Vs B. Red Blood Cell Production, Hemoglobin/Hgb, Sicklecell Hgb G&H Pp .

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Fun Discussion w/WBC differential count! BI 358 Lecture 6 I. Announcements Quiz 2 GI Nutrition next T! Nutrition reports (.doc/.docx .pdfs) by e-mail due 5 pm to Mae, Abbie, Bella. II. Blood Immunology G&H ch 33, 34, 35; Nilsson, Davey, Fox A. Blood: cell fragments vs liquid. Plasma vs serum? LS B. Red blood cell production, hemoglobin/Hgb, sickle cell Hgb G&H pp 445-51, fig 33-1, 33-2, 33-6 Fox, LS C. White blood cell differential, ID & functions, platelets LS, GH D. Immune response, pathogens Davey fig 2.1, 2.2 pp 12-13 E. WBC phagocytosis, lymphoid tissue. Nat Geographic, The Wars Within, Lennart Nilsson http://www.lennartnilsson.com/ F. Medical Physiology News Handwashing to prevent infection! Laughter as medicine! Centers for Disease Control & SEBB G. Innate vs adaptive immunity cf: G&H pp 465-70,LS . Innate immunity: inflammation, interferon, complement; HIV H. Antibody (Ab Ig) structure, subclasses, mechanisms G&H fig 35-4 LS Davey fig 2.4 p 19, fig 4.2 p 42, tab 4.1 p 49 I. OHSU Researcher Louis Picker HIV/AIDS cure? Oregon Live J. Mom’s milk overview Scientific American K. Immune Regulation Allergy: G&H fig 35-7, 35-8, 35-3

Dr. Kraig Jacobson of Oregon Allergy Associates is coming next Tuesday! Yes, Sherlock! Avian & human immune systems evolved from a common reptilian ancestor!! Whoopee! For the birds?

What's in Blood? Plasma & Blood Cells LS 2012 fig 11-1

2000 x GMBH, Nat Geog 1986 Jun p 714

Dermal bone production of red blood cells G&H 2016 fig 33-1 p 446 G&H 2011 fig 32-1 p 414

Pluripotent Hematopoietic Stem Cell Lines G&H 2016 fig 33-2 p 446 G&H 2011 fig 32-2 p 414

S&W 2011 fig 6-5 p 194

Hemoglobin Structure L Sherwood 2011 fig 11-2

Heme Structure NB: CO carbon monoxide binds w/ 200-fold affinity than O2 G&H 2016 fig 33-6 p 450 G&H 2011 fig 32-6 p 418

SI Fox 1987 p 376

Granulocytes Neutrophil 58-62% Eosinophil 2-3% Basophil 1% Monocyte 3-5% Lymphocytes 28-32% Agranulocytes

Megakaryocyte D Chiras. Human Biology 7th ed, 2012, fig 7-8 p 144. Platelets/Thrombocytes

Immune Response 1. Detect invader or ID toxic product. 2. Communicate to network. 3. Recruit coordinated, multi-pronged attack. 4. Amplify & if yes to success, then – 5. Suppress Limit Destroy Davey 1990 p 6

Pathogen? Microbes that cause disease! Fungi Bacteria Viruses Davey 1990 p 5 Protozoa Multicellular Parasites, e.g., ticks & lice

Pathogens & Parasites Cause: 1. 70-80% of deaths in less developed countries 2. Tens of millions of deaths due to infectious diseases 3. 20 million childhood deaths per year in Asia, Africa & Latin America due to diarrheal infections alone 4. Yet 2% deaths in modern, industrialized countries! World Health Organization 2018 Statistics Davey 1990 p 5 http://www.who.int/gho/publications/world health statistics/en/

Why such striking differences across the world? 1. Poor sanitation 2. Contaminated water supply 3. Contaminated food supply 4. Malnutrition 5. Existing infections 6. Patchy, inadequately-funded vaccinations 7. AIDS superimposed on top of 1-6! Davey 1990 p 5

Barriers to Infection Davey 1990 p 12

Good phagocytes! Davey 1990 p 13

G&H 2011 cf: fig 34-2 G&H 2016

10,000 x GMBH Nat Geog 1986

4000 x GMBH Nat Geog 1986

7000 x GMBH Nat Geog 1986

3000 x GMBH Nat Geog 1986

10,000 x GMBH Nat Geog 1986

7000 x GMBH Nat Geog 1986

Lymphoid Tissues BALT GALT L Sherwood 2012

Widespread Location of Lymphoid Tissues! Davey 1990 p 36

NB: Happy Birthday Song 20-30 sec!! http://www.squidsoap.com/

Laughter Medicine! Laughter’s most profound effects occur on the immune system. Laughter γ-interferon, B-cells, T-cells and stress hormones The average child laughs 100s of x/day The average adult laughs 12 x/day We need to find these lost laughs—and use them to our advantage! Ah Ha! SEBB Newsletter 1997

Immunity Innate/Inborn/Nonspecific Adaptive/Acquired/Specific 1. Immediate, upon exposure to threatening agent 1. Delayed, selective targetting based on prior exposure 2. 10 effectors phagocytic specialists: neutrophils & macrophages 2. 10 effectors lymphocytes: T- & B-lymphocytes 3. "Eyes" are Toll-like receptors (TLRs) which recognize & bind with generic invader markers 3. "Eyes" are T- and B-cell receptors which bind with specific antigens 4. Inflammation, interferon, 4. Cell-mediated & Humoral natural killer cells, (Ab mediated) immunity complement (plasma proteins) Really, a false separation, as incredible overlap & synergism!

