1. Chapter 43: The Immune System

2. Essential Knowledge 2.d.2 - Homeostatic mechanisms reflect both common ancestry and divergence due to adaptation to different environments (43.3). 2.d.3 – Biological systems are affected by disruptions to their dynamic homeostasis (43.2-43.4). 2.d.4 – Plants and animals have a variety of chemical defenses against infections that affect dynamic homeostasis (43.1-43.4). 3.d.2 Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling (43.2).

3. Focus Topics Immunological responses to pathogens, toxins, and allergens Vertebrate immune systems have nonspecific and nonheritable defense mechanisms against pathogens The mammalian immune system includes two types of specific responses: cell mediated and humoral In the cell-mediated response, cytotoxic T cells, a type of lymphocytic white blood cell, “target” intracellular pathogens when antigens are displayed on the outside of the cells.

4. Focus Topics In the humoral response, B cells, a type of lymphocytic white blood cell, produce antibodies against specific antigens. Antigens are recognized by antibodies to the antigen. Antibodies are proteins produced by B cells, and each antibody is specific to a particular antigen. A second exposure to an antigen results in a more rapid and enhanced immune response.

5. Introduction to Immunity Defense system Defense system Protects from bacteria, viruses, other pathogens, early-stage cancer cells Three types of immunity: 1. Innate: nonspecific defense mechanisms  external physical barriers of skin mucous membranes  internal defenses of chemicals and phagocytic cells  Ex: gastric juices, histamines, inflammatory response

6. Introduction to Immunity Three types of immunity: 2.Acquired: adaptive immunity, line of defense in which lymphocytes react specifically to threat, two types  Humoral – antibodies produced by cells mark microbes for destruction, involves B cells  Cell-mediated – cytotoxic lymphocytes destroy infected body cells, cancer cells and foreign tissue, involves helper T cells 3. Passive: acquired temporarily ◦ Ex: through breast-feeding

8. Organs/Tissues/ Glands involved: ◦ Bone/bone marrow ◦ Spleen ◦ Stomach/Intestines ◦ Skin ◦ Lungs ◦ Lymph nodes

9. Introduction to Immunity Leukocytes are the cells which are the bulk of your immune system. ◦ Produced or stored in:  Thymus, spleen, and bone marrow (called the lymphoid organs)  There are also clumps of lymphoid tissue throughout the body (primarily as lymph nodes) that hold leukocytes

10. Introduction to Immunity The two basic types of leukocytes are: ◦ Phagocytes, cells that chew up invading organisms  Ex: neutrophils ◦ Lymphocytes, cells that allow the body to remember and recognize previous invaders and help the body destroy them  Ex: B and T cells

11. The leukocytes circulate through the body between the organs and nodes via lymphatic vessels and blood vessels. In this way, the immune system works in a coordinated manner to monitor the body for germs or substances that might cause problems. Introduction to Immunity

13. Innate Immunity External defenses ◦ Skin – secretions lower pH (discourage microbial attack) ◦ Mucous membranes (line digestive, respiratory, genitourinary tracts)  Gastric juice – lowers pH to acidic  Epilethial lining of respiratory – traps microbes ◦ Lysozyme – enzyme that attacks bacterial cell walls  Present in tears, saliva, and mucus ◦ Serve as physical barriers to microbes

14. Innate Immunity Internal defenses ◦ Systemic response may include:  Increase in number of circulating WBCs  Fever  Triggered by toxins produced by pathogen or chemicals released by immune system  Stimulates phagocytosis and thus tissue repair and immune response  Inflammation  Redness, swelling, heat  Occurs when damaged mast cells (in connective tissue) release histamine  Histamine: triggers dilation and leakiness of blood vessels

16. Innate Immunity Internal defenses ◦ Relies upon phagocytosis by special WBCs (phagocytes)  These cells release antimicrobial proteins to help initiate an inflammation response  Rely upon cell surface rectors to bind to microbial surface receptors  Then, engulfs microbe and kill them using lysosome toxins  Neutrophils: most numerous phagocytic WBCs  Eosinophils: WBCs that attack multicellular parasites  Dendritic cells: stimulate acquired immunity

