The Immune System

1. The Immune System By Max Soghikian and Frank Yü

2. Immune System: Overview • Animals must not only protect themselves from predators but also pathogens. • An animal’s collective defense against pathogens is known as the immune system. • All animals have an innate immunity • Vertebrates also have acquired immunity Phagocyte engulfing a bacterium

3. Innate Immunity • Innate Immunity is found in all animals • It is active either constantly, or immediately when a pathogen is discovered. • Innate Immunity is divided into: • barrier defenses (i.e. the skin) • internal defenses (i.e. phagocytic cells) The human skin (left) and a typical phagocyte (right)

4. Barrier Defenses • Barrier Defenses are the first line of an animal’s innate immunity. They include: • The skin, which physically blocks most pathogens from entering the body • Mucous membranes, which secrete a viscous fluid (known as mucus) that traps microbes and other harmful particles. • Other body secretions, such as tears, oil, and sweat also prevent the growth of many harmful microorganisms. In the trachea, ciliated cells sweep mucus and the stuff trapped in them away from the lungs.

5. Internal (Cellular) Defenses • Internal Defenses tend to activate as soon as a pathogen enters the body. • Many times, the defenses are triggered by TLRs (toll-like receptors) that recognize various characteristics of microbes. • These can be cell based. • Neutrophils, the most abundant phagocytic cells, are attracted to infected tissues. • Macrophages patrol the bloodstream for foreign particles and organisms and reside in lymph nodes • Eosinophils are specialized cells that attach to multicellular invaders and secrete destructive enzymes • Dendritic cells stimulate acquired immunity against encountered microbes Phagocytosis

6. Internal (Protein) Defenses • After a pathogen is recognized by the organism, various antimicrobial proteins and peptides attack foreign organisms in various ways. • Interferons are proteins that disrupt viral infection and help contain exposure in the body • The complement system consists of some 30 or so proteins that, when activated, cause invading cells to undergo lysis (burst).

7. Internal (Inflammatory) Defenses Pathogen Splinter • When the body recognizes that it’s being attacked, the area in question undergoes various changes. • For example, when near microinvaders, mast cells release histamine, a hormone, which, along with the secretions from endothelial cells, activates various cell reception cascades that make the blood vessels more permeable and attract various phagocytic cells. • An example of an inflammatory response that affects the entire body is fever, which may encourage phagocytosis and tissue repair. Chemical Signals (i.e. Histamine) Macrophage Fluid Mast cell Capillary Phagocytosis Red blood cells Phagocytic cell

8. Internal (NK) Defenses • Natural Killer Cells are cells that are alerted to infected cells by the Class I MHC molecule. • The NK cells then proceed to cause infected/cancerous cells to undergo apoptosis to limit damage

9. Acquired Immunity • Acquired Immunity is a branch of immunity found only in vertebrates. • It is centered around lymphocytes which are split into T Cells and B Cells, which act as memory cells that record and store information about various pathogens • This is known as immunological memory, which results in an enhanced defense against a repeat attacker • Foreign organisms are recognized by antigens, which is any molecule that is recognized and remembered by a lymphocyte 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

10. Acquired Immunity (Antigen Receptors) • The cell membrane of a lymphocyte is coated with these receptors. • The parts of the antigen that binds to the binding sites are known as epitopes Antigen- binding sites Epitopes (antigenic determinants) Antigen-binding sites Antigen Antibody A Antibody C V V V V C C C C Antibody B

11. Acquired Immunity (B Cells) • B Cells have two antigen binding sites formed by heavy and light chains. • They also can form plasma cells, which secrete antibodies (also known as immunoglobin proteins) which are essentially mobile/soluble antigen receptors • The antigen receptors of B cells form the well known Y-shape of antibodies

12. Acquired Immunity (T Cells) • The antigen receptors of T Cells have two heavy chains, labeled alpha and beta. • T Cells tend to work in conjunction with major histocompatibility complexes (MHCs) • When cells are infected by a particular pathogen, they present the corresponding antigen with either a Class I or Class II MHC molecule • The antigen receptors of T cells thus bind to these presented antigen and execute their various tasks • For example, cytotoxic T Cells destroy infected cells displaying the MHC molecule with antigen attached • Class II MHCs are used by more specialized cells and often are binded to by helper T Cells, which assist B and cytotoxic T Cells

13. Acquired Immunity (Primary response) • One of the most important abilities of acquired immunity is the ability to fight repeat attackers with greater strength • In primary immune response, which peaks about 10 to 17 days after initial exposure, plasma cells, other effector cells and memory cells are cloned with “memories” of the particular antigen.

14. Acquired Immunity (Secondary Response) • After an immune system has gone through primary response, the next exposure to the antigen will result in a much stronger response because cloned memory cells will be able to further assist phagocytic and other types of immunity • Because memory cells are relatively long lived, secondary response can be activated years after primary response in some cases

15. Acquired Immunity (Humoral Response) • Humoral immune response involves the cloning of B effector cells, known as plasma cells, secrete large amounts of antibodies which cover pathogens, disabling some of their harmful functions and making them easier targets for phagocytosis • After primary response, the B cell clones itself into memory B cells and the body is prepared against a repeat attack

16. Acquired Immunity (Cell-Mediated Response) • Cell-mediated response centers around cytotoxic T cells, which seek and destroy infected cells that display antigens with MHC molecules • As stated before, cytotoxic T cells cause apoptosis in infected cells. • Eventually, surviving T cells clone into memory T Cells, much like memory B cells in that they preserve Immunological Memory for years to come

17. Acquired Immunity (Overview of Humoral and Cell-Mediated Reponse) Antigen- presenting cell Peptide antigen Bacterium Class II MHC molecule CD4 TCR (T cell receptor) Helper T cell + Cytokines Humoral immunity (secretion of antibodies by plasma cells) + Cell-mediated immunity (attack on infected cells) + + B cell Cytotoxic T cell

18. Acquired Immunity (Antibody classes) • There are various types of antibodies used by the immune system • Their varying structures all allude to their respective functions.

19. Acquired Immunity (Active Immunity) • Active Immunity is essentially the result of primary response. • Cloned memory cells of both the T and B line will allow for strong secondary responses long into the future. • Vaccination is used as a way to confer active immunity

20. Acquired Immunity (Passive Immunity) • Because the immune system of most mammalian infants are not quite up to their full protective potential, passive immunity can be extended to the child through the mother • The two most common ways this occurs is through breast feeding and through the placenta of a pregnant mother • These two Ig classes assist the child in fending off possible infection

21. Various Diseases and Complications • The immune system is the body’s defense against pathogenic disease. Thus, when the immune system is misfiring or weakened, serious/annoying problems can occur. • Allergies are when the immune system overreacts to a harmless particle • This can result in irritation and in serious cases, death • Autoimmune diseases occur when the immune system fails to determine between self and nonself, instead, attacking all cells. • Immunodeficiency syndrome is when the immune system itself is weakened by a pathogen. • The most well known pathogen that causes this is HIV (human immunodeficiency virus). • A mis-functioning immune system can also lead to cancer, if cytotoxic T cells cannot destroy cancerous cells well enough

22. References • AP Biology Textbook • http://en.wikipedia.org/wiki/Antibody_opsonization • http://en.wikipedia.org/wiki/Skin • http://en.wikipedia.org/wiki/Basophil_granulocyte • http://en.wikipedia.org/wiki/Antibody