PHYSIOLOGY OF LEUKOCYTES. BLOOD TYPES.
LEUCOCYTES
Leukocytes, or white blood cells, are nucleated and are larger and less numerous than erythrocytes. Leukocytes can be divided into 2 main groups, granulocytes and agranulocytes, according to their content of cytoplasmic granules.
Each of these groups can then be further divided on the basis of size, nuclear morphology, ratio of nuclear to cytoplasmic volume, and staining properties. Two classes of cytoplasmic granules occur in leukocytes, specific and azurophilic granules. Specific granules are found only in granulocytes; their staining properties (neutrophilic, eosinophilic, or basophilic) distinguish the 3 granulocytes types.
Azurophilic granules are found in both agranulocytes and granulocytes. Azurophilic granules stain purple and are lysosomes.
The 5 types of human leukocytes. Neutrophils, eosinophils, and basophils have granules that stain specifically with certain dyes and are called granulocytes. Lymphocytes and monocytes are agranulocytes; they may show azurophilic granules, which are also present in other leukocytes.
Unlike the RBCs, all leukocytes can leave the capillaries by passing between endothelial cells, and penetrating the connective tissue by means of the process called diapedesis. The types and levels of activity expressed by extravascular leukocytes depends upon the specific cell type.
GRANULOCYTES
Granulocytes have segmented nuclei and are described as polymorphonuclear leukocytes (PMNLs). Depending on the cell type, the mature nucleus may have from 2 to 7 lobes connected by thin strands of nucleoplasm. Granulocyte types are most easily distinguished by their size and staining properties, and by the appearance (as seen with an electron microscope) of the abundant specific granules in their cytoplasm. These granules are all membrane-limited and bud off the Golgi complex. All granulocytes have a life span of a few days, dying by apoptosis (programmed cell death) in the connoctive tissue. The resulting cellular removed by macrophages and does not elicit an inflamatory response.
Neutrophils – are the most abundant leukocytes in the blood. They usually constitute 60-72 % of the white blood cells in healthy adults. They are also found outside the bloodstream, especially in loose connective tissue. Neutrophils are the first line of cellular defense against the invasion of bacteria. Once they leave the bloodstream, they spread out, develop amoeboid motility, and become active phagocytes. Unlike lymphocytes, neutrophils are all terminally differentiated cells and so are incapable of mitosis.
Size – neutrophils in the blood are approximately 12 μm in diameter, while those in the tissues spread to a diameter of up to 20 μm.
Nucleus – neutrophil nuclei contain highly condensed chromatin both in the lobes and in the attenuated chromatin bridges between them. Most have 3 lobes; however, lobe number increases from a single horseshoe-shaped nucleus in immature neutrophils, called band neutrophils, to more than 5 lobes in aging ones. The nuclei of certain diseased neutrophils, called hypersegmented neutrophils, also have more than 5 lobes (they are typically old cells). In females, a small heterochromatic body often extends from one of the nuclear lobes. This represents the inactive X chromosome, or Barr body, and is referred to as a drumstick – like appendage because of its characteristic shape.
Neutrophil cytoplasm is abundant and filled with specific membrane-bound granules. These granules are modified lysosomes and have a bacteriocidal function.
Azurophilic granules (primary, or type A) stain with azure dye and are diagnostic for neutrophils. These large (0.4 um) electron-dense granules comprise about 20 % of the granule population and are visible in the light microscope.
Specific granules (secondary, or type B) are smaller (0.2 μm) and may contain crystalloids. They comprise 80 % of the granule population and are not visible in the light microscope. They stain salmon pink with typical bloodstains. The less numerous azurophilic granules stain a reddish-purple. The specific granules contain alkaline phosphatase and bactericidal cationic proteins called phagocytins. Azurophilic granules contain lysosomal enzymes and peroxidase. Neutrophils also contain more glycogen than other leukocytes.
Neutrophils are short-lived cells with a half-life of 6-7 hours in blood and a life span of 1-4 days in connective tissues, where they die by apoptosis.
The primary function of neutrophils is the phagocytosis and destruction of bacteria. Neutrophils are active phagocytes of small particles and have sometimes been called microphages to distinguish them from macrophages, which are larger cells. Neutrophils are inactive and spherical while circulating but change shape upon adhering to a solid substrate, over which they migrate via pseudopodia.
Bacteria first adhere to the neutrophil surface and then are surrounded and engulfed by pseudopodia; in this way bacteria eventually occupy vacuoles (phagosomes) delimited by a membrane derived from the cell surface. Immediately thereafter, specific granules fuse with and discharge their contents into the phagosomes. Azurophilic granules then discharge their enzymes into the acid environment, killing and digesting the microorganisms.
The mechanism of phagocytosis
Phagocytosis – is active devourment of the solid substances by cells. Cells, which are capable of phagocytosis, are called phagocytes. There are poly phagocytes (neutrophils) and mononuclear phagotyces (monocytes).
