Innate Immune Response

1. Innate Immune Response Kathy Huschle Northland Community and Technical College

2. The Human Body • we are made up of warm, moist, nutrient rich substances, an ideal environment for the housing of microorganisms • every drop of water we drink contains 100’s of bacteria • the air we breath introduces millions of bacteria daily to our lungs • every time we brush our teeth we drive microorganisms into our gums Bacteria on just brushed teeth

3. The Human Body • despite this environment our body is relatively sterile (pathogen free) • in most cases the presence of microorganisms are controlled by our defense mechanisms • innate immunity • adaptive immunity • these 2 systems interact to keep out microorganisms, remove microorganisms if they get in, and combat them if they remain inside

4. Immunity • immunity is the ability to ward off diseases through nonspecific and specific defenses • our bodies normally have 2 defense mechanisms against pathogens • innate immunity • nonspecific resistance that refers to all body defenses that protect the body against any kind of pathogen • adaptive immunity • specific resistance that refers to defenses against specific microorganisms

5. Innate Immunity • the protection provided by the innate immune system is one the human body is born with • initially it was thought to be a very generalized system and was often referred to as the non-specific immune system

6. Innate Immunity • recent research has determined that though the system will attack a variety of microbial pathogens, the system does rely on recognition of patterns of invading pathogens • innate immunity is supplemented by the adaptive immune response which will be discussed in the next lecture

7. Innate Defenses Overview • first-line defenses • physical barriers • antimicrobial substances • normal flora • sensor systems • toll like receptors • complement • phagocytes • inflammation • interferons • fever First-line Defenses

8. First Line Defenses: Physical Barriers • skin and mucosa • body’s first line of defense • the function of defense is both mechanical and chemical

9. First Line Defenses: Physical Barriers • skin and mucosa • mechanical function involves physical barriers that block entry or processes that remove microbes • chemical function include substances that the body makes that inhibit microbial growth or destroys microbes

10. First Line Defenses: Physical Barriers This figure is a representation of the human body. The purple represents skin, the pink the mucous membranes. You can easily visualize the complete protection offered our body by intact skin and mucous membranes

11. First-Line Defenses: Skin • intact skin physically blocks the entrance of microorganisms • made up of 2 distinct layers • dermis • thick inner portion made up of tight connective tissue • epidermis • outer layer of skin made up of many layers of epithelial cells • the top layer of the epidermis contains dead cells embedded in a protective protein called keratin • keratin is a water-repelling protein

12. First-Line Defenses: Skin • the presence of dead cells and keratin in the outer layers of our skin plays a major role in inhibiting any microorganisms from gaining a foot hold • microorganisms require water to survive: keratin repels water keratin and dead cells on the surface of skin

13. First-Line Defenses: Skin • viruses require a living host to invade: dead cells are obviously not suitable for viral invasion • the outer layer of cells are periodically shed which helps remove any microbes that may have found a home on the skin’s surface Dead skin cells

14. First-Line Defenses: Mucous Membranes • mucous membranes line the internal spaces of organs and tubes that open to the outside, and also line the body cavities some examples of the location of mucous membranes

15. Mucous Membranes • mucous membranes inhibit the entrance of microorganisms, but offer less protection than intact skin • mucous, the sticky fluid found in mucous membranes, functions to keep the membranes moist Mucous secreting cells

16. Mucous Membranes • this moist environment enhances the presence of some microorganisms • these microorganisms, if present in a large enough number, are often capable of penetrating the membrane • but on the other hand, the bathing of mucous membranes by mucosa can in some cases wash the microorganisms from the surfaces Esophagus

17. Mucous Membranes • in the digestive tract, many microorganisms are directed towards elimination by a process called peristalsis

18. Mucous Membranes • peristalsis is the rhythmic contraction of the intestinal tract that moves food through the system • this process also enhances the removal of microorganisms Gastic gland in digestive tract secrete mucous

19. Mucous Membranes • cilia line the respiratory tract • with a constant beating upward by the cilia, microorganisms are propelled away from the lungs to the throat where they are either swallowed or coughed away Trachial cell with cilia in green and mucousal glands in yellow Cilia actions removing debris

20. Mucous Membranes • more penetrable than skin • dry conditions thin mucous layer making them even more penetrable • this explains why we are more vulnerable to colds and respiratory infections during dryer winters • cells of the mucous membranes are alive • high concentrations of viruses and pathogens can overwhelm them Bacteria in yellow on nasal epithelium in mauve

21. Mucous Membranes • mechanical methods of microbial removal from mucous membranes • respiratory: coughing, sneezing, gagging • gastrointestinal: peristalsis, vomiting, defecation • genitourinary: urination

22. First Line Defenses: Antimicrobial • many of the body fluids found in or on the skin or mucous membranes are antimicrobial • they can effectively limit ability of invading organisms to infect by • inhibiting growth: bacteriostatic • killing: bactericidal • examples include • sweat • lysozyme • acids • lactoferrin

23. First Line Defenses: Antimicrobial • sweat has a high salt content • as it evaporates on our skin, it leaves behind a residue that is high in salt • a salty environment on the skin is not conducive to growth for most microorganisms Sweat gland cells

24. First Line Defenses: Antimicrobial • lysozyme • an enzyme that is found in tears, saliva, sweat, and mucus • lysozyme degrades peptidoglycan which is found in bacterial cell walls • particularly effective against Gram – cells • the degradation of the cell wall causes the organism to die from osmotic shock: it no longer has the rigid protection of the cell wall lysozyme

