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Chapter 16: Nonspecific Responses The immune system functions to recognize and destroy that which is foreign (non self) - including invading microbes and their secretions, toxins, and enzymes and non normal cells The immune system consists of 2 components: Nonspecific or innate (inherent) immunity Specific or adapted (acquired after birth) immunity
Innate or nonspecific immunity Acts to prevent microbes from getting into the body and the elimination of those that have already penetrated Defenses are present at birth Acts against all microbes in the same way  Is not specific Always ready to respond to damage or invasion
1 st  line of defense – physical barriers Skin – the dermis and epidermis provide mechanical protection however this barrier can be broken by cuts and abrasions, insect bites, and injections.  The top layer of dead epidermal cells contain a protein called keratin which is a poor source of carbon for microbes. These dead cells are continually being sloughed off along with the microbes that are on the them.
1 st  line of defense – physical barriers Skin cont.  It is home to normal microbiota which are antagonistic to pathogens Flushing effects of sweat glands helps to remove microbes A cut in the skin allows Staphylococci to enter the blood An arthropod bite acts like a hypodermic needle – allow microbes that cause disease like malaria or plague to enter
The Body’s Surfaces (from a microbe’s persepctive)
1 st  line of defense – physical barriers Mucous membranes line the internal body cavity and act as a mechanical barrier to microbes. Cilia in airways propel microbes and mucus into the pharynx (throat) where they are swallowed into the stomach  Stomach acid destroys the microbes
1 st  line of defense – physical barriers Lacrimal apparatus manufactures and drains away tears – flushing action, blinking of eyes Saliva carries microbes to the harsh environment of the stomach Hairs and cilia Nasal hairs trap large particles, may initiate a sneeze to expel  Ciliated epithelium (respiratory tract) called the ciliary escalator moves microbes trapped in mucus out of the respiratory tract
1 st  line of defense – physical barriers Epiglottis – covers the larynx when swallowing and keeps microbes from entering the lower respiratory tract Flow of urine removes microbes from the urogenital tract Vaginal secretions remove microbes from the female body Defecation and vomiting expel pathogens and toxins
First-Line Defense
1st line of defense chemical factors Sebaceous glands of the skin produce an oily substance called sebum which forms a protective film over the skin and lowers the pH of the skin to pH 3-5 Which inhibits the growth of pathogenic fungi and bacteria Sweat, tears and saliva contain the enzyme lysozyme which hydrolyzes the peptidoglycan in the cell walls of bacteria
1st line of defense chemical factors Gastric juice (pH 1.2 – 3) and enzymes destroy microbes and toxins Except toxins of  Clostridium  and  Staphylococcus Helicobacter pylori  – neutralizes acid and causes ulcers Vaginal tract has a low pH due to the normal microbiota  Lactobacillus producing various acids Ab therapy kills off bacteria allowing Candida to overgrow causing a yeast infection
1 st  line of defense genetic components Species immunity – some hosts are immune to diseases of other hosts Ex. Cats don’t get mumps and humans don’t get distemper Not true for zoonotic pathogens that attack a broad spectrum of animals Differences in susceptibility in the same species ex. Gene for sickle cell anemia – resistant to malaria
2 nd  line of defense – formed elements in the blood Phagocytes  are WBCs that originate in the bone marrow, circulate in the bloodstream for awhile, then leave the circulation, and develop in the tissues Macrophages  are found in the spleen, bone marrow, lymph nodes, brain They develop from  monocytes  and monocytes are not phagocytic Wandering macrophages  – roam tissues and go to sites of infection or inflammation Fixed macrophages  enter tissues and organs and remain there
2 nd  line of defense – formed elements in the blood Phagocytes continued Neutrophils (PMNs) –phagocytic and motile, active in the initial stages of an infection Eosinophils – produce toxic substances against some parasites, some phagocytosis
Leukocytes = White Blood Cells
The Phagocytic Process Chemotaxis  = phagocytes are attracted to the area of invading microbes Adherence  = phagocyte’s plasma membrane  attaches to a microbe or particle surface Ingestion  = pseudopods surround the bacterium and bring it into the phagocyte’s cytoplasm where fusion with lysosomes take place – now called phagolysosome
The Phagocytic Process Digestion  =lysosomal enzymes digest the bacterium in newly formed phagolysosomes The process ends with the elimination of bacterial debris during  egestion
Phagocytosis “ It is the toll-like receptors on macrophages that enable them to sense that the material is microbial in origin, and must therefore be eliminated quickly.” Chemotaxis = movement toward infections.
