play a role in the progression of HIV disease, and perhaps in individuals susceptibility to meningococcal meningitis are described.

41 Host defense factors Intact skin and mucous membranes help us resist disease. So do the gastric acid in our stomachs, the cilia in our respiratory tracts and the cough reflex.

42 Specific acquired immunity This immunity is specific to a particular disease agent, and it may be acquired naturally or artificially

43 Summarize – 6 chains of infection Infectious agent Reservoir Portals of exit Means of transmission Portal of entry Susceptible host

44 Horton & Parker: Informed Infection Control Practice REVIEW - Chain of Infection

45 The Infectious Disease Spectrum The impact of disease agents on human host populations is very different. If a large number of individuals are equally exposed to an infectious agent, they do not all respond in the same manner. It may be a broad range of responses.

46 No infection Clinical Sub-clinical Carrier Death Carrier Immunity No immunity Outcome Exposure to Infectious Agents Infectious agents Host

47 Manifestations of infectious process (Infection spectrum) a. Clearance of pathogen b. Subclinical infection c. Clinical infection or apparent infection d. Carrier state - Health carrier - after subclinical infection - Convalescent carrier - after clinical infection - Incubatory carrier - before onset of diseases According to carrier time: - acute (transient) carrier - chronic carrier. a. Latent infection

48 Iceberg Concept of Infection

49 Clinical features of infectious disease Incubation period – the time between exposure to a pathogenic organism and when first symptoms apparent. Prodromal period – the time during which a disease process has begun but is not yet clinically manifest. May appear some prodromal symptoms. Period of apparent manifestation - the acute phase when specific symptoms appear. Convalescent period - during this time the body systems return to normal. Relapse - is the return of a disease after its apparent recovering. Recrudescence - the recurrence of symptoms after a temporary abatement. The distinction between a recrudescence and a relapse is the time interval. A recrudescence occurring after some days or weeks, a relapse after some weeks or months.

50 Dynamics of disease and infectiousness/contagiosity Latent periodInfectious period Contagious period Non-infectious period Incubation periodClinical diseaseRecovery Infection Time Onset of symptoms Resolution of symptoms

51 Common symptoms and signs Fever: Three stages: effervescence fastigium deffervescence Five kinds of fever: sustained fever, remittent fever, intermittent fever, relapsing fever, saddle type fever. And irregular fever

52 Common symptoms and signs Rash eruption Date of eruption chickenpox scarlet fever smallpox measles typhus typhoid fever Location of eruption Form of rash - Exanthema : maculo-papular rash petechia vesiculo-pustular rash urticaria - Enanthema

53 Common symptoms and signs Toxemic symptoms Mononuclear phagocyte system reactions Hepato-splenomegale Lymphonodus enlarged Clinical types acute, subacute, mild, common, severe, fulminate, typical, atypical, abortive.

54 Types of Diseases Diseases are given different names on the mode of their transmission, geographic area of distribution, or severity etc. 1. Communicable Diseases 2. Noncommunicable Diseases 3. Endemic Diseases 4. Epidemic Diseases 5. Pandemic Diseases 6. Other type of Diseases

55 Disease occurrence in populations Sporadic: occasional cases occurring at irregular intervals; Endemic: continuous occurrence at an expected frequency over a certain period of time and in a certain geographical location; Epidemic or outbreak: occurrence in a community or region of cases of an illness with a frequency clearly in excess of normal expectancy; Pandemic: epidemic involves several countries or continents, affecting a large population.

