Immunology

1. By : Pooja Patel & Sarah Gianopoulos Immunology

2. Innate Immunity Innateimmunity—nonspecific, used against many organisms: • First line of defense includes barriers, such as skin and molecules toxic to invaders • Second line of defense includes phagocytic cells, which ingest foreign cells and particles • Most animals use innate immunity

3. Adaptive Immunity AdaptiveImmmunity—specific, used to distinguish between substances that were made by the organism or if they are foreign substances: • Uses antibody proteins to recognize, bind to, assist in destroying specific bacteria and viruses • Adaptive immunity is slow to develop and long lasting • Innate immunity is much quicker to develop (0-96 hours)

5. Two Major Types of White Blood Cells • Phagocytes • Large cells that engulf pathogens and harmful substances • Lymphocytes • Include B and T cells • B Lymphocytes differentiate and form antibody producing cells and memory cells • T Lymphocytes kill the virus infected cells and regulate white blood cell activity

6. Immune System Proteins • Cytokines bind to cell surface receptors and alter the behavior of their target cells • Some can activate or inactivate B and T cells and macrophages • Antibodies are proteins, produced by B cells that bind specifically to nonself substances • Acts as a flag to make it easier for the immune system cells to attack the invader • Destruction done by inactivating/destroying harmful pathogens, toxins and other microorganisms

7. Immune System Proteins Contd. • Major histocompatibility complex (MHC) • MHC proteins are important self-identifying labels that make sure the appropriate type of T cell binds during immune responses. • T cell receptors are integral membrane proteins on T cells, recognize and bind to nonself molecules

8. Immunity: Barriers and Local Agents • Skin • Rarely penetrated by bacteria • Skin’s saltiness is not an ideal environment for bacterial growth • Both harmless and helpful bacteria will have to compete for space and nutrients on the skin against pathogens and harmful substances

10. Barriers and Local Agents Contd. • Mucus • Traps microorganisms and pathogens and is carried away by cilia • Lysozome (enzyme) • Produced by mucus membranes and cleaves on the cell walls of the bacteria, thus making the harmful cell ‘lyse’ • Use of internal substances

11. Barriers and Local Agents Contd. • Defensins (peptides) • Made by mucus membranes • Hydrophobic and toxic to several other pathogens • Insert themselves into the plasma membrane to make the it permeable to water and solutes, thus killing the harmful substances

12. Complex Innate Defenses • Phagocytes ingest the harmful substance and destroy it by 1 of 2 ways: • Hydrolysis within lysosomes • Defensins

13. Complex Innate Defenses Contd. • Natural Killer Cells • Distinguishing between healthy and unhealthy cells • Apoptosis for cancerous cells • For other cells, Innate and Adaptive defenses combine by lysing antibody –labeled target cells

14. Complex Innate Defenses Contd. • Complement Proteins • A system that activates several proteins in sequence in order to lyse the invaded cell • One complement protein acts as a flag to the phagocytes as it binds to the invaded cells • Next protein is activated to initiate the inflammation response and signals to the phagocytes to the infection site • Then many other proteins now lyse the invaded cell

15. Complex Innate Defenses Contd. • Interferons • Proteins that help increase resistance of neighboring cells to infection • Bind to receptors on the plasma membranes of the uninfected cells to stimulate a pathway that inhibits viral reproduction the other cells become infected

16. Inflammation Inflammation • Isolates the infected area to stop spreading the damage • Brings in cells and molecules to kill off any remaining pathogens and initiates the healing process • Mast cells are cells adhering to skin and organ linings; release chemical signals. • Tumor necrosis factor—cytokine that kills target cells and activates immune cells

18. Adaptive Immunity’s 4 Key Features • Adaptive Immunity is: • Specific • Diverse • Can distinguish between self and nonself substances • Clonal deletion • Has immunological memory

19. Specificity • Specificity: • T cell receptors and antibodies bind to specific nonself molecules (antigens). • Specific sites on the antigens are called antigenic determinants. • The host responds to an antigen’s presence with highly specific defenses using T cell receptors and antibodies.

20. Distinguishing Self from Nonself • Lymphocytes are usually activated by binding to antigens to induce production of clones of B Cells and T Cells-clonal selection. • To protect Self substances: • Clonal deletion—Anyimmature B and T cells that show the potential to mount an immune response to self antigens undergo apoptosis.

