The Immune System

1. The Immune System By Sarah Kellogg, Anna Smith, and Nicole Sinno

2. Function: • To recognize and neutralize potentially harmful substances • Two types: • Innate immunity • Acquired/Adaptive immunity

3. Innate Immunity • Acquired/Adaptive immunity • Present before any exposure to pathogens • Effective from time of birth • Nonspecific, responding to broad range of microbes • Develops only after exposure to inducing agents such as microbes or toxins • Highly specific- distinguish one inducing agent from another

4. Innate Immunity: External Defenses First Line of Defense • Skin is barrier that viruses and bacteria cannot normally penetrate • However, tiny abrasions may allow them to get past • Therefore… Mucous membranes lining digestive, respiratory, and genitourinary tracts prevents entry of microbes, and produce mucus to trap the microbes • Secretions from skin and mucous membranes contain antimicrobial proteins that wash microbial colonization away (saliva and tears) • Lysozyme: an enzyme that digests cell walls of many bacteria • Present in saliva, tears, and mucous secretions • Destroy bacteria as enter upper respiratory tract or openings around eyes

5. Mucous membranes provide hostile environment to microbes • In humans, secretions from sweat glands give skin pH of 3 to 5 • Thus, skin too acidic for colonization of microbes • Stomach too acidic for most microbes • Hepatitis A virus can survive the acidic stomach

6. Innate Immunity: Second Line of Defense: Internal Cellular and Chemical Defenses • Phagocytosis: the ingestion of invading organisms by certain types of white blood cells • Phagocytes • Defend against microbes that have managed to enter the body • Attach to their prey via surface receptors and engulf them, forming vacuole that fuses with lysosome

7. White Blood Cells (Leukocytes) • Attracted by chemical signals released by damaged cells • 4 types of phagocytic white blood cells • Neutrophils • Macrophages • Eosinophils • Dendritic cells

8. 1. Neutrophils: • engulf microbes in infected tissue • Self destruct in process of phagocytosis • 60%-70% of all white blood cells 2. Macrophages • more effective • Develop from monocytes • Most are permanent residents in organs and tissue • Play role in acquired immunity 3. Eosinophils • Defend against parasitic invaders by positioning themselves near parasites wall and discharging hydrolytic enzymes 4. Dendritic cells • Ingest microbes like macrophages do • Main role: trigger acquired immunity

9. Antimicrobial Proteins • function in innate defense by attacking microbes directly or by impeding their reproduction • Complement system • Include 30 serum proteins • In absence of infection, these proteins are inactive • Substances on surfaces of microbes trigger steps that activate this system and cause lysis of invading cells • Interferon • Secreted by virus infected body cells • Induce neighboring cells to produce substances that inhibit viral reproduction

10. Inflammatory responseInnate Defense • Histamine is release by mast cells • When injured, mast cells release their histamine, and trigger dilation and permeability of nearby capillaries • Helps deliver clotting agents to injured area • Blood flow also brings large numbers of phagocytes to the infected area • Proteins called chemokines direct migration of phagocytes • Increased blood flow to injured site causes the redness and typical of inflammation • The blood filled capillaries leak fluid into neighboring tissues causing the swelling

11. Natural Killer Cell (NKC)Innate Defense • Patrol body and attack virus infected body and cancer cells • Once attached to virus infected cell (surface receptors) it releases chemicals that triggers apoptosis in cells they attack • Prevents cancer and viral infections

12. Acquired Immunity (body’s 2nd major kind of defense) • Lymphocytes provide the specificity and diversity of the immune system • Recognize particular microbes and foreign molecules (antigens) by means of antigen specific receptors in plasma membrane • Originate from pluripotent stem cells in bone marrow and later develop into either B or T cells • Vertebrates have two types of lymphocytes: • B lymphocytes (B Cells) • Proliferate in bone marrow • T lymphocytes (T Cells) • Migrate from bone marrow to mature in the thymus and develop into T cells

13. New Vocabulary • Antigens: any foreign molecule • Antibodies: proteins secreted by B cells during an immune response • Antigen receptors: located on antigen and allow B and T cells to recognize them

