Ch 43- Immune system

1. Ch 43- Immune system

2. Function of Immune system • To defend the body against disease • Pathogens– agents of disease (bacteria, viruses, protists)

3. Immune system • Non specific immunity (Innate immunity) • All animals & plants have defenses effective immediately upon infection • Specific immunity • (Adaptive or Acquired immunity) • All vertebrates have immunity after exposure to specific pathogens (slower response).

4. 1. Non-specific (Innate) Immunity • 1st line of defense: barrier • Skin, mucous membrane, secretions • 2nd line of defense: internal defenses • Phagocytosis, natural killer cells, antimicrobial proteins, inflammatory response

5. Invertebrate defenses • 1st barrier – exoskeleton made of chitin • Digestive system is protected by a chitin-based barrier and lysozyme, an enzyme that breaks down bacterial cell walls • The immune system recognizes bacteria and fungi by structures on their cell walls

6. Pathogen Hemocytes - circulate within hemolymph and carry out phagocytosis, the ingestion and digestion of foreign substances including bacteria - also secrete antimicrobial peptides that disrupt the plasma membranes of fungi and bacteria PHAGOCYTICCELL Vacuole Lysosomecontainingenzymes

7. Non-specific immunity in Vertebrates • Include barrier defenses, phagocytosis, antimicrobial peptides • Unique to vertebrates: natural killer cells, interferons, inflammatory response

8. Barrier defenses • Skin • Mucous membranes • Body secretions: saliva ,mucus, tears • Low pH in skin & membranes

9. Phagocytosis • “Cell eating” – white blood cells ingest invading pathogens • Engulfs microbe & fuses with lysosyme to destroy it • White blood cell attacking bacterium • http://www.youtube.com/watch?v=qvGVoxdy-yM

10. Phagocytes use Toll-like receptors (TLRs) that recognize molecular patterns characteristic of certain pathogens • This increases efficiency of phagocytes • i.e. one type recognizes double stranded RNA (in viruses) • Flagellin – protein found in bacteria flagella

11. Types of phagocytes in mammals 2 main types: • Neutrophils – short lived white blood cells • move through bloodstream • Macrophages – largest phagocytes • Found fixed in parts of lymphatic system (spleen, lymph nodes, thymus) • Some travel throughout body

12. Other cells • Dendritic cells – phagocytic - in tissues, stimulate adaptive immunity • Eosinophils – (low phagocytic) help defend against multicellular invaders, release destructive enzymes • Natural killer cells • Destroy virus-infected body cells, cancer cells • Attack cells membrane, so cell lyses

13. Lymphatic system • A network of vessels that distributes lymph through the body • Lymph nodes hold many macrophages help trap foreign substances

14. Interstitialfluid Bloodcapillary Adenoid Tonsils Lymphaticvessels Thymus Lymphatic vessel Tissuecells Lymphatic vessel Spleen Lymphnodes Lymphnode Masses ofdefensive cells

15. Antimicrobial proteins • Proteins involved in attacking microbes or stopping their reproduction • Lysozyme- present in tears & saliva, mucous • Complement proteins – 30 serum proteins – carry out steps to lyse microbes • Interferons – secreted by virus-infected cells, induce neighboring cells to produce chemicals to inhibit viral reproduction

16. Inflammatory response • Response to cut or entry of microorganisms • Area becomes inflamed, red, swollen • Result of chemical signals- • From invader • Nearby mast cells release histamines – released by body cells in response to injury • Histamines dilate capillaries and increase permeability, so fluid & clotting elements leave can enter site

17. Acute inflammatory response http://www.youtube.com/watch?v=suCKm97yvyk

18. Inflammatory response Pathogen Splinter Movementof fluid Macro-phage Signalingmolecules Mastcell Phagocytosis Capillary Neutrophil Redblood cells

19. Clotting begins • Other cells release chemokines, which attract phagocytes to area • Phagocytes consume pathogens & debris • Pus - a fluid rich in white blood cells, dead pathogens, and cell debris from damaged tissues http://www.youtube.com/watch?v=CmbWE3jLUgM&list=UUDwoLF9pXx4RgB7BgmsnY0w

20. 2. Specific Immunity • Specific immune responses to particular microorganisms • Found in vertebrates • Lymphocytes – type of white blood cells • 2 types: • T cells – mature in thymus • B cells – mature in bone marrow

21. Antigens • Substances that can elicit a response from a B or T cell • B or T cells have antigen receptors specific for parts of that pathogen – so they can recognize specific antigens Antigen receptors Mature B cell Mature T cell

22. Recognizing antigens

24. The specificity of the T & B receptors (and antibodies) is a result of shuffling and recombining several gene segments to produce the protein • There are more than 1 million different B cells and 10 million different T cells • Due to random arrangment, some receptors are specific for epitopes on organism’s own molecules, so B & T cells must be tested for self- reactivity.

