Transcript 19 Physiology of leukocytes

PHYSIOLOGY OF
LEUKOCYTES .
IMMUNITY
Function of leukocytes
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1. Protective
2. Transport
3. Metabolic
4. Regenerator
Quantity of leukocytes and their
changes
Most white blood cells are the body outside the
vascular:
 in the intercellular space
 in the bone marrow.
 In the bloodstream is about 20 % of white blood
cells of the body.
 It is believed that the blood of a healthy person
contains 4-9 G/l leukocytes. If the number of white
blood cells is less than 4 , then talk about
leucopenia. Leukopenia occurs only in pathology. If
you exceed the number of leukocytes than 9 , it will
leukocytosis. There leukocytosis : first one is,
physiological, and secondly on - pathological
(inflammatory , infectious processes) .
Physiological leukocytosis are:
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1. food , after eating ,
especially protein ;
2. myogenic , after hard
physical work
3. stress (psycho-emotional)
4. pregnant
5. ovulation
6. in newborns.
The number of leukocytes
ranges during the day ,
there is a maximum in the
evening.
Physiological leukocytosis in
newborn
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The number of leukocytes in
them is 16,7-30 G / l . Explain
this by saying that in the early
days is a resolution of the
decay products of tissues,
bleeding that occurred during
childbirth. At the end of the
first month of life and reduced
number of white blood cells is
12-15 G / l . At the end of the
first year of life -7 ,5 -12 , 5. At
the age of 10-14 years, the
number of white blood cells is
almost adult size and is 4,5-10
G/l.
Development of monocytes
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common progenitor cell –
uncommited stem cell –
commited stem cell –
monoblast –
promonocyte –
monocyte –
tissue macrophage.
Development of lymphocytes
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common progenitor cell –
bone marrow lymphocytes precursor –
lymphoblast –
prolymphocyte –
large lymphocyte –
small lymphocyte.
Lymphocytes in the fetus are thought to arise
first in the thymus. Later they are found in
lymph nodes, spleen, and other lymphoid
tissues as well as in bone marrow.
Development of gtanulocytes
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common progenitor cell –
uncommited stem cell –
commited stem cell –
myeloblast (basophil, neutrophil, eosinophil)
– promyelocyte –
myelocyte –
metamyelocyte –
juvenile –
rod-shaped neutrophil (basophil, eosinophil),
segmented neutrophil, basophil, eosinophil.
Functional features of
neutrophils
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Located in the bloodstream up to 20
hours, quickly migrate into tissue,
mucous membranes, where they live
about 3 days. Days produced 100 • 109
granulocytes.
Neutrophils phagocytosis of bacteria,
fungi, and tissue breakdown products of
its enzymes break down hydrogen
peroxide.
In addition to responses to infection,
neutrophils also secrete transkobalamin.
For neutrophils can determine the sex of
the person: the presence of the female
genotype neutrophils "Drumsticks".
Functional features of
eosinophilic granulocytes
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Stay period of eosinophils in the blood is very
short. Especially many of these cells in the
mucous membranes of the gastrointestinal tract,
respiratory tract and urinary organs. Number
eosinophils is subject to fluctuations during the
day: the day of eosinophils approximately 20%
less, and in the night by 30 % compared with an
average number . These oscillations are associated
with the level of secretion of glucocorticoids
adrenal cortex . Increase of corticoids leads to a
decrease in eosinophils and vice versa. This
functional test Thorne .
Features : 1) anti-allergic , and 2) phagocytic .
Eosinophils contain histaminase , which
neutralizes histamine, which abound with
allergies.
Functional features of basophilic
granulocytes
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The residence time of cells in the
bloodstream for about 12 hours.
They are capable of phagocytosis.
Granules in the cytoplasm of
basophils stained intensely
basophilic dyes and contain heparin
and histamine, which actively affect
the blood vessels.
Functional features of
lymphocytes
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Lymphocytes are formed in the
lymph nodes, spleen, retrosternal
gland, appendix and bone marrow.
They play a major role in shaping the
immune system and carry out
immune surveillance.
After the bone marrow of the
lymphocyte differentiation in the
thymus is (retrosternal gland) and
converted into T-lymphocytes. Other
cells undergo differentiation in the
lymphoid tissue of the tonsils,
appendix, intestines Peyer's plaques B-lymphocytes.