2 nd  line of Defense - Inflammation Inflammation  – is a reaction to injury or infection, it is a local response Ex. Cat scratch, blistering of a burn, infection, allergy sxs Acute  inflammation – short lived, responsible for a single episode or injury Chronic  inflammation – lasts for weeks or years, response to continuous or multiple episodes of injury Inflammation is a process that limits the extent of injury
The Process of Inflammation Tissue damage  ex. Nail in skin w/ bacteria Mast cells are tissue cells that trigger an inflammatory rx. By releasing histamine which is a chemical mediator that dilates blood vessels and increases vascular permeability to plasma proteins Dilation of blood vessels increase the flow of blood at the site of irritation Dilation BVs increases delivery of leukocytes -WBCs
The Process of Inflammation Margination  – neutrophils and monocytes  stick to endothelium of blood vessels close to the injury  Emigration  – the WBCs start getting between the endothelial cells and squeeze there way out of the vessels to reach the injured area Phagocytosis  – neutrophils augment phagocytosis while monocytes differentiate into macrophages .
Inflammation
Inflammation
4 Cardinal signs of inflammation 1.  redness  (rubor) – due to increased blood flow to the area of injury – vasodilation  2.  swelling  (tumor) – edema – blood leaks from vessels and you get an accumulation of fluid Fluid dilutes toxic substances Fluid may contain pus  which is a mixture of plasma, dead tissue cells, WBCs, dead bacteria
4 Cardinal signs of inflammation 3.  heat  (calor)- due to increased blood flow and the action of pyrogen ( a fever producing substance in the blood) 4.  pain  (dolor) – caused by injury to the local nerves 5.  the final stage if inflammation is tissue repair
Fever is a systemic response that accompanies inflammation Body temperature is set and maintained by the hypothalamus (brain) Fever is initiated when a circulating substance called pyrogen sets the hypothalamus to a higher setting Pyrogens are exogenous (coming from outside of the body) or endogenous (originating internally) Exogenous pyrogens are products of infectious agents Endogenous pyrogens are liberated by monocytes, neutrophils, macrophages during phagocytosis
Fever is a systemic response that accompanies inflammation Benefits of fever: Inhibits multiplication of temperature sensitive microbes Increases metabolism and stimulates the immune response Complications of fever are tachycardia, dehydration, electrolyte imbalance, seizures, delirium, coma
2 nd  line of defense: The Complement System Consists of 30 different proteins circulating in the bloodstream that act in an ordered sequence or cascade – 1 protein activates another, etc. There are 9 major components C1-C9 that are sequentially activated to participate in inflammation, phagocytosis, and cytolysis
3 different complement pathways 1. Classical pathway – rapid, efficient  Antibody-microbe complex binds to and activates C1 which triggers the complement cascade C3 initiates cytolysis and opsonization (coating of microbes) to promote attachment of phagocyte to microbe
3 different complement pathways 2.  Alternative pathway  – slower, less efficient Does not involve antibodies like the classical pathway Pathogen surface binds to C3  Once the complement proteins combine and interact – C3 participates in inflammation, cytolysis, and opsonization
3 different complement pathways 3. Lectin pathway Macrophages stimulate the liver to release lectins which enhance microbial opsonization by binding to cell CH2Os Lectin coated pathogens bind to C4, C2
Results of complement activation Cytolysis  5 complement proteins bind to form a complex called the  Membrane attack complex  (MAC) which embeds itself in the plasma membrane of the microbe Channels are created in the membrane and water and salt leak into the microbe causing the cell to lyse.  Inflammation  can develop from complement proteins which combine with mast cells and trigger the release of histamine. Histamine increases blood vessel permeability.
Results of complement activation Opsonization  – promotes attachment of a phagocyte to a microbe. Complement C3 coats the microbe and then reacts with receptors on the phagocytes for attachment Complement can be inactivated by regulatory proteins in the blood that cause the break down of activated complement
Complement 1. Inactive complement proteins are in constant circulation. 2. Complement proteins are activated by various mechanisms. 3. These are the consequences...