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57 Host Agent Environment Factors influencing disease transmission

58 Agent Host Environment Host defence Age, Sex Genotype Behaviour Nutritional status Health status Infectivity Pathogenicity Toxigenicity Virulence Immunogenicity Weather Housing Geography Occupational setting Air quality Food Factors influencing disease transmission:

59 Infectivity: Infectivity: Multiplication of an infectious agent within the body. Multiplication of an infectious agent within the body. Multiplication of the bacteria that are part of normal flora of gastrointestinal tract, skin, etc, is generally not considered an infection. Multiplication of the bacteria that are part of normal flora of gastrointestinal tract, skin, etc, is generally not considered an infection. On the other hand, multiplication of pathogenic bacteria (e.g. Salmonella species), even if the person is asymptomatic, is deemed an infection. On the other hand, multiplication of pathogenic bacteria (e.g. Salmonella species), even if the person is asymptomatic, is deemed an infection. Basic terms frequently used in describing aspects of pathogen agents:

60 Pathogenicity: Pathogenicity: The ability of an infectious agent to cause disease. The ability of an infectious agent to cause disease. Virulence: Virulence: The quantitative ability of an agent to cause disease. The quantitative ability of an agent to cause disease. Virulent agents cause disease when introduced into the host in small numbers. Virulent agents cause disease when introduced into the host in small numbers. Virulence involves invasiveness and toxigenicity. Virulence involves invasiveness and toxigenicity.

61 Toxigenicity: Toxigenicity: The ability of a microorganism to produce a toxin that contributes to the development of disease. The ability of a microorganism to produce a toxin that contributes to the development of disease. Invasion: Invasion: The process which bacteria, parasites, fungi and virusesenter the host cells or tissues and spread in the body. The process which bacteria, parasites, fungi and virusesenter the host cells or tissues and spread in the body. Basic terms frequently used in describing aspects of pathogenesis:

62 Bacterial virulence factors Many factors determine the virulence of bacteria, or their ability to cause infection and disease. Many factors determine the virulence of bacteria, or their ability to cause infection and disease. Toxins Toxins Enzymes Enzymes Antiphagocytic factors Antiphagocytic factors Adherence factors Adherence factors

63 Toxins Toxins produced by bacteria are generally classified into two groups: Toxins produced by bacteria are generally classified into two groups: Endotoxins Endotoxins Exotoxins Exotoxins

64 Endotoxins of gram-negative bacteria The endotoxins of gram-negative bacteria are complex lipopolysaccharides derived from bacterial cell walls and are often eliberated when the bacteria lyse. The endotoxins of gram-negative bacteria are complex lipopolysaccharides derived from bacterial cell walls and are often eliberated when the bacteria lyse. The substances are heat-stable and can be extracted (e.g. with phenol-water). The substances are heat-stable and can be extracted (e.g. with phenol-water). The presence of endotoxins in the blood is called endotoxemia. The presence of endotoxins in the blood is called endotoxemia. It can lead to septic shock, if the immune response is severely pronounced. It can lead to septic shock, if the immune response is severely pronounced.septic

65 Effects of endotoxins fever fever leukopenia leukopenia hypotension hypotension acidosis acidosis activation of C3 and complement cascade activation of C3 and complement cascade disseminated intravascular coagulation (DIC) disseminated intravascular coagulation (DIC) death death

66 Exotoxins Many gram-positive and gram-negative bacteria produce exotoxins of considerable medical importance. Many gram-positive and gram-negative bacteria produce exotoxins of considerable medical importance. Some of these toxins have had major role in world history (e.g. toxin of Clostridium tetani). Some of these toxins have had major role in world history (e.g. toxin of Clostridium tetani).

67 Exotoxin Excreted by a microorganism, including bacteria, fungi, algae, and protozoa. Can cause damage to the host by destroying cells or disrupting normal cellular metabolism. Exotoxin may be secreted, or may be released during lysis of the cell. Most exotoxins can be destroyed by heating. They may exert their effect locally or produce systemic effects. Exotoxins are susceptible to antibodies produced by the immune system, but many exotoxins are so toxic that they may be fatal to the host before the immune system has a chance to mount defenses against it. Well-known exotoxins include the botullinum toxin produced by Clostridium botulinum.