Physiological role of lymphocytes
Function of T-lymphocytes:
 1. Immune memory.
 2. Anti viruses immunity.
 3. Anti tissue immunity.
 4. Regulate phagocytosis.
Function of В-lymphocytes:
 1. Immune memory.
 2. Specific immunity. B-lymphocytes syntheses the
immunoglobulins such as IgM, IgN, IgA, IgG, IgB,
IgE.
Functional features of monocytes
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Formed in the bone marrow. As blood is about 72
hours. From blood monocytes entering into the
surrounding tissue. Here they grow, the content of
lysosomes and mitochondria increases. Upon
reaching maturity, monocytes are converted to fixed
cells or tissue macrophages. These cells are in
connective tissue and are called histiocytes, in the
liver - Kuppherovsky‘s cells, in the lungs - alveolar
macrophages, in spleen, bone marrow, lymph nodes,
glia, pleura - macrophages.
System of mononucleares
phagocytes
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These is the system,
which common the
cells with one
nucleus, common
origin from red bone
marrow, common
function of high
specific phagocytosis
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The specific functional
characteristics of
macrophages is
phagocytosis of
microorganisms, tumor
cells, collecting and
directing lymphocytes
to the antigenic
material, the formation
of tissue growth factor,
pinocytosis
LEUKOCYTE FORMULA
The index of nuclear’s changing of
neutrophyls, it interpretation
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NCN=(M+J+S1)/S2, where
M – myelocytes,
J– juvenile,
S1 – stab neutrophils,
S2 – segmented neutrophils
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Norm is 0,06-0,09
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IMMUNITY
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The body is under constant attack by
micro-organisms. They may enter the body
via an orifice eg mouth nasal passage or
vagina, or through broken skin. The micro
–organisms feed on the body tissues and
/or pass toxins into the bloodstream. This
causes disease. Disease causing organisms
are called pathogenic. Inside the body the
micro-organism has ideal conditions of
food, water and temperature, so flourish.
Immunity is the body’s ability to resist infection by a disease-causing
organism (pathogen) or to destroy it after invasion.
Immunity can be innate or acquired.
Innate immunity
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This is inborn and unchanging and occurs in several non-specific ways.
1. Skin. This is an effective physical barrier
2. Stomach acid. This destroys the protein membrane of any invading
mico-organism.
3.Lysozyme. An enzyme found in tears, saliva and nasal secretions which
digests bacterial cell walls
4. Interferon. This is released by an infected cell , binds to a non-invaded
cell inducing it to produce antiviral proteins in readiness for invasion.
5. Phagocytosis. Some types of white blood cells
engulf invading bacterial cells and digest them using enzymes enclosed in
lysosomes ( diagram P 50)
Phagocytic white blood cells, monocytes, and macrophages derived from
monocytes, are produced in the bone marrow. They are found static or
fixed in the lining of tubules in the liver, spleen and lymph nodes, and
remove pathogens as blood or lymph passes by. Pus at an infected wound
is the remains of dead pathogens and phagocytic white blood cells.
Acquired immunity
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This type of immunity is acquired
throughout a lifetime, and depends on the
production of special protein molecules
called antibodies. These antibodies are
produced in response to specific foreign
molecules called antigens.
An antigen is a polysaccharide or protein
which is recognised as foreign by special
white blood cells, lymphocytes. These
lymphocytes respond by producing
specific antibodies for that antigen.
An antibody is a Y shaped protein which
has specific receptor or binding sites on
each arm.
There are thousands of different
lymphocytes each capable of
responding to a specific antigen
and producing a specific
antibody.
Acquired immunity can be
developed either naturally or
artificially.
Naturally acquired immunity
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This occurs when the body suffers an
infection.
Lymphocytes are derived from unspecialised
cells in the bone marrow. On production some
of these cells migrate to the thymus
gland and the lymph nodes where they
reproduce to form colonies.
Thymus lymphocytes are called T lymphocytes
or T cells. Those from the lymph nodes are
called B cells.
B cell action. Humoral response,
the release of free antibodies
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When a B cell encounters an antigen it
divides repeatedly to produce identical
daughter cells, which make and release
the specific antibody for that antigen. In
the blood or lymph these antigens bind
with the antigen to form an
antigen/antibody complex. This acts as
a signal for phagocytic white blood
cells to engulf and destroy the whole
complex.
