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Immune System
Is a self / non-self recognition and achieved by
having every cell display a marker based on the
major histocompatibility complex.
RBCs
Normal Adult Blood Cell Counts
Red Blood Cells
5.0*106/mm3
Platelets
2.5*105/mm3
Leukocytes
7.3*103/mm3
Neutrophil
50-70%
Lymphocyte
20-40%
Monocyte
1-6%
Eosinophil
1-3%
Basophil
<1%
Source of immune cells (Lymphoid organs)
• Primary organs: bone marrow and the thymus
gland .
• Secondary organs: Adenoids, tonsils, spleen ,
lymph nodes , Peyer's patches and the appendix.
Surface barriers or mucosal immunity:
1. Skin.
2. Mechanically, pathogens are expelled from the
lungs by coughing , sneezing and ciliary movement of
respiratory cells. 3. Sticky mucus in respiratory and gastrointestinal
tracts. 4. Saliva, tears and nasal secretions contain lysoenzyme
antinfective agents. 5. Vaginal secretions are also slightly acidic .
Spermine and zinc in semen destroy pathogens. Lactoperoxidase
is a powerful antinfective enzyme found in mother's milk. 6.
Highly acidity of stomach.
Kinds of phagocytes according to their origin:
1. Promonocytes made in bone marrow and released
into the blood and called circulating monocytes.
2. Macrophages of liver called Kupffer cells.
3. Macrophages of brain called microglia.
4. Macrophages of kidney called mesoangial cells.
Types Of Phagocytes :
1. Natural killer cells (large granular lymphocytes ) move in the
blood and lymph and attach to the glycoproteins on the
surfaces of infected virus and bacteria and kill them.
2. Polymorphonuclear neutrophils, phagocytes that have no
mitochondria and get their energy from stored glycogen.
3. Eosinophils are attracted to cells coated with complement
Types of Immunity
1.
2.
Innate immunity: The innate immunity system is
what we are born with and it is nonspecific; all
antigens are attacked pretty much equally. Each
immu ne cells conjugate with the antigen by
pattern-rcognition receptors.
Acquired immunity: Occurred as a response to
the infection and is of two types:
A. Humoral immunity.
B. Cell mediated immunity.
1.
Cell mediated Immunity:
T- cells originated from bone marrow lymphocyte which migrate to
thymus gland to multiply and carry genetic information and tested
for recognition and binding to antigen. Processing of T-cells
occurs largely during foetal life and early childhood .
There are three types of T-cells :
A. Helper T-Cells: Secrete lymphokines that stimulate cytotoxic T
cells and B cells to grow and divide , attract neutrophils and
enhance the ability of macrophages to engulf and destroy
microbes.
B. Killer T-cells : Known as cytotoxic T-cells: Secrete
lymphotoxins which cause cell lysis.
C. Memory T-cells : Are programmed to recognize and
respond to a pathogen once it has invaded.
D. suppressor T cell : Suppresses the immune response of
B cells and other T cells once the end of destroy the
invaders.
2. Humoral Immunity:
The humoral immune response involves a complex series of
events after antigens enter the body. First, macrophages
take up some of the antigen and attach it to class II MHC
molecules, then bind the antigen to T helper cells which
become stimulated and divide and secrete stimulatory
molecules called interleukins. The interleukins activate any
B lymphocytes to bind to the antigen. The activated B cells
then divide and secrete antibodies. Finally, the secreted
antibodies bind the antigen and help to destroy it.
Antibodies:
Antibodies are Y-shaped proteins called immunoglobulins
(Ig) and are made only by B cells
Categorize antibodies into five main classes: IgM, IgG, IgA,
IgD, and IgE .
The antibodies
inactivate antigens
by:
(a) Complement
fixation.
(b) Neutralization.
(c) Agglutination.
(d) Precipitation.
Stem cells
Some call them magic seeds, for their
ability to replicate indefinitely and
morphologically into any kind of tissue. Stem
cells have traditionally been characterised as
either embryonic (pluripotent) or tissuespecific (multipotent). Stem cells are the
source of all cells - brain, skin, heart and
others - that make up the human body. Just
like a plant stem that branches into leaves and
flowers, stem cells branch out to form
different bits of our bodies.
Source of stem cells
• Pre-implantation embryos.
• Embryo from IVF.
• The fluid that surrounds a developing baby in the
womb pre-implantation embryos.
• Embryo from IVF.
• Fluid that surrounds a developing baby in the womb.
• Umbilical cord.
• Bone marrow cells (Haematopoietic & stromal stem
cells).
Advantage of adult stem cells :
Adult stem cells offer the opportunity to utilize small
samples of adult tissues, to obtain an initial culture of a
patient's own cells for expansion and subsequent
implantation in the same person (Autologous
transplant). This process avoids immune rejection by
the recipient and also protects the patients from viral,
bacterial or other contamination from another
individual (donor) as in case of allogenic transplant.
