Exam 4: How do mammals protect themselves from mo’s?

1. Exam 4: How do mammals protect themselves from mo’s? A. Intro 1. The environment is rife with mo’s (bact., fungi, viruses, protozoa) 2. The vast majority are not able to infect or even enter the human body. 3. A minority of mo’s have the ability to cause infections that range from the benign to life- threatening. 4. Animals have evolved means to exclude pathogens from the body and evict those who do enter.

2. How do mammals protect themselves from mo’s? (cont) B. The Concept ofNormal Flora 1. animal bodies are excellent habitats for mo’s (provide food, warmth, moisture) 2. Over time, organisms and mo’s have evolved commensal relationships that benefit both the organisms and the mo. 3. These mo’s are the normal flora mo’s

3. B. The Concept of Normal Flora (cont) 4. The characteristics of normal flora a. grow on internal or external body surfaces b. able to withstand body defenses in significant numbers c. but they are still held in check by body defenses d. the host is unharmed by their presence

4. B. The Concept of Normal Flora (cont) 5. What do the normal flora provide to the host? a. occupy prime habitat on the body b. some gut mo’s can produce useful products c. in infants, can provide digestive enzymes d. however, if the host is compromised, normal flora can colonize new tissues and cause disease

5. B. The Concept of Normal Flora (cont) 6. Normal flora of the human body (a very abbreviated list) a. skin: Staphylococcus spp., Streptococcus spp., diphtheroids, Propionibacterium acnes b. oral cavity: Streptococcus spp., Fusobacterium spp., diphtheroids, spirochetes, Gm negative cocci c. URT: Staphylococcus spp., Streptococcus spp., diphtheroids, Gm negative cocci

6. B. The Concept of Normal Flora (cont) 6. Normal flora of the human body (cont) d. GI tract 1) stomach: very few mo’s overall, Streptococcus spp., Lactobacillus spp., Helicobacter spp. 2) small intestine: upper region is similar to stomach; lower regions are more similar to large intestine

7. B. The Concept of Normal Flora (cont) 6. Normal flora of the human body (cont) d. GI tract (cont) 3) large intestine: huge variety and numbers of mo’s Enterococcus spp., variety of anaerobes, coliforms, and lots more •~2/3 of bulk of feces is composed of bacteria

8. B. The Concept of Normal Flora (cont) 6. Normal flora of the human body (cont) e. Genitourinary tract (GU) 1) distal urinary epithelium has resident Gm- rods and cocci, etc. 2) vagina: Lactobacillus spp., Streptococcus spp., yeast and others f. circulation and lower RT: sterile!

9. C. Bacterial characteristics that aid infection 1. Invasive factors (coded for by inv genes) a. def: a trait that helps a particular bact. specie invade a host or host tissue. b. examples 1) adhesins: a bacterial surface protein that attaches to a host cell surface receptor. (adhesins are often found on pili and fimbriae)

10. C. Bacterial characteristics that aid infection (cont) 1. Invasive factors (cont) b. examples (cont) 2) glycocalyx or capsule: attaches to host cell surface receptor and is antiphagocytic 3) “M” protein: cell surface protein of S. aureus that is antiphagocytic 4) bacterial enzymes Hyaluronidase: degrades cell cement Coagulase: clots blood others

11. C. Bacterial characteristics that aid infection (cont) 2. Virulence factors (coded for by vir genes) a. Def: a trait that helps a particular bacterial specie cause disease b. examples 1) toxinsor poisons Botulin Lipid A 2) physiological factors that allow growth of a specific bacterium in the host 3) tissue degrading enzymes: Hyaluronidase, Collaginase (note that some traits are both inv. and vir. factors)

12. C. Bacterial characteristics that aid infection (cont) 3. Ability to induce a hypersensitivity reaction a. has some similarities to an autoimmune reaction b. often fatal c. poorly understood d. e.g. syphilis, scarlet fever

13. C. Bacterial characteristics that aid infection (cont) 4. Details on the 2 types of bacterial toxins a. Exotoxins 1) Usually produced by Gm+ bacteria 2) secreted proteins are released to circ. 3) each has a specific biological activity and set of symptoms 4) among the most potent toxins known e.g. Botulin, diphtheria toxin

14. C. Bacterial characteristics that aid infection (cont) 4. Details on the 2 types of bacterial toxins a. Exotoxins (cont) 5) treatment of purified toxin with formaldehyde coagulates the protein a) product is called a toxoid b) toxoids often make good vaccines

15. C. Bacterial characteristics that aid infection (cont) 4. Details on the 2 types of bacterial toxins b. Endotoxins 1) mostly made by Gm – bacteria 2) primarily lipopolysaccharide of the Gm – cell membrane (Lipid A portion of LPS) 3) endotoxins are released into the circ. upon lysis of bacteria 4) endotoxins don’t form toxoids 5) less potent than exotoxins

