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Blood, Oxygen and Immunity • Blood everywhere—Circulation • Oxygen for Cell Respiration • Immunity • AIDS

Blood is everywhere…how? • Circulatory system • Big vessels leave from pump—heart • Divide and split to all major parts of body: • Limbs • Head • Guts • Major organs • Body wall • Skeleton, muscles

“Stuff” moves in and out of blood • From/to outside world • O2, CO2 in lungs • Nutrients in guts/digestive system • metabolic wastes—kidneys/urinary system • From/To cells of body • Every single tissue • O2, CO2, nutrients, waste

“Stuff” moves in and out by diffusion Inside organs, muscles, structures, bones, big vessels divide into smaller and smaller vessels and then into network-like capillary beds. This is where diffusion can happen rapidly, at the microscopic level. Then, to get blood back to heart, capillaries feed into smaller veins into larger and larger veins into major veins that return to heart

Capillaries infiltrate every tissue of the body (so blood is everywhere!) • Why? Because the cells that make up every tissue need • Oxygen (for cellular respiration) • Nutrients (for cell metabolism) • Immune cells nearby (to eliminate invading microbes) • Removal of waste (from cell metabolism)

Capillaries—schematic view • Very schematic view of what happens in a capillary • Arteries bring blood from heart. Veins take blood to heart. • Network of capillaries really connects artery to vein • Diffusion of needed substances only happens in microscope, thin-walled capillaries • See next slide for more realistic view of capillary network or “capillary bed.”

Capillaries—more realistic views Photomicrograph of stained blood vessels of retina showing intricate capillary network Electron micrograph showing arterioles, tiniest of arteries, splitting into virtual sheet of capillary network that brings blood into very close proximity with almost every cell in the tissue. More realistic drawing showing network of capillaries connecting arteries to veins and threading through tissue. Open-ended lymph capillaries pick up excess fluid from tissue and also give immune cells route back into blood circulation

Heart pumps blood • If more oxygen is needed, heart pumps faster • Brain, guts are big users of oxygen • But muscles under physical activity are biggest user. • During exercise, more muscles are active, more oxygen is needed so heart pumps faster • Pulse is measure of how fast heart is pumping • Learn to measure your own pulse—you’ll need to do this for the Lab Project

Blood Pressure • Blood pressure measures force of blood against wall of vessels • Systolic pressure is highest point, as blood is being forced out of heart by contraction of heart muscle • Diastolic pressure is lowest point, between heart “beats,” when heart is inactive • Would you expect these values to be affected by physical exercise—find out in Lab Project for this unit!

Why do cells need oxygen? • Remember Cell Respiration (breaks down glucose to make high-energy ATP bonds that can be used for cell metabolic reactions) • Glycolysis (can happen in absence of oxygen=fermentation) • Citric acid cycle • Electron transport chain

Every step of respiration catalyzed by proteins that are coded for in the DNA • Can you find cellular respiration on the E. coli metabolic map?

How does oxygen get into blood? • Oxygen diffuses into blood in lungs • In lungs, bronchioles (air tubes) branch and branch, finally ending in tiny sacs called alveoli. • Each alveolus is surrounded by capillaries • Oxygen diffuses across super-thin epithelial tissue of alveolus, across super-thin epithelial tissue of capillary, across red blood cell membrane and is held by Hemoglobin protein molecules in red blood cells

Blood Cells • Red blood cells are one of several types of blood cells • Each second, 3 million new red blood cells are formed by a special kind of mitosis • Red blood cells have no nucleus or organelles. They are just full of Hemoglobin (Hb) • Thus, Hb was one of the earliest proteins to be isolated and understood. • It’s role in sickle cell anemia also helped to unlock the genetics and molecular structure of Hemoglobin (see web links on the course website)

Blood Cells • White blood cells fight invading microbes as part of the immune system • Include • Lymphocytes—recognize invaders • Monocytes and neutrophils—actually consume or engulf microbes • Basophils—release substances that trigger the other cells.

What are foreign invaders? • Bacteria are prokaryotic cells. Most life on Earth is bacterial. Most is not disease-causing. But immune system must recognize those that do cause disease • Viruses are escaped parts of genome or DNA of different organisms. They cannot live independent of the cells they escape from.

