1. Misericordia University
Immunity
General Physiology
Tony Serino, Ph.D.
Biology Department
Misericordia University

2. Immune System
Provide defense of the body against infectious agents, toxins, foreign bodies, and cancers
Two types of defenses:
General (Non-specific or Innate) Defense
Barriers
Normal Flora and Fauna
Fever
Surveillance
Inflammation
Non-specific Phagocytic WBCs and NK cells
Protective Chemicals
Specific (Adaptive) Defense --Lymphocytes

3. Barriers
Prevent infectious agents from penetrating internal environment
Epithelium ( thickness, tight junctions, keratin) -especially the skin
Cilia and mucus
Watery secretions (tears, saliva)
Acidity (stomach, urine, vaginal secretions)
Normal Flora and Fauna –resident bacteria prevent infectious agents from growing on body surfaces

4. Fever Rise in Body Temperature
Inhibits invading cell growth; increase body metabolism to increase defense/repair cell activity
Produced by release of pyrogens from leukocytes
Low grade fever is beneficial in fighting infection, high sustained fever may be life threatening

5. Surveillance Number of cells and organs to detect invading agents
Langerhans cells of skin, Mast cells, Dendritic cells, and organs like: Tonsils, GALT cells
Gather antigens and present them to lymphocytes

6. Inflammation Allows more blood defenses into damaged areas
Triggered by release of paracrines from damaged tissues (PG), attacking WBCs (cytokines), mast cells (heparin and histamine), and activation of blood protective chemicals (complement and bradykinins)
Increases:
blood flow through vasodilation (hyperemia)
capillary permeability
Both lead to local edema
If prolonged or systemic, can become life threatening

7. Inflammatory Response

8. Phagocytic WBC and NK cells
WBCs can distinguish the sugars in mammalian cells and those found on bacteria or other parasites
PMNs, macrophage, and mast cells can injure or destroy cells that do not display normal sugars
NK cells –related to T-cells but attack any cell not displaying MHC I proteins
Kill by secreting perforins and other chemicals

9. Fig
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10. Phagocytosis

11. Fig
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12. Fig
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13. Fig
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15. Fig
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16. Fig
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17. Fig
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19. Protective Chemicals
Chemicals that aid in destroying or retarding infectious agents
Interferon –cytokine released when cell attacked by virus; warns other cells in area
Lysozyme –antibacterial enzyme present in tears and saliva
Complement –blood proteins which can detect and destroy bacteria

20. Interferon

21. Fig
18.04.jpg

22. Complement
MAC –membrane attack complex (C3-C9)

23. Specific (Adaptive) Immunity
Individual targets are selected for attack by the lymphocytes that can bind that target (antigen)
Antigens (Ag) – any large substance not normally found in the body; these illicit an immune response (immunogenic and immuno-reactive)
Haptens are small molecules that can trigger an immune response only if bound to larger molecules (like: pollen, some cosmetics, detergent fragrances, poison ivy animal dander and drugs); they are immuno-reactive but not immunogenic by themselves

24. Antigenic Determinants
Large macromolecules illicit immune response because they have many sites to which immune molecules will attach; proteins have the most of any molecule

25. Identifying “Self” from “Non-self”
T-cells migrate to thymus, B-cells remain in bone marrow (the primary lymphoid tissues)
Become immunocompetent -selected for their ability to produce a surface receptor against an antigen and to tolerate self antigens
Those that bind weakly to self-antigens are selected, the others are eliminated
The strongest self-antigens are the MHC proteins
Once competent, the cells are released to move through the blood and aggregate in the secondary lymphoid tissues

26. Fig
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27. Thymic Selection

28. Movement of Lymphocytes

29. Cells Involved in Specific Immunity
Lymphocytes (B and T cells) -attack antigen bearing agents either chemically (humoral immunity –the B-cells) or physically (cellular immunity –the T-cells)
T and B-cell activation to an antigen works best when they are presented with the antigen by another cell
APCs (Antigen Presenting Cells) (macrophage, surveillance cells, B-cells, infected cells) display foreign antigenic determinants on their MHC II cell surface proteins to activate the lymphocytes

30. Fig
Usually presented by APC
18.09.jpg

31. Memory T cell

32. B-cell Clonal Expansion

33. Fig
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34. Antibody Structure

37. Antibody Actions
Opsonization –Ag-Ab complex makes ID for phagocytosis easier

38. Humoral Response

39. Fig
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40. Control of Lymphocyte Response
B-cells can be activated by the antigen alone, but it is more effective if they are presented the antigen by APCs or stimulated by T-helper cells
Activation of T-helper cells stimulates complete lymphocyte response

41. MHC I –found on all body’s cells except RBCs
Surface proteins usually bound to pieces of intracellular proteins, but when infected they present fragments of the infectious agent

42. 2. Antigens are transported into the rough endoplasmic reticulum.
1. Foreign proteins or self- proteins within the cytosol are broken down into fragments that are antigens.
2. Antigens are transported into the rough endoplasmic reticulum.
Protein
fragments
(antigens) 2 3
MHC class I
molecule
3. Antigens combine with MHC class I molecules. 1
4. The MHC class I/antigen complex is transported to the Golgi apparatus, packaged into a vesicle, and transported to the plasma membrane.
Lumen 4
Membrane
Foreign antigen
Protein
Rough
endoplasmic
reticulum 5
5. Foreign antigens combined with MHC class I molecules stimulate cell destruction.
Self-antigen
Golgi apparatus 6
6. Self-antigens combined with MHC class I molecules do not stimulate cell destruction.

43. MHC II –found on APCs
-bound to phagocytized outer coat molecules of immuno-agent

44. 2. The antigen is broken down into
1. The unprocessed extracellular antigen is ingested by endocytosis and is within a vesicle.
Vesicle
containing
MHC class II
molecules
2. The antigen is broken down into
fragments to form processed antigens. 2
3. The vesicle containing the processed antigen fuses with vesicles produced by the
Golgi apparatus that contain
MHC class II molecules. The processed antigen and the MHC class II molecule combine. 1 3
Vesicle
containing
processed
antigen
Unprocessed
antigen 4
4. The MHC class II/antigen complex
is transported to the plasma
membrane.
MHC class II
molecule
Processed
antigen
5. The displayed MHC class II/antigen
complex can stimulate immune cells. 5

45. T-cell Types

47. Fig
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48. Helper T-Cell Activation
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Fig

49. Fig
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50. Fig
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51. Helper T-cells

52. Clonal Selection of T-cell

53. Fig
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54. Cytotoxic T-cell Attack

55. Fig
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56. Primary Immune Response

57. Vaccine Production

58. Types of Acquired Immunity

59. Acute Allergic Reaction

60. Acute Phase Response
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61. Fig
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62. Fig
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63. Fig
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64. Pathologies
AIDS –HIV invades T-helper cells, diminishing effectiveness of immune response; may have as long as 8 year incubation time, 100% fatal
Autoimmune Diseases –Immune system targets naturally occurring compounds of the body (usually sequestered proteins) MS, rheumatoid arthritis, Diabetes mellitus (I), etc.
Cancer –cancers cells spontaneously form during life, but the immune system keeps them in check; failure results in tumors and metastasis