The Immune System – A Play in 3 acts

1. The Immune System – A Play in 3 acts • The Body’s Defenses

2. Lines of Defense Innate Immune System Adaptive Immune System

3. 1st line: Non-specific External defense Lining of trachea: ciliated cells & mucus secreting cells • Barrier • skin • Traps • mucous membranes, cilia,hair, earwax • Elimination • coughing, sneezing, urination, diarrhea • Unfavorable pH • stomach acid, sweat, saliva, urine • Lysozyme enzyme • digests bacterial cell walls • tears, sweat

4. Inflammatory response • Damage to tissue triggers local non-specific inflammatory response • release chemical signals • histamines & prostaglandins • capillaries dilate, becomemore permeable (leaky) • delivers macrophages, RBCs, platelets, clotting factors • fight pathogens • clot formation • increases temperature • decrease bacterial growth • stimulates phagocytosis • speeds up repair of tissues

5. Fever • When a local response is not enough • system-wide response to infection • activated macrophages release interleukin-1 • triggers hypothalamus in brain to readjust body thermostat to raise body temperature • higher temperature helps defense • inhibits bacterial growth • stimulates phagocytosis • speeds up repair of tissues • causes liver & spleen to store iron, reducing blood iron levels • bacteria need large amounts of iron to grow

6. 2ndline: Main Actors • Leukocytes: • leuko= white, cyte = cell, “white cells” • produced in bone marrow from stem cells • found in the circulatory and • lymphatic systems • Specific and non-specific • several types of Leukocytes: • Macrophages • Neutrophils • Lymphocytes

7. Main Actors – Innate Immune System • Macrophages (lymphocyte) • macro – large, phage – eater, “large eater” • type of lymphocyte • non-specific killer cell • “phagocytose” engulf and digest foreign microbes • signal other lymphocytes • Video of phaocytosis

8. Main Actors – Innate Immune System • Neutrophils: • most abundant leukocytes in mammals • first responders to site of injury or infection • highly mobile and move quickly • Attack pathogens through a variety of means • Video of Neutrophil attack

9. Main Actors – Innate Immune System • Natural Killer Cells: • only discovered in 1970’s • attack infected/abnormal cells • respond to cytokines – messenger molecules • important response to viral infections • play a role in suppressing cancerous cells • Video of Killer Cell attack

10. Main Actors – Innate Immune System • Complement System: • proteins circulating in blood plasma • recognize pathogens and for • membrane attack complexes

11. 3rd Line: Main Actors – Adaptive Immune System • T cells and B cells (Lymphocytes): • Helper T cells activate killer T cells and B cells • T cells are specific to pathogen type • B cells produce antibodies and mark pathogens for attack by other killer cells • B cells include “memory”cells that provide immunity from future infections

12. B cells • Attack, learn & remember pathogens circulating in blood & lymph • Produce specific antibodiesagainst specific antigen • Types of B cells • plasma cells • immediate production of antibodies • rapid response, short term release • memory cells • continued circulation in body • long term immunity

13. T cells • Attack, learn & remember pathogens hiding in infected cells • recognize antigen fragments • also defend against “non-self” body cells • cancer & transplant cells • Types of T cells • helper T cells • alerts rest of immune system • killer (cytotoxic) T cells • attack infected body cells • memory T cells • long term immunity T cell attacking cancer cell

14. How are invaders recognized? • Antigens • cellular name tag proteins • “self” antigens • no response from WBCs • “foreign” antigens • response from WBCs • pathogens: viruses, bacteria, protozoa, parasitic worms, fungi, toxins • non-pathogens: cancer cells, transplanted tissue, pollen “self” “foreign”

15. MHC proteins displaying foreign antigens TH cell WANTED How do T cells know a cell is infected? • Infected cells digest some pathogens • MHC proteins carry pieces to cell surface • foreign antigens now on cell membrane • called Antigen Presenting Cell (APC) • macrophages can also serve as APC • tested by Helper T cells infectedcell T cell with antigen receptors

16. MHC protein T or Bcell MHC proteins displaying self-antigens How is any cell tagged with antigens? • Major histocompatibility (MHC) proteins • proteins which constantly carry bits of cellular material from the cytosol to the cell surface • “snapshot” of what is going on inside cell • give the surface of cells a unique label or “fingerprint” Who goes there? self or foreign?

17. Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Antibodies Y Y Y Y Y Y Y • Proteins that bind to a specific antigen • multi-chain proteins • binding region matches molecular shape of antigens • each antibody is unique & specific • millions of antibodies respond to millions of foreign antigens • tagging “handcuffs” • “this is foreign…gotcha!” Y Y antigen-binding site on antibody Y antigen Y Y Y variable binding region Y Y each B cell has ~50,000 antibodies

18. Y Y Y Y Y Y Y Y Y Y Y Y Y Y antibodies antibodies Y Y Y Y Y Y Y Y Immune response summary pathogen invasionantigen exposure skin skin free antigens in blood antigens on infected cells macrophages (APC) humoral response cellular response alert alert helperT cells B cells T cells plasmaB cells memoryB cells memoryT cells cytotoxicT cells

19. Attack mechanisms - review • B cells mark pathogens for attack by other killer cells • B cells mark virus which is recognized and expelled once they are incorporated into cells • Killer cells recognize self vs. foreign using various marking systems • Antigen/Antibody systems (used by B cells) • major histocompatability complex proteins • generalized microbial toxicity

20. Induction of Immune Responses • Primary immune response:lymphocyte proliferation and differentiation the 1st time the body is exposed to an antigen • Plasma cells: antibody-producing effector B-cells • Secondary immune response: immune response if the individual is exposed to the same antigen at some later time~ Immunological memory

21. Vaccinations • Immune system exposed to harmless version of pathogen • stimulates B cell system to produce antibodies to pathogen • “active immunity” • rapid response on future exposure • creates immunity without getting disease! • Most successful against viruses

22. Albert Sabin 1962 oral vaccine 1914 – 1995 Jonas Salk April 12, 1955 • Developed first vaccine • against polio • attacks motor neurons

23. Immunity in Health & Disease • Active immunity: long term/ natural: conferred immunity by recovering from disease • artificial: immunization and vaccination; produces a primary response • Passive immunity: short term transfer of immunity from one individual to another • natural: mother to fetus; breast milk • artificial: rabies antibodies • ABO blood groups (antigen presence) • Rh factor(blood cell antigen); Rh- mother vs. an Rh+ fetus (inherited from father)

25. Abnormal immune function I • Allergies • hypersensitive responses to environmental antigens (allergens); mast cells release histamine causes dilation and blood vessel permeability, epinephrine • Antihistamines can relieve symptoms anaphylactic shock: life threatening reaction to injected or ingested allergens.

26. Abnormal immune function II • Autoimmune disease: • The system turns against the body’s own molecules • Examples: multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus Rheumatoid arthritis

27. Abnormal immune function III • Immunodeficiency disease: • Immune components are lacking, and infections recur • Ex: SCIDS Severe combined immunodeficiency (bubble-boy); A.I.D.S., Acquired Immunodeficency syndrome

28. Abnormal immune function IV • Human Immunodeficiency Virus • virus infects helper T cells • helper T cells don’t activate rest of immune system: killer T cells & B cells • also destroys helper T cells • AIDS: Acquired ImmunoDeficiencySyndrome • infections by opportunistic diseases • death usually from • “opportunistic” infections • pneumonia, cancers HIV infected T cell