Course Summary BBS2001
Course Summary BBS2001 – Threats &
Defence Mechanism
CASE I – Blood cells, coagulation & inflammation
Different blood cells – their structure, function & origin
Erythrocytes – red blood cells → 42% of total BV
Mature Erythrocytes are bound by a plasma membrane but lack a
nucleus and have no organelles. It contains haemoglobin (which gives
them the colour red) and other proteins, such as antioxidant enzymes &
structural proteins. Spectrin for examples is attached to the cytoplasm
of the RBC plasma membrane to maintain the shape. The erythrocytes
are formed in a biconcave shape to ensure a high surface area. It is
suited for gas exchange because no point within is far from the
membrane. Their lack of organelles such as mitochondria ensures that
the erythrocytes are not using the oxygen, they should transfer to the tissue all by themselves.
The function of erythrocytes is to pick up oxygen in the capillaries of the lungs and release it to the tissue at the
capillaries throughout our body. It is also involved in transporting part of the carbon dioxide waste released by
the tissue back to the lungs (about 20%).
A red blood cell can defend itself against bacteria and has a lifespan of 120 days.
The production of red blood cells is called Erythropoiesis and occurs in the red bone marrow. The bone marrow
contains a precursor cell from which the erythrocytes develop – the hematopoietic stem cell (hemocytoblast).
Erythropoiesis begins when a hematopoietic stem cell descendent called a myeloid stem cell transforms into a
proerythroblast. Those give rise to basophilic erythroblasts that produce a huge number of ribosomes.
Haemoglobin is synthesized and iron accumulates as the basophilic erythroblast transforms into a polychromatic
erythroblast, followed by the transformation into an orthochromatic erythroblast. When the orthochromatic
erythroblast has accumulated almost all of its haemoglobin, it rejects most of its cell organelles. Its nucleus
degenerates and is pinched off allowing the cell to form its biconcave shape. This results in the reticulocytes. This
whole process takes about 15 days.
Now they are transported into the blood and mature. They are fully formed erythrocytes when they rejected
their ribosomes and are free from the cell organelles and their nucleus.
Regulated is this process by the hormonal control Erythropoietin (EPO).
Leukocytes – white blood cells
Leukocytes (white blood cells) are the only completely formed elements that are complete cells, with nuclei and
the usual organelles. They are crucial to our defence against diseases. They form a mobile army that helps protect
the bod from damage by bacteria, viruses, parasites, toxins, and tumour cells.
The production of white blood cells is called Leukopoiesis and is stimulated by chemical messengers. Those
chemical messengers fall into the families of interleukins & colony-stimulating factors (CSFs). All of the different
types arise from the hematopoietic stem cell. An early branching of this differentiation divides the lymphoid stem
cells from the myeloid stem cells. The lymphoid stem cell will give rise to the lymphocyte and the natural Killer
cells, while the myeloid stem cell is the precursor for all other formed elements.
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Leukocytes can be categorized into two groups:
- Granulocytes
Granulocytes include the blood cell types neutrophils, eosinophils & basophils. They are larger and shorter lived
than erythrocytes. They have lobed nuclei and have membrane-bound cytoplasmic granules. All granulocytes are
phagocytes in some degree.
If the myeloid stem cell will develop into a myeloblast it first will differentiate into a promyelocyte. Afterwards
the three remaining cell types will be separated by developing either into eosinophilic myelocyte, basophilic
myelocyte or neutrophilic myelocyte. After the myelocytes develop they differentiate into band cells which will
eventually end up in the mature forms of the eosinophils, basophils & neutrophils.
Neutrophils
They are the most numerous white blood cells that can be found in the bloodstream. Neutrophilic granulocytes
are usually circular. The diameter is around 14μm. The granules are very fine. When a patient has too many
neutrophils, it is known as neutrophilia and when the patient has not enough it is called neutropenia.
One of the main tasks of neutrophils is the defence against bacterial infections, by phagocytising the pathogens
and killing them. Neutrophils can leave the bloodstream and move to the surrounding tissue, to fight infections.
Neutrophils can be distinguished by their age. Young neutrophils are called band and their nucleus is bent and
oblong partly with constrictions which have not yet resulted in a filament. Older neutrophils are called
segmented. Their nucleus is only 1/3 of the cell and has a threadlike and constricted shape.
Eosinophils
With a diameter of 16μm, eosinophil granulocytes are round and slightly larger than neutrophils. The granules
are coarse and very densely packed. The nucleus is normally bilobed. The state in which a patient has too many
is called eosinophilia and when there are not enough eosinophils it is called eosinopenia.
