DEFENSE MECHANISMS

The body is protected against pathogenic microorganisms by two mechanisms

Phagocytosis of the invading organism
Formation of antibodies
Phagocytosis of the invading microorganisms is carried out by white blood cells and the
reticuloendothelial system. Formation of antibodies against invading microorganisms or
destroying them by lymphocytes through the immune response.
WHITE BLOOD CELLS
These are large nucleated cells that constitute the mobile units of the body's defense mechanism.
They look for invading microorganisms and destroy them.
The Caucasian value is about 4000 to 11000
Classification based on Granulation.
1. Granulocytes or polymorphonucleocytes
2. Non-granulocyte
Granulocytes
Have granules in their cytoplasm
 Neutrophils (Macrophages 50 to 70%
 Eosinophil 0 to 4.0%
 Basophils 0.4 to 1%
Neutrophils constitute 50 to 70% of the total white blood cell count
Non granulocytes
These cells do not have granules in their cytoplasm.
Lymphocytes 20 to 40%
Monocytes 2 to 8%.
Formation of leukocytes (Leukopoiesis)
All granulocytes and monocytes as well as a few lymphocytes are formed in the bone marrow
while most lymphocyte are formed in the lymphoid organs especially the lymph nodes and
the spleen.
Requirements
Dietary factors necessary for cell growth and division are vitamin B12 and proteins of high
quantity and biological value. Leukopoiesis is stimulated by colony stimulating factors produced
by macrophages, fibroblasts, endothelial cells, certain lymphocytes and even products of
inflammation.
Colony-stimulating factors act locally within the bone marrow and cause proliferation of a
particular committed stem cell.
Lifespan and fate of leukocytes
Some of them are lost from the body via the gastrointestinal tract. Lifespan in circulation is 4 to
8 hours then then they enter the tissues. They stay there in the tissues for about 4-5 days and are
destroyed due to infection by invading microorganisms.
Lifespan of monocytes is about 20 to 72 hours in blood after which the enter the tissues and
enlarge to become tissue macrophages. In the tissues they stay for 2 months or more.
Large lymphocytes mature into small Lymphocytes which now reach the bloodstream via the
lymphatic vessels.
Remember lymphocytes are produced from lymphoid organs and reach the general circulation
via the lymphatic vessels.
After a few hours they cross the capillary wall back into the tissue and re-enter the lymphatic
vessels. They live relatively longer periods.
Functions of leukocytes
Neutrophils (Polymorphonucleocytes) or macrophages 50 to 70% of the total white blood cell
count.
There function is to exert powerful defense against bacterial infections.
Main function is phagocytosis and destruction of the invading bacteria.
What happens in terms of bacterial infection?
Macrophages present in tissues, attack the bacteria within 1 hour. Neutrophils invade the infected
area.
Remember we have fixed macrophages and wandering macrophages.
Macrophages are the first line of defense against bacterial infection while neutrophils are the
second line of defense against bacterial infections.
A bacterial infection is associated with marked increase in the number of neutrophils. This
increase is called neutrophilia.
A blood count that shows a high number of neutrophils raises suspicion of a bacterial infection.
Neutrophilia is as a result of stimulation of the bone marrow to release large numbers of
neutrophils stimulated by certain products of inflammation.
How do neutrophils in blood reach the site of infection? By the following mechanisms.
Attraction to the surface endothelium: They are first attracted to the surface capillary
endothelium wall by proteins called selectins.
Rolling: They roll along the endothelium.
Margination: The movement of neutrophils closer to the endothelium. The rolling of
neutrophils on the endothelial surface.
Adhesion: Neutrophils bind to adhesion molecules called integrins. Adhesion molecules are
proteins. After binding firmly, they now insinuate themselves in between the capillary wall
cells or endothelial cells by a process called Diapedesis.
Chemotaxis: After diapedesis they now move to the site of infection by amoeboid motion.
They are attracted to such as site by chemicals called chemoattractants or chemotactic agents.
This process of attraction is called the chemotaxis
Examples of chemoattractants;
 Components of the complement system
 Polypeptides from lymphocytes, mast cells and basophils
 Bacterial or viral toxins
 Degenerative products of inflamed tissues
 Leukotrienes
MECHANISMS OF ACTION OF NEUTROPHILS
1. Opsonization: Certain plasma factors coat the bacteria making it tasty for neutrophils to
digest them.
Chemicals that coat the bacteria are called opsonins.
The main opsonins are;
Components of the complement system and
Immunoglobulin G (IgG).
The coated bacterial now bind to receptors on the neutrophil cell membrane.
2. Phagocytosis: The coated bacteria is ingested by a process called endocytosis. When
endocytosed it forms phagocytic vacuoles called phagosomes.
Certain cytoplasmic granules come in contact with phagosomes and discharge their contents
into the phagosome through a process called degranulation.
Contents of cytoplasmic granules
Proteases or proteolytic enzymes that digestive bacteria
Microbial proteins called defensins
3. Myeloperoxidase: Catalyzes the reaction between hydrogen peroxide and chloride to form
hypochloride which is a powerful bactericidal substance. Bactericidal means it kills bacteria.
