PHYSIOLOGY OF PHYSIOLOGY OF LEUKOCYTES .LEUKOCYTES .

IMMUNITYIMMUNITY

Function of leukocytesFunction of leukocytes

1. Protective1. Protective 2. Transport2. Transport 3. Metabolic3. Metabolic 4. Regenerator4. Regenerator

Quantity of leukocytes and their Quantity of leukocytes and their changes changes

Most white blood cells are the body outside the vascular: Most white blood cells are the body outside the vascular: in the intercellular spacein the intercellular space in the bone marrow. in the bone marrow. In the bloodstream is about 20 % of white blood cells of the body.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 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 leukocytes. If the number of white blood cells is less than 4 , then talk about leucopenia. Leukopenia occurs only in pathology. If you talk about leucopenia. Leukopenia occurs only in pathology. If you exceed the number of leukocytes than 9 , it will leukocytosis. exceed the number of leukocytes than 9 , it will leukocytosis. There leukocytosis : first one is, physiological, and secondly on - There leukocytosis : first one is, physiological, and secondly on - pathological (inflammatory , infectious processes) .pathological (inflammatory , infectious processes) .

Physiological leukocytosis are:Physiological leukocytosis are: 1. food , after eating , 1. food , after eating ,

especially protein ;especially protein ; 2. myogenic , after hard 2. myogenic , after hard

physical workphysical work 3. stress (psycho-emotional)3. stress (psycho-emotional) 4. pregnant4. pregnant 5. ovulation5. ovulation 6. in newborns. 6. in newborns. The number of leukocytes The number of leukocytes

ranges during the day , there ranges during the day , there is a maximum in the evening.is a maximum in the evening.

Physiological leukocytosis in Physiological leukocytosis in newbornnewborn

The number of leukocytes in The number of leukocytes in them is 16,7-30 G / l . Explain them is 16,7-30 G / l . Explain this by saying that in the early this by saying that in the early days is a resolution of the decay days is a resolution of the decay products of tissues, bleeding that products of tissues, bleeding that occurred during childbirth. At the occurred during childbirth. At the end of the first month of life and end of the first month of life and reduced number of white blood reduced number of white blood cells is 12-15 G / l . At the end of cells is 12-15 G / l . At the end of the first year of life -7 ,5 -12 , 5. the first year of life -7 ,5 -12 , 5. At the age of 10-14 years, the At the age of 10-14 years, the number of white blood cells is number of white blood cells is almost adult size and is 4,5-10 almost adult size and is 4,5-10 G / l .G / l .

Development of mDevelopment of monocytesonocytes

common progenitor cell – common progenitor cell – uncommited stem cell – uncommited stem cell – commited stem cell – commited stem cell – mmonoblast – onoblast – proprommonocyte – onocyte – mmonocyte – onocyte – tissue macrophage. tissue macrophage.

Development of Development of lymphocyteslymphocytes common progenitor cell – common progenitor cell – bone marrow bone marrow lymphocyteslymphocytes precursor – precursor – lymphoblast – lymphoblast – prolymphocyte – prolymphocyte – large lymphocyte – large lymphocyte – small lymphocyte. small lymphocyte. Lymphocytes in the fetus are thought to arise Lymphocytes in the fetus are thought to arise

first in the thymus. Later they are found in first in the thymus. Later they are found in lymph nodes, spleen, and other lymphoid lymph nodes, spleen, and other lymphoid tissues as well as in bone marrow.tissues as well as in bone marrow.

Development of gtanulocytesDevelopment of gtanulocytes common progenitor cell – common progenitor cell – uncommited stem cell – uncommited stem cell – commited stem cell – commited stem cell – myeloblast (basophil, neutrophil, eosinophil) myeloblast (basophil, neutrophil, eosinophil)

–– pro promyelocytemyelocyte – – myelocytemyelocyte – – metametamyelocyte – myelocyte – juvenile – juvenile – rod-shaped neutrophil (rod-shaped neutrophil (basophil, eosinophil), basophil, eosinophil), segmented segmented neutrophil, neutrophil, basophil, eosinophil. basophil, eosinophil.