68 Ex. Botulotoxin ( toxin of Clostridium botulinum ) Clostridium botulinum is found in soil or water and may grow in foods if the environment is appropriately anaerobic. Clostridium botulinum is found in soil or water and may grow in foods if the environment is appropriately anaerobic. An exceedingly potent toxin (the most potent toxin known) is produced by Clostridium botulinum strains. It is heat-labile and is destroyed by sufficient heating. There are eight disctinct serological types of toxin. Types A, B and E are most commonly associated wih human disease. Toxin is absorbed from the gut and carried to motor nerves, where it blocks the release of acetylcholine at synapses and neuromuscular junctions. Muscle contraction does not occur, and paralysis results. An exceedingly potent toxin (the most potent toxin known) is produced by Clostridium botulinum strains. It is heat-labile and is destroyed by sufficient heating. There are eight disctinct serological types of toxin. Types A, B and E are most commonly associated wih human disease. Toxin is absorbed from the gut and carried to motor nerves, where it blocks the release of acetylcholine at synapses and neuromuscular junctions. Muscle contraction does not occur, and paralysis results.

69 Ex. Tetanospasmin ( toxin of Clostridium tetani ) Clostridium tetani is an anaerobic gram-positive rod that is widespread in the environment. Clostridium tetani is an anaerobic gram-positive rod that is widespread in the environment. Clostridium tetani contaminates wounds, and the spores germinate in the anaerobic environment of the devitalized tissue. The vegetative forms of Clostridium tetani produce toxin tetanospasmin. Clostridium tetani contaminates wounds, and the spores germinate in the anaerobic environment of the devitalized tissue. The vegetative forms of Clostridium tetani produce toxin tetanospasmin. Toxin reaches the central nervous system by retrograde transport along axons and through the systemic circulation. Toxin reaches the central nervous system by retrograde transport along axons and through the systemic circulation. The toxin acts by blocking release of an inhibitory mediator in motor neuron synapses. The result is initially localized then generalized, muscle spasms. Extremely small amount of toxin can be lethal for humans. The toxin acts by blocking release of an inhibitory mediator in motor neuron synapses. The result is initially localized then generalized, muscle spasms. Extremely small amount of toxin can be lethal for humans.

70 Ex. Streptococcal erythrogenic toxin Some strains of hemolytic lysogenic streptococci produce a toxin that results in a punctate maculopapular erythematous rash, as in scarlet fewer. Some strains of hemolytic lysogenic streptococci produce a toxin that results in a punctate maculopapular erythematous rash, as in scarlet fewer. Production of erythrogenic toxin is under the genetic control of temperate bacteriophage. If the phage is lost, the streptococi cannot produce toxin. Production of erythrogenic toxin is under the genetic control of temperate bacteriophage. If the phage is lost, the streptococi cannot produce toxin.

71 Ex. Toxic shock syndrom toxin - 1 (TSST-1) Some Staphylococcus aureus strains growing on mucous membranes (e.g. on the vagina in association with menstruation), or in wounds, elaborate TSST-1. Some Staphylococcus aureus strains growing on mucous membranes (e.g. on the vagina in association with menstruation), or in wounds, elaborate TSST-1. Although the toxin has been associated with toxic shock syndrome, the mechanism of action in unknown. Although the toxin has been associated with toxic shock syndrome, the mechanism of action in unknown. The illness is characterized by shock, high fever, and a diffuse red rash that later desquamates; multiple other organs systems are involved. The illness is characterized by shock, high fever, and a diffuse red rash that later desquamates; multiple other organs systems are involved.

72 Toxins associated with diarrheal diseases Vibrio cholerae toxin Vibrio cholerae toxin Staphylococcus aureus enterotoxin Staphylococcus aureus enterotoxin Other enterotoxins are also produced by some strains of: Other enterotoxins are also produced by some strains of: Yersinia enterocolitica Yersinia enterocolitica Vibrio parahaemolyticus Vibrio parahaemolyticus Aeromonas species Aeromonas species

73 Enzymes Many species of bacteria produce enzymes that are not intrinsically toxic but play important role in the infectious process. Many species of bacteria produce enzymes that are not intrinsically toxic but play important role in the infectious process. Collagenase: Collagenase: degrades collagen, the major protein of fibrous connective tissue, and degrades collagen, the major protein of fibrous connective tissue, and promotes spread of infection in tissue. promotes spread of infection in tissue. Coagulase: Coagulase: Staphylococccus aureus produce coagulase, which works in conjuction with serum factors to coagulate plasma. Staphylococccus aureus produce coagulase, which works in conjuction with serum factors to coagulate plasma. contributes to the formation of fibrin walls around staphylococcal lesions, which helps them persist in tissues. contributes to the formation of fibrin walls around staphylococcal lesions, which helps them persist in tissues.