Some of the activated B cells remain in
the body fluids as memory cells, and
continue to produce the antibody. This
means that on further infection by the
same antigen many antibodies can be
released very quickly reducing response
time.
(Antibodies or immunoglobulins are
proteins that are able to act against
what they recognise as foreign
(antigens). There are 5 major classes
of immunoglobulin, IgA,IgD ,IgG
IgM and IgE. IgG is the only one that
can cross the placenta, and food or
environmental allergies involve IgA,
IgM and IgE.)
T cell action. Cell mediated
response
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On invasion of a body cell by a micro-organism, microbial
proteins are released. These move to the body cell membrane
and act as antigens. The antigens are recognised as foreign
by Killer –T cells. The killer T cells attach to the infected body
cell releasing chemicals, which perforate the body cell
membrane. This destroys the body cell and the microorganisms inside.
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Another type of T cell , Helper T cells do not kill the cells but
act as ’lookouts’ by patrolling the body, recognising antigens
and activating B cells and Killer T cells.
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Primary and Secondary responses
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After invasion by a micro-organism
the individual will suffer the disease
until there are sufficient antibodies
produced. This is the primary
response. If the individual is
infected by the same microorganism, memory B cells in the
body will quickly produce many
antibodies, and memory killer T
cells will attack the infected cells,
so the response is much faster
preventing the disease. This is the
secondary response.
Artificially acquired immunity
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Inoculation. This is the deliberate introduction
of an antigen into the body to stimulate an
immune response.
Vaccination is a form of inoculation, where the
antigen is introduced either by injection or
orally. The antigen is first rendered harmless
by heat or chemical treatment but will still
induce an immune response by production of
B and T cells. Treated micro-organism toxins
can also be used in this way.
Active and Passive immunity
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Active. When the body produces its
own antibodies either by infection or
inoculation.( as already described)
Passive. When the body receives
readymade antibodies.
Naturally acquired passive immunity.
Where antibodies are passed across the
placenta or in breast milk. This gives
ready made immunity until
the babies immune system can produce
its own antibodies.
Allergy
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The word allergy means ‘altered
working’, and is used to describe an
over reaction to harmless foreign matter
.eg. feathers, pollen animal fur or
antibiotics. These antigenic triggers of
allergies are called allergens.
B cells stimulated by the allergen
release antibodies (IgE) which are
picked up, by and attach to ,the surface
of mast cells in connective tissue. If
these cells encounter the allergen again
they release a
substance, histamine. Histamine causes
dilation of surrounding blood vessels,
loss of fluid from the vessels and
damage to the tissues. This causes
localised heat and swelling.
Antihistamine is needed to
counteract the reaction.
Anaphylaxis is a life threatening
rapid allergic response.
Self and non-self.
The human body recognises its own cells due to the antigens found
on their surface. These ‘self’ cells will be accepted and not
attacked by the immune system. Cells lacking these antigen
markers are identified as foreign ( non-self) ,an immune response
occurs and the cells are destroyed.
 Antigen signature
Body cells have antigens on their membranes (other than those on
red blood cells- see later.) which make up the human leukocyte
antigen H.L.A. The H.L.A. is controlled by 4 genes each with
many alleles which can code for many antigens.
This allows for a wide range of different combination of
antigens. As a result onepersons antigen signature has an almost
unique combination of these antigens, and the possibility of this
combination being repeated in another person is very low. The
exception to this is in monozygotic twins.
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Rejection of transplanted tissue
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Living tissue transplanted from
one body to another is
identified as foreign by T cells
and is destroyed. This is tissue
rejection. Prevention of
rejection is by tissue typing and
matching to ensure the donor
tissue or organ has an antigen
signature as close to the
recipient antigen signature as
possible. Identical twins
would be the ideal donor and
recipient.
Immunosuppressor drugs are used to prevent
rejection but this leaves the recipient open to
infection by diseases such as pneumonia .
New drugs are being developed to inhibit the
activity of killer T cells without affecting the B
cell activity. In addition new agents are being
developed to induce immunological tolerance
before the transplant.
Autoimmunity
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This is when the body fails to recognise the
antigen self markers on its own cells and
attacks them. Examples of autoimmunity
are, rheumatoid arthritis where the immune
system attacks and destroys the cartilage at
joints, and multiple schlerosis where the
immune system attacks the myelin coating of
nerves.