Phagocytes must be selective of the material that is phagocytized; otherwise, normal cells and structures of the body might be ingested. Whether phagocytosis will occur, depends especially on three selective procedures. Firstly, most natural structures in the tissues have smooth surfaces, which resist phagocytosis. But if the surface is rough, the likelihood of phagocytosis is increased. Secondly, most natural substances of the body have protective protein coats that repel the phagocytes. Conversely, most dead tissues and foreign particles have no protective coats, which make them subject to phagocytosis. Thirdly, the immune system of the body develops antibodies against infectious agents such as bacteria. The antibodies then adhere to the bacterial membranes and thereby make the bacteria especially susceptible to phagocytosis. To do this, the antibody molecule also combines with the C3 product of the complement cascade, which is an additional part of the immune system discussed in the next chapter. The C3 molecules, in turn, attach to receptors on the phagocytic membrane, thus initiating phagocytosis. This selection and phagocytosis process is called opsonization.
Stages of phagocytosis:
I Conjugation stage. Phagocyte moves to direction of not self agent (chemotaxis).
II Adhesion stage. Phagocyte interacts with the agent. There are two mechanisms:
1) without receptor: electrostatic and hydrophobic interaction (phagocyte is negatively charged, positive particles);
2) with receptor. On the surface of macrophages there are receptors for opsonin-substances that can interact with bacteria.
III Devourment stage. Its steps:
· invagination of phagocyte membrane on the contact place;
· the formation of phagosome, which contains the agent;
· the formation of phagolysosome: consolidation of phagosome with lysosomes (secondary granules).
IV Digestive stage. Its steps:
· The disposal of bacteria – intercellular cytolysis with the help of germicide systems of phagocytes (myeloperoxidase system, which produces hypochloride ion ClO–, free radicals and peroxides O30, HO20, OH0, lisocim, lactoferin, non-enzymatic cationic proteins, lactic acid).
· Digestion – hydrolysis of killed bacteria with the help of hydrolytic enzymes.
Eosinophils – constitute only 0,5-54 % of the circulating leukocytes in healhty adults. They may leave the bloodstream by diapedesis, spread out, and move about in the connective tissues. They are capable of only limited phagocytosis, showing a preference for antigen-antibody complexes. The number of circulating eosinophils typically increases (eosinophilia) during allergic reactions and in response to parasitic (helmintic) infections, and rapidly decreases in response to treatment with exogenous corticosteroids. These cells produce substances that modulate inflammation by inactivating the leukotriens and histamine produced by other cells.
Eosinophil nuclei contain condensed chromatin and usually have 2-3 lobes connected by a thin chromatin bridge (bilobed nucleus). The nuclei are often partially obscured by the numerous specific granules in the cytoplasm.
Cytoplasm – The most characteristic structural feature of eosinophils is the presence of numerous large (0.5-1.5 μm in diameter), brightly eosinophilic granules (specific granules) in their cytoplasm (about 200 per cell). These granules are specialized lysosomes that lack lysozyme but contain acid phosphatase, cathepsin, and ribonuclease. In electron micrographs, each specific granule has an oblong shape and an elongated, centrally located, electron-dense crystalloid, or internum, lying parallel to its long axis. It contains a protein called the major basic protein – with a large number of arginine residues. This protein constitutes 50% of the total granule protein and accounts for the eosiniphilia of these granules. The major basic protein also seems to function in the killing of parasitic worms such as schistosomes. Between the granule membrane and the internum lies the electron-lucent matrix, or externum. Microfilaments are prominent in the eosinophil cortex.
Functions. Eosinophils kill parasitic larvae as they enter peripheral blood or the lamina propria of the gut. They help to regulate mast cell response to inflammation by releasing an enzyme that degrades the histamines released by mast cells at inflammation sites. Eosinophilic granule crystalloids have a dominant component called the major basic protein, which has a poorly understood antiparasitic function. Eosinophilic granules contain lysosomal enzymes that destroy dead parasites.
Basophils are the least numerous of the circulating leukocytes, constituting from 0 to 1% of the white blood cells of healthy adults. Like other white blood cells, basophils may leave the circulation, but they are capable of only very limited ameboid movement and phagocytosis in the tissues. Extravascular basophils are most often found at sites of inflammation and may be the major cell type at sites of cutaneous basophil hypersensitivity.
Basophils vary in diameter from 12 μm to 15 μm but are usually slightly smaller thaeutrophils. Their nuclei are less heterochromatic than other granulocytes and usually consist of 3 irregular lobes which are often obscured by the large, dark-staining cytoplasmic granules. The specific granules of basophils are their most characteristic feature. These granules have irregular shapes and vary in size; the largest are the size of the specific granules of eosinophils, the smallest nearly as small as those of neutrophils. The granules stain metachromatically and appear reddish-violet to nearly black in stained blood smears. The specific granules of basophils (like those of the mast cells of connective tissue) contain heparin and histamine, which may be released by exocytosis in response to certain types of antigenic stimuli. The granules may contain inclusions, but they appear more homogeneously electron-dense than do those of eosinophils.
Functions. Basophils mediate the inflammatory response and secrete eosinophil chemotactic factor. In response to certain antigens, basophils stimulate the formation of immunoglobulin E(IgE)-a class of antibodies. Subsequent exposure to the same antigen can cause a basophil and mast cell response restricted to specific organs (e.g., bronchial asthma in the lungs or a severe and systemic response such as anaphylactic shock brought on by a bee sting).
Agranulocytes
Agranulocytes have round unsegmented nuclei and are described as mononuclear leukocytes. They lack specific granules, but they contain various number of azurophilic granules (lysosomes) that bind the azure dies of the stain. This group includes the lymphocytes and monocytes.
