Symbiosis, Disease and Host Defenses

1. Symbiosis, Disease and Host Defenses An evolutionary arms race

2. Symbiosis: Organisms ‘living together’ Three types based on effects: Commensalism- positive for one organism and neutral for the other Mutualism-positive for both organisms Parasitism-positive for one negative for the other Parasite (Greek parasitos, to dine along side of) As a matter of convention, parasitology usually covers protist and animals even though bacteria and viruses can be parasites . Microbes are often referred to as pathogens even though they are parasitic.

3. Parasitic Organisms • Overarching questions • How do parasites affect their hosts? • What makes an efficient parasite? • Why are some organisms parasitic and others are not? • Why is a particular organisms pathogenic sometimes but not always? Obligate parasite- can not live without host Opportunistic parasite/pathogen- can be parasitic under certain circumstances Virulence Factor-structural or physiological characteristics that contribute to the effect that we call disease

4. Endosymbiosis Ancestral symbiotic event between primitive cells What are the possible costs or benefits to each organism involved? How does that affect the evolutionary process?

5. Selective pressure Relationship is commensal Relationship is mutual Relationship is parasitic

6. A biological arms race? Parasite increases fitness if: • Continues to benefit from the host by resisting defenses Host increases fitness if: • Excludes parasite • Destroys parasite outside • Destroys/digests parasite inside

7. All living things have some defense mechanisms • Restriction enzymes in bacteria • Vesicles with chemical defenses in single-celled eukaryotes • Specialized phagocytic cells in most animals, including arthropods and helminthes • Pinnacle of host defenses are found in vertebrates (fish, amphibians, reptiles, birds, mammals)

8. Non-Specific Host Defenses of Vertebrates Defense “strategies” include: External (Exclusion) chemical-sweat, tears physical-keratinized structures Internal cellular-leukocytes other than lymphocytes chemical and molecular- complement, interferon inflammation, fever etc.. Note: regulation is important for all internal defense mechanisms

9. Physical barriers: the human integument

10. Pathogens subvert physical barriers Portals of entry include: Ears Nose Mouth Urogenital tract Gastrointestinal tract Wounds

11. Leukocytes in non-specific defenses

12. Phagocytic cells are non-specific defenses that destroy invaders Lysosome containing digestive chemicals Phagocytosis of invader Phagolysosome formed

13. Mechanisms for subverting non-specific defenses • Structural adaptation-formation of special cell walls, capsules, endospores, cysts • Physiological adaptations- enzymes that neutralize host chemicals, digest host physical barriers or destroy phagocytes • Vectors, vehicles, fomites aid in gaining entry into host

14. Specific Immunity: defensive cells get ‘smarter’ • “Remembering” invaders allows for faster response upon subsequent encounters of that specific invader • Specific immunity can be divided into two branches • Humoral immunity- antibodies produced by B cells • Cell-mediated immunity- T cells recognized invaders and stimulate defense mechanisms • Antigen any molecule that generates an immune response (antibody generating) • Antibody- a protein that can bind to specific antigens and help with the immune response in various ways

15. Types of Specific Immunity • Active- antibodies formed by the host • Natural- host forms antibodies naturally upon natural exposure to antigen • Artificial- host is artificially exposed to antigen i.e. immunization, vaccination • Passive-antibodies not made by host • Natural-Maternal antibodies • Artificial-antibodies from other source (horse, cow etc..), for example antivenin administered after snake bite

16. Cells of the Specific Immune System • B lymphocytes produce antibodies which are special proteins that bind to foreign molecules (antigens) and facilitate an immune response • Plasma cells • Memory B cells • Natural Killer cells Kill virus- infected cells, bacteria and cancer cells extracellularly • T lymphocytes differentiate into several types with different immunological functions • Helper T cells ( TH), CD4 (T4) • Cytotoxic cells (TC), CD8 (T8) • Memory T cells

17. B lymphocytes produce antibodies (immunoglubulins) • Antibodies are proteins and therefore are synthesized from the instructions in DNA • Antibodies can be constructed to fit a variety of immunological functions from cell surface receptors to circulation, or excretion • The sections of DNA that encode the part the antibody that binds to antigen is highly variable allowing the formation of millions of different antigens so antibodies may be formed to any foreign molecule that is complex enough

18. Antibodies Binds to antigen here Y Cell with antibody as cell-surface receptor Basic structure of and antibody

19. Antibodies (immunoglobulins) IgG-circulating in blood serum, can cross placenta IgM-first to blood serum, on B cell membrane IgA-Body secretions, epithelium of GI, Resp, UG tracts IgD-B cell membrane IgE-body fluids and skin, affinity for mast cells and basophils, main mediator for type 1 hypersensitivity

20. B Cells and Humoral Immunity Whichever B-cell binds to a specific antigen will be produced in greater numbers to mount an immune response Some of the newly created B cells will become memory cells and the others will become plasma cells produce and secrete various forms of that specific antibody Countless B cells are produced expressing a variety of antibodies on the cell surface

21. Overview of Cell-mediated Immunity • Antigen is processed by non-specific immune cells (e.g. macrophages) which present the antigen at the cell surface • T cells that have a matching receptor bind to the antigen • If the MHC protein is correct, the T cell is activated and it divides and differentiates MHC proteins • made from highly variable gene which makes ‘self’ different for almost all individuals • class I MHC on all body cells • class II MHC only on some immune cells

22. Cell-mediated Immunity Helper T cell Antibody in the form of T-cell surface receptor Y antigen * MHC class II Helper T cells are activated. They differentiate into Th1 or Th2 cells which stimulate intracellular destruction of antigen (Th1) or stimulate B cells (Th2) Macrophage presenting antigen in MHC II protein

23. Cell-mediated Immunity Cytotoxic T cell Antibody in the form of T-cell surface receptor Y antigen * MHC class I Cytotoxic T cell are stimulated to attack infected cells Infected cell presenting antigen in MHC I protein

24. Phases of Infection incubation acme Prodromal period decline invasive Convalescence period

25. Immune System Disorders:hypersensitivities • Hypersensitivities • Type 1 - anaphylactic, immediate, IgE mediated • Type 2- cytotoxic, reaction to cell surface antigens • Type 3- immune complex, persistent antibody-antigen complexes formed • Type 4 –cell (T cell) mediated, delayed hypersensitivity

26. Immune System Disorders: Autoimmunity • Caused by lack of self recognition-T-cells and/or antibodies act against self tissues • Triggers of autoimmunity include: • failure of lymphocyte programming process • new self antigens • mutation in genes • Haptens (incomplete antigen) • foreign antigens stimulate cross-reactive antibody production

27. Immune System Disorders: Immunodeficiency and Immunosupression • Causes may be: • Genetic (SCIDS) • Environmental, Chemical (pollution etc..) • Infections (AIDS) • Psychoneuroimmunological (Severe stress)

28. Herd Immunity • Populations of hosts in close proximity may be similarly exposed to diseases (especially crowd diseases) • The more host there are in the population that are immune to a specific disease, the harder it is for the disease to spread • Herd immunity can occur naturally as host are exposed over their lifetimes and nature selects for the fittest individuals • Vaccines can confer artificial herd immunity to limit the spread of disease