74 Enzymes Hyaluronidases: Hyaluronidases: hydrolyze hyaluronic acid, a constituent of the ground substance of connective tissue hydrolyze hyaluronic acid, a constituent of the ground substance of connective tissue produced by many bacteria (e.g. staphylococci, streptococci and anaerobes) produced by many bacteria (e.g. staphylococci, streptococci and anaerobes) aid in their spread through tissues. aid in their spread through tissues. Streptokinase (fibrinolysin): Streptokinase (fibrinolysin): by many hemolytic streptococci, by many hemolytic streptococci, activates a proteolytic enzyme of plasma. activates a proteolytic enzyme of plasma. able to dissolve coagulated plasma and probably aids in the spread of streptococci through tissues. able to dissolve coagulated plasma and probably aids in the spread of streptococci through tissues. used in treatment of acute myocardial infarction to dissolve fibrin clots. used in treatment of acute myocardial infarction to dissolve fibrin clots.

75 Enzymes Hemolysins and leukocidins: Hemolysins and leukocidins: Many bacteria produce substances that are cytolysins - they dissolve red blood cells (hemolysins) or kill tissue cells or leukocytes (leukocidins). Many bacteria produce substances that are cytolysins - they dissolve red blood cells (hemolysins) or kill tissue cells or leukocytes (leukocidins). Streptolysin O, for example, is produced by group A streptococci and is letal for mice and hemolytic for red blood cells from many animals. Streptolysin O, for example, is produced by group A streptococci and is letal for mice and hemolytic for red blood cells from many animals.

76 Antiphagocytic factors Many bacterial pathogens are rapidly killed by polymorphonuclear cells or macrophages. Many bacterial pathogens are rapidly killed by polymorphonuclear cells or macrophages. Some pathogens evade phagocytosis by adsorbing normal host componets to their surfaces. Some pathogens evade phagocytosis by adsorbing normal host componets to their surfaces. For example, Staphylococcus aureus has surface protein A, which binds to the Fc portion of IgG. Other pathogens have surface factors that impede phagocytosis, e.g. Streptococcus pneumoniae and many other bacteria have polysaccharide capsules. For example, Staphylococcus aureus has surface protein A, which binds to the Fc portion of IgG. Other pathogens have surface factors that impede phagocytosis, e.g. Streptococcus pneumoniae and many other bacteria have polysaccharide capsules.

77 Adherence factors Once bacteria enter the body of the host, they must adhere to cells of a tissue surface. If they do not adhere, they would be swept away by mucus and other fluids that bathe the tissue surface. Once bacteria enter the body of the host, they must adhere to cells of a tissue surface. If they do not adhere, they would be swept away by mucus and other fluids that bathe the tissue surface. Adherence (which is only one step in the infectious process) is followed by development of microcolonies and subsequent complex steps in the pathogenesis of infection. Adherence (which is only one step in the infectious process) is followed by development of microcolonies and subsequent complex steps in the pathogenesis of infection.