Functional features of Functional features of neutrophilsneutrophils

Located in the bloodstream up to 20 Located in the bloodstream up to 20 hours, quickly migrate into tissue, hours, quickly migrate into tissue, mucous membranes, where they live mucous membranes, where they live about 3 days. Days produced 100 • 109 about 3 days. Days produced 100 • 109 granulocytes.granulocytes.Neutrophils phagocytosis of bacteria, Neutrophils phagocytosis of bacteria, fungi, and tissue breakdown products of fungi, and tissue breakdown products of its enzymes break down hydrogen its enzymes break down hydrogen peroxide.peroxide.In addition to responses to infection, In addition to responses to infection, neutrophils also secrete transkobalamin.neutrophils also secrete transkobalamin.For neutrophils can determine the sex of For neutrophils can determine the sex of the person: the presence of the female the person: the presence of the female genotype neutrophils "Drumsticks".genotype neutrophils "Drumsticks".

Functional features of Functional features of eosinophilic granulocyteseosinophilic granulocytes

Stay period of eosinophils in the blood is very Stay period of eosinophils in the blood is very short. Especially many of these cells in the mucous short. Especially many of these cells in the mucous membranes of the gastrointestinal tract, respiratory membranes of the gastrointestinal tract, respiratory tract and urinary organs. Number eosinophils is tract and urinary organs. Number eosinophils is subject to fluctuations during the day: the day of subject to fluctuations during the day: the day of eosinophils approximately 20% less, and in the eosinophils approximately 20% less, and in the night by 30 % compared with an average number . night by 30 % compared with an average number . These oscillations are associated with the level of These oscillations are associated with the level of secretion of glucocorticoids adrenal cortex . secretion of glucocorticoids adrenal cortex . Increase of corticoids leads to a decrease in Increase of corticoids leads to a decrease in eosinophils and vice versa. This functional test eosinophils and vice versa. This functional test Thorne .Thorne .Features : 1) anti-allergic , and 2) phagocytic .Features : 1) anti-allergic , and 2) phagocytic .Eosinophils contain histaminase , which neutralizes Eosinophils contain histaminase , which neutralizes histamine, which abound with allergies.histamine, which abound with allergies.

Functional features of basophilic Functional features of basophilic granulocytesgranulocytes

The residence time of cells in the The residence time of cells in the bloodstream for about 12 hours. bloodstream for about 12 hours. They are capable of phagocytosis. They are capable of phagocytosis. Granules in the cytoplasm of Granules in the cytoplasm of basophils stained intensely basophils stained intensely basophilic dyes and contain heparin basophilic dyes and contain heparin and histamine, which actively affect and histamine, which actively affect the blood vessels.the blood vessels.

Functional features of Functional features of lymphocyteslymphocytes

Lymphocytes are formed in the Lymphocytes are formed in the lymph nodes, spleen, retrosternal lymph nodes, spleen, retrosternal gland, appendix and bone marrow. gland, appendix and bone marrow. They play a major role in shaping the They play a major role in shaping the immune system and carry out immune system and carry out immune surveillance.immune surveillance.After the bone marrow of the After the bone marrow of the lymphocyte differentiation in the lymphocyte differentiation in the thymus is (retrosternal gland) and thymus is (retrosternal gland) and converted into T-lymphocytes. Other converted into T-lymphocytes. Other cells undergo differentiation in the cells undergo differentiation in the lymphoid tissue of the tonsils, lymphoid tissue of the tonsils, appendix, intestines Peyer's plaques - appendix, intestines Peyer's plaques - B-lymphocytes.B-lymphocytes.

Physiological role of lymphocytes Physiological role of lymphocytes

Function of TFunction of T--lymphocytes:lymphocytes: 1. 1. Immune memoryImmune memory.. 2. 2. Anti viruses immunityAnti viruses immunity.. 3. 3. Anti tissue immunity.Anti tissue immunity. 4. 4. Regulate phagocytosisRegulate phagocytosis..Function of Function of В-В-lymphocytes:lymphocytes: 1. 1. Immune memoryImmune memory.. 2. 2. SpecificSpecific immunityimmunity. B-lymphocytes syntheses the . B-lymphocytes syntheses the

immunoglobulins such as IgM, IgN, IgA, IgG, IgB, immunoglobulins such as IgM, IgN, IgA, IgG, IgB, IgE. IgE.