17. Innate Immunity Internal defenses ◦ Natural killer (NK) cells: nonphagocytic cells that also participate in innate defenses  Recognize general features of viral-infected or cancer cells  Attaches to them and triggers apoptosis ◦ Complement system: 30 proteins that can lyse microbes, trigger inflammation or assist in acquired immunity ◦ Interferons: stimulate neighboring cell to produce anti-viral reproduction substances

18. Acquired Immunity Introduction ◦ First visit: Immune System PreviewImmune System Preview ◦ Key cells: lymphocytes (WBCs) ◦ Activated by contact with microbes OR by cytokines (proteins secreted by macrophages) ◦ Recognizes antigens (foreign molecules)  Most are large proteins or polysaccharides  Often protrude from surface of microbe  Epitope: region of antigen to which lymphocyte attaches

19. Acquired Immunity Antigen Recognition ◦ Performed by B and T cells  B lymphocytes (B cells) and T lymphocytes (T cells) circulate in blood and lymph  Found in spleen and lymph nodes  Recognized by antibodies to the particular antigen  Both contain membrane-bound antigen receptors which allows them to recognize specific epitopes (where they will bind)

20. Acquired Immunity Antigen Recognition ◦ B cell receptor  Y-shaped  Consists of 4 polypeptide chains (two light chains and two heavy chains) ◦ T cell receptor  One alpha chain and one beta chain  Recognize special cell-surface proteins made by MHC (major histocompatibility complex – a family of genes)

23. Acquired Immunity Primary immune response ◦ Begins this response upon first exposure to an antigen (foreign molecule) ◦ Requires about 10-17 days to yield maximum response via T and B-cells ◦ Immunological memory: secondary immune response that provides long-term protection against a previously encountered pathogen  “To avoid illness, expose yourself to germs, enabling your immune system to develop antibodies. I don’t know why everyone doesn’t do this. Maybe they have something against living forever.” ~Dwight Schrute

24. Acquired Immunity Two types: ◦ Humoral immune response  Involves B cell activation and production of antibodies  Antibodies then circulate in blood and lymph  Provide defense against pathogens and toxins in the extracellular fluid ◦ Cell-mediated response  Involves cytotoxic T cells that destroy infected body cells, cancer cells and transplanted tissues  Relies upon Helper T cells to activate B cells and cytotoxic T cells

26. Acquired Immunity Only found in vertebrates T cells and B cells ◦ Types of WBCs called lymphocytes ◦ Originate from stem cells in the bone marrow ◦ Some lymphocytes migrate from the marrow to the thymus  These mature into T cells ◦ Some lymphocytes remain in the marrow  These develop into B cells ◦ Other lymphocytes stay in the blood and become the natural killer cells of innate immunity

27. Acquired Immunity Antigens are substances that prompt a response from a B or T cell Antigen receptor proteins allow B and T cells to bind to antigens ◦ Specific enough to bind to just one part of one molecule from a particular pathogen ◦ Millions of antigen receptors (AR) are produced, but all AR’s are identical on each B and T cell ◦ Up to 100,000 AR’s on the surface of each B and T cell! ◦ See Fig. 43.9, page 935

28. Antigen Specifics Usually foreign Large molecules ◦ Proteins or polysaccharides Protrude from the surface of foreign cells or viruses Some, such as bacterial toxins, are released into the extracellular fluid Small, accessible portion that binds to an AR is called an epitope or antigenic determinant ◦ Each antigen has several different epitopes, each binding a receptor with a different specificity

29. B Cell and Antibody-Antigen Recognition Each B cell AR is a Y-shaped molecule of 4 polypeptide chains ◦ Two identical heavy chains ◦ Two identical light chains ◦ Fig. 43.9, page 935 Light and heavy chains have a constant region where amino acid sequences don’t vary much and a variable region on which the amino acid sequence varies extensively from one B cell to another