78 Agent Host Environment Immunity Age, Sex, Genotype Behaviour Health status, Nutritional status Host defence Infectivity Pathogenicity Toxigenicity Virulence Immunogenicity Weather Housing Geography Occupational setting Air quality Food Factors influencing disease transmission

79 Lecture 5 Infectious process. Non-specific host defence. Immunity. Immune system.

80 The action of immune reaction of host in infectious process Non specific host-defence Specific immunity

81 HOST DEFENSE MECHANISMS

82 1st LINE OF DEFENSE - intact skin mucous membranes & their secretions 2nd LINE OF DEFENSE - phagocytic white blood cells inflammation-complement fever -interferon 3rd LINE OF DEFENSE- B & T lymphocytes specific antibodies nonspecific

83 1st LINE OF DEFENSE 1. PHYSICAL BARRIERS 2. CHEMICAL BARRIERS 3. GENETIC BARRIERS

84 PHYSICAL BARRIERS First line of defense are barriers that shield interior of body from external surroundings Anatomical barriers include skin and mucous membranes Provide physical separation Membranes bathed in antimicrobial secretions

85 PHYSICAL BARRIERS Physical barriers Skin is most visible barrier. Covers majority of surfaces in contact with environment. Mucous membranes barrier that lines digestive tract, respiratory tract and genitourinary tract Mucous protect these surfaces from infections.

86 Skin Provides the most difficult barrier to penetrate Composed of two main layers Dermis Contains tightly woven fibrous connective tissues Makes extremely tough Epidermis Composed of many layers of epithelial cells As cells reach surface, they become increasingly flat Outermost sheets of cells embedded with keratin Makes skin water-repellent Outer layers slough off taking microbes with it PHYSICAL BARRIERS

87 SKIN Dermis Inner thicker portion Epidermis Outer, thinner portion Keratin (waterproofing)

88 SKIN INFECTIONS Rare in unbroken skin Sweat washes microbes off Cuts and burns may get infected Subcutaneous infections Staphylococcus spp.

89 MUCOSAL MEMBRANE Epithelial layer Connective tissue Bronchi Intestine

90 MUCOSAL SURFACES (cont.) 1. Reproductive tract 2. Urinary tract 3. Gastrointestinal tract 4. Respiratory tract 12 43

91 PHYSICAL BARRIERS Mucous membranes Constantly bathed with mucus Helps wash surfaces Some mucous membranes have mechanisms to propel microorganisms and viruses to areas where they can be eliminated

92 MUCOSAL SURFACES (cont.) Mucosal irritation or damage facilitates infection (smoking) Substances produced by pathogens Treponema pallidum

93 CHEMICAL BARRIERS Sebaceous secretions Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tears High lactic acid & electrolyte concentration in sweat

94 CHEMICAL BARRIERS Skins acidic pH Hydrochloric acid in stomach Digestive juices and bile of intestines Semen contains antimicrobial chemical Vagina has acidic pH

95 CHEMICAL FACTORS Skin Sebaceous glands Unsaturated fatty acids pH 3-5

96 Antimicrobial substances Both skin and mucous membranes are protected by variety of antimicrobial substances including Lysozyme Enzymes that degrade peptioglycan Found in tears, saliva, blood and phagocytes Peroxidase Found in saliva, body tissues and phagocytes Breaks down hydrogen peroxide to produce reactive oxygen Lactoferrin Sequesters iron from microorganisms Iron essential for microbial growth Found in saliva, some phagocytes, blood and tissue fluids Defensins Antimicrobial peptides inserted into microbial membrane Found on mucous membranes and in phagocytes SPECIALIZED CHEMICAL BARRIERS

97 Enzyme that degrades peptidoglycans Gram + are more susceptible than Gram - Secreted in Sweat Saliva Tears Nasal secretions LYSOZYME

98 GASTRIC JUICE Hydrochloric acid (pH 1.2 to 3) Helicobacter pylori Neutralizes acidic pH Enzymes Mucus

99 Normal flora Defined as microorganisms found growing on body surfaces of healthy individuals Not technically part of immune system However, provides significant protection Protects through competitive exclusion Covers binding sites Pathogens cant bind Competes for nutrients Nutrients unavailable for pathogens NORMAL FLORA

100 GENETIC IMMUNITY Some hosts are genetically immune to the diseases of other hosts. Some pathogens have great specificity. Some genetic differences exist in susceptibility.