Functional features of monocytesFunctional features of monocytes Formed in the bone marrow. As blood is about 72 Formed in the bone marrow. As blood is about 72

hours. From blood monocytes entering into the hours. From blood monocytes entering into the surrounding tissue. Here they grow, the content of surrounding tissue. Here they grow, the content of lysosomes and mitochondria increases. Upon lysosomes and mitochondria increases. Upon reaching maturity, monocytes are converted to fixed reaching maturity, monocytes are converted to fixed cells or tissue macrophages. These cells are in cells or tissue macrophages. These cells are in connective tissue and are called histiocytes, in the connective tissue and are called histiocytes, in the liver - Kuppherovsky‘s cells, in the lungs - alveolar liver - Kuppherovsky‘s cells, in the lungs - alveolar macrophages, in spleen, bone marrow, lymph nodes, macrophages, in spleen, bone marrow, lymph nodes, glia, pleura - macrophages.glia, pleura - macrophages.

System of mononucleares System of mononucleares phagocytesphagocytes

These is the system, These is the system, which common the which common the cells with one cells with one nucleus, common nucleus, common origin from red bone origin from red bone marrow, common marrow, common function of high function of high specific phagocytosisspecific phagocytosis

The specific functional The specific functional characteristics of characteristics of macrophages is macrophages is phagocytosis of phagocytosis of microorganisms, tumor microorganisms, tumor cells, collecting and cells, collecting and directing lymphocytes directing lymphocytes to the antigenic to the antigenic material, the formation material, the formation of tissue growth factor, of tissue growth factor, pinocytosispinocytosis

LEUKOCYTE FORMULALEUKOCYTE FORMULA

TThe index of nuclear’s changing of he index of nuclear’s changing of neutrophyls, it interpretation neutrophyls, it interpretation

NCN=(M+J+S1)/S2, whereNCN=(M+J+S1)/S2, where M – myelocytes, M – myelocytes, J– juvenile, J– juvenile, S1 – stab neutrophils, S1 – stab neutrophils, S2 – segmented neutrophilsS2 – segmented neutrophils

Norm Norm is is 0,06-0,090,06-0,09

IMMUNITYIMMUNITY The body is under constant attack by The body is under constant attack by

micro-organisms. They may enter the body micro-organisms. They may enter the body via an orifice eg mouth nasal passage or via an orifice eg mouth nasal passage or vagina, or through broken skin. The micro vagina, or through broken skin. The micro –organisms feed on the body tissues and –organisms feed on the body tissues and /or pass toxins into the bloodstream. This /or pass toxins into the bloodstream. This causes causes diseasedisease. Disease causing organisms . Disease causing organisms are called are called pathogenic. pathogenic. Inside the body the Inside the body the micro-organism has ideal conditions of micro-organism has ideal conditions of food, water and temperature,food, water and temperature,  so flourish.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 immunityInnate immunity This is inborn and unchanging and occurs in several non-specific ways.This is inborn and unchanging and occurs in several non-specific ways. 11. Skin. Skin. This is an effective physical barrier. This is an effective physical barrier 2. 2. Stomach acidStomach acid. This destroys the protein membrane of any invading mico-organism.. This destroys the protein membrane of any invading mico-organism. 3.3.LysozymeLysozyme. An enzyme found in tears, saliva and nasal secretions which digests . An enzyme found in tears, saliva and nasal secretions which digests

bacterial cell wallsbacterial cell walls 44. Interferon. Interferon. This is released by an infected cell , binds to a non-invaded cell inducing . This is released by an infected cell , binds to a non-invaded cell inducing

it to produce antiviral proteins in readiness for invasion.it to produce antiviral proteins in readiness for invasion. 5. Phagocytosis. Some types of white blood cells engulf invading  bacterial cells and 5. Phagocytosis. Some types of white blood cells engulf invading  bacterial cells and

digest them using enzymes enclosed in lysosomes ( diagram P 50)digest them using enzymes enclosed in lysosomes ( diagram P 50) Phagocytic white blood cellsPhagocytic white blood cells, monocytes, monocytes, and , and macrophagesmacrophages derived from monocytes,  derived from monocytes,

are produced in the bone marrow. They are found static or fixed in the lining of tubules are produced in the bone marrow. They are found static or fixed in the lining of tubules in in the liverthe liver, , spleenspleen and  and lymph nodes,lymph nodes, and remove pathogens as  blood or lymph passes  and remove pathogens as  blood or lymph passes byby. Pus. Pus at an infected wound is the remains of dead pathogens and phagocytic white  at an infected wound is the remains of dead pathogens and phagocytic white blood cells.blood cells.

