Invading microbes (pathogens)

1. Innate immunity is present before any exposure to pathogens and is effective from the time of birth • It involves nonspecific responses to pathogens • Key internal defenses are macrophages and other phagocytic cells

2. Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances • Recognition is by white blood cells called lymphocytes • Some lymphocytes produce antibodies; others destroy infected cells, cancer cells, or foreign tissue

3. ACQUIRED IMMUNITY Slower responses to specific microbes INNATE IMMUNITY Rapid responses to a broad range of microbes External defenses Internal defenses Skin Phagocytic cells Humoral response (antibodies) Mucous membranes Antimicrobial proteins Secretions Inflammatory response Invading microbes (pathogens) Cell-mediated response (cytotoxic lymphocytes) Natural killer cells

4. The phagocytic cells called neutrophils constitute about 60–70% of all white blood cells (leukocytes). • Cells damaged by invading microbes release chemical signals that attract neutrophils from the blood. • The neutrophils enter the infected tissue, engulfing and destroying microbes there. • Neutrophils tend to self-destruct as they destroy foreign invaders, and their average life span is only a few days.

5. Monocytes, about 5% of leukocytes, provide an even more effective phagocytic defense. • After a few hours in the blood, they migrate into tissues and develop into macrophages, which are large, long-lived phagocytes. • Some macrophages migrate throughout the body, while others reside permanently in certain tissues, including the lungs, liver, kidneys, connective tissues, brain, and especially in lymph nodes and the spleen.

6. Eosinophils, about 1.5% of all leukocytes, contribute to defense against large parasitic invaders, such as the blood fluke, Schistosoma mansoni. • Eosinophils position themselves against the external wall of a parasite and discharge destructive enzymes from cytoplasmic granules. • Dendritic cells can ingest microbes like macrophages. However, their primary role is to stimulate the development of acquired immunity

7. Secretions of the skin and mucous membranes provide an environment hostile to microbes • Secretions give the skin a pH between 3 and 5, acidic enough to prevent colonization of many microbes • Skin secretions include proteins such as lysozyme, which digests bacterial cell walls

8. Internal Cellular and Chemical Defenses • Internal cellular defenses depend mainly on phagocytosis • White blood cells called phagocytes ingest microorganisms and initiate inflammation

9. Phagocytic Cells • Phagocytes attach to prey via surface receptors and engulf them, forming a vacuole that fuses with a lysosome • Macrophages, a type of phagocyte, migrate through the body and are found in organs of the lymphatic system • The lymphatic system defends against pathogens

10. Microbes Pseudopodia MACROPHAGE Vacuole Lysosome containing enzymes

11. Lymphatic capillary Interstitial fluid Adenoid Tonsil Blood capillary Lymph nodes Lymphatic vessel Spleen Tissue cells Peyer’s patches (small intestine) Appendix Lymphatic vessels Masses of lymphocytes and macrophages Lymph node

12. Inflammatory Response • In local inflammation, histamine and other chemicals released from injured cells promote changes in blood vessels • These changes allow more fluid, phagocytes, and antimicrobial proteins to enter tissues

13. Pin Blood clot Pathogen Macrophage Blood clotting elements Chemical signals Phagocytic cells Phagocytosis Capillary Red blood cell

14. Natural Killer Cells • Natural killer (NK) cells attack virus-infected body cells and cancer cells • They trigger apoptosis in the cells they attack

15. In acquired immunity, lymphocytes provide specific defenses against infection • Acquired immunity is the body’s second major kind of defense • An antigen is a foreign molecule that is recognized by lymphocytes and elicits a response from them • A lymphocyte recognizes and binds to a small portion of the antigen called an epitope

16. Antigen- binding sites Epitopes (antigenic determinants) Antibody A Antigen Antibody B Antibody C

17. Antigen Recognition by Lymphocytes • Two main types of lymphocytes circulate in the blood of vertebrates: B lymphocytes (B cells) and T lymphocytes (T cells) • All antigen receptors on a single cell recognize the same epitope

18. B Cell Receptors for Antigens • B cell receptors bind to specific, intact antigens • Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane

19. Antigen- binding site Antigen- binding site Antigen- binding site Disulfide bridge V V V V Light chain Variable regions V V C C C C C C Constant regions Transmembrane region Plasma membrane b chain  chain Heavy chains Disulfide bridge T cell B cell Cytoplasm of B cell Cytoplasm of T cell A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. A T cell receptor consists of one a chain and one b chain linked by a disulfide bridge.