21. Immunological Memory • Primary Immune Response • Memory Cells • Secondary Immune Response • Produces a quicker and more powerful response

22. 3 Phases of Adaptive Immunity • Recognition phase—theorganism discriminates between self and nonself to detect a pathogen. • Activation phase—therecognition event leads to a mobilization of cells and molecules to fight the invader. • Effector phase—themobilized cells and molecules destroy the invader.

23. Cellular Immune Response • Cytotoxic T (TC) cells power the cellular immune response. • An antigen is inserted into the membrane of an antigen-presenting cell. • The antigen is recognized by a T-helper (TH) cell,with a specific T cell receptor protein. • TH cell binding to the antigen-presenting cell causes cytokine release. • Cytokines stimulate TC cells to divide.

24. Humoral Immune Response • Humoral immune response involves B cells that make antibodies. • Antigen is recognized when the it binds to a B cell that has an antibody specific to that antigen. • Antigen binding readies a B cell for division. • The TH cell bound to the B cell secretes cytokines that stimulate the B cell to divide and form a clone.

25. Interaction of Two Immune Responses • The result of both types of immunities: • A clone of B cells that can produce antibodies specific for the antigen • A clone of TC cells that express a T cell receptor that can bind to any cell expressing the antigen on its surface • In the effector phase, B clone cells produce antibodies that bind to free antigen— results in inactivation and destruction of the antigen. • TC clone cells bind to cells bearing the antigen and destroy them.

28. Humoral Immunity: Antibody • B cells give rise to clones of plasma and memory cells upon activation. • Plasma cells and B Cells secrete antibodies into the blood stream. • Some bind to the antigen on surface of a pathogen. • Some may use cross-linking function to form large complexes to be destroyed by phagocytes.

29. Antibody Structure • Antibodies all contain a tetramer of four polypeptides. • In each molecule are two light chains and two heavy chains, held together by disulfide bonds. • Each polypeptide chain has a constant region and a variable region. • The constant region determines the general structure and function of an immunoglobulin. • The variable region is different for each specific immunoglobulin—responsible for antibody specificity.

32. Five Classes of Antibodies • IgG is secreted by B cells and constitutes about 80 percent of circulating antibodies. • IgD is the cell surface receptor on a B cell. • IgM is the initial surface and circulating antibody released by a B cell. • IgA protects mucosa on epithelia exposed to the environment. • IgE binds to mast cells and is involved with inflammation.

33. B Cell • Each mature B cell can produce only one specific antibody with a specific amino acid sequence. • The B cell genome: • Each gene encoding an antibody is a supergene assembled from many smaller genes. • During B cell development the genes are cut out and rearranged. • DNA is rearranged or mutated to create high diversity of antibodies.

35. Cellular Immunity: T Cells • Cellular immune response involves: • T-helper cells (TH) • Cytotoxic T cells (TC) • Histocompatibility proteins (MHC) proteins • T cells have specific membrane receptors—glycoproteins, with two polypeptide chains. • Each chain is encoded by a different gene • T cell receptors can bind a piece or fragment of an antigen, on the surface of an antigen-presenting cell.

37. T Cells Contd. • TC cells bind to cells carrying the antigen–MHC I protein complex. • When bound, the TC cells do two things to eliminate the antigen-carrying cell: • They produce perforin, which lyses the bound target cell. • They stimulate apoptosis in the target cell.

38. Regulatory T Cells • Regulatory T cells (Tregs) regulate the immune response. • Tregs recognize and mediate tolerance to self antigens—when activated they release the cytokine interleukin 10. • This blocks T cell activation and leads to apoptosis of TC and TH cells bound to the same antigen.

40. Immune Deficiency Disorders: HIV/AIDS • Immune deficiency disorders can be inherited or acquired. • T or B cells may never form, or B cells lose their ability to give rise to plasma cells • Acquired immune deficiency syndrome (AIDS) results from infection by human immunodeficiency virus (HIV).

41. HIV/AIDS • HIV initially infects TH cells, macrophages, and antigen-presenting dendritic cells. • Numbers of TH cells decline after infection. • HIV-infected cells activate the humoral immune system and symptoms abate. • During the dormant period, people with HIV feel fine.

42. HIV/AIDS Contd. • Eventually more TH cells are destroyed and the person is susceptible to opportunistic infections: • Pneumonia • Lymphoma tumors • Drug treatments for HIV are focused on inhibiting processes necessary for viral entry, assembly, and replication.