Acquired immunityAcquired immunity This type of immunity is acquired This type of immunity is acquired

throughout a lifetime, and depends on the throughout a lifetime, and depends on the production of special protein molecules production of special protein molecules called called antibodies.antibodies. These antibodies are  These antibodies are produced in response to produced in response to specificspecific foreign  foreign molecules called molecules called antigens.antigens.

An antigen is a polysaccharide or protein An antigen is a polysaccharide or protein which is recognised as foreign by special which is recognised as foreign by special white blood cells, white blood cells, lymphocytes.lymphocytes. These  These lymphocytes respond by producing lymphocytes respond by producing specific antibodies for that antigen.specific antibodies for that antigen.

An antibody is a Y shaped protein which An antibody is a Y shaped protein which has specific receptor or binding sites on has specific receptor or binding sites on each arm.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 immunityNaturally acquired immunity This occurs when the body suffers an infection.This occurs when the body suffers an infection. Lymphocytes are derived from unspecialised cells Lymphocytes are derived from unspecialised cells

in the bone marrow. On production some of these in the bone marrow. On production some of these cells migrate to the cells migrate to the thymus glandthymus gland and  and the lymph the lymph nodesnodes where they reproduce to form colonies. where they reproduce to form colonies.

Thymus lymphocytes are called Thymus lymphocytes are called T lymphocytes or T lymphocytes or T cellsT cells. Those from the lymph nodes are called . Those from the lymph nodes are called B B cellscells..

  

B cell action.  Humoral response, B cell action.  Humoral response, the release of free antibodiesthe release of free antibodies

When a B cell encounters an antigen it When a B cell encounters an antigen it divides repeatedly to produce identical divides repeatedly to produce identical daughter cells, which make and release daughter cells, which make and release the specific antibody for that antigen. In the specific antibody for that antigen. In the blood or lymph these antigens bind the blood or lymph these antigens bind with the antigen to form an with the antigen to form an antigen/antibody complex. This acts as a antigen/antibody complex. This acts as a signal for phagocytic white blood cells to signal for phagocytic white blood cells to engulf and destroy the whole complex.engulf and destroy the whole complex.

Some of the activated B cells remain in Some of the activated B cells remain in the body fluids as the body fluids as memorymemory  cellscells, and , and continue to produce the antibody. This continue to produce the antibody. This means that on further infection by the means that on further infection by the same antigen many antibodies can be same antigen many antibodies can be released very quickly reducing response released very quickly reducing response time.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 T cell action. Cell mediated responseresponse

On invasion of a body cell by a micro-organism, microbial proteins On invasion of a body cell by a micro-organism, microbial proteins are released. These move to the body cell membrane and act as are released. These move to the body cell membrane and act as antigens. The antigens are recognised as foreign by antigens. The antigens are recognised as foreign by Killer –T cellsKiller –T cells. . The killer T cells attach to the infected body cell releasing The killer T cells attach to the infected body cell releasing chemicals, which perforate the body cell membrane. This destroys chemicals, which perforate the body cell membrane. This destroys the body cell and the micro-organisms inside.the body cell and the micro-organisms inside.

Another type of T cell , Another type of T cell , Helper T cellsHelper T cells do not kill the cells but act as  do not kill the cells but act as ’lookouts’ by patrolling the body, recognising antigens and ’lookouts’ by patrolling the body, recognising antigens and activating B cells and Killer T cells.activating B cells and Killer T cells.

Primary and Secondary responsesPrimary and Secondary responses After invasion by a micro-organism After invasion by a micro-organism

the individual will suffer the disease the individual will suffer the disease until there are sufficient antibodies until there are sufficient antibodies produced. This is the produced. This is the primary primary responseresponse. If the individual is . If the individual is infected by the same micro-infected by the same micro-organism, memory B cells in the organism, memory B cells in the body will quickly produce many body will quickly produce many antibodies, and memory killer T antibodies, and memory killer T cells will attack the infected cells, cells will attack the infected cells, so the response is much faster so the response is much faster preventing the disease. This is preventing the disease. This is the the secondarysecondary  responseresponse..

Artificially acquired immunityArtificially acquired immunity InoculationInoculation. This is the deliberate introduction of . This is the deliberate introduction of

an antigen into the body to stimulate an immune an antigen into the body to stimulate an immune response.response.