Lymphocytes – constitute a diverse class of cells; they have similar morphologic characteristics but a variety of highly specific functions. They normally account for 20-25 % of the white blood cells in adult blood, with a considerable range of normal variation (20-45%). Lymphocytes are also found outside the blood vessels, grouped in lymphatic organs or dispersed in connective tissues. They respond to invasion of the body by foreign substances and organisms and assist in their inactivation. They also have diverse functional roles, all related to immune reactions in defending against invading microorganisms, foreign macromolecules and cancer cells. Unlike other leukocytes, lymphocytes never become phagocytic.
They can be classified into several groups due to distinctive surface molecules (markers), which can be distinguished only by immunocytochemical methods.
The 2 major functional classes of lymphocytes are T cells and B cells. Lymphocytes in the blood are predominantly (about 80 %) T cells.
Lymphocytes vary from 6 to 18 μm in diameter. Most of those found in blood are small lymphocytes in the 6- to 8 μm range, making them the smallest leukocytes, comparable in size to erythrocytes. A small number of medium-sized and large lymphocytes are also ground in the circulation and probably represent lymphocytes activated by an antigen.
Lymphocyte nuclei are spheric and often flattened on one side. In small lymphocytes, the nucleus is densely heterochromatic, staining purplish-blue to black, and nearly fills the cell. In large lymphocytes, the nucleus is larger and less dense and stains reddish-purple.
Lymphocyte cytoplasm exhibits a pale basophilia and occasionally contains a few purplish azurophilic granules but lacks specific granules. In the smaller cells, the cytoplasm forms a thin rim around the nucleus; in the larger cells, it is more abundant. It contains many free ribosomes, few mitochondria, sparse endoplasmic reticulum, and a small Golgi complex. When stimulated by an antigen, lymphocytes undergo blast transformation, a process of enlargement and sequential mitotic divisions. Some of the daughter cells, called memory cells, return to an inactive state but retain the capacity to respond more quickly to the next encounter with the same antigen. Other daughter cells, called effector cells, become activated to carry out an immune response to the antigen. Effector cells may be derived from either B lymphocytes (B cells) or T lymphocytes (T cells). While circulating B and T cells are morphologically indistingushable, they carry different cell-surface components (antigens recognized by other species) and can be identified by special procedures.
B Lymphocytes differentiate into plasma cells, which secrete specific antigen-binding molecules (antibodies or immunoglobulins) that circulate in the blood and lymph and serve as a major component of humoral immunity.
T Lymphocyte derivatives serve as the major cells of the cellular immune response. They produce a variety of factors, termed lymphokines (eg, interferon) that influence the activities of macrophages and of other leukocytes involved in an ammune response. There are several types:
(i) Cytotoxic (killer) cells secrete substances that kill other cells and in some cases kill by direct contact; they play the major role in graft rejection.
(ii) Helper T cells enhance the activity of some B cells and other T cells.
(iii) Suppressor T cells inhibit the activity of some B cells and other T cells.
The primary (central) lymphoid organs include the thymus, where lymphocyte precursors are programmed to become T cells and, in birds, the bursa of Fabricius, where lymphocyte precursors are programmed to become B cells. Humans have no bursa; our B cells appear to be programmed in the bone marrow.
According to the electron-microscopic studies there are 4 different types:
1. Small dark lymphocytes;
2. Small light lymphocytes;
3. Medium lymphocytes;
4. Plasmocytes or lymphoplasmocytes.
Lymphocytes vary in life span; some live only a few days, and others survive in the circulating blood for many years. Lymphocytes are the only type of leukocytes that return from tissue back to the blood, after diapedesis.
Monocytes are often confused with large lymphocytes, but they are larger and constitute only 3-8 % of the white blood cells in healthy adults. Monocytes are found only in the blood, but they remain in circulation for less than a week before migrating through capillary walls to enter other tissues or to become incorporated in the lining of sinuses. Once outside the bloodstream, they become phagocytic and apparently do not recirculate. Monocytes are the direct precursors to macrophages. The mononuclear phagocyte system (portions of which were formerly referred to as the reticuloendothelial system) consists of monocyte-derived phagocytic cells distributed throughout the body. Examples include the Kupffer cells of the liver and some of the macrophages of connective tissues.
Monocytes in the blood of healthy adults have a diameter of 12-15 μm, but when they attach to surfaces they flatten and spread out, often reaching 20 μm in diameter they are the largest among leukocytes).
Monocyte nuclei may be ovoid, but are usually kidney- or horseshoe shaped and eccentrically placed; unlike lymphocyte nuclei, they are rarely spherical. The chromatin is less condensed than that of lymphocyte nuclei, has a “smudgy” appearance, and stains reddish-purple. There may be 2-3 nucleoli, but these are often difficult to distinguish.
Cytoplasm – The faint blue-gray cytoplasm of monocytes is more abundant than that of lymphocytes and contains many small azurophilic granules, which are distributed through the cytoplasm, giving it a bluish-gray color in stained smears. In the lectrone microscope, one or two nucleoli are seen in the nucleus, and a small quantity of rough endoplasmic reticulum, polyribosomes. It also contains many small mitochondria, a well-developed Golgi apparatus. Many microvilli and pinocytotic vesicles are found at the cell surface.
