The Immune System: April 24 Five Types of Pathogen :

1. The Immune System: April 24Five Types of Pathogen: • Bacterial • Viral • Parasites • Fungi • Prions Three Types of Human Pathogen Defense: 1) Avoidance- handwashing, cooking etc 2) Innate Response- inflammation, fever 3) Acquired Immune Response- antibody production

2. What is Immunity? • A complicated web of cells and chemical signals that work in concert to protect the body from pathogens and injury • Cells are educated to distinguish between “self” and “non-self” • Cells learn to create antibodies to bind antigenic items • Antibodies help destroy/incapacitate antigenic items • Lymphocytes that make antibodies become immortal to “remember” the antigen during future exposures

3. Innate Response is a “general” response and non-specific (one-size-fits-all) Parameters of the Innate Response: • Physical/Chemical Barriers- prevent entry i.e. skin, pH, mucous membranes, cilia, sweat glands, others • Microbiogical- Direct competition of good microbes over bad microbes i.e. we all have “good” E.coli in our gut • Cellular- Macrophages, Phagocytosis, Granulocytes and Inflammation (generalists in lung and pus)

4. Where do our immune cells originate?

5. Cells without Memory (innate) These are the Generalist Cells that protect right after exposure: • Macrophages-very important cell of the immune system. An antigen presenting cell (APC), phagocytic cell, and recruiting cell in the inflammatory response • Neutrophils-phagocytic cell that is often the first line of defense. Short lived but effective. • Dendritic Cells- Professional APC • Mast Cells- tissue dwelling cell, often involved with allergies • Eosinophils- responsible for killing parasites, often involved with allergies/asthma • Basophils- similar to eosinophils • Natural Killer Cell (NK)- direct cell killing and/or recruiting cell

6. Inflammation (Innate Response):Detect bacteria Vasodilate/Increase Cap. Permability Recruit more macrophages Destroy stimulus Classic Negative feedback/ Classic “zit”

7. Signs of Inflammation • Heat, Pain, Redness, Swelling • “calor, dolor, rubor, tumor”. • V.I.P. Contrast with “EDEMA”-swelling that is cold to the touch (i.e. Rt Side Heart Failure or a blocked lymphatic duct) • Cells involved- Macrophages, Neutrophils • Other substances involved- cytokines, complement

8. What does the standard macrophage do when it encounters a bacteria after recruitment to an injury site?

9. Specific Antigenic Resistance (Cells with Memory) • These are the “Heavy Hitters” that potentially protect you for life from a “repeat exposure”. • Terminology: • Antigens- chemical substances capable of stimulating the immune response (mostly proteins) • Antigenic determinant (epitope)- the small part of an antigen that the lymphocytes recognize in order to stimulate the specific response • Epitopes can be a protein, polysaccharide or even a lipid that is unique to pathogen • Epitopes can also be on the cells of self…i.e. B-cell in pancreas (resulting in Type-1 diabetes by accident)

10. Cells with Memory of exposure to a specific epitope (antigen) • B lymphocytes (B Cells)- differentiate into antibody secreting plasma cells for immediate defense in presence of antigen or later recruitment (memory) • T lymphocytes (T Cells)- • CD4 (T Helper Cells)- help with the inflammatory response and/or help B Cells make antibodies • CD8 (Cytotoxic T Cells)- directly kill virally infected cells

11. Adaptive Response and the Clonal Selection Theory of Immune System Development: • Random unique receptors cell/epitope specificity • Rapidly Clone cells with Antigen-Antibody “match” • Some clones make Antibodies • Some clones become memory cells • Response gets better over time (more cells, faster response, better specificity) • Cells capable of recognizing “self” molecules are destroyed (hopefully). • “Autoimmune Disorders” are an aberration of this process and potentially LETHAL • Bad Apple AI Examples Include: Type 1 Diabetes, Rheumatoid arthritis, Lupus etc

13. Antibody-Mediated Immunity(Humoral Immunity) • B Cell recognizes (binds to) antigen within a lymph node. • B Cell processes antigen and displays it on MHC class II • Meanwhile, a macrophage activates a T Cell which clones itself many many times • T Cell activates B Cell by binding with the MHC displayed on B Cell surface (positive feedback loop) • T Cell activates B Cell • Some B Cells become plasma cells and secrete antibodies while others become memory B Cells

14. Humoral (blood borne) Immunity

15. Structure of a Human Antibody: All Antibodies are proteinsAll Antibodies bind antigens (foreign/autoimmune)

16. There are several types of antibodies: each with a specific target or function • The green structures on each Ig confer their selective functions in the immune system (i.e. antigen destined for milk, plasma, etc) • The red tops determine antigen binding: antigens can be a unique peptides, carbohydrates, lipids, or other chemical.

17. Antibody Isotype DifferencesDifferent kinds of Ab and why? • IgG- most abundant in blood/serum. Crosses the placenta. Found in extracellular fluids. • IgM-first antibody produced, excellent at activating complement (proteins used in immune reactions) • IgA-protects the mucosal surfaces, passed in breast milk • IgE-specific for parasitic infections, often seen in allergic reactions (i.e. anaphyactic shock) • IgD- receptor on B Cell surfaces

18. What happens when the Immune System Goes to Far? Hypersensitivity Reactions • 4 Types of Hypersensitivity Reactions • Type I- Classic “Allergies”(hayfever, foods, drugs, latex) • Type II- Cytotoxic- antibodies to cell surface antigens (incompatible blood types or hemolytic disease of the newborn) Type AB blood transfusion to type-O recipient • Type III- Immune complex hypersensitivity- accumulation of immune complexes in blood tissues Systemic lupus erythematosus-SLE or Rheumatoid arthritis • Type IV- Delayed or cellular hypersensitivity- T Cell mediated, takes 24-72 hours for effects. Poison ivy and other chemical/skin reactions

19. Allergy Sensitization: How do we develop a response to an irritant?

20. Allergy Elicitation

21. Why does injury site become red, warm and swollen with hypersensitivity due to mast cell release of histamine? What is the biological advantage of having tissues accumulate fluid?Inflammation IS and Edema is NOT!! (that is the question)

22. Three Types of Human Pathogen Defense: • 1) Avoidance- handwashing, cooking etc Good hygeine • 2) Innate Response- Inflammation and Fever Heat,Pain,Redness,Swellingcalor, dolor, rubor, tumor V.I.P. Contrast of inflammation with “EDEMA” • 3) Acquired Immune Response- antibody production Production of antibody secreting cells Production of memory cells Destruction of initial epitope bearing pathogens Creation of occassional “problems” such as allergies and autoimmune disorders

23. Vaccination:What is at risk for everyone?Acquired Immune Response- antibody production Please consider Smallpox (an extinct disease) and the continued need for vaccination against other potential diseases even if very rare. CDC Vaccination schedule: https://www.cdc.gov/vaccines/schedules/easy-to-read/child.html?s_cid=bb-vaccines-Child-HP08-NCIRD