They play an important role in allergic diseases/reactions as well as in parasitic infections. Like neutrophils, the
eosinophils are capable of phagocytosis and migration into surrounding tissue. Their granules are lysosome-like
and filled with a unique variety of digestive enzymes but lack enzymes that specifically digest bacteria.
Basophils
Basophils are the rarest white blood cells and smaller than the other granulocytes (10-14μm). Their large granules
are tightly packed and extensively overlay the nucleus and cytoplasm. They are filled with histamine. An increase
of basophil count is termed as basophilia.
Histamine is an inflammatory chemical that acts as a vasodilator and attracts other white blood cells to the
inflamed site. They play an important role in hypersensitivity reactions and they are able to leave the blood steam
and enter the surrounding tissue.
- Agranulocytes
Agranulocytes are white blood cells that lack visible cytoplasmic granules. Their nuclei are typically spherical, or
kidney shaped.
Monocytes
With a diameter of 15-20μm, monocytes are the largest cells in the peripheral blood. Their form is diverse.
Monocytes have many pseudo-podi formations on their outer membrane. They have fine azure granules and
vacuoles. The nucleus can be bean-shaped or lobulated. An increase in monocytes is called monocytosis and a
decrease is called monocytopenia.
While circulating monocytes leave the bloodstream and enter the tissue. Then they differentiate into highly
mobile macrophages. Macrophages are actively phagocytic, and they are crucial in the body’s defence against
viruses, certain intracellular bacterial parasites, and chronic infections. They are also important in activating
lymphocytes to mount the immune response.
If the myeloid stem cell develops into a monoblast the cell will become a promonocyte and after maturing it will
be a monocyte.
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Lymphocytes
Lymphocytes have a round to oval nucleus and are approximately the size of erythrocytes. Their cell size can vary
between 9 and 20μm and there are three size categories: small, medium & large. They are the second most
frequent leukocytes in the blood film. If a lymphocyte count is low, lymphopenia is present while if it is increased,
it is called lymphocytosis.
A lot of lymphocytes are present in the body but relatively few are found within the bloodstream. Lymphocytes
are associated with lymphoid tissue where they play a crucial role in immunity. They participate in cellular and
humoral defence against infections.
They are produced from an early branch from the hematopoietic stem cell – lymphoid stem cell.
There are three types of lymphocytes:
- B-Lymphocytes: they give rise to plasma cells, which in return produce antibodies (immunoglobins) that
are released into the blood
- T-lymphocytes: function in the immune response by acting directly against virus-infected cells & tumour
cells
- Natural Killer cells: They help in the innate immune system
Thrombocytes – platelets
Platelets are cytoplasmic fragments of extraordinary large cells called megakaryocytes. The platelets contain
granules that are filled with chemicals that act in the clotting process (including serotonin, Ca2+, a variety of
enzymes, ADP & platelet-derived growth factors (PDGFs)).
Platelets are essential for the clotting process that occurs in plasma when blood vessels are ruptured, or their
lining is injured. Platelets form a temporary plug that helps to seal the break.
The formation of platelets is regulated by a hormone called thrombopoietin.
Platelets derive from a progeny of the hematopoietic stem cell and the myeloid stem cell called megakaryoblast.
In this line the cell undergoes mitosis several times without undergoing cytokinesis. The final result will be the
mature stage IV megakaryocyte, a cell with a huge multilobed nucleus and a large cytoplasm mass.
After its formation, the megakaryocyte presses against the sinusoid and sends cytoplasmic extensions through
the sinusoid wall into the bloodstream. These extensions rupture, releasing the platelet fragments.
Haemostasis – Three steps to stop a bleeding
Haemostasis is the process in stopping the bleeding when a blood vessel wall is damaged. Without this plug-the-
hole defensive reaction, we would quickly bleed out our entire blood volume from even the smallest cuts. The
Haemostasis response is fast, localized and carefully controlled.
During Haemostasis, three steps occur in rapid sequences:
Step 1 – Vascular Spasm / Vasoconstriction
After the injury, the damaged blood vessel will be constricted by the surrounding smooth muscle. This
vasoconstriction can significantly reduce blood loss and allows time for the next two steps.
The Vasoconstriction is triggered by the direct injury, by chemicals released from the endothelial cells or reflexes
initiated by pain receptors.
Collagen is exposed at the site of injury; the collagen promotes platelets to adhere to the injury site. Platelets
release cytoplasmic granules which contain serotonin, ADP, and thromboxane A2, all of which increase the effect
of vasoconstriction. The spasm response becomes more effective as the amount of damage is increased. Vascular
spasm is much more effective in smaller blood vessels.
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