1 / 73

Immune System

Immune System. Dr. Anderson GCIT. 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?. Innate Immunity. Innate Immunity.

lorand
Download Presentation

Immune System

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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

More Related