An increase in the number of leukocytes is called leukocytosis; this occurs in most systemic and localized infectious processes, such as appendicitis or abscesses. It is a normal response to infection. On the other hand, a decrease in the number of leukocytes is called leukopenia; this may occur in certain acute and chronic diseases, such as typhoid fever or tuberculosis. Leukopenia is also a constant finding in radiation sickness, the clinical result of excessive exposure to gamma rays. For example, victims of the atomic bomb expositions were exposed to intensive radiation and as result suffered a marked depression of bone marrow function; the absolute white count in the more severe cases ranged from 1500 to zero per cu. mm. of blood. There also was anemia, due to interference with formation of red blood cells.
Life of white blood cells
Lifespan of white blood cells are not constant. It depends upon the demand in the body and their function. Lifespan of these ceils may be as short as half a day or it may be as long as 3-6 months. However, the normai lifespan of white biood cells is as follows:
Neutrophils — 2-5 days
Eosinophils — 7-12 days
Basophils — 12-15 days
Monocytes — 2-5 days
Lymphocytes — 1/2-1 day
The amount in peripheral blood – 4-9 · 109/liter.
The decrease of leucocytes amount is called leucopenia, the increase – leucocytosis.
There are 2 types of leucocytes:
V Physiological – is normal, physiological reaction of the organism in some irritations. There are following types, dependently on their causes:
1) emotional leucocytosis (occurs in result of emotional stresses);
2) myogenic (occurs in result of intensive physical exercises);
3) static (occurs in result of change of the position of the human body from horizontal to vertical);
4) alimental (occurs during or after eating);
5) painful (occurs during strong painful feelings);
6) leucocytosis of pregnant;
7) leucocytosis of newborn.
II Pathological (reactive) – it is connected with the pathological process in the organism. Its reasons:
1) infectious diseases;
2) inflammatory processes;
3) allergic reactions;
4) intoxications of endo- and exogenous origin.
The difference between physiological
and reactive leucocytosis
Physiological leucocytosis:
1) it is redistributing (leucocytes from the parietal pool are moving into circulation);
2) it has transient character (it is normalizing fast after the cause disappears);
3) leukogram does not change (the correlation between different forms persists);
4) degenerative forms of leucocytes do not appear.
Reactive leucocytosis is connected with the increase of proliferation and maturating of leucocytes in red bone marrow or increase of moving of reserve leucocytes from RBM to the blood. During pathological leucocytosis the correlation between different forms of leucocytes is disturbed.
Percentage ratio between different forms of leucocytes is called leukogram (formula of Arnet-Shilling).
Differential white blood cell count (Differential leukocyte count)
Physiological values of leukocyte count: 5-10 x 109/L blood
Neutrophil granulocytes
Physiological values: 2-7.5 x 109/l (60-70%)
Increased number – neutrophilia: bacterial infections, trauma, scorch, bleeding, inflamations, infarction, polymialgy, myeloproliferative disorders, reaction to certain medications (e.g. chorticosteroides). Significantly increased in leukemia, disseminated malignant diseases and complicated childhood infections.
Decreased number – neuthropenia: viral infections, brucellosis, thyphoid, Kala-azar, TBC, sepsis, lupus erithematodes, rheumatoid arthritis, avitaminosis B12 i bone marrow dissorders. Medications like carbamazepine or sulphonamides can decrease a number of neuthrophils.
Band neutrophils (stab neutrophils) cells are younger forms of cells presented with kidney-shape, curved nucleus and not segmented, lobar nucleus. Usually they are represent 3-5% of leukocytes. Increased value indicates a higher demand and expenditure of neutrophils, and is called “left shift” (referring to ratio of immature to mature forms of neutrophils).
Lymphocytes
Physiological values: 1.3-3.5 x 109/l (20-40%).
Increased number – lymphocytosis: viral infections (EBV-Epstein Barr virus, CMV-cytomegalovirus, rubeola), toxoplasmosis, pertusis, brucellosis, chronic lymphatic leukemia.
Decreased number – lymphopenia: corticosteroid treatment, lupus erithematodes, uremia, legionella disease, AIDS, bone marrow infiltration (tumor), after chemotherapy and radiotherapy.
Subclases: CD4: 537-1571/mm3 (decreased in HIV infection); CD8: 235-753/mm3; CD4/CD8 ratio: 1.2-3.8.
Eosinophil granulocytes
Physiological values: 0.04-0.44 x 109/l (1-4%).
Increased number – eosinophilia: asthma i allergic disease, parasitic infestations, skin diseases (especially pemphigus), urticaria, egzema, malignant diseases (including eosinophilic leukemia), irradiation, Loeffler syndrome, recovery after infections. Hypereosinophilic syndromecan be observed in terminal organ damage (restrictive cardiomyopathy, neuropathy, hepatosplenomegaly), withincreased eosinophile number for more than 6 weeks (>1.5 x 109/l).
Eosinophilia-myalgi syndrome – muscle pain (myalgia), joint pain (arthralgia), increased body temperature, rash, arms swelling and intense eosinophilia.
Monocytes
Physiological values: 0.2-0.8 x 109/l (2-6%).
Increased number – monocytosis: acute and chronic infection (TBC, brucellosis, protozoal infections), malignant diseases (acute myeloid leukemia, Hodgkin lymphoma), myelodisplasia.
Basophil granulocytes
Physiological values: 0.01 x 109/l (0.5-1%).
Increased number – basophilia: viral infections, urticaria, myxedema, after splenectomy, chronic myeloid leukemia, malignant disease, systemic mastocytosis (urticaria pigmentosa), hemolysis, policitemia rubra vera.
