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Immune System

Immune System

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Immune System

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  1. Immune System Dr. Anderson GCIT

  2. Immune Branches • Innate – immune function present at birth • Acquired (Adaptive) – immune function that develops over time from exposure to pathogens in the environment • Like what?

  3. Innate Immunity

  4. Innate Immunity • Barriers to pathogens that are inherent at birth, they do not require previous exposure to pathogens • Integument (skin) • White blood cells

  5. Integument • Establishes a physical barrier between vulnerable cells and infectious agents

  6. Skin Defenses • Physical Barriers • Dead dry skin cells • Dendritic cells – modified monocytes -phagocytose invading microorganisms • Chemical Barriers • High salt concentration • Antimicrobial peptides (AMPs), e.g. defensins • Lysozyme – lyses bacterial cell membranes

  7. Mucus Membranes • Line all openings of the body (respiratory, digestive, urinary and reproductive) • Consist of epithelial cells with a basement layer of connective tissue (collagen)

  8. Epithelial Defense • Shedding of cells carries away pathogens that may try to invade the body • Chemical Agents – • Mucus (physical barrier) that contains lysozyme and AMPs to destroy bacterial cell walls

  9. Second Line of Defense • If primary (integument) barrier is breached, pathogens must be eliminated • Pathogens “reveal” themselves to the immune system via PAMPs (Pathogen-Associated Molecular Patterns) • Depending on the PAMP, specific immune responses will be initiated

  10. Leukocytes • Specifically engage different invaders of the body (pathogen types) • Divided into granulocytes and agranulocytes due to their appearance under the microscope • Granulocytes – many stained organelles giving them a “grainy” appearance • Agranulocytes – few or no organelles

  11. Specific Jobs of Leukocytes - Granulocytes • Basophils – produce histamine leading to inflammatory response • Neutrophils – phagocytose bacteria and viruses • Eosinophils – lead attack against parasitic worms

  12. Specific Jobs of Leukocytes - Lymphocytes • Lymphocytes – produce antibodies against specific invaders • B lymphocytes – produce antibodies to pathogens • T lymphocytes • produce cytokines that direct immune response • Destroy infected cells • These cells the heart of adaptive immunity, as they will “remember” the antibodies they produced, and be able to make them again quickly upon re-exposure to a pathogen (memory cells)

  13. Specific Jobs of Leukocytes - Monocytes • Monocytes – function to phagocytose bacteria and other invading pathogens • Will mature into macrophages which can leave the blood vessels and enter tissues (diapedesis) where pathogens frequently enter

  14. Differential Hemocyte Count • Depending on the pathogen, infection will cause changes in the proportion of WBC’s in the blood

  15. Phagocytosis • WBC’s (Macrophages, eosinophils and neutrophils) surround and engulf pathogens • WBC then adheres to the pathogen via binding of cell membrane components • This process can be facilitated by opsonization- antibodies or other proteins mark the pathogen for death

  16. Phagocytosis • Once adherence is complete, pathogens are engulfed via endocytosis, which forms a phagosome • The contents of the phagosome are then digested by merging with a lysosome (vesicle in the cell containing digestive enzymes)

  17. Toxin Secretion • Cells such as eosinophils and lymphocytes can kill cells by secreting toxic compounds directly on to them • Enzymes in the cell membrane of these cells can form reactive oxygen species (ROS) such as hydrogen peroxide to kill nearby cells

  18. Non- Specific Chemical Defenses of Blood • Interferons – Protein molecules released by host cells to inhibit virus spread • Infected cells produce interferon which causes neighboring cells to produce antiviral proteins • Anti-viral proteins inhibit viral mRNA synthesis and protein translation at ribosomes

  19. Complement • Proteins in the blood plasma that bind to pathogens and mark them for destruction (opsonization) • After pathogen detection, a complex molecular pathway results in complement products that • Facilitates Chemotaxis – recruits WBC’s to the pathogen • Produces membrane attack complex (MAC) which bores a hole in the pathogen’s cell membrane, killing the cell

  20. Inflammation • Acute Inflammation – quick, short-lived response to infection, usually beneficial • Chronic Inflammation – Long lasting, generally damaging reaction to infection which itself can cause disease • Signs include: Reddened skin, localized heat, edema and pain

  21. Inflammation (Acute) • Dilates blood vessels and makes them more permeable • Delivers more blood and resources to the site of infection • This results in rapid healing • Recruits phagocytes • To kill infectious pathogens and prevent the spread of infection

  22. Fever • Presence of certain PAMPs (pyrogens) results in another chemical cascade that triggers the hypothalamus to increase the normal temperature of the body • Fever increases the efficiency of complement and decreases pathogen replication rates resulting in faster recovery from infection

  23. Temperature • All organisms function optimally within a relatively narrow temperature range 22C 30C 37C

  24. Acquired Immunity

  25. Acquired Immunity • Acquired immunity is built up over time and after exposure to certain pathogens • Acquired immunity is largely through the production of antibodies which recognize antigens on germs • Example?