16. C. Bacterial characteristics that aid infection (cont) 4. Details on the 2 types of bacterial toxins b. Endotoxins (cont) 6) symptoms of endotoxin poisoning are more generalized: •fever •inflamm. response kicks into high gear leading to drop in b.p. and shock. 7) big problem in Gm- systemia

17. D. Sources of Human infections 1. Animals cause Zoonoses: caused by the spread of animal normal flora or animal pathogens that are also pathogenic to man. •Toxoplasmosis-cats •Hantavirus-field mice •Malaria-mosquitoes •Shigella/Salmonella-birds esp. chicken 2. Non-living objects that spread disease are called fomites caused by the contamination of a fomite and then contact with the victim. • tissues • doorknobs • bandages

18. D. Sources of Human infections (cont) 3. Humans: diseased person passing a pathogen to another •droplet nuclei •blood to blood contact •STD •hands

19. E. Nosocomial Infections 1. Def: Hospital acquired infections 2. About 10% of hospitalized patients acquire a nosocomial infection 3. What leads to a nosocomial infection? 4. Spread a. doctors and nurses are in prime positions to spread hospital infections

20. E. Nosocomial Infections (cont) 4. Spread (cont) b. prevention of spread 1) wash hands between patients 2) change gloves between patients 3) practice good housekeeping 4) isolate patient when appropriate 5. Why are nosocomial infections so dangerous? a. mo’s are often multiply drug resistant b. patients often are already very sick

21. F. How do body surfaces protect themselves from infection? (1st level of protection) 1. Skin a. skin is a barrier that is a dry, physical (tough) and physiological (low pH) barrier b. intense competition from normal flora 2. Mucous membranes (note that all mm’s have 2nd and 3rd level protection as well) a. inhaled mo’s 1) ciliated epith. of nasopharynges and trachea sweep mo’s upward

22. F. How do body surfaces protect themselves (1st level of protection from infection)? 2. Mucous membranes (note that all mm’s has 2nd and 3rd level protection as well) a. inhaled mo’s (cont) 2) mucous catches mo’s which are then swallowed or spit out. 3) competition from normal flora

23. F. How do body surfaces protect themselves (cont)? 2. Mucous membranes (cont) b. swallowed mo’s are usually killed by stomach acid c. eyes 1) lysozyme 2) tears wash (lavaging action) d. vagina 1) intense competition from normal flora 2) low pH 3) lavaging and trapping by secretions and mucous

24. G. How do infections start (how do mo’s get past the 1st level of protection)? 1. skin a. parenteral route: any action that breaks the skin will allow entry of mo’s to underlying tissues 2. inhalation a. inhaled mo’s must adhere to respiratory epith. (this is a specific interaction, therefore the disease is tissue specific and adherence defines the host/tissue specificity) b. mo enters cells, etc.

25. G. How do infections start? (cont) 3. ingestion a. specific adherence to GI epith. b. growth on surface or taken in through a specific endocytosis. 4. Sexually transmitted (STD’s) a. sex transmits the pathogen b. specific adherence and endocytosis

26. Review of initiation of infection

27. H. Non-specific resistance to infection (2nd level of defense) 1. Intro a. AKA Non-specific immunity, innate immunity b. they are immune defenses directed against mo’s in general c. not a learned response, i.e. it happens the 1st time the immune system encounters any pathogen. d. mo’s encounter non-specific immunity when they evade the physical & physiologically protection of the skin or mm. e. mm have components of the 2nd and 3rd line defenses

28. H. Non-specific resistance to infection (cont) 2. Components of non-specific immunity a. blood and lymphatic system: in brief 1) importance: a) provide mobility to specific and non-specific immunity b) move O2 and CO2 about the body c) move nutrients and wastes about the body d) move chem. signals and hormones about the body e) importance role in homeostasis

29. 2. Components of non-specific immunity (cont) b. components of the blood 2) cells (all are derived from stem cells in the bone marrow) a) erythrocytes (AKA red blood cells, red blood corpuscles, RBC’s) (1) anucleate (2) disc shaped (3) contain the red pigment hemoglobin (4) hemoglobin carries O2 and RBC’s distribute O2 about the body. (5) has no role in immunity

30. 2. Components of non-specific immunity (cont) b. components of the blood 2) cells (cont) b) Leukocytes (AKA White blood cells, WBC’s) def: nucleate cells involved in specific and non-specific immunity (1) granulocytes (1st class of WBC’s) (a) prominent cytoplasmic granules when stained with Wright’s stain (b) have a lobed nucleus (c) few in number (d) mobile and chemotactic