Healthy human has instant white blood cell count and any changes in it – is the signal to different sicknesses. The disturbance in correlation between immature and mature forms of neutrophils is called shift of leukogram. There is shift to the left and shift to the right.
Shift to the left is characterized byincrease in the content of immature neutrophils. Myelocytes appear in blood, the amount of metamyelocytes increase. This happens during leucocytosis.
Shift to the right is characterized with domination of mature neutrophils with big amount of segment (5-6) on the background of disappearance of immature forms. This testifies the development of inflammatory process.
The correlation between mature and immature forms of neutrophils is Bobrov’s index:
The important index is correlation between neutrophils and lymphocytes.
Newborns have larger neutrophils content than lymphocytes (Fig. 4.2). On 4-5 day the amount of neutrophils decreases and the amount of lymphocytes increases. And till the age of 5-6 the child has more lymphocytes thaeutrophils. In the age of 5-6 the amount of neutrophils increases, and the amount of lymphocytes decreases. Starting from this age the amount of neutrophils is higher than lymphocytes.
Production of leucocytes
Granulopoiesis
The maturation process of granulocytes takes place with cytoplasmic changes characterized by the synthesis of a number of proteins that are packed in two organelles: the azurophilic and specific granules. These proteins are produced in the rough endoplasmic reticulum and the Golgi complex in two successive stages. The first stage results in the production of the azurophilic granules. In the second stage, a change in synthetic activity takes place with the production of several proteins that are packed in the specific granules. These granules contain different proteins in each of the three types of granulocytes and are utilized for the various activities of each type of granulocyte.
Maturation of Granulocytes
The myeloblast is the most immature recognizable cell in the myeloid series. It has a finely dispersed chromatin, and nucleoli can be seen. In the next stage, the promyelocyte is characterized by its basophilic cytoplasm and azurophilic granules. These granules contain lysosomal enzymes and myeloperoxidase.
The promyelocyte gives rise to the three known types of granulocyte. The first sign of differentiation appears in the myelocytes, in which specific granules gradually increase in quantity and eventually occupy most of the cytoplasm. These neutrophilic, basophilic, and eosinophilic myelocytes mature with further condensation of the nucleus and a considerable increase in their specific granule content.
Kinetics of Neutrophil Production
The total time taken for a myeloblast to emerge as a mature neutrophil in the circulation is about 11 days. Under normal circumstances, five mitotic divisions occur in the myeloblast, promyelocyte, and neutrophilic myelocyte stages of development.
Neutrophils pass through several functionally and anatomically defined compartments:
1- The medullary formation compartment can be subdivided into a mitotic compartment (≈3 days) and a maturation compartment (≈4 days).
2- A medullary storage compartment. Neutrophils remain in this compartment for about 4 days.
3- The circulating compartment consists of neutrophils suspended in plasma and circulating in blood vessels.
4- The marginating compartment is composed of neutrophils that are present in blood but do not circulate. These neutrophils are in capillaries and are temporarily excluded from the circulation by vasoconstriction, or—especially in the lungs—they may be at the periphery of vessels, adhering to the endothelium, and not in the main bloodstream.
The marginating and circulating compartments are of about equal size, and there is a constant interchange of cells between them. The half-life of a neutrophil in these two compartments is 6–7 h. The medullary formation and storage compartments together are about 10 times as large as the circulating and marginating compartments.
Neutrophils and other granulocytes enter the connective tissues by passing through intercellular junctions found between endothelial cells of capillaries and postcapillary venules (diapedesis). The connective tissues form a fifth compartment for neutrophils, but its size is not known. Neutrophils reside here for 1–4 days and then die by apoptosis, regardless of whether they have performed their major function of phagocytosis.
Maturation of Lymphocytes & Monocytes
Study of the precursor cells of lymphocytes and monocytes is difficult, because these cells do not contain specific cytoplasmic granules or nuclear lobulation, both of which facilitate the distinction between young and mature forms of granulocytes. Lymphocytes and monocytes are distinguished mainly on the basis of size, chromatin structure, and the presence of nucleoli in smear preparations.
Lymphocytes
Circulating lymphocytes originate mainly in the thymus and the peripheral lymphoid organs (eg, spleen, lymph nodes, tonsils). However, all lymphocyte progenitor cells originate in the bone marrow. Some of these lymphocytes migrate to the thymus, where they acquire the full attributes of T lymphocytes. Subsequently, T lymphocytes populate specific regions of peripheral lymphoid organs. Other bone marrow lymphocytes differentiate into B lymphocytes in the bone marrow and then migrate to peripheral lymphoid organs, where they inhabit and multiply in their own special compartments.
The first identifiable progenitor of lymphoid cells is the lymphoblast, dividing two or three times to form prolymphocytes.
Monocytes
The monoblast is a committed progenitor cell that is almost identical to the myeloblast in its morphological characteristics. Further differentiation leads to the promonocyte, a large cell (up to 18 µm in diameter) with a basophilic cytoplasm and a large, slightly indented nucleus. The chromatin is lacy, and nucleoli are evident. Promonocytes divide twice in the course of their development into monocytes. A large amount of rough endoplasmic reticulum is present, as is an extensive Golgi complex in which granule condensation can be seen to be taking place. These granules are primary lysosomes, which are observed as fine azurophilic granules in blood monocytes. Mature monocytes enter the bloodstream, circulate for about 8 h, and then enter the connective tissues, where they mature into macrophages and function for several months.