101 1st LINE OF DEFENSE - intact skin mucous membranes & their secretions 2nd LINE OF DEFENSE - phagocytic white blood cells inflammation-complement fever -interferon 3rd LINE OF DEFENSE- B & T lymphocytes specific antibodies nonspecific

102 2nd LINE OF DEFENSE

103 A HEALTHY IMMUNE SYSTEM IS RESPONSIBLE FOR: 1. Recognition of foreign material 1. Surveillance of the body 1. Destruction of foreign entities

104 SYSTEMS INVOLVED IN IMMUNE DEFENSE The reticuloendothelial system The blood The lymphatic system The extracellular fluids (ECF) - spaces surrounding tissue cells

105 SYSTEMS INVOLVED IN IMMUNE DEFENSE

106 RETICULOENDOTHELIAL SYSTEM This system is formed of reticular fiber which form a support network for each cell. This network connects one cell to another within a tissue or organ. Provides phagocytic white blood cell (WBC) the ability to move within and between tissues

107 CELLS OF THE IMMUNE SYSTEM Always found in normal blood Numbers increase during infection Some cells play dual roles in both innate and adaptive immunity Blood cell formation called hematopoiesis Blood cells including immune cells originate from hematopoietic stem cells in bone marrow Blood cells stimulated to differentiate by colony- stimulating factor

108 General categories of blood cells Red blood cells (RBC) erythrocytes carry oxygen in blood Platelets fragments of megakaryocytes important component in blood clotting White blood cells (WBC) leukocytes important in host defenses divided into four categories Granulocytes - Mononuclear phagocytes Dendritic cells- Lymphocytes CELLS OF THE IMMUNE SYSTEM

109 BLOOD CELLS

110 CELLS OF THE IMMUNE SYSTEM Granulocytes Contain cytoplasmic granules Divided into three types Neutrophils Basophils Eosinophils

111 CELLS OF THE IMMUNE SYSTEM Neutrophils Most abundant and important in innate response Sometimes called polymorphonuclear neutrophilic leukocytes (PMNs) Basophils Involved in allergic reaction Eosinophils Important in expelling parasitic worms Active in allergic reactions

112 CELLS OF THE IMMUNE SYSTEM Mononulcear phagocytes Constitute collection of phagocytic cells called mononuclear phagocyte system Include monocytes Circulate in blood Macrophages differentiate from monocytes Present in most tissues Abundant in liver, spleen, lymph nodes, lungs and peritoneal cavity

113 CELLS OF THE IMMUNE SYSTEM Dendritic cells Branched cells involved in adaptive immunity Function as scout in tissues Engulf material in tissue and bring it to cells of adaptive immunity

114 CELLS OF THE IMMUNE SYSTEM Lymphocytes Involved in adaptive immunity Two major groups B lymphocytes B cells T lymphocytes T cells Another type Natural killer Lacks specificity of B and T cells

115 LYMPHOCYTES

116 LEUKOCYTES Neutrophils % - lobed nuclei with lavender granules; phagocytes Eosinophils – 1-3% - orange granules & bilobed nucleus; destroy eucaryotic pathogens Basophils, mast cells – 0.5% constricted nuclei, dark blue granules; release potent chemical mediators Lymphocytes – 20-35% - large nucleus B & T cells involved in the specific immune response Monocytes, macrophages – 3-7%- large nucleus; phagocytic

117 CHARACTERISTICS OF LEUKOCYTES Diapedesis – migration of cells out of blood vessels into the tissues Chemotaxis – migration in response to specific chemicals which have passed through the 1 st line of defense

118 Chemotaxis Diapedesis

119 CHARACTERISTICS OF LEUKOCYTES Group 1 - Toll-like receptors and NOD proteins Found on variety of cells Recognize families of compounds Enable cells to sense invasion Send signal to body to respond

120 LYMPHATIC SYSTEM 1. Provides an auxiliary route for return of extracellular fluid to the circulatory system 1. Acts as a drain-off system for the inflammatory response 1. Renders surveillance, recognition, and protection against foreign material