How do immune cells recognize invaders? • Invaders are viruses, bacteria and any other substance that is not part of our body. Remember symbiotic bacteria and other organisms that normally in and on our body are part of it (we are more bacterial cells than human cells!) • During fetal/childhood/adolescent development, immune cells are exposed to body’s own cells and the proteins that they have on their surface. This happens mostly in the thymus and bone marrow. Those immune cell precursors that attack our own cells are eliminated. Those that recognize other cells continue to develop as T-cells and B-cells. • This process is called clonal selection. • The T-cells and B-cells recognize the foreign proteins that are on invaders but have been selected so that they don’t recognize (and try to kill) the body’s own cells

Antibody editing by clonal selection or deletion • Variety of B-cells produced by random recombination of genes for variable regions of antibody • During B-cell development, certain clonal lines are eliminated because their antibodies glom onto the bodys own antigens • B-cell production and clonal selection occurs in bone marrow during early years of life • BCRs (B-Cell Receptors or antibodies recognize

Antibodies • Antibodies are the highly variable proteins that are produced by B-cells in order to recognize the foreign proteins on the invaders (called antigens). • Antibodies are free in the blood stream. When they are on the surface of B-cells, they are called BCRs or B-Cell Receptors. T-cells also make variable proteins that can recognize antigens called TCRs or T-Cell receptors. • Don’t forget that these proteins are made by transcription and translation of certain regions of the DNA

How can each cell have its own different antibody if they all have the same DNA? • Nobel Price for Susumu Tonegawa • DNA is processed and can change as new cells are formed • Recombining regions of DNA that make the antibody recognition site produces all the billions of different combinations of antibodies (and BCRs, TCRs) that recognize any possible invader by the proteins it has on its surface (so we hope!)

How do immune cells actually get rid of invaders? • Phagocytes move through blood and lymph and into connective tissues (part of inflammation response as cells and fluid move out of capillaries into surround aleolar tissues--diapedesis)

Then, these macrophages actually engulf and dissolve the invading microbes. • There are several different sources or kinds of macrophages • Langerhans cells in skin • Phagocytes in blood • Microglial cells in Central Nervous System • This is called “non-specific immunity. It does not depend on the antibodies or B-cells and T-cells. It does not work very well once an infection spreads. Then we need “specific” immunity based on those specific antibodies that recognize the invader.

Specific Immune Response • This gets complicated. • In simple terms: • Antibodies, or BCRs or TCRs glom onto invaders. • This calls in cytotoxic T-cells or macrophages and they kill or engulf the invading microbe • See weblinks for animated graphic of this process Cytotoxic (“cyto” = cell; “toxic” = kills)

Mader text view of B-cell and T-cell action

HIV and AIDS HIV—Human Immunodeficiency Virus AIDS—Acquired Immune Deficiency Syndrome

AIDS is caused by HIV virusHow viruses replicate and are transmitted

HIV life cycle

How is HIV transmitted? • Virion (loose virus) doesn’t live long outside blood • So transmission is through blood and body fluid contact • Other STD’s (sexually transmited diseases) are more easily transmitted, but none is as fatal.

HIV infects Helper T-cells • Type 1—stimulate cytotoxic T-cells • Type 2—stimulate B-cells • Helper T-cells recognize antigens, but can do nothing about it on their own. They secrete cytokines (such as interleukin) to direct what kind of immune response should be activated. • For most infections, Helper T’s are crucial for a robust response. • Thus, in AIDS, these cells are killed, as they themselves present viral antigens and invite cytotoxic T-cells or macrophages to ingest them. • Without the helper T-cells, good response to most infections cannot be mounted.

Typical progress of HIV infection

Immune Response: • Complicated because HIV infects cells of immune system • HIV doesn’t kill, just lowers body defenses as T-cell levels drop

As immune system function is lost, many unusual and rarely seen infections begin to take hold

Epidemiology of spread of AIDS (population dynamics—Unit IV of Human Biology!) • Mostly African and Asian disease • In U.S., new cases down throughout 1990’s, now on rise again—why? • See web links on HIV/AIDS

REVIEW: Blood, Oxygen and Immunity • Blood everywhere—Circulation • Oxygen for Cell Respiration • Immunity • AIDS