30. Formation of Antibodies When a B cell AR binds to an antigen, that will elicit B cell activation eventually leading to the formation of cells that secrete a soluble form of the receptor ◦ The secreted protein is an antibody or immunoglobulin (Ig) Antibodies are Y-shaped like the B cell AR’s ◦ But are secreted rather than membrane-bound ◦ Antibodies are the proteins that defend against pathogens ◦ Differences in amino acid sequences of variable regions on the B cell AR’s allow highly specific binding B cell AR’s and antibodies bind to intact antigens in the blood and lymph Fig. 43.10, page 936

32. T Cell Antigen Recognition T cell AR’s are two different polypeptide chains, an α chain and a β chain, linked by a disulfide bridge (fig. 43.11, page 936) Outer tips of each chain consist of the variable region and are where the antigen binds Remainder of the molecule is the constant region Bind to fragments of antigens that are presented on the surface of host cells ◦ The host protein that displays the antigen fragment on the cell surface is the MHC (major histocompatibility complex) molecule

33. Recognition of Protein Antigens by T Cells Begins when a pathogen or part of a pathogen either infects of is taken in by a host cell (Fig. 43.12, page 937) Enzymes in the host cell break the antigen into smaller peptides called antigen fragments ◦ These bind to MHC molecules inside the cell ◦ MHC molecule with the bound antigen fragment move to the cell surface resulting in antigen presentation  This advertises that the host cell contains a foreign substance If the cell displaying an antigen fragment encounters a T cell that is the right match, the AR on the T cell will bind to the antigen fragment and the MHC molecule ◦ This binding is necessary for a T cell to participate in an adaptive immune response

34. Acquired Immunity Active immunity: acquired when body produces antibodies and develops immunological memory from either exposure to actual pathogen OR from immunization/vaccinization ◦ Vaccine can be:  1) inactive toxic  2) killed/weakened microbe  3) portion of microbe  3) genes for microbial proteins

35. Passive Immunity Passive immunity: temporary immunity provided by antibodies ◦ Supplied through:  Placenta to fetus  Milk to nursing infant  Antibody injection

36. Tissue Transplant Limited by immune system’s ability to distinguish self from nonself Immune system responds negatively to chemical markers (unlike itself) during blood transfusions (and tissue transplantation) Mother and fetus: Rh factor ◦ Rh: protein, RBCs antigen ◦ If fetal blood is different from mother, fetal blood can leak across placenta (creating immunological response from mother)

37. Tissue Transplantation Organ and Tissue Transplants ◦ May be rejected b/c the foreign MHC molecules are antigenic ◦ Triggers immune response ◦ Use closely related donors and immune system suppressor drugs to minimize risk of rejection

38. Immune System Diseases Allergies ◦ Hypersensitivity to certain environmental antigens (allergens) ◦ Releases histamines – creating inflammatory response that may include:  Sneezing  Runny nose  Difficulty breathing ◦ Antihistamine drugs – those that combat these symptoms by blocking histamine receptors ◦ Ex: Asthma, eczema (dry skin), environmental allergies (dust, dust mites, grass)

39. Immune System Diseases Autoimmune Disease ◦ Ex: Lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus, multiple sclerosis ◦ May be caused by failure in regulation of self- reactive lymphocytes ◦ Causes immune system to turn against itself ◦ Ex: Scleroderma, a chronic autoimmune disease that can lead to inflammation and damage of the skin, joints, and internal organs ◦ Ex: Ankylosing spondylitis, a disease that involves inflammation of the spine and joints, causing stiffness and pain

40. Immune System Diseases Immunodeficiency diseases ◦ Ex: AIDS (caused by HIV), cancer, Hodgkin’s disease, stress ◦ Suppress the immune system ◦ Become highly susceptible to opportunitistic infections (like pneumonia, flu, etc) ◦ Ex: DiGeorge syndrome (thymic dysplasia), a birth defect in which kids are born without a thymus gland ◦ Ex: Chediak-Higashi syndrome and chronic granulomatous disease both involve the inability of the neutrophils to function normally

41. Exclusion Statements Memorization of the structures of specific antibodies is beyond the scope of the course and the AP Exam.