2 nd  line of defense: Interferons Interferon  is a group of proteins that act to interfere with viral replication. They are small proteins that are in 3 different types: Alpha and Beta INFs are produced by virus infected host cells and  diffuse to neighboring uneffected cells They induce uninfected cells to manufacture mRNA for synthesis of antiviral proteins that interfere w/ viral multiplication They have no effect on viral multiplication of cells already infected
2 nd  line of defense: Interferons Interferons of a species are active against a number of different viruses – they are not virus specific Gamma INF is produced by lymphocytes and induce nuetrophils and macrophages to kill bacteria by phagocytosis

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Chp.16

  • 1. Chapter 16: Nonspecific Responses The immune system functions to recognize and destroy that which is foreign (non self) - including invading microbes and their secretions, toxins, and enzymes and non normal cells The immune system consists of 2 components: Nonspecific or innate (inherent) immunity Specific or adapted (acquired after birth) immunity
  • 2. Innate or nonspecific immunity Acts to prevent microbes from getting into the body and the elimination of those that have already penetrated Defenses are present at birth Acts against all microbes in the same way Is not specific Always ready to respond to damage or invasion
  • 3. 1 st line of defense – physical barriers Skin – the dermis and epidermis provide mechanical protection however this barrier can be broken by cuts and abrasions, insect bites, and injections. The top layer of dead epidermal cells contain a protein called keratin which is a poor source of carbon for microbes. These dead cells are continually being sloughed off along with the microbes that are on the them.
  • 4. 1 st line of defense – physical barriers Skin cont. It is home to normal microbiota which are antagonistic to pathogens Flushing effects of sweat glands helps to remove microbes A cut in the skin allows Staphylococci to enter the blood An arthropod bite acts like a hypodermic needle – allow microbes that cause disease like malaria or plague to enter
  • 5. The Body’s Surfaces (from a microbe’s persepctive)
  • 6. 1 st line of defense – physical barriers Mucous membranes line the internal body cavity and act as a mechanical barrier to microbes. Cilia in airways propel microbes and mucus into the pharynx (throat) where they are swallowed into the stomach Stomach acid destroys the microbes
  • 7. 1 st line of defense – physical barriers Lacrimal apparatus manufactures and drains away tears – flushing action, blinking of eyes Saliva carries microbes to the harsh environment of the stomach Hairs and cilia Nasal hairs trap large particles, may initiate a sneeze to expel Ciliated epithelium (respiratory tract) called the ciliary escalator moves microbes trapped in mucus out of the respiratory tract
  • 8. 1 st line of defense – physical barriers Epiglottis – covers the larynx when swallowing and keeps microbes from entering the lower respiratory tract Flow of urine removes microbes from the urogenital tract Vaginal secretions remove microbes from the female body Defecation and vomiting expel pathogens and toxins
  • 10. 1st line of defense chemical factors Sebaceous glands of the skin produce an oily substance called sebum which forms a protective film over the skin and lowers the pH of the skin to pH 3-5 Which inhibits the growth of pathogenic fungi and bacteria Sweat, tears and saliva contain the enzyme lysozyme which hydrolyzes the peptidoglycan in the cell walls of bacteria
  • 11. 1st line of defense chemical factors Gastric juice (pH 1.2 – 3) and enzymes destroy microbes and toxins Except toxins of Clostridium and Staphylococcus Helicobacter pylori – neutralizes acid and causes ulcers Vaginal tract has a low pH due to the normal microbiota Lactobacillus producing various acids Ab therapy kills off bacteria allowing Candida to overgrow causing a yeast infection
  • 12. 1 st line of defense genetic components Species immunity – some hosts are immune to diseases of other hosts Ex. Cats don’t get mumps and humans don’t get distemper Not true for zoonotic pathogens that attack a broad spectrum of animals Differences in susceptibility in the same species ex. Gene for sickle cell anemia – resistant to malaria
  • 13. 2 nd line of defense – formed elements in the blood Phagocytes are WBCs that originate in the bone marrow, circulate in the bloodstream for awhile, then leave the circulation, and develop in the tissues Macrophages are found in the spleen, bone marrow, lymph nodes, brain They develop from monocytes and monocytes are not phagocytic Wandering macrophages – roam tissues and go to sites of infection or inflammation Fixed macrophages enter tissues and organs and remain there
  • 14. 2 nd line of defense – formed elements in the blood Phagocytes continued Neutrophils (PMNs) –phagocytic and motile, active in the initial stages of an infection Eosinophils – produce toxic substances against some parasites, some phagocytosis
  • 15. Leukocytes = White Blood Cells
  • 16. The Phagocytic Process Chemotaxis = phagocytes are attracted to the area of invading microbes Adherence = phagocyte’s plasma membrane attaches to a microbe or particle surface Ingestion = pseudopods surround the bacterium and bring it into the phagocyte’s cytoplasm where fusion with lysosomes take place – now called phagolysosome
  • 17. The Phagocytic Process Digestion =lysosomal enzymes digest the bacterium in newly formed phagolysosomes The process ends with the elimination of bacterial debris during egestion
  • 18. Phagocytosis “ It is the toll-like receptors on macrophages that enable them to sense that the material is microbial in origin, and must therefore be eliminated quickly.” Chemotaxis = movement toward infections.
