Chapter 43: The Immune System

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 • Protects from bacteria, viruses, other pathogens, early-stage cancer cells • Three types of immunity: • 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: • 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 • 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. Introduction to Immunity • 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.

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 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: Ankylosingspondylitis, 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.