20. T cells bind to antigen fragments that are bound to cell-surface proteins called MHC (major histocompatibility complex) molecules

21. Infected cells produce MHC molecules, which bind to antigen fragments and are transported to the cell surface, a process called antigen presentation • A nearby T cell can then detect the antigen fragment displayed on the cell’s surface • Depending on their source, peptide antigens are handled by different classes of MHC molecules

22. Class I MHC molecules are found on almost all nucleated cells of the body • They display peptide antigens to cytotoxic T cells

23. Infected cell Microbe Antigen- presenting cell Antigen fragment Antigen fragment Class II MHC molecule Class I MHC molecule T cell receptor T cell receptor Cytotoxic T cell Helper T cell

24. Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells • They display antigens to helper T cells

25. Lymphocyte Development • Lymphocytes arise from stem cells in bone marrow • Newly formed lymphocytes are alike but later develop into B cells or T cells, depending on where they mature

26. Bone marrow Thymus Lymphoid stem cell B cell T cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others)

27. Testing and Removal of Self-Reactive Lymphocytes • As B and T cells mature in the bone and thymus, their antigen receptors are tested for self-reactivity • Lymphocytes with receptors for antigens that are already in the body are destroyed by apoptosis or rendered nonfunctional

28. Clonal Selection of Lymphocytes • In a primary immune response, binding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation • This process is called clonal selection • Clonal selection of B cells generates a clone of short-lived activated effector cells and a clone of long-lived memory cells • In the secondary immune response, memory cells facilitate a faster, more efficient response

29. Antigen molecules B cells that differ in antigen specificity Antigen receptor Antibody molecules Clone of plasma cells Clone of memory cells

30. Humoral and cell-mediated immunity defend against different types of threats • Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies • Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells

31. Helper T Cells: A Response to Nearly All Antigens • A surface protein called CD4 binds the class II MHC molecule • This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs • Activated helper T cells secrete cytokines that stimulate other lymphocytes

32. Peptide antigen Cytotoxic T cell Dendritic cell Class II MHC molecule Cell-mediated immunity (attack on infected cells) Helper T cell Bacterium TCR Humoral immunity (secretion of antibodies by plasma cells) CD4 Dendritic cell B cell Cytokines

33. Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells • Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell • Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer • The activated cytotoxic T cell secretes proteins that destroy the infected target cell

34. Released cytotoxic T cell Cytotoxic T cell Perforin Cancer cell Granzymes TCR Apoptotic target cell CD8 Class I MHC molecule Pore Target cell Peptide antigen Cytotoxic T cell

35. B Cells: A Response to Extracellular Pathogens • Activation of B cells is aided by cytokines and antigen binding to helper T cells • Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity

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

37. Antibody-Mediated Disposal of Antigens • The binding of antibodies to antigens is also the basis of antigen-disposal mechanisms • Microbes are eliminated by phagocytosis and complement-mediated lysis

38. Binding of antibodies to antigens inactivates antigens by Viral neutralization (blocks binding to host and opsonization increases phagocytosis) Agglutination of antigen-bearing particles, such as microbes Activation of complement system and pore formation Precipitation of soluble antigens Complement proteins Bacteria Virus MAC Pore Soluble antigens Bacterium Foreign cell Leads to Enhances Phagocytosis Cell lysis Macrophage

39. Active and Passive Immunization • Active immunity develops naturally in response to an infection • It can also develop following immunization, also called vaccination • In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory

40. Passive immunity provides immediate, short-term protection • It is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk • It can be conferred artificially by injecting antibodies into a nonimmune person

41. Blood Groups and Transfusions • Antigens on red blood cells determine whether a person has type A, B, AB, or O blood • Antibodies to nonself blood types exist in the body • Transfusion with incompatible blood leads to destruction of the transfused cells • Recipient-donor combinations can be fatal or safe • A red blood cell antigen called the Rh factor creates difficulties when an Rh-negative mother carries successive Rh-positive fetuses

43. Allergies • Allergies are exaggerated (hypersensitive) responses to antigens called allergens • Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms

44. IgE Histamine Allergen Granule Mast cell

45. Animations and Videos • Cytotoxic T-cell Activity Against Target Cells • Monoclonial Antibody Production • Antibody Diversity • IgE Mediated Hypersensitivity • Humoral Immunity and Cell-Mediated Immunity • How Antibodies Work • Nonspecific Inflammatory Response • Cytotoxic (Type II Hypersensitivity)

46. Animations and Videos • The Immune Response • T-cell Dependent Antigens • Bozeman - The Immune System • Cytotoxic T Lymphocytes Attack a Melanoma Cell • Cells of the Immune System • Nonspecific Inflammatory Response • The Humoral Immune Response • The Immune Response

47. Animations and Videos • Antigenic Determinants (Epitopes) • Humoral Immunity • A B Cell Builds Immunity • Chapter Quiz Questions – 1 • Chapter Quiz Questions – 2