The Immune System

1. The Immune System

2. Overview • Barriers = 1st line of defense against pathogens • Immune system recognizes foreign bodies  responds with the production of leukocytes and proteins • 2 kinds of defense: • innate immunity • acquired immunity

3. Pathogens (microorganisms and viruses) Barrier defenses: Skin Mucous membranes Secretions INNATE IMMUNITY • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Internal defenses: Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells • Rapid response Humoral response: Antibodies defend against infection in body fluids. ACQUIRED IMMUNITY • Recognition of traits specific to particular pathogens, using a vast array of receptors Cell-mediated response: Cytotoxic lymphocytes defend against infection in body cells. • Slower response

4. Innate immunity • present from birth • recognition and rapid response rely on shared traits of pathogens • nonspecific responses to pathogens • external barriers • internal cellular defense • chemical defenses • inflammation

5. Barriers • Skin - continuous keratinized stratified squamous layers of epithelium • Mucus traps and allows for the removal of microbes • Saliva, mucus, and tears are hostile to microbes (hydrolytic enzymes, high salinity) • low pH of skin and digestive system prevents microbial growth

6. Cellular Innate Defenses EXTRACELLULAR FLUID Lipopolysaccharide Helper protein • Phagocytic leukocytes engulf pathogens in the body • Groups of pathogens are recognized by TLR, Toll-like receptors of leukocytes Flagellin TLR4 WHITE BLOOD CELL TLR5 VESICLE TLR9 CpG DNA Inflammatory responses TLR3 ds RNA

7. Phagocytic Cells 4 types: • Neutrophils engulf and destroy microbes • Macrophages (of lymphatic system) and are found throughout the body • Eosinophils discharge destructive enzymes • Dendritic cells stimulate acquired immunity

8. Chemical Defenses • Proteins and enzymes attack microbes directly or impede their reproduction • Interferon proteins: • innate defense against viruses • activate macrophages • ~ 30 proteins form the complement system: lysis of invading cells, trigger inflammation

9. Inflammatory Response • Following an injury, mast cells release histamine: • Dilates blood vessels • increase local blood supply • more phagocytes and antimicrobial proteins enter tissues • Pus, a fluid rich in white blood cells, dead microbes, and cell debris, accumulates at the site of inflammation

10. Inflammatory Response • Fever • 100 – 102 Fahrenheit = beneficial • Slows growth and reproduction of microbes • denature their proteins

11. Pathogen Splinter Chemical signals Macrophage Fluid Mast cell Capillary Phagocytosis Red blood cells Phagocytic cell

12. Natural Killer Cells • All cells in the body (except red blood cells) have a class 1 MHC protein on their surface (major histocompatibility complex) • Cancerous or infected cells lack this protein; natural killer (NK) cells attack these damaged cells

13. Innate Immune System Evasion by Pathogens • Some pathogens avoid destruction by modifying their surface to prevent recognition or by resisting breakdown following phagocytosis • Ex. Tuberculosis (TB); • kills more than a million people/year

14. Acquired immunity • develops after exposure to foreign substances • specific responses • Antibody-mediated • Cell-mediated response • Slower

15. Lymphocyte-Dependent • lymphocytes recognize, remember, and respond to antigens, foreign molecules • Cytokines, secreted by macrophages and dendritic cells, recruit and activate lymphocytes • T cells Lymphocytes mature in the thymus above the heart • B cells mature in bone marrow

16. B and T-cell Specificity • Each lymphocyte is specialized to recognize ONE specific type of antigen (foreign body) • A single B cell or T cell has about 100,000 identical antigen receptors • B cells give rise to plasma cells,which secrete proteins called antibodies or immunoglobulins (Ig) specific to the antigen

17. Fig. 43-9 Antigen- binding site Antigen- binding site Antigen- binding site Disulfide bridge V V V V Variable regions V V C C Constant regions C C C C Light chain Transmembrane region Plasma membrane  chain  chain Heavy chains Disulfide bridge B cell Cytoplasm of B cell Cytoplasm of T cell T cell (a) B cell receptor (b) T cell receptor

18. The Role of Antibodies • Neutralization occurs when a pathogen can no longer infect a host because it is bound to an antibody • Opsonization occurs when antibodies bound to antigens increase phagocytosis • Antibodies together with proteins of the complement system generate a membrane attack complex and cell lysis Animation: Antibodies

19. Fig. 43-10 Antigen- binding sites Epitopes (antigenic determinants) Antigen-binding sites Antigen Antibody A Antibody C V V V V C C C C Antibody B

20. Primary Immune Response • The first exposure to an antigen • Slow response • B cells called plasma cells are generated, • T cells are activated • In secondary immune response, B-cell memory facilitate a faster, more efficient response Animation: Role of B Cells

21. Two branches of Acquired immunity • Humoral (antibody-mediated) immune response • activation and clonal selection of B cells, resulting in production of secreted antibodies • Cell-mediated immune response • activation and clonal selection of cytotoxic T cells • Helper T cells aid both responses

22. Fig. 43-16 Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) Stimulates Gives rise to + Engulfed by Antigen- presenting cell + + + B cell Helper T cell Cytotoxic T cell + + Memory Helper T cells + + + Antigen (2nd exposure) Memory Cytotoxic T cells Active Cytotoxic T cells + Plasma cells Memory B cells Secreted antibodies Defend against extracellular pathogens by binding to antigens, thereby neutralizing pathogens or making them better targets for phagocytes and complement proteins. Defend against intracellular pathogens and cancer by binding to and lysing the infected cells or cancer cells.

23. Active Immunity • Active immunity develops naturally in response to an infection • It can also develop following vaccination • a nonpathogenic form of a microbe or part of a microbe is used to initiate a primary immune response and immunological memory