121

122 LYMPHATIC FLUID Lymph is a plasmalike liquid carried by lymphatic circulation Formed when blood components move out of blood vessels into extracellular spaces Made up of water, dissolved salts, 2-5% proteins Transports white blood cells, fats, cellular debris & infectious agents

123 LYMPH NODES Small, encapsulated, bean-shaped organs stationed along lymphatic channels & large blood vessels of the thoracic and abdominal cavities Contains both T and B lymphocytes

124 RESULTS OF A MICROBE PASSING THE 2 ND LINE OF DEFENSE

125 In order for immune system to respond to trauma or invasion, cells must communicate with environment and with each other Cell surface receptors are the eyes and ears of the cell Cytokines are the voice Adhesion molecules act as the hands CELL COMMUNICATION

126 Surface receptors Membrane proteins to which signal molecules bind Receptors specific to molecule to which it bonds Binding molecules called ligands When ligand binds, receptor becomes modified and sends signal to cell Cell responds by initiating some action like chemotaxis CELL COMMUNICATION

127 Cytokines are proteins made by certain cells as a mechanism to communicate with other cells. Cytokines bind to surface receptors; and regulate cell function Binding of a cytokine to its receptor induces a change in the cell such as growth, differentiation, movement, or cell death. They can act locally, regionally, or systemically CELL COMMUNICATION

128 CYTOKINES Numerous cytokine classes Chemokines – important in chemotaxis Enhance ability of cells to migrate to appropriate site in body Colony stimulating factors – Important in multiplication and differentiation of leukocytes During immune response, directs immature leukocytes to correct maturation pathway Interferons – important in control of viral infections Also associated with inflammatory response Interleukins – produced by leukocytes Important in innate and adaptive immunity Tumor necrosis factor – kill tumor cells Instrumental in initiation of inflammation

129 Adhesion molecules Allow cells to adhere to each other Responsible for the recruitment of phagocytes to area of injury Causes phagocytes to slow and leak out of vessels to area of injury CELL COMMUNICATION

130 SENSOR SYSTEMS Systems within blood detect signs of tissue damage or microbial invasion Responds to patterns associated with danger by Directly destroying invading microbe Recruiting other host defenses

131 SENSOR SYSTEMS Toll-like receptors (TLR) and NOD proteins Pattern recognition receptors TLR allow cells to see molecules signifying presence of microbes outside the cell TLR found in variety of cell types Recognize distinct danger compounds Signal is transmitted Results in change of gene expression of cell NOD proteins are intracellular receptors that recognize bacterial cell wall components within cytoplasm

132 Complement system Series of proteins circulating in blood and fluids Circulate in inactive form Augment activities of adaptive immune response Stimulation of inactive proteins initiates cascade of reactions Results in rapid activation of components Complement system composed of nine proteins C1 – C9 Numbered as discovered, not order of activation Certain proteins split into a and b fragments after activation C3 can spontaneously split to C3a and C3b Insures enough C3b for activation of alternative pathway SENSOR SYSTEMS

133 Complement activation Three pathways of activation of the complement system Classical pathway Alternative pathway Lectin pathway

134 SENSOR SYSTEMS Classical pathway Activation requires antibodies Antibodies interact complement C1 Activates protein Leads to activation of all complex proteins

135 SENSOR SYSTEMS Alternative pathway Quickly and easily initiated Relies on binding of complement protein C3b to cell surface Initiates activation of other complement proteins Allows formation of complement complex C3b always circulating in blood so nearly any cell automatically triggers the pathway unless the bodys own cells stop the process

136 SENSOR SYSTEMS Lectin pathway Activation requires mannose/mannan-binding lectins (MBL) on host cells MBLs are pattern recognition molecules Detect mannane Polymer of mannose Found in microbial cells MBL attaches to surface of the microbe if mannan is present Activates complement proteins

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138 Activation of complement leads to major protective outcomes Inflammation Opsonization Lysis of foreign cells SENSOR SYSTEMS

139 Inflammation Complement components C3a and C5a induce changes in endothelial cells Effects vascular permeability associated with inflammation Opsonization C3b binds foreign material Allows phagocytes to easily grab particles