4. NADPH oxidase formed by organelles called peroxisomes binds to phagosome membrane.
This leads to their activation. NADPH oxidase catalyzes the formation of superoxide from
free radicals. Superoxide then reacts with hydrogen ions to form hydrogen peroxide by the
activity of the enzyme superoxide dismutase.
Superoxide and hydrogen peroxide are powerful oxidants and effective bacterial agents.
EOSINOPHILS
Just like neutrophils, they have a short lifespan in circulation of about 4 to 6 hours. They are
attracted to endothelial cells by selectins, bind to integrins and enter tissues by diapedesis.
They are abundant in the gastrointestinal tract mucosa where they defend against parasites.
When you hear the word, eosinophils think of parasitic infection and allergic diseases.
Eosinophils follow the same process like neutrophils.
They are present in abundance in the urinary and respiratory tracts.
They are phagocytic and exhibit chemotaxis.
They are less motile and weaker than neutrophils.
They are produced in large numbers in conditions of parasitic infestations in which they attack
parasites and kill them by hydrolytic enzymes.
They are produced in large quantities in allergic diseases such as Bronchial asthma or allergic
diseases.
During periods of eosinophilia, the eosinophils are attracted to site of allergic reaction by
chemotactic factors from mast cells and Basophils.
For example, in the GIT we have enterochromaffin like cells that resemble mast cells and
basophils.
In the respiratory tract we have mast cells and basophils and eosinophils.
They are attracted to site of infection where they decrease and prevent the spread of the
inflammatory process.
How do eosinophils prevent the spread of inflammatory reactions?
1. Detoxification of inflammation or substances released by mast cells and basophils.
2. They also phagocytose and destroy allergic antibody complexes.
BASOPHILS
Are non-phagocytic cells that resemble mast cells. Both mast cells and basophils release
heparin, histamines and other inflammatory mediators such as leukotrienes.
Assignment 1
Outline the morphological functional and structural similarities and differences between
mast cells and basophils.
Substances produced causes local vascular and tissue reactions that occur in allergic conditions
and are responsible for the immediate hypersensitivity reactions which may be urticaria or
allergic rhinitis or anaphylactic shock.
MONOCYTES
Lifespan is about 72 hours. They enter the tissues and become tissue macrophages.
They are concentrates of the reticuloendothelial system.
They provide the first line of defense against bacterial infections. While neutrophils offer the
second line.
In cases of severe inflammation, they are released into the bloodstream from the bone marrow in
large numbers. They move to the site of infection by the diapedesis, amoeboid motion and
chemotaxis. Same process like neutrophils, although the movement process is slower than
neutrophils.
Monocytes engulf necrotic tissues and play an important role in immunity.
LYMPHOCYTES
Are the major players of the immune system.
Assignment 2: What are the pathological and physiological variations of leukocyte count?
RETICULOENDOTHELIAL SYSTEM OR TISSUE MACROPHAGE SYSTEM
This system mainly consists of tissue macrophages originally monocytes which have entered
tissues from the blood stream.
We have as well a few specialized endothelial cells in the bone marrow, spleen and lymph nodes.
Functions of the Reticuloendothelial System.
1. Defense: Tissue macrophages attack and phagocytose the invading organisms in the
following sites.
Skin and subcutaneous tissue called histocytes. Help to remove microorganisms that enter
via the skin.
Lungs: Are called pulmonary alveolar macrophages in which bacteria and foreign particles
like carbon and silica are engulfed.
In the liver, they are called Kupffer cells, which attack bacteria that are continuously passed
from the gastrointestinal tract.
In lymph nodes attack bacteria that has spread from tissues
Bone marrow and spleen: In the bone they are called osteoclasts and attack bacteria that
spread from the bloodstream.
2. Removal of old red blood cells from circulation.
3. Breakdown hemoglobin, form bile pigments and store iron. Examples of bile pigments
are bilirubin and biliverdin.
4. They repair damaged tissues after inflammation by releasing tissue growth factors.
5. They serve as extramedullary hematopoietic sites.
Remember during blood formation, red blood cells are formed from the embryonic stage, extra-
medullary stage and the medullary stage.
6. Erythropoietin formation: A small percentage is formed from the Kupffer cells of the
liver
FUNCTIONS OF THE SPLEEN
The spleen is part of the lymphoid organs and performs the following functions.
1. Defense: Produces large numbers of macrophages, helps in the formation of lymphocytes and
plasma cells which play an important role in immunity. Removal of the spleen renders an
individual to be prone to bacterial infections.
2. Blood cell formation: Red blood cells in the fetus and lymphocytes in the adult.
3. Blood cell removal; old and abnormal cells. Examples of abnormal cells are spherocytes,
elliptocytes and Sickle cells. They are removed by macrophages in the spleen. There are
 instances of excessive platelet breakdown in the spleen which can cause thrombocytopenic
purpura.
4. The spleen helps in blood storage, it accommodates about 50mls of concentrated blood
in sinusoids which can be added to the general circulation by spleenic contraction of smooth
muscles in the spleenic capsule during excitation of the sympathetic neurons. During
hemorrhage the sympathetic nervous system is activated and can stimulate the smooth
muscles that are present in the splenic capsule leading to contraction of the spleen and release
of 50 mils of blood. The quantity is small and contraction of the muscles is weak.