The Immune System

1. The Immune System CAMPBELL and REECE Chapter 43

2. Innate Immunity • nonspecific defense that is active immediately upon infection • found in all animals & plants • includes: • outer covering • skin or shell • chemical secretions • @ openings to interior of body

3. Immune System • must be able to identify nonself from self • detection determined by molecular recognition of receptor molecules

4. Adaptive Immunity • found only in vertebrates • very specific • aka acquired immune response • activated after innate responses & develops more slowly

5. Innate Immunity of Insects • only have innate immunity • 1st line of defense (barrier defenses) • Exoskeletons: effective against most pathogens: made of polysaccharide, chitin

6. Innate Immunity in Insects: Barrier Defenses • lining of intestine: • has chitin where it blocks infection by pathogens ingested in food • secretes lysozyme, enzyme that breaks down bacterial cell walls

7. Insect’s Internal Immune Responses • if pathogen gets by barrier defenses: • hemocytes: immune cells in hemolymph • some can phagocytose • others secrete chemicals that kill pathogens & help entrap large parasites (like Plasmodium) • interaction with pathogens  some secrete antimicrobial peptides  circulate in hemolymph

8. Phagocytosis

9. Insect Immune Cells • bind to molecules unique to outer layers of fungi, or bacteria • fungal cells: polysaccharides • bacteria: combinations of sugars & a.a. not found in animal cells

10. Innate Responses • unique for different classes of pathogens

11. Innate Immunity in Vertebrates • coexists with adaptive immunity mechanisms • 2 are strongly interdependent • basis same as innate immunity in invertebrates but there are additions • most research done on mammals

12. Barrier Defenses • epithelial tissues block entry of many pathogens • skin • mucous membranes • line organs that have opening to outside of body • mucus: viscous fluid that blocks microbes & other particles • saliva, tears have “washing” action keeping microbes from colonizing

13. Barrier Defenses • cellular secretions • lysozyme kills by breaking down cell walls • saliva, tears dilute & prevent colonization • sweat pH 3 – 4 • stomach pH 2

14. Internal Innate Defenses 1. phagocytes • cells that can detect fungi & bacteria • use several types of receptors: • Toll-like receptor (TLR) binds to fragments of molecules characteristic of set of pathogens • similar mechanism used in insects

15. TLR Signaling Pathway

16. TLR • TLR3 • sensor for dsRNA (viral) • TLR4 • recognizes lipopolysaccharide (surface of many bacteria) • TLR5 • recognizes flagellin (bacterial flagella protein)

18. Types of Phagocytic Cells • Neutrophils • circulate in blood • attracted by signals sent from infected cells • Macrophages • larger cells migrate thru tissues or reside permanently in organs/tissues likely to have invaders

19. Types of Phagocytic Cells 3. Dendritic cells • mainly found in tissues that contact outside (skin) • stimulate adaptive immunity after engulfing pathogen 4. Eosinophils • found beneath mucous membranes • low phagocytic activity • speciality: able to defend against parasitic worms  secrete enzymes

22. Natural Killer Cells • circulate thru body detecting abnl surface proteins of cells infected with virus or cancer cells • on detection  secrete chemicals that kill affected cell

23. Lymphatic System • network of vessels that connect lymphatic tissues thru out body • ICF  lymph vessels  venous drainage • some macrophages in lymph nodes

24. Lymphatic System • dendritic cells migrate to lymph node after interacting with pathogen  interact with other immune cells stimulating adaptive immunity attack • aka APCs: Antigen-Presenting Cells

25. Lymphatic System

26. Pathogen Recognition Triggers: • release of peptides & proteins  attack pathogens or impede their reproduction

27. Interferons • proteins released in response to viral infection • vertebrates only • now used in early treatment

28. Complement System • ~30 proteins in plasma • circulate in inactive state • activated by substances on surfaces of some microbes • activation starts cascade of reactions   lysis of invading cells

29. Inflammatory Response • innate immune defense triggered by physical injury or infection of tissue involving the release of substances that promote swelling, enhance the infiltration of WBCs, & aid in tissue repair & destruction of invading pathogens

30. Histamine • 1 of inflammatory signaling molecules • stored in granules of mast cells (in CT)

31. Cytokines • group of small protein secreted by # of cell types: • macrophages • helper T cells • regulate function of other cells to enhance immune response • promote increased blood flow to injured area • causes redness & increased skin temp • engorged capillaries leak fluid  localized swelling

32. Inflammatory Response

33. Some Pathogens Evade Innate Immunity • Bacteria: • some have outer capsule that interferes with recognition & phagocytosis • Streptococcus pneumoniae

35. Adaptive Immunity • unique to vertebrates • relies on lymphocytes

36. Thymus • organ in thoracic cavity • some new lymphocytes travel from bone marrow  thymus & are “taught” how to respond in immune attack  mature into T cells

37. B Cells • lymphocytes that stay in bone marrow to mature • become effector cells for humoral immune response

38. Antigen (agn) • substance that elicits an immune response by binding to receptors of B cells, antibodies, or of T cells • example: bacterial or viral protein • agn receptor: general term for a surface protein, on B or T cells, that binds to agns, initiating adaptive immune responses

39. agn receptors • specific enough to bind to just one part of 1 molecule from particular pathogen • 1 B cell or 1 T cell makes only 1 specific receptor • ~ 100,000 agn receptors on 1 B or T cell

41. B Cell or T Cell Receptors

42. agns • usually large foreign molecules (proteins or polysaccharides most often) • stick out surface of foreign cells or virus • molecule of toxin secreted by bacteria

43. Epitopes • small, accesible region of agn to which an agn receptor or antibody (aby) binds • aka: agn determinant

44. Epitopes • single agn typically has several different epitopes each will bind to receptor with different specificity • agn receptors of B & T cells encounter agns differently

45. Recognition of agn by B Cells B cell agn receptors “Y” shaped made of 4 polypeptide chains2 identical heavy chains 2 identical light chains disulfide bridges link them

46. B Cell Antigen Receptor • heavy chains extend into cytoplasm anchor receptor • light & heavy chains have “constant”(C) region (nearly same on all B cells) & “variable” (V) regions (great amt variation from 1 B cell to another) • includes tail (heavy chain only)that extends thru membrane & into cytoplasm and all disulfide bridges

48. B Cell Activation • starts when agn binds to a B cell agn receptor • ends with B cell secreting soluble form of its agn receptor = antibody (aby) or immunoglobulin (Ig) • abys have same “Y” shaped organization as the B cell agn receptor

49. B Cell recognition of agn

50. T Cell Recognition of agn • agn receptors made of 2 chains: α chain & a β chain linked by disulfide bridges • both chains pass thru plasma membrane & into cytoplasm • both have C regions & V regions