Larry M. Frolich, Ph.D. Biology Department, Yavapai College Blood Cells White blood cells fight invading microbes as part of the immune system Include.

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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.

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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.

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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!)

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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)

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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.

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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)

Larry M. Frolich, Ph.D. Biology Department, Yavapai College Mader text view of B-cell and T-cell action

Larry M. Frolich, Ph.D. Biology Department, Yavapai College HIV and AIDS HIV—Human Immunodeficiency Virus AIDS—Acquired Immune Deficiency Syndrome

Larry M. Frolich, Ph.D. Biology Department, Yavapai College AIDS is caused by HIV virus How viruses replicate and are transmitted

Larry M. Frolich, Ph.D. Biology Department, Yavapai College HIV life cycle

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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.

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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.

Larry M. Frolich, Ph.D. Biology Department, Yavapai College Typical progress of HIV infection

Larry M. Frolich, Ph.D. Biology Department, Yavapai College Complicated because HIV infects cells of immune system HIV doesn’t kill, just lowers body defenses as T-cell levels drop Immune Response:

Larry M. Frolich, Ph.D. Biology Department, Yavapai College As immune system function is lost, many unusual and rarely seen infections begin to take hold

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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

Larry M. Frolich, Ph.D. Biology Department, Yavapai College Blood everywhere— Circulation Oxygen for Cell Respiration Immunity AIDS REVIEW: Blood, Oxygen and Immunity

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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.”

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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

Larry M. Frolich, Ph.D. Biology Department, Yavapai College 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 How does oxygen get into blood?