25. First Line Defenses: Antimicrobial • acids • generally microorganisms require a neutral environment • the presence of acid kills or prevents the growth of most microorganisms • vaginal tract has a pH of 4.4 - 4.6 • digestive tract has a pH of 1-2 Endoscopic view of digestive tract

26. First Line Defenses: Antimicrobial • the presence of normal “friendly” microorganisms on the skin break down the sebum found in the skin • the break down of sebum releases fatty acids which make the skin more acidic, inhibiting the growth of invading microorganisms Sebum on skin

27. First Line Defenses: Antimicrobial • blood and body fluids also contain antimicrobial chemicals • iron-binding proteins • transferrin • found in blood and tissue fluids • lactoferrin • found in saliva, mild and mucus Transferrin-HeLa cells Lactoferrin

28. First Line Defenses: Antimicrobial • transferrin and lactoferrin • inhibit bacterial growth by reducing the amount of available iron • bind the available iron so the pathogens can’t • the probability of contracting a STD during menstruation is increased due to increased amount of blood in the vaginal tract: more iron available for the invading microorganism

29. First Line Defenses: Fluid Flow • the cleansing action of fluids also assists in the removal of microorganisms from mucous membranes • saliva • dilutes the number of microorganisms and washes them from the surface of the teeth and the mucous membranes of the mouth bacteria in saliva

30. First Line Defenses: Fluid Flow • urinary tract • the cleansing of the urethra by the flow of urine prevents colonization of microorganisms

31. First Line Defenses: Fluid Flow • eye • production of tears by the lacrimal apparatus continually washes over the eyes lacrimal gland secretes tears: tears are drained by the nasalacrimal duct

32. First Line Defenses: Fluid Flow • this continuous washing of the eyes with tears prevents microorganisms from settling on the surface of the eye

33. First Line Defenses: Microbial Barriers • on a cellular basis, our body is made up of 90% microbial cells and only 10% “human” • most of the bacterial cells found in our body are associated with the gastrointestinal tract • S. aureus is prevalent on skin • Lactobacilli are prevalent in the vaginal tract S. aureus

34. First Line Defenses: Microbial Barriers • this large number of microbial cells are indigenous (naturally occurring) and are referred to as normal microbita or normal flora • microbial barriers play a key role in our immune system by inhabiting specific body surfaces

35. First Line Defenses: Microbial Barriers many of the normal flora found in various parts of the human body

36. First Line Defenses: Microbial Barriers • normal flora are nonpathogenic • colonize body tissues thus preempting other microorganisms from colonizing • they are capable of producing antimicrobial substances that interfere with the growth of other microorganisms • they reduce the availability of oxygen • they compete for nutrients

37. First Line Defenses: Microbial Barriers • the normal flora found in our body are a balanced complex • but an imbalance can lead to disease • nonpathogenic normal flora are opportunistic and will take advantage of any opportunity to invade which can lead to disease • opportunities that can lead to an imbalance can be injury or a depressed or non-functioning immune system

38. First Line Defenses: Microbial Barriers • the process of acquisition of our normal flora begins during birth • the human fetus is sterile and through a successional process occurring in stages, acquires the microbiota necessary for survival • the first step of acquiring the normal flora for some newborns is the transfer of microorganisms from mother’s milk

39. Cells of the Immune System • cells are capable of moving around the body through the circulatory system • cells of the immune system are found in normal blood • develop in the bone marrow • increase in amounts during infection • leukocytes: white blood cells • granulocytes • mononuclear phagocytes • lymphocytes • stem cell is the common ancestor to all blood cells: red, white, and platelets

40. Granulocytes • presence of large granules in their cytoplasm filled with biologically active chemicals critical to their function • granulocytes differentiate into three types of cells • neutrophils • basophils • eosinophils granulocytes

41. Neutrophils • neutrophils • professional phagocytes – 50% of the leukocytes found in the body are neutrophils • these numbers increase during the presence of a bacterial infection

42. Neutrophils • chemical found in their granules assists in the degradation of engulfed material • often referred to as polymorphonuclear neutrophilic leukocyte or poymorphs (PMN) SEM pictogram of neutrophil Neutrophil Neutrophil in collagen

43. Neutrophils • have the ability to leave the blood, enter an infected tissue and destroy microbes and foreign particles • always present for protection and surveillance

44. Basophils • the role of basophils is not particularly well understood • they are involved in allergic reactions and inflammation

45. Eosinophils • important defense against parasites • capable of leaving the blood and infiltrating tissue • major function is to produce toxic proteins against parasites • physically too small to ingest parasites, eosinophils are able to attach to the outer surface of a parasite and discharge a toxin that destroys them

46. Mononuclear Phagocytes • 2 types of phagocytic cells arise from monocytes • monocytes circulate in the blood after leaving the bone marrow

47. Mononuclear Phagocytes • monocytes migrate to tissue and form: • macrophages • also considered to be professional phagocytes • abundant in spleen, liver, lymph nodes, lungs, peritoneal cavity macrophage

48. Mononuclear Phagocytes • dendritic cells • scout phagocytes; highly mobile cells • more involved with adaptive immune system which will be discussed later

49. Leukocyte Invasion

50. Lymphocytes • cells that are players in the adaptive immune system • these cells are not phagocytes • occur in the lymphoid tissue of the lymphatic system; tonsils, spleen, red bone barrow, lymph nodes