  26. Antigens • Substances on cell surfaces or produced by cells that can provoke an immune response e.g. PAMPs (non-self!) • Lipopolysaccharide (LPS) e.g. - bacteria • Peptidoglycan (PG) e.g. – bacteria • Beta 1,3, Glucans (fungi) • ANY OTHER foreign proteins that the immune system can mount a response to (non-self)

  27. Complete Antigens • Can stimulate the proliferation of lymphocytes and antibodies (immunogenicity) • React to activated lymphocytes and antibodies produced by the immune response (reactivity) • Examples?

  28. Antigenic Determinants (Epitopes) • The immunogenic part of an antigen • This is where antibodies or leucocyte receptors bind to attack • Large proteins can have many antigenic determinants – why?

  29. Haptens • Very small molecules that are foreign to the body, but not immunogenic • However, a combination of a hapten and a “self” protein can mount an immune response • Have reactivity, but not immunogenicity • Usually results in a harmful immune response

  30. What’s the Hapten?

  31. Lymphocytes – Acquired Immunity • B- Lymphocytes • Primarily produce antibodies against a very specific species of pathogen • T-lymphocytes • Cytotoxic “killer” cells – destroy infected body cells (CD8) • Helper cells (CD4) • How do lymphocytes know what to kill?

  32. Major Histocompatibility Complex (MHC) • The protein matrix on your cells that displays either “self” proteins” or “non-self” proteins

  33. MHC – Normal vs. Infected Cells • Uninfected cells display a small protein derived from normal cell processes (metabolism) • Correct password! • Infected cells display protein, but parts of the foreign (pathogen) antigen are attached • Incorrect password (and consequences)

  34. MHC Classes • Body cells – Possess MHC I complex that will “display” either: • “Self” Proteins – Healthy cells • Antigens (parts of pathogens) – Sick cell • Immune Cells (Lymphocytes, antigen presenting cells, etc.) will display • “Self” Proteins – Healthy cells • Antigens (parts of pathogens) – To activate other immune cells

  35. MHC in Lymphocytes

  36. Antigen-Presenting Cells • Cells that present antigen fragments to T-cells (in thymus) for maturation • Dendritic cells (in connective tissue) • Macrophages • B-lymphocytes • These cells engulf pathogens and then present portions of their antigens to T-cells

  37. Dendritic Migration • After phagocytizing a pathogen, dendritic cells will move to the lymph vessels where they express antigens on their surface • T-cells encounter these presented antigens and start their specific immune response • Dendritic cells are the bridge between innate and adaptive immunity!!!

  38. Humoral (Plasma-based) Immune Response • Starts when a B-cell (lymphocyte) encounters a pathogen antigen • Antigen-receptor complex is brought into the cell • This stimulates the cell to “clone” itself via mitosis, thus making more cells that are competent against the pathogen that started the cascade

  39. B-Cell Proliferation

  40. Plasma Cells • Most cloned B-lymphocytes become plasma cells • Secrete antibodies to the antigen (up to 2000 molecules/second) • Antibodies mark any cell with that antigen for destruction • Memory (B) cells are also produced • Exist for years to “prime” the immune system in case of reinfection

  41. Memory Cells and Primary Immune Response • Primary Immune Response (1st exposure) • Newly “presented” antigen causes B-lymphocyte clones to proliferate over 3-6 days • Secondary Immune Response • The now “primed” immune system can mount a much faster response when re-exposed to the same pathogen • Cloned cells left over from primary response bind better to antigens, live longer

  42. Active Humoral Immunity • Active – B-cells encounter antigens and make antibodies • Naturally acquired • How else? • Unfortunately, while providing lots of immediate protection, killed or weakened pathogens sometimes do not result in a strong cell-mediated (TH1) response. • Immune memory suffers

  43. Passive Humoral Immunity • Passive Immunity • Immune response is solely due to “artifical” antibodies • Horses, rabbits, bacteria, etc. • Protection ends when naturally degraded in the body • Maternal antibodies • Antivenom

  44. Antibodies (Immunoglobulins) • Proteins secreted by effector B-cells • Bind specifically to ONE pathogen antigen, making them highly specific • Five classes of Ig (Immunoglobulins)

  45. Antibody Classes • IgM – large antibody (pentamer) – released by plasma cells • IgA – monomer and/or dimer – mucus membranes • IgD– acts as B-cell receptor • IgG – most abundant, small, can cross placental barrier • IgE – involved in allergic reactions • See pg. 784 in the text for more details

  46. Basic Antibody Structure Heavy Chain Light Chain Stem region = variable region

  47. Antibody Structure • Heavy Chains(2) – identical structure, long chains (>400 aa long) • Light Chains (2) – much shorter than H chains, loop around heavy chains • Variable (V) regions – very different between individual antibodies • Constant (C) regions – very similar (almost identical) between antibodies in the same class