  • 19. 2 nd line of Defense - Inflammation Inflammation – is a reaction to injury or infection, it is a local response Ex. Cat scratch, blistering of a burn, infection, allergy sxs Acute inflammation – short lived, responsible for a single episode or injury Chronic inflammation – lasts for weeks or years, response to continuous or multiple episodes of injury Inflammation is a process that limits the extent of injury
  • 20. The Process of Inflammation Tissue damage ex. Nail in skin w/ bacteria Mast cells are tissue cells that trigger an inflammatory rx. By releasing histamine which is a chemical mediator that dilates blood vessels and increases vascular permeability to plasma proteins Dilation of blood vessels increase the flow of blood at the site of irritation Dilation BVs increases delivery of leukocytes -WBCs
  • 21. The Process of Inflammation Margination – neutrophils and monocytes stick to endothelium of blood vessels close to the injury Emigration – the WBCs start getting between the endothelial cells and squeeze there way out of the vessels to reach the injured area Phagocytosis – neutrophils augment phagocytosis while monocytes differentiate into macrophages .
  • 24. 4 Cardinal signs of inflammation 1. redness (rubor) – due to increased blood flow to the area of injury – vasodilation 2. swelling (tumor) – edema – blood leaks from vessels and you get an accumulation of fluid Fluid dilutes toxic substances Fluid may contain pus which is a mixture of plasma, dead tissue cells, WBCs, dead bacteria
  • 25. 4 Cardinal signs of inflammation 3. heat (calor)- due to increased blood flow and the action of pyrogen ( a fever producing substance in the blood) 4. pain (dolor) – caused by injury to the local nerves 5. the final stage if inflammation is tissue repair
  • 26. Fever is a systemic response that accompanies inflammation Body temperature is set and maintained by the hypothalamus (brain) Fever is initiated when a circulating substance called pyrogen sets the hypothalamus to a higher setting Pyrogens are exogenous (coming from outside of the body) or endogenous (originating internally) Exogenous pyrogens are products of infectious agents Endogenous pyrogens are liberated by monocytes, neutrophils, macrophages during phagocytosis
  • 27. Fever is a systemic response that accompanies inflammation Benefits of fever: Inhibits multiplication of temperature sensitive microbes Increases metabolism and stimulates the immune response Complications of fever are tachycardia, dehydration, electrolyte imbalance, seizures, delirium, coma
  • 28. 2 nd line of defense: The Complement System Consists of 30 different proteins circulating in the bloodstream that act in an ordered sequence or cascade – 1 protein activates another, etc. There are 9 major components C1-C9 that are sequentially activated to participate in inflammation, phagocytosis, and cytolysis
  • 29. 3 different complement pathways 1. Classical pathway – rapid, efficient Antibody-microbe complex binds to and activates C1 which triggers the complement cascade C3 initiates cytolysis and opsonization (coating of microbes) to promote attachment of phagocyte to microbe
  • 30. 3 different complement pathways 2. Alternative pathway – slower, less efficient Does not involve antibodies like the classical pathway Pathogen surface binds to C3 Once the complement proteins combine and interact – C3 participates in inflammation, cytolysis, and opsonization
  • 31. 3 different complement pathways 3. Lectin pathway Macrophages stimulate the liver to release lectins which enhance microbial opsonization by binding to cell CH2Os Lectin coated pathogens bind to C4, C2
  • 32. Results of complement activation Cytolysis 5 complement proteins bind to form a complex called the Membrane attack complex (MAC) which embeds itself in the plasma membrane of the microbe Channels are created in the membrane and water and salt leak into the microbe causing the cell to lyse. Inflammation can develop from complement proteins which combine with mast cells and trigger the release of histamine. Histamine increases blood vessel permeability.
  • 33. Results of complement activation Opsonization – promotes attachment of a phagocyte to a microbe. Complement C3 coats the microbe and then reacts with receptors on the phagocytes for attachment Complement can be inactivated by regulatory proteins in the blood that cause the break down of activated complement
  • 34. Complement 1. Inactive complement proteins are in constant circulation. 2. Complement proteins are activated by various mechanisms. 3. These are the consequences...
  • 35. 2 nd line of defense: Interferons Interferon is a group of proteins that act to interfere with viral replication. They are small proteins that are in 3 different types: Alpha and Beta INFs are produced by virus infected host cells and diffuse to neighboring uneffected cells They induce uninfected cells to manufacture mRNA for synthesis of antiviral proteins that interfere w/ viral multiplication They have no effect on viral multiplication of cells already infected
  • 36. 2 nd line of defense: Interferons Interferons of a species are active against a number of different viruses – they are not virus specific Gamma INF is produced by lymphocytes and induce nuetrophils and macrophages to kill bacteria by phagocytosis