Origin of Platelets
In adults, platelets originate in the red bone marrow by fragmentation of the cytoplasm of mature megakaryocytes,which, in turn, arise by differentiation of megakaryoblasts.
Megakaryoblasts
The megakaryoblast is 15–50 µm in diameter and has a large ovoid or kidney-shaped nucleus with numerous nucleoli. The nucleus becomes highly polyploid (ie, it contains up to 30 times as much DNA as a normal cell) before platelets begin to form. The cytoplasm of this cell is homogeneous and intensely basophilic
Megakaryocytes
The megakaryocyte is a giant cell (35–150 µm in diameter) with an irregularly lobulated nucleus, coarse chromatin, and no visible nucleoli. The cytoplasm contains numerous mitochondria, a well-developed rough endoplasmic reticulum, and an extensive Golgi complex. Platelets have conspicuous granules, originating from the Golgi complex, that contain biologically active substances, such as platelet-derived growth factor, fibroblast growth factor, von Willebrand’s factor (which promotes adhesion of platelets to endothelial cells), and platelet factor IV(which stimulates blood coagulation).
IMMUNITY
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.
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
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.
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.
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.
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 micro-organisms inside.
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.
Primary and Secondary responses.
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 micro-organism, 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.
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.
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.
Artificially acquired passive immunity.
Where antibodies produced by another animal are introduced into the body. The animal, eg horse ,is injected with an antigen, specific antibodies are produced, extracted from the horse’s blood, and injected into the human This is short lived, but can save lives during the time delay when the body is producing their own antibodies in a primary response.
Allergy.
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 one persons 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.
Rejection of transplanted tissue.
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 additioew agents are being developed to induce immunological tolerance before the transplant.
Autoimmunity.
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.
Immunity and blood grouping.
Original blood transfusions were very risky , but we now know there are four different blood groups and successful transfusion depends on the antigens and antibodies present in the donor and recipient’s blood type. The four groups are known as A, B, AB and O. Each group has specific antigen markers on the red blood corpuscles and specific antibodies in the plasma. Each group is named for the antigen present on the red blood corpuscles.
Blood group Antigen on the R.B.C. Antibody in the plasma.
A A B
B B A
AB AB NEITHER
O NEITHER BOTH A and B
If the wrong type of blood is transfused agglutination occurs ie clotting of red blood corpuscles. This incompatibility is caused by the recipient’s antibodies and the donor’s antigens
Eg if a blood group A recipient receives B type blood, antibody B in the recipient’s plasma would attach to antigen B on the donor red blood cells causing clumping of the red cells which can block blood vessels.
In this situation, the antibody A in the donor plasma is so dilute in comparison to the recipient’s antigen A on the red blood cells that it causes no adverse affect.
Blood group O has both antibodies in the plasma so can only receive O blood, but as O blood has no antigens it is the universal donor blood.
Group AB has no antibodies so can receive blood from any donor ie AB is the universal recipient.
Blood Group Systems
Blood is grouped on the basis of the type of agglutinogen present on its erythrocytes. Thus, blood group A has A agglutinogen on its erythrocytes while blood group M has agglutinogen-M on its erythrocytes. All blood groups obey, in whole or in part, Landsteiner’s law which states that: (1) when the blood contains a particular agglutinogen, its corresponding agglutinin is always absent in that blood, and (2) when a particular agglutinogen is absent in the blood, its corresponding agglutinin is always present in the blood. The first clause of the law is always true but the second clause is valid only for the ABO blood groups.
While innumerable agglutinogens have been deciphered in the blood, the important ones are those which are widely prevalent in the population and those which cause the worst transfusion reactions. These are called the major blood group systems, e.g., the ABO and the Rhesus (CDE) systems. Some blood groups are found only in a small proportion of the population and occasionally produce mild transfusion reactions. These are called the minor blood group systems, e.g., MN, P, etc. In addition to the major and minor blood groups, there are familial blood groups such as the Kell, Duffy, Diego, Lewis, Lutheran, Kidd, and many others that are named after individuals, mostly women, whose blood groups were detected during childbirth. These blood agglutinogens are prevalent only in a few families.
The ABO system comprises two agglutinogens A and B whose corresponding agglutinins are α and β. Accordingly, there are 4 blood groups in the ABO system: Group A, which has A agglutinogen, group B which has B agglutinogen, group AB having both, and group O having neither. Group A has α agglutinin, group B has β agglutinin, group AB has neither, and group O has both Both α and β agglutinins are immunoglobulin-M (IgM), which is very effective in causing agglutination (clumping) of the red cells.
In India, about 22% of the population have A group, 33% have B group and 40% have O group blood. Only 5% have AB group blood. 85% of Caucasians are D+. Among Asians, over 99% are D+.
The Rhesus blood group agglutinogens were first discovered in the erythrocytes of rhesus monkeys, and hence the name. Rhesus blood group comprises a system of 3 agglutinogens: C, D, and E. However, for all practical purposes, the term Rhesus agglutinogen refers to the D agglutinogen which produces the worst transfusion reactions. Accordingly, the Rhesus system comprises only two blood groups: the Rhesus positive (Rh positive or D+) and the Rhesus negative (Rh negative or D–) blood groups depending on the presence or absence of D agglutinogen
Unlike in the ABO system, there are no natural antibodies to rhesus agglutinogens. Anti-D antibodies develop only when a D– person is transfused with D+ blood. Once produced, these antibodies persist in blood for years and can produce serious reactions during a second transfusion.