14. Antigen- binding sites Epitopes (antigenic determinants) Antibody A Antigen Antibody B Antibody C • A lymphocyte actually recognizes and bindsto just a small, accessible portion of the antigen called an epitope

15. B Cell Receptors T Cell Receptors • Bind to specific, intact antigens • Bind to fragments of antigens displayed by other cells

16. T Cell Receptors and MHC • While receptors on B cell receptors recognize intact antigens, the receptors on T cells recognize small fragments of antigens bound to normal cell surface proteins • These cell surface proteins are called MHC molecules (major histocompatibility complex) • Newly synthesized MHC molecules are transported toward the plasma membrane, bind with a peptide antigen within the cell, and bring it to the surface of the cell • Antigen presentation

17. T Cell Receptors and MHC Continued • Two ways a foreign antigen can end up inside cells of body, depending on source, antigens are handled by a different class of MHC molecule and recognized by specific T cell: • Class 1 MHC molecules • All nucleated cells of body • Bind peptides synthesized within the cell • Any body cell infected or cancerous display antigens • Recognized by subgroup cytotoxic T cells • Class II MHC molecules • Cell types dendritic, macrophages, and B cells • Bind peptides from foreign molecules internalized and fragmented through phagocytosis or endocytosis • Dendritic cells, macrophages, and B cells display antigens • Helper T-cells recognize antigens

18. Antigen- presenting cell Microbe A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. 1 Antigen fragment 2 Class II MHC molecule The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. T cell receptor Helper T cell (b) T Cell Receptors and MHC Continued

19. Clonal Selection of Lymphocytes • Antigen binds to B or T cell • Lymphocyte becomes activated and forms two clones of cells • Effector cells (combat pathogens) • Memory cells (long lived and have receptors for same antigen)

20. Primary Immune Response • When body is first exposed to antigen: • Antigen binds to to a mature lymphocyte • Lymphocyte is activated (clonal selection) • takes 10 to 17 days for effective response to an antigen

21. Secondary Immune Response • Upon second exposure to the antigen: • Some of the B cells produced during clonal selection differentiate into another kind of white blood cell called a memory cell • Memory cells can last a very long time—years, decades, or a whole lifetime • If particular pathogen happens to enter body again, memory cells trigger a second round of clonal selection called the secondary immune response • Faster response (2-7 days) and greater magnitude • So effective that all the invaders are usually destroyed before any symptoms appear

22. Types of B and T Cells B- Cells Plasma B-Cells- Secrete antibody molecules, which prevent pathogens from working Memory B-Cells-Long living cells that are created during the primary immune response, if they recognize the pathogen that triggered their creation, they start a secondary immune response. T-Cells Cytotoxic T Cell- Destroys cells infected with pathogens or that have turned cancerous. Memory Cytotoxic T Cells-Long living cells that are created during the primary immune response, if they recognize the pathogen that triggered their creation, they start a secondary immune response. Helper T Cells-Recognize pathogens and trigger a primary immune response and signal other lymphocytes to activate.

23. The Two Branches of Acquired Immunity • Humoral Immune Response-The activation of B cells, which results in the production of secreted antibodies that circulate in the blood. • Cell-Mediated Immune Response-The activation of cytotoxic T cells , which destroy cells that have been infected by viruses or other pathogens. They can also destroy cancer cells

25. Helper T Cell Response

26. Cytotoxic T Cell Response

27. B Cell Response (T-dependent Antigens)- antigens that induce antibody production only with assistance from helper T cells

28. Antibodies(Immunoglobulin) • Some antigens can evoke B cell response without helper T cells called T-independent antigens • Most antigens recognized by B cells contain multiple epitopes • Exposure to single antigen stimulates variety of B cells giving rise to thousands of plasma cells • Plasma cells in one clone secrete antibodies specific to epitope that provoked production • Bind to antigens to inactivate pathogens

29. Antibodies • Secreted antibody has general Y-shaped structure as B cell receptor but lacks transmembrane region that would anchor it to plasma membrane • Antigen binding sites on antibody responsible for ability to identify antigen • Tail of Y shaped body responsible for distribution in body and mechanisms for removing antigens (constant (C) regions of heavy chains) • Five major types of heavy-chain constant regions • Determine five major classes of antibodies • Based on immunoglobulin (Ig)

30. Active and Passive Immunization • Active Immunity-Immunity created by natural exposure to a pathogens. It can also be created by vaccination • Passive Immunity-Immunity that is conferred by the transfer of antibodies from an outside source into an organism.

