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
Immune Response:
• Complicated because HIV infects cells of
immune system
• HIV doesn’t kill, just lowers body defenses
as T-cell levels drop
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
REVIEW:
Blood, Oxygen and Immunity
• Blood everywhere—
Circulation
• Oxygen for Cell
Respiration
• Immunity
• AIDS
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
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 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
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
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
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
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
Immune Response:
• Complicated because HIV infects cells of
immune system
• HIV doesn’t kill, just lowers body defenses
as T-cell levels drop
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