Anti-D agglutinins are predominantly immunoglobulin G (IgG) and partly immunoglobulin M (IgM ). Unlike IgM which is very effective in agglutinating agglutinogen-bearing red cells, IgG does not agglutinate the red cells although they do react with the agglutinin. Such immunoglobulins which do not cause agglutination are called incomplete antibodies. Although they do not agglutinate red cells, IgG-coated red cells still get lysed due to the activation of complement on their surface
Blood grouping
For ABO blood grouping, the test sample of blood or erythrocyte suspension is reacted with sera containing α and β (called antiserum-A and antiserum-B). The sample is grouped according to the serum that agglutinates its red cells.
Rhesus blood grouping can be done in the same way as ABO grouping if the anti-D agglutinin used is of the IgM type. If the anti-D agglutinin used is IgG, the D+ red cells will get coated with anti-D agglutinin but there will be no agglutination of the cells. The coated red cells will agglutinate only on subsequent addition of Coombs’ (anti-immunoglobulin) serum .
Agglutination will also occur if the IgG anti-D is potentiated by adding albumin to it.
Genotypes and inheritance
The ABO phenotypes are controlled by a pair of codominant alleles A and B. An individual who has inherited A-agglutinogen from one parent and B agglutinogen from the other parent will have the AB blood group. Similarly, an individual whose phenotypic blood group is B may have either the genotype BB (homozygous) or BO (heterozygous).
The Rh phenotypes are controlled by three sets (C, D, and E) of two alternative alleles (dominant and recessive). Each phenotype has a variable number of possible genotypes. For example, cde has only one possible genotype, i.e., ccddee. CDE on the other hand can have eight possible genotypes, viz., CCDDEE, CCDDEe, CCDdEE, CCDdEe, CcDDEE, CcDDEe, CcDdEE, and CcDdEe.
Agglutinogens and agglutinins
The ABO agglutinogens represent only a few of the approximately one million agglutinogens present on an erythrocyte. The ABO agglutinogens are glycosphingolipids (oligosaccharide plus sphingolipid). The antigenicity of the agglutinogens resides in the oligosaccharide moiety. The ABO agglutinogens are present on the red cell membrane as peripheral proteins. O group cells contain a non-antigenic H substance from which both A and B agglutinogens are derived. The genes for A and B agglutinogens are located on chromosome 9. They code the synthesis of transferase-A and transferase-B, the two enzymes that are responsible for conversion of substance H into A and B agglutinogens.
ABO agglutinogens are not confined to erythrocytes alone; they are widely found in the secretory glands of gastrointestinal, respiratory, and genitourinary tracts. The secreted agglutinogens are however not glycosphingolipids but glycoproteins (oligosaccharide plus protein). Only about 80% of the population secretes ABO agglutinogens. They are called secretors. The rest are nonsecretors.
Rhesus agglutinogens Unlike the ABO agglutinogens, Rhesus agglutinogens are integral membrane proteins. They are not found anywhere other than on red cells.
ABO agglutinins The agglutinins α and β are absent at birth but develop over the first 3 to 6 months of life. They are produced as a result of exposure to ABO-like polysaccharides that are abundant in microbes, seeds, and plants. These natural antibodies are immunoglobulins of the IgM type. Subsequent exposures to ABO agglutinogens, as in the course of mismatched transfusion, also produce agglutinins. Such immune agglutinins are often of the IgG type.
Rhesus agglutinins There are no natural antibodies to Rhesus agglutinogens. Agglutinins formed against them are of the IgG type.
RHESUS FACTOR
Around 85% of. population have an additional antigen termed D antigen on their erythrocyte membranes, they are designated rhesus* positive (RhD+). There are no innate antibodies to D antigen but the immune system in rhesus negative individuals (RhD-) can produce anti-D antibodies in response to a RhD+ transfusion. Anti-D antibodies can result in haemolysis and agglutination of RhD+ erythrocytes so it is important that Rhesus positive blood is not given to Rhesus negative recipients.
*The name rhesus comes from the antigen’s first discovery in the Rhesus monkey.
Pregnant women who are RhD- may be carrying a RhD+ baby because the gene which codes for antigen D may be inherited from the father and it is possible that this could cause problems during future pregnancies if the maternal and foetal blood are mixed during the trauma of birth. In this case, the mother will produce antibodies to antigen D. Thus, during subsequent pregnancies, the RhD- mother, previously sensitised to antigen D, could react to a RhD+ foetus by producing more anti-D antibodies and these could be passed on to the foetus via the placenta*, causing haemolytic disease of the newborn. This is a disease where breakdown of the baby’s blood cells releases haemoglobin that may result in jaundice and possible brain damage. It is therefore normal practice to inject RhD- mothers immediately after birth with anti-D antibodies and these destroy any RhD+ foetal cells before the mother produces any of her own anti-D antibodies.
*in the ABO system, it is quite possible for a mother to carry a baby with an incompatible blood group because there is no mixing of the blood. Anti-A and anti-B antibodies will not cross the placenta as they are large IgM type antibodies. The rhesus anti-D antibodies are smaller and therefore can gain access to foetal circulation via the placenta.