31. 2. Components of non-specific immunity (cont) b. components of the blood 2) cells (cont) b) Leukocytes (cont) (1) granulocytes (cont) (e) examples Neutrophil •most common granulocyte •neutral grey cyto. granules •non-specific phagocytes •granules are lysosomes with enzymes that specifically degrade peptidoglycan

32. 2. Components of non-specific immunity (cont) b. components of the blood 2) cells (cont) b) Leukocytes (cont) (1) granulocytes (cont) (e) examples (cont) Eosinophil •nextmost common granulocyte •pink cyto. granules •non-specific phagocytes •granules kill worms/flukes •moderates basophils

33. 2. Components of non-specific immunity (cont) b. components of the blood 2) cells (cont) b) Leukocytes (cont) (1) granulocytes (cont) (e) examples (cont) Basophil •least common granulocyte •dark blue to purple granules •granules are histamines, which are released as a tissue injury signal

35. 2. Components of non-specific immunity (cont) b. components of the blood 2) cells (cont) b) Leukocytes (cont) (2) agranulocytes (2nd of the 2 classes of WBC’s) (a) cytoplasmic granules not evident when stained with Wright’s stain (b) phagocytic (c) few in number (d) mobile and chemotactic

36. 2. Components of non-specific immunity (cont) b. components of the blood 2) cells (cont) b) Leukocytes (cont) (2) agranulocytes (cont) (e) 2 classes of agranulocytes lymphocyte •cytoplasm scant, light blue and clear •nucleus round and large •very important in specific and non-specific immunity

37. 2. Components of non-specific immunity (cont) b. components of the blood 2) cells (cont) b) Leukocytes (cont) (2) agranulocytes (cont) (e) 2 classes of agranulocytes monocyte •cytoplasm light blue, clear •nucleus lobed •active non-specific phagocyte

39. 2. Components of non-specific immunity (cont) b. components of the blood (cont) 3) non-cellular components of blood a) platelets 1) cell fragments 2) free in the blood 3) gather at site of tissue damage 4) release chemotactic signals to recruit phagocytes 5) initiates blood clotting

40. 2. Components of non-specific immunity (cont) b. components of the blood (cont) 3) non-cellular components of blood (cont) b) soluble factors 1) serum albumin 2) hormones and other chem signals 3) opsonins 4) antibodies 5) blood clotting factors

41. 3. Mechanisms of Non-specific immunity (5) a. Phagocytosis (1st) 1) act of engulfment and digestion of a foreign particle by a cell 2) targets of phagocytosis: viruses, bacteria, cellular debris, fungal hyphae or spores (i.e. particulate matter) 3) cells that do it: lymphocytes (specific), monocytes, neutrophils, eosinophils, other macrophages 4) these cells can be found in blood, interstitial spaces, and surfaces of mm’s

42. 3. Mechanisms of Non-specific immunity (5) a. Phagocytosis (cont) 5) mechanism a) chemotaxis b) adherence (opsonins help here) c) engulfment

43. 3. Mechanisms of Non-specific immunity (5) a. Phagocytosis (cont) 5) mechanism d) digestion e) expulsion of debris Animation link (#2)

44. 3. Mechanisms of Non-specific immunity (5) b. Inflammation response (2nd) 1) A complex series of events in response to allergy, infection or trauma, characterized by localized swelling, increase in temp., reddening of the affected area and pain. 2) inflammation is a 2 edged sword a) tends to check the spread of infection b) can cause tissue damage, discomfort and even death (in extreme cases)

45. 3. Mechanisms of Non-specific immunity (5) b. Inflammation response (cont) 3) factors involved a) serum proteins regulate inflam. b) opsonizing proteins (both specific and non- specific) help targeting c) phagocytic cells d) fever activation

46. 3. Mechanisms of Non-specific immunity (5) b. Inflammation response (cont) 4) mechanism a) trauma, infection or allergy initiate response

47. 3. Mechanisms of Non-specific immunity (5) b. Inflammation response (cont) 4) mechanism (cont) b) cells release histamines, cytokines, etc, which act as chemotactic factors, activation factors, vasodilators and contactors of smooth muscle

48. 3. Mechanisms of Non-specific immunity (5) b. Inflammation response (cont) 4) mechanism (cont) c) effects 1) vasodilation: brings wandering macrophages but also reddening and swelling 2) chemotactic and activation factors: draw macrophages, activates them and keeps them active 3) opsonins: mark targets for destruction 4) smooth muscle contraction of vessel walls allows diapedesis

49. 3. Mechanisms of Non-specific immunity (5) b. Inflammation response (cont) 4) mechanism (cont)

50. 3. Mechanisms of Non-specific immunity (5) b. Inflammation response (cont) 4) mechanism (cont) d) often the fever mechanism activated •advantage: mo’s must grow at non- optimal temp. •disadvantage: patient’s biochemistry can be disrupted too e) clotting factors initiate blood clotting (stops bleeding and slow spread of infection)