1. Phagocytosis 2. Enzymatic rxns, Q10? 3. Bacterial replication by Fe2 requirement Prostaglandins Set point Hypothalamus NO, nitric oxide toxic to microbes NETs! Neutrophil Extracellular Traps EP, endogenous pyrogen X Lactoferrin binds Fe2 Replication Should we use? . . . . . . . . Kinins activated Neutrophil Pain receptors Chemotaxis NSAIDs e.g. Aspirin Mast Cells Macrophage Anti-histamines Histamine Vasodilation Capillary permeability

3000 x GMBH Nat Geog 1986

Allergic Reactions, Mast Cells & Basophils? Allergen IgE Y Y Y up to ½ million per cell! Y Mucous Membranes/Blood Bradykinin Eosinophil & Neutrophil Chemotactic Substances Heparin Histamine Platelet Activating Factors Protease Serotonin Toxic Leukotrienes/SRSA

Inflammation Steps 1 Break in skin Bacteria enter & reproduce 2 Mast cells release histamine 3 Vessel wall becomes sticky Neutrophils & monocytes attach diapedesis chemotaxis 4 Chemotaxins attract more Neutrophils & monocytes 5 Monocytes swell Macrophages Redness, Heat, Swelling, Pain! L Sherwood 2012

Glucocorticoids throw blanket over entire inflammatory process! 1. Certainly warranted to quiet down immune system during extreme flare ups of arthritis, asthma, poison ivy, rash, but must consider: 2. Destroy lymphocytes in lymphoid tissues. 3. Antibody/Immunoglobulin (Ig) production. 4. Make susceptible to bacterial infections.

Viruses coming! Don’t breathe on me, Paul! L Sherwood 2012 Interferon Mechanisms

Activated Complement The Big MAC to ! Osmotic explosion! L Sherwood 2012

WBC Adverse Effects Body defense vs. μ organisms! X Leukocytes Anti-cancer drugs Benzene Nuclear blast Radiation Professional phagocytes esp: Neutrophils Macrophages Savior Lymphoid tissues or bone marrow transplant? cf: Leukemia uncontrolled WBC proliferation, yet inadequate defense other cell lines displaced overwhelming infections & bleeding.

30,000 x GMBH Nat Geog 1986

Commander-in-Chief of the Immune System!! HIV tips the balance!! Davey 1990 p 30

G&H fig 34-1 2011 cf: fig 35-1 G&H 2016

G&H fig 34-7 2011 cf: fig 35-7 G&H 2016

Nat Geog 1986, p 710

8500 x GMBH Nat Geog 1986

Typical IgG Antibody Structure How do antibodies work? L Sherwood 2012; cf: G&H 2011, fig 34-4; G&H 2016 fig 35-4.

Immunoglobulin G Source: Visual Science http://visualscience.ru/en/

1 Agglutination 2 Complement 3 Opsonization 4 Killer Cells L Sherwood 2012

G A M D E IgE skyrockets in allergies, parasitism, vasculitis, Hodgkin's disease! Davey 1990 p 49

G A M E D!

IgA Secretory Ab Antigen/Ag Dimer!! Valence? 4 Davey 1990 p 50

IgM Macroglobulin Pentamer!!!!! Valence? 10 Antigen/Ag Davey 1990 p 51

Macrophages, Dendritic Cells G&H 2011 fig 34-8 G&H 2016 fig 35-8

Dendritic Cells: Specialized Antigen-Presenting Cells (APCs) Sentinels in Almost Every Tissue! L Sherwood 2012

Immunology Websites for Fun Learning! udent view0/chapter24/ animation the immune response.html http://www.guardian.co.uk/science/video/2010/ nov/01/immune-system-viruses-cells /

Dr. Louis Picker of OHSU on track to cure HIV! / louis pickers hiv vaccine erad.html / superstar scientist dr louis p.html https://www.youtube.com/watch?v ITwG6O9G81g

SOURCE: J Newman. How breast milk protects newborns. Scientific American 1995, 273, 6, 76-9. Sci Am Dec 1995 Dana Burns-Pizer

http://www.who.int/topics/breastfeeding/en/ ng/Pages/default.aspx

http://www.scientificamerican.com/article.cfm?id got-smarts-mothers-milk-m study-pinpoints-breast-milk.html

http://pinterest.com/pin/50947039506317536/

Nat Geog 1986

G&H 2011 cf: fig 35-3 G&H 2016

of Oregon Allergy Associates is coming next Tuesday! Whoopee! For the birds? Yes, Sherlock! Avian & human immune systems evolved from a common reptilian ancestor!! What's in Blood? Plasma & Blood Cells LS 2012 fig 11-1. 2000 x GMBH, Nat Geog 1986 Jun p 714. Dermal bone production of red blood cells

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