31. BLOOD GROUPS • Type A red blood cells have A antigen molecules on their surface • Thus, the A antigen may be recognized as foreign if placed in the body of another person. Individuals with the A antigen do not produce antibodies against the A antigen, because they are self-tolerant, but they have antibodies against the B antigen, even if not exposed to foreign blood. • IgM antibodies • Type B antigen found on type B red blood cells • Both A and B antigens found on type AB red blood cells • Neither antigen found on type O

32. TISSUE AND ORGAN TRANSPLANTATION • MHC molecules responsible for stimulating immune response that leads to rejection of tissue and organ transplants and grafts • At least some MHC molecules on donated tissue are foreign to recipient • No danger of rejection if donor and recipient are identical twins or if tissue is grafted from one part of the body and inserted on another part • To minimize rejection: • In bone marrow transplant,

33. ALLERGIES • Hypersensitive responses to antigens (allergens) which could include foods, animals, or plants • Most common allergens involve antibodies of IgE class • Example: hay fever occurs when plasma cells secrete IgE antibodies specific for antigens on surface of pollen grains • These antibodies attach to mast cells in connective tissues • When pollen grains re-enter body, they attach to antigen-binding sites of mast cell associated IgE antibody molecules inducing the mast cell to release histamine and other inflammatory agents • Leads to allergy symptoms- difficulty breathing, sneezing, runny nose, etc, or • Anaphylactic shock from dilation of peripheral blood vessels that leads to a drop of blood pressure and potential death

34. AUTOIMMUNE DISEASE • Immune system looses tolerance for itself and turns against certain molecules in the body • Example: systemic lupus erythematosus • Immune system generates antibodies against wide range of self molecules including histones and DNA released by normal breakdown of body cells • Symptoms: skin rashes, fever, arthritis, kidney dysfunction

35. IMMUNODEFICIENCY DISEASES Inborn (Primary) Immunodeficiencies • Result from defects in development of various immune system cells or defects in production of specific proteins, such as IgA antibodies or complement components • Innate defense, acquired defense, or both may be impaired • Severe combined immunodeficiency (SCID) • Both humoral and cell-mediated branches of acquired immunity fail to function • Bone marrow transplant necessary to supply functional lymphocytes

36. IMMUNODEFICIENCY DISEASES Acquired (Secondary) Immunodeficiencies • Stress and the Immune System • Healthy immune system depends on endocrine and nervous system • People suffering from depression more likely to develop cancer • Physical and emotional stress can harm immunity • Hormones secreted by adrenal glands during stress affected number of white blood cells a may suppress immune system • Neurotransmitters secreted when relaxed and happy may enhance immunity

37. Acquired Immunodeficiency SyndromeAIDS • AIDS is caused by the loss of helper T cells • Crippling both the humoral and cell-mediated immune responses • The loss of T Cells is caused by human immunodeficiency virus (HIV), a retro virus that targets T Cells • Cannot be cured • Some drugs slow the progress of the disease • Frequent mutations limit the efficiency the drugs • Contracted by transfer of bodily fluids • Estimated in 2003 that 40 million people were infected

38.  1. Phagocytosisis best defined as _____. The process by which a white blood cell engulfs and destroys a bacterium The process by which a cell engulfs and takes up liquid the fusion of an intracellular vesicle with the plasma membrane of a cell the process of activating memory T cells

39. Which of the following is not part of the body’s innate nonspecific defense system? Natural killer cells Inflamation Phagocytosis by neutrophils Phagocytosis by macrophages antibodies

40. An epitope associates with which part of an antibody? a. The antibody binding site • The heavy chain constant region only • The variable regions of a heavy chain and light chain combined • The light chain constant regions only • The antibody tail

41. 4. A macromolecule produced in the body, which recognizes another molecule as "foreign" to the body, is a(n) _____. • Antigen • Antibody • Lymphocyte • macrophage

42. 5. The first line of defense against infection is _____. • The skin and mucous membranes • The inflammatory response • The immune system • Antibiotics