VaccinationVaccination is a form of inoculation, where the  is a form of inoculation, where the antigen is introduced either by injection or orally. antigen is introduced either by injection or orally. The antigen is first rendered harmless by heat or The antigen is first rendered harmless by heat or chemical treatment but will still induce an immune chemical treatment but will still induce an immune response by production of B and T cells. Treated response by production of B and T cells. Treated micro-organism toxins can also be used in this way.micro-organism toxins can also be used in this way.

  

Active and Passive immunityActive and Passive immunity

ActivActive. When the body produces its own e. When the body produces its own antibodies either by infection or antibodies either by infection or inoculation.( as already described)inoculation.( as already described)

PassivPassive. When the body receives e. When the body receives readymade antibodies.readymade antibodies.

Naturally acquired passive immunityNaturally acquired passive immunity .. Where antibodies are passed across the Where antibodies are passed across the

placenta or in breast milk. This gives placenta or in breast milk. This gives ready made immunity until ready made immunity until the babies immune system can produce the babies immune system can produce its own antibodies.its own antibodies.

  

AllergyAllergy The word allergy means ‘altered The word allergy means ‘altered

working’, and is used to describe an working’, and is used to describe an over reaction to harmless foreign over reaction to harmless foreign matter .eg. feathers, pollen animal fur or matter .eg. feathers, pollen animal fur or antibiotics. These antigenic triggers of antibiotics. These antigenic triggers of allergies are called allergies are called allergens.allergens.

B cells stimulated by the allergen B cells stimulated by the allergen release antibodies (IgE) which are release antibodies (IgE) which are picked up, by and attach to ,the surface picked up, by and attach to ,the surface of of mast cellsmast cells in connective tissue. If  in connective tissue. If these cells encounter the allergen again these cells encounter the allergen again they release a they release a substance, substance, histamine.histamine. Histamine causes  Histamine causes dilation of surrounding blood vessels, dilation of surrounding blood vessels, loss of fluid from the vessels and loss of fluid from the vessels and damage to the tissues. This causes damage to the tissues. This causes localised heat and swelling.localised heat and swelling.

Antihistamine is needed to counteract the reaction.Anaphylaxis is a life threatening rapid allergic response.

Self and non-selfSelf and non-self..

The human body recognises its own cells due to the antigens found on 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 their surface. These ‘self’ cells will be accepted and not attacked by the immune system. Cells lacking these antigen markers are the immune system. Cells lacking these antigen markers are identified as foreign ( non-self) ,an immune response occurs and identified as foreign ( non-self) ,an immune response occurs and the cells are destroyed.the cells are destroyed.

Antigen signatureAntigen signature

Body cells have antigens on their membranes (other than those on red Body cells have antigens on their membranes (other than those on red blood cells- see later.)  which make up the blood cells- see later.)  which make up the human leukocyte antigen human leukocyte antigen H.L.AH.L.A. The H.L.A. is controlled by 4 genes each with many alleles . 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 which can code for many antigens. This allows  for a wide range of different  combination of antigens. As a result onepersons different  combination of antigens. As a result onepersons antigen antigen signaturesignature has an almost unique combination of these antigens, and  has an almost unique combination of these antigens, and the possibility of this combination being repeated in another person the possibility of this combination being repeated in another person is very low. The exception to this is in monozygotic twins.is very low. The exception to this is in monozygotic twins.

Rejection of transplanted tissueRejection of transplanted tissue Living tissue transplanted from Living tissue transplanted from

one body to another is one body to another is identified as foreign by T cells identified as foreign by T cells and is destroyed. This is tissue and is destroyed. This is tissue rejection. Prevention of rejection. Prevention of rejection is by rejection is by tissue typing and tissue typing and matchingmatching to ensure the donor  to ensure the donor tissue or organ has an antigen tissue or organ has an antigen signature as close to the signature as close to the recipient antigen signature as recipient antigen signature as possible. possible. Identical twins Identical twins would be the ideal donor and would be the ideal donor and recipient.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.

AutoimmunityAutoimmunity

This is when the body fails to recognise the This is when the body fails to recognise the antigen self markers on its own cells and antigen self markers on its own cells and attacks them. Examples of autoimmunity attacks them. Examples of autoimmunity are, are, rheumatoid arthritis rheumatoid arthritis  where the immune  where the immune system attacks and destroys the cartilage at system attacks and destroys the cartilage at joints, and joints, and multiple schlerosismultiple schlerosis where the  where the immune system attacks the myelin coating of immune system attacks the myelin coating of nerves.nerves.