Immune
System
The influenza
epidemic of 19181919 killed 22 million people in 18
months. With 25
million American
infected, the Red
Cross often worked
around the clock. 3
million people will die
from malaria this
year.
Innate immunity is one that you are born with and does not require
the exposure to the disease to activate it. First line of defenseThis defense works to keep the pathogen out of the body.
Integuments System-skin & mucous membranes
-contains keratin which is an enzyme resistant to many bacterial
enzymes
-skin's fatty acids and secretion from sweat and oil glands are
toxic to bacteria
Body passages-the mucous produced
by the respiratory system traps
microorganisms and the cilia sweeps it
out
The first line of defense in the
respiratory tract (trachea). The orange
cells produce mucus that that traps
microorganisms that enter. The yellow
cells are ciliated which beat in unison
to expel mucus and trapped
microorganisms upward to pharynx.
Stomach- the pH
kills ingested
bacteria. Tears
contain lysozymes
which destroy cell
walls of bacteria
Urine flushes
bacteria out.
Natural fauna of our
own bacteria are
harmless can out
compete other
bacteria.
This is skin that has been cleaned with
soap and rinsed clean. Even with this
treatment, skin cells may be home to
million of harmless bacteria (green rodshaped cells).
Second line of defense of innate immunity
I. Non-specific- direct; immediate invader
can be anything:
A. Chemical Response- The injured cells release chemicals to help
destroy invaders
1. Histamine- Mast cells are cells found lining nasal passages
and in connective tissue, and basophile cells are leukocytes are
circulating in the body. When antigens such as pollen attach to
these cells, they are damaged and release histamine. Histamine
is a chemical that causes a.) vasodilatation b.) increase
permeability of capillary beds. This causes the area to become
The picture on the left is ragweed pollen. The other picture are mast
cells being attacked by antigens. They will lyse and release
histamine. Antihistamines will suppress this response.
2. Kinins (or chemokines)- polypeptides
a.) increase circulation and capillary permeability
b.) attract leukocytes to site of injury
c.) affect nerve cells making area tender
3. Complement proteins (approx. 20 proteins)
a.) Directly- form protein rings on bacteria membranes
forming pores, water rushes in, bursts cells
b.) Indirectly- The
complement protein coats
the surface bacteria. There
are recognition sites on the
phagocytes that bind with
proteins coating the
bacteria. The phagocytes
engulf the bacteria in a
process called opsonization4. Interferon- is made and attaches to surface receptors on
other cells making harder for viruses to attack.
B. Innate immunity-Second line
of defense. Nonspecific CellularUses leukocytes (white blood
cells made in bone marrow).
These include phagocytes,
basophiles and natural killer cell
which is a lymphocytes.
1. Phagocytes are commonly
found in connective tissue that
help form the lining of the many
organs (i.e. liver, lungs and
kidneys), and they are found
circulating in the blood and
lymph nodes.
Phagocytes go to the site of infection and start engulfing bacterial
cells and cellular debris. Pathogens are surrounded by a
membrane. The vacuoles fuse with lysosomes to destroy the
The lysosomes contain
hydrolytic enzymes
that destroy the
bacteria. Phagocytes
can literally eat
themselves to death.
Pus are the remains of
phagocytes that have
been destroyed.
*Types of Phagocytes
-Eosinophils- weakly phagocytic cells attracted to area, kills
invaders that have been clumped together. Will also kill parasitic
worms by depositing toxic granules in them.
-Neutrophils- first to arrive; numerous (1 billion made each day);
survive only a few days. Expendable.
-Monocytes arrive- transform into
large macrophages; very efficient also
involved in primary immune
response. A monocyte that has been
transformed into a macrophage. This
macrophage is engulfing bacterial
cells and destroying them.
-Basophiles are leukocytes containing
histamines. These are release when these
circulating cells are damaged.
A natural killer cell (in the foreground) is killing a cancer cell by
punching holes in the plasma
membrane. Water will rush in and
lyse the cell.
-Natural killer cells are (lymphocytes) roam the body contacting cells
looking for infected cells by viruses and/or cancer cells. Eukaryotic
cells are transformed when infected by viruses and cancer cells are
also transformed.
Natural killer cells can differentiate these cells and will destroy these
cells. It destroys cells by lysing the cells.
A number of natural killer cells are
attacking a cancer cell. Water will rush in
and lyse the cell. In general phagocytes in
mammals have the ability to distinguish
pathogens because they contain receptor
sites called Toll-like receptors (TLR). TLR
recognizes certain molecules that are
common to pathogens but not mammals.