140 SENSOR SYSTEMS Lysis of foreign cells Complexes of C5b, C6, C7, C8 and multiple C9 spontaneously assemble Forms donut-shaped structure called membrane attack complex (MAC) Creates pores in membrane Most effective on Gram + Little effect on Gram + cells

141 ACTIVITIES OF PHAGOCYTES 1. To survey tissue compartments & discover microbes, particulate matter & dead or injured cells 1. To infest and eliminate these materials 1. To extract immunogenic information from foreign matter

142 PHASES OF PHAGOCYTOSIS

143 PHAGOCYTOSIS Process of phagocytosis Chemotaxis Cells recruited to infection Recognition/attachment Use receptors to bind invading microbes Engulfment Phagocyte engulfs invader forming phagosome Phagosome lysosome fusion Phagosome binds lysosome, forming phagolysosome Destruction and digestion Organism killed due to lack of oxygen and decreased pH Exocytosis Phagocyte expels material to external environment

144 INFLAMMATION STAGES OF INFLAMMATION 1.Blood vessels dilate in response to chemical mediators and cytokines. 1.Edema swells tissues, helping prevent spread of infection 3. WBCs, microbes, debris and fluid collect to form pus 4. Pyrogens may induce fever 5. Macrophages and neutrophils engage phagocytosis

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146 INFLAMMATION Inflammation occurs in response to tissue damage Four cardinal signs Heat Pain Redness Swelling Loss of function Fifth sign that can also be present

147 INFLAMMATION Factors that initiate inflammatory response Microbial products trigger toll-like receptors of macrophages Causes release of pro-inflammatory cytokines Microbial cell surface can trigger complement Leads to the production of C3a and C5a Tissue damage results in enzymatic cascade Cascades initiate inflammation

148 INFLAMMATION The inflammatory process Initiation leads to a cascade of events Results in dilation of blood vessels, leakage of fluid from vessels and migration of leukocytes and phagocytes Leakage of phagocytes from blood vessels called diapedesis Certain pro-inflammatory mediators cause the diameter of blood vessels to increase Results in increased blood flow Increased blood flow responsible for cardinal signs of inflammation

149 INFLAMMATION Outcomes of inflammation Intent is to limit damage and restore function Inflammation itself can cause considerable damage Release of toxic products and enzymes from phagocytic cells is responsible for tissue damage If inflammation is limited to area of injury, damage is usually nominal If inflammation results in delicate systems, consequences are more severe Inflammation around brain and spinal cord can lead to meningitis

150 FEVER One of the strongest indicators of infection Especially of bacterial infection Important host defense mechanism Temperature regulation center of body responds to fever-inducing substances called pyrogens Fever-inducing cytokines termed endogenous pyrogens Microbial products termed exogenous pyrogens Resulting fever inhibits growth of pathogens by Elevating temperature above maximum growth temperature Activating and speeding up other body defenses

151 Summary of Innate Immunity External and mechanical barriers Receptors for pathogen Soluble antimicrobial proteins Pattern of cytokines produced influences adaptive response

152 Natural immunity active natural immunity - may be acquired by experiencing an infection. Many diseases confer immunity after a single infection, but many others do not. For ex. a single bout of measles or chickenpox, confers lifelong immunity to that disease. Influenza and salmonella are examples of infections that do not confer immunity and therefore may recur. passive natural immunity - the transfer of antibodies from the mother to the newborn child, via the placenta and/or breast milk. It is diminishes after varying lengths of time. It is very important in giving infants a good head start in life.

153 Artificial immunity may be acquired through the use of vaccines, toxoids and immune globulins. Active immunity: Receiving a vaccine or toxoid stimulates active immunity, since the recipient responds by producing his/her own antibodies. Passive immunity: Receiving an antitoxin or immune globulin confers passive immunity, essentially by borrowing the antibodies of other people. Passive immunity lasts for only a short time, while active immunity usually lasts much longer, even for a lifetime.