25. http://www.youtube.com/watch?v=JiOwZsTO02w

26. B cells: • Mature in bone marrow • Produce antibodies • Receptors bind to intact antigens • T cells: • Mature in thymus • Do not produce antibodies • Receptors bind to antigens displayed by antigen-presenting cells (APCs) on their MHCs Both: Activated by cytokines, from helper T cells

27. MHC – major histocompatability complex – cell surface glycoproteins that differ among individuals - aid in recognition of “self” - Class I – found on nearly all body cells - can present fragments of proteins made by infecting microbes to cytotoxic T cells - Class II – made by some cells of immune system - macrophages & B cells - molecules collect remnants of microbes and present them to helper T cells

28. Clonal selection • Activation occurs when antigen binds to B or T cell. • Clones formed in clonal selection – two types produced: • Effector cells – fight the antigen • Memory cells – have receptors for same antigen, so allow quick response to subsequent infection • http://www.youtube.com/watch?v=HUSDvSknIgI

29. Responses • Primary response- when body first exposed to antigen and lymphocyte is activated • Secondary response – when same antigen is encountered later, faster more efficient response due to memory cells

30. Primary immune responseto antigen A producesantibodies to A. Secondary immune response toantigen A produces antibodies to A;primary immune response to antigenB produces antibodies to B. 104 103 Antibodiesto A Antibody concentration(arbitrary units) Antibodiesto B 102 101 100 7 35 56 49 0 14 21 28 42 Exposure to antigens A and B Exposureto antigen A Time (days)

31. Cell- mediated immunity • Activation & clonal selection of cytotoxic T- cells • Macrophages engulf antigens, process them internally, then display parts of them on their surface together with some of their own proteins. This sensitizes the T cells to recognize these antigens.

32. T-cells are trained in thymus • T- cells are chosen that have correct receptors to recognize MHC molecules • T- cells that can recognize MHC molecules complexed with foreign peptide are allowed to pass out of thymus

33. Cytotoxic T cells (Killer T cells) bind to class 1 MHC molecules, display fragments on surface of body cells. Destroy infected cells. • Helper T-cells: secrete cytokines in response to interaction with class 2 MHC molecules – stimulate & activate both cytotoxic T cells & B cells • Memory T cells – recognize & respond to antigen once it has already been encountered. • http://www.youtube.com/watch?v=1tBOmG0QMbA

34. Humoral response • Activation & clonal selection of effector B cells • Fight pathogens in body fluids • Activated B cells produce plasma & memory cells • Plasma cells –(effector cells) produce antibodies • Memory cells – for secondary response

35. Antibodies – soluble proteins secreted by B cells during an immune response • Antibodies destroy antigens through: • Neutralization: bind & block activity of antigen • Lysis: caused by activation of complement system- form a hole in membrane of pathogen • Agglutination: clumping of bacteria or viruses • Opsonization: results in increased phagocytosis of antigen (attracts macrophages)

36. Humoral response: • http://www.youtube.com/watch?v=hQmaPwP0KRI&list=UUDwoLF9pXx4RgB7BgmsnY0w&index=7 • Specific immunity • http://www.dnatube.com/video/194/Specific-Adaptive-immunity-humoral-and-cell-mediated

37. Active immunity – when body is exposed directly to pathogen, body responds • (infection, vaccination) • Passive immunity – when an individual receives antibodies • (to fetus from mother across placenta)

38. What can go wrong- • Over reaction of immune system – allergies • Reaction against self – autoimmune disease • Defects or problems with immune system - immunodeficiency

39. Allergy reaction animation • http://www.youtube.com/watch?v=IGDXNHMwcVs • Our immune system/ autoimmune diseases • http://www.youtube.com/watch?v=MI-BLaj5nFk