Disadvantages :
• Culturing adult stem cells in-vitro is very difficult and
has not been possible for some types.
• They have a very short life, when cultured in-vitro as
compared to embryonic cells.
Stem cells & Heart disease:
Congestive heart failure results from loss or dysfunction
of heart muscle cells. The disease afflicts 4.8 million
people , with 400,000 new cases each year. The disease
result from coronary heart disease , heart attack , the
sudden close of the blood vessels supplying oxygen to the
heart.
Two major cells of the heart :
• Cardiomyocyte that contracts to eject the blood out of the
heart's main pumping chamber ( ventricle).
• Vascular endothelial cells which form the inner lining of the
blood vessel.
• Smooth muscle cells which form the wall of the blood
vessel.
The heart has a large demand for blood flow, and these
specialized cells are important for developing a new
network of arteries to bring nutrients and oxygen to the
cardiomyocytes after a heart has been damaged.
Stem cell therapy of heart failure :
Injection of selected bone marrow cells with a high capacity to
develop into cells of multiple types ( haematopoietic stem cells).
When these cells injected into the damaged wall of the ventricle,
these cells led to the formation of the of new cardiomyocytes ,
vascular endothelium, and smooth muscle cells. Thus generating de
novo myocardium , including coronary arteries, arterioles, and
capillaries. The newly formed myocardium occupied 68 percent of
the damaged portion of the ventricle nine days after the bone
marrow cells were transplanted. The partial repair of the damaged
heart muscle suggest that the transplanted haematopoietic stem
cells respond to signals in the environment near the injured
myocardium.
• Vasculogenesis: Is the in situ differentiation of mesodermal
precursors to angioblasts that differentiate into endothelial cells to
form the primitive capillary network. Vasculogenesis is limited to
early embryogenesis and is believed not to occur in the adult.
• Angiogenesis : the sprouting of new capillaries from the preexisting
blood vessels and occurs in both the developing embryos and
postnatal life.
Neuronal stem cells
Every sensation, action and thought explains the complicated
processes of the central nervous system (CNS), which consists of
the brain and the spinal cord. The brain is the central computer
of our body interpreting outside information and controlling every
action. The spinal cord connects the brain with the rest of the
body by sending out millions of electrical signals. Neuronal cells
are responsible for receiving and processing every piece of
information the brain sends the rest of the body. Neurons are
made up of four parts—the cell body which houses the nucleus
and most of the cell organelles, dendrites, an axon, and axon
terminals. Dendrites are bush like projections that bring
information from other neurons to the cell body. The axon, a
longer projection, sends information away form the cell body.
Injuries of spinal cord is irreversible and cause paralysis and the
information from brain and other regions of the body are blocked.
This disease affects many millions of people around the world .
Defects of spinal cord injury led to :
• Swelling causes additional damage to the
spinal cord as pressure builds in the confined
space between the cord and vertebrae as a
result of scar tissue that builds up around the
area of injury which blocks the neurons from
reconnecting once the cord has been severed.
• Swelling cuts off the blood supply to the
neurons and glial cells which intern lead to
additional neuronal cell death and migration of
more immune cells to the injury site.
• Stem cell therapy:
Reconnection must be reestablished and activate
new neurons and glial cells to regenerate and replace
the injured ones. Once nerve cells were damaged they
were gone, eliminating hope for complete recovery
from paralysis.
Scientists recently discovered that new neurons in
specific regions of the adult mammalian brain . Neural
stem cells were isolated from the dentate gyrus of the
hippocampus and the walls of the ventricular system
called the ependymal layer. The progeny of these stem
cells differentiate in the granule cell layer, meaning
neurogenesis continues late into adult rodent life.
These stem cells also migrate along the rostral
migratory stream to the olfactory bulb, where they
differentiate into neurons and glial cells .
• Derived undifferentiated embryonic stem cells (ES
cells) from fetal spinal cord tissue and then mature
them into cells that are suitable to implant into the
damaged spinal cord. When using ES cells, researchers
have two options: they can treat ES cells, allowing them
to mature into CNS cells in vitro before transplantation,
or they can directly implant differentiated cells and
depend on signals from the brain mature the cells.
• Treating injured spinal cord of rats with undifferentiated
embryonic stem cells (ES cells) from fetal spinal cord
tissue led to marked differentiation of it , filling the area
normally occupying by glial scarring. After five weeks
the stem cells had migrated further away from the
implantation site. Although a number of them had died,
there was still enough for the rats to have a growing
supply of neurons and glial cells. Most of the surviving
cells were oligodendrocytes and astrocytes, but some
neurons were found in the middle of the cord. The rats
regained limited use of their legs. Paralysis had been
cured!!
Stem cells
Sources of Stem cells
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