-TLR4 found on phagocytes recognizes a lipopolysaccharide found
on many bacteria.
-TLR3 found inner membrane of vesicles from endocytosis
recognizes DS RNA from viruses.
TLR causes phagocytosis to occur. The vesicles then fuse with a
lysosome. The lysosome releases nitric oxide to kill pathogen and
then releases hydrolytic enzymes to break pathogens down.
This illustrates the
interaction of the cellular
and chemical interaction of
the nonspecific immune
response to produce the
inflammatory response.
1. Chemical such as histamine are released by mast
cells and macrophages.
2. Histamine increases
capillary permeability. The
area becomes swollen.
3. Phagocytes leave the
capillary bed attracted to the
site .
4. They clean up pathogens.
Specific response-or immune
response is slower and
requires time. The
lymphocytes arise in bone
marrow. Then the
lymphocytes either stay in the
bone marrow or migrate to
the thymus gland to mature
and differentiate. The bone
marrow and thymus are
primary lymphoid tissue.
Once mature and differentiated, the lymphocytes migrate to
secondary lymphoid tissue where they remain and are later
activated. Secondary lymphoid tissue include, adenoids, tonsils,
lymph nodes, the spleen and Peyer's patches found on the small
intestines.
Lymph vessels include lymph capillary beds connected to lymph
veins. (No lymph arteries). These veins move lymph like circulatory
veins. As the lymph is moved through veins, it is filtered by lymph
nodes where pathogens are removed. Lymph is a clear fluid that
is clear fluid that is left over from the circulatory capillaries. Lymph
veins work like circulatory veins. The fluid is filtered by the lymph
nodes. The lymph is returned to the circulatory system dumping
into vena cava near the heart.
There are 2 types of lymphocytes involved in the immune response.
When immature, the 2 cells are indistinguishable. T-cells mature in
thymus and have a large amount of ribosomes. B-cells mature in red
bone marrow and have a large amount of E.R.
The first cell is an immature lymphocyte. The second cell is a
mature B- cell with extensive E.R. The last cell is a mature Tcell with its extensive amount of ribosomes.
Mature B-cells secrete
AB and some are
memory cells used to
prevent a second
infection. They are
involved in the humoral
response.
Mature T-cells are
involved in the cell
mediated response and
also the humoral
response.
Antibodies bind to
epitopes on the
surface of an
antigen. In the
above example, 3
different AB
molecules react with
3 epitopes on the
same large AG
molecule
Antibodies (AB) are special proteins secreted in response to the
presence of foreign substance or antigen.
Antigen (AG) can be nucleic acid, carbohydrates, protein. AG
usually large, over 5000 Daltons. AG can be free floating OR
attached to invading virus or bacterial cells. A particular molecule,
virus or bacteria may activate many different AB to be made. The
part of the AG that causes an AB to be synthesized is termed an
antigenic determinant or epitope.
Antibodies are proteins made of 4 polypeptides. 2 identical, heavy,
polypeptide chains and 2 identical, light polypeptide chains. A light
chain is bonded to a heavy chain by disulfide bonds. The part of the
AB that binds to the AG is found on the variable regions of the light
and heavy chains. AB are made by B-cell lymphocytes.
At the end of the of the AB are 2 binding sites for AG.
These ends are called the variable regions and are
specific for particular AG. The other parts are
constant regions and are the same for each type of AB.
Five Different Classes of AB or
immunoglobulins Ig
-IgG- monomer- found late in
response crosses placenta
-IgA- dimer and monomer form
-IgM- pentamer- monomer
form helps with virgin B cells
-IgD- monomers found surface
B cells
-IgE- monomer found in area
with connective tissue helps
with release histamine
Not only do B cells make AB but they have AB on the surface of the
plasma membrane that is used as receptor site. T-cells also have
antibody like receptor sites. This T-cell receptor site has both a
variable and constant region.
How Do AB Work
1. Agglutination-AB bind to
several AG clumping them
together so phagocytes can
devour them
2. Neutralization-AB will coat
the epitopes so that the
pathogen cannot interact with
the receptor sites of cells
3. Certain interaction with AB and AG trigger complement system,
the complement proteins cause holes in invading cells, H2O goes in,
cell bursts
4. Precipitation-AB will attach to soluble AG so that it will
precipitate out and can be easily engulfed (phagocytosis).
4. Opsonization can occur- bacterial cells will have so
many AG determinants that the AB may coat the
bacteria cell- the constant regions stick out- called
the FC region. The phagocytes have FC receptor, so
the phagocyte literally rolls over the invader and
engulfs it.