1. Immunology Chapter 43

2. Immune System A wide variety of pathogens (including parasites) think that animal hosts are excellent habitats and very tasty To stop from becoming a bacterial hotel, animals have ways to fight back Most critical component – know self from non- self cells and tissues Next, know how to kill the invaders without harming yourself

3. Two main components of vertebrate immune response:

4. Why is the innate immune response critical ? Time!

5. Innate Immunity - External Skin –Barrier, oil glands and sweat modify pH, salt level Mucous Membranes –Barrier, mucous traps and cilia removes particles Secretions –Stomach acid, lysozyme

6. Innate Immunity – Internal Phagocytic cells –Recognize non-self –Phagocytosis – engulf invader –Digest and display

9. Innate Immunity – Internal Phagocytic cells –Recognize non-self –Phagocytosis – engulf invader –Digest and display Antimicrobial proteins –Defensins, etc. - lysis of bacterial walls –Complement – lysis by cascade

10. The Defensins and cathelicidins home Jan, 2001. The Defensins and cathelicidins [online]. Seacroft and St James's University Hospitals, UK. Available from http://www.cysticfibrosismedicine.comhttp://www.cysticfibrosismedicine.com Anti microbial peptides called defensins and cathelicidins are innate immune factors present in airway surface liquid and make up part of the lung's natural defences (Bals et al, 1998; Bals et al, 1998; Singh et al, 1998). These peptides are produced by several different cell types including airway epithelial cells, macrophages and neutrophils. The defensins appear to be present in equivalent or higher concentrations in cystic fibrosis lungs as compared to controls. In cystic fibrosis their ability to kill bacteria may be impaired by the presence of abnormally high sodium concentrations within airway surface fluids (Bals et al, 1998; Bals et al, 1998, Goldman et al, 1998). Cathelicidin peptides also appear to have a wide range of antimicrobial activity although they may be under expressed in cystic fibrosis airways. The development of topically administered antimicrobial peptides may have a future role in the treatment of cystic fibrosis.

11. Innate Immunity – Internal Phagocytic cells –Recognize non-self –Phagocytosis – engulf invader –Digest and display Antimicrobial proteins –Defensins, etc. lysis of bacterial walls –Complement – lysis by cascade Inflammatory response –Injury causes release of signals (eg. Histamines) which increase blood flow to site –Causes heat and swelling

12. Chemical signals released by mac’s and mast cells Capillaries get leaky, agents move from blood to site Chemokines released, attract more cells Neutrophils and Mac’s eat em’ up

13. Innate Immunity – Internal Natural killer cells –Recognize and attack infected cells or cancer cells –Surface receptors recognize foreign antigens on self cell –NK attach and kill target cell (apoptosis) Invertebrate Immunity –Only innate but still complex –Has recognition factors and antibacterials

14. Two main components of vertebrate immune response:

15. Acquired Immunity Lymphocyte –White blood cell that recognizes specific component (usually protein) of an invader Antigen –Any foreign component that can elicit an immune response T cells –Develop in thymus, recognize antigens by specific receptor (T cell receptor) B cells –Develop in bone marrow, recognize antigen by specific receptor (B cell receptor)

18. Specificity – what does he mean by that? Do T cells and B cells have specific receptors?

20. Specificity – what does he mean by that? Do T cells and B cells have specific receptors? –They have different types of receptors –Each cell’s receptors recognize only one antigen –Your lymphocytes can recognize thousands of antigens, only one antigen/clone There are many of each clone in your bloodstream or lymph nodes

21. Humoral Immunity Antigen presenting cell contacts and activates helper T cells Cytokines (protein signals) released –Eg. interleukins B and T cells activated

23. Humoral Immunity Antigen presenting cells contacts and activates helper T cells Cytokines (protein signals) released B and T cells activated –Cell binding produces greater response

25. Humoral Immunity Antigen presenting cells contacts and activates helper T cells Cytokines (protein signals) released B and T cells activated –Cell binding produces greater response B cells divide (clones) B-cells release antibody (Plasma cells) Memory cells saved for later

26. 2 1 3 B cell Bacterium Peptide antigen Class II MHC molecule TCR Helper T cell CD4 Activated helper T cell Clone of memory B cells Cytokines Clone of plasma cells Secreted antibody molecules Endoplasmic reticulum of plasma cell Macrophage

28. Cell-mediated Immunity Cytotoxic T cells recognize infected self cells Bind to cell and initiate apoptosis (process of cell self-destruction)

29. Cytotoxic T cell Perforin Granzymes CD8 TCR Class I MHC molecule Target cell Peptide antigen Pore Released cytotoxic T cell Apoptotic target cell Cancer cell Cytotoxic T cell A specific cytotoxic T cell binds to a class I MHC–antigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell. 1 The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. 2 The granzymes initiate apoptosis within the target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells. 3 1 2 3

33. Antibodies Soluble proteins that recognize antigens on invaders Found in blood, mucus, and mother’s milk Antibody binding neutralizes invaders or activates immune response

35. Immunity Active Immunity –Produced by contact with an infectious agent –Can be natural (poked with a stick) or artificial (stuck with a needle - vaccination) –See Jenner, milkmaids, and cowpox Passive Immunity –Transfer of serum from survivor to you –Eg. Mother’s milk, snake anti-venom

36. Acquired Immunodeficiency Syndrome (AIDS) Human immunodeficiency virus (HIV) infects and kills helper T cells

38. Acquired Immunodeficiency Syndrome (AIDS) Human immunodeficiency virus (HIV) infects and kills helper T cells HIV is an RNA virus, it mutates rapidly Once in your cells it incorporates into your DNA Transmission requires someone’s body fluid getting into you

41. Herpes virus – fast growth, bursts cell quickly

42. AIDS Virus – Slow growth, maximum virus production