3. During a subsequent pregnancy with an Rh-positive fetus, Rh-positive red blood cells cross the placenta, enter the maternal circulation, and stimulate the mother to produce antibodies against the Rh antigen. Antibody production is rapid because the mother has been sensitized to the Rh antigen.
4. The anti-Rh antibodies from the mother cross the placenta, causing agglutination and hemolysis of fetal red blood cells, and hemolytic disease of the newborn (HDN) develops.
Importance of Blood Groups
Transfusion of blood The main importance of blood groups lies in ensuring compatible blood transfusion. This is discussed in detail below.
Medicolegal importance When the blood types of the parents are known, it can be stated with certainty which of the blood groups cannot be present in the offspring. This knowledge is useful in exclusion of pretenders in cases of disputed paternity. It is however not possible to state conclusively that a certain person is indeed the parent of a child. The predictive value is increased if several blood group systems are considered. With the use of DNA fingerprinting, the exclusion rate for paternity rises close to 100%.
Association with diseases The incidence of certain diseases is related to the blood group. For example duodenal ulcers are twice as common in group O nonsecretors than in group A or B secretors, and tumors of the salivary glands, stomach, and pancreas are more common in group A than in group O individuals.
Blood Transfusion
Autologous blood transfusion
Autotransfusion is completely free from the risks of transfusion reactions and transfusion-transmitted diseases. In this, the patient’s own blood is withdrawn in advance of elective surgery and then transfused back if needed during the surgery. Up to
Blood grouping and cross-matching
Autotransfusion is only occasionally possible. Mostly, the patient needs a blood donor. Preferably, the blood groups of the donor and the recipient should be the same. In emergency situations, there may be no time for finding out the blood group of the patient and even when known, the blood of the same group may not be available. In such situations, blood group O– may be transfused indiscriminately to all patients in dire need of transfusion. This is because O– group blood has no agglutinogens and the chances of fatal reactions occurring following a mismatched transfusion (O– group blood donated to persons with A+, B+ or AB+ blood groups) are the lowest. Persons with O– blood group are therefore called universal donors. In the same way, persons with AB blood group are universal recipients. In emergency situations, they can be transfused with any of the ABO blood groups. This is because AB group blood has neither α nor β agglutinins.
The idea of a universal donor is not always safe. Normally, the α and β agglutinins present in the transfused O group blood are greatly diluted by the recipient’s plasma and therefore, are unable to lyse the recipient’s erythrocytes. However, the O group donor may have very high titers of α and β agglutinins, and these may cause hemolysis of the recipient’s erythrocytes. Such O group donors are called dangerous universal donors.
Transfusion of blood of the same group does not guarantee a reaction-free transfusion. The donor and recipient’s blood may be ABO and Rhesus compatible but the donor might have P agglutinogens and the recipient might have anti-P agglutinins. Since there are innumerable minor and familial blood groups that are never ascertained, the donor and recipient’s blood have to be directly tested (cross-matched) against each other. Cross matching may be major or minor. Major cross-matching involves testing the donor’s erythrocytes against the recipient’s serum. Minor cross-matching involves testing the recipient’s erythrocytes against the donor’s serum.
Blood grouping, however, does help iarrowing down the search for compatible blood. For example, if the recipient is B+, the blood bank techniciaeeds to test only a few samples of B+ blood for the perfect compatibility. Without blood grouping, a much larger number of random blood samples would have to be cross-matched.
Complications of transfusion
Fatal hemolytic reactions can occur in mismatched transfusion. Rapid hemolysis results in liberation of free hemoglobin into the plasma, often resulting in severe jaundice and renal tubular damage. When reactions occur, transfusion must be stopped immediately and the patient intravenously injected with rapid-acting corticosteroids. Febrile reactions occur due to destruction of leukocytes and platelet by antibodies against them.
Circulatory overload can develop if transfusion is too rapid. The rate of transfusion therefore should not exceed 1ml per kilogram body weight per hour.
Hemosiderosis is caused by repeated blood transfusions, as in thalassemic patients. There is iron deposition in, and consequent damage to, several organs like the liver, heart, and endocrine organs.
Electrolyte disturbances, especially hyperkalemia and hypocalcaemia, are not uncommon. Hyperkalemia occurs because in stored blood the erythrocytes leak out intracellular K+ into the plasma. Hypocalcemia occurs because stored blood contains citrates as anticoagulant. When transfused into a recipient the citrates are metabolized. However, if the rate of transfusion exceeds the rate of citrate metabolism, the citrates chelate Ca2+ in recipient’s blood causing hypocalcemia.
Anemia hypoxia can be a problem in patients receiving a large transfusion of stored blood. Red cells in stored blood have very low amounts of 2,3 diphosphoglycerate (DPG) in them. Hence, stored blood has high affinity for O2 and consequently, tends to give off less O2 to the tissues.
Transmission of diseases like hepatitis B or C and AIDS constitutes a serious risk.
Short review:
WBC Physiology
Less numerous than RBCs
5,000 to 10,000 cells per drop of blood
1 WBC for every 700 RBC
Only 2% of total WBC population is in circulating blood at any given time
Heavily populate lymph, lymph nodes, skin, lungs, & spleen
Requires colony stimulating factor (local bone marrow/WBC hormone)
Neutrophil Function
Fastest response of all WBC to bacteria and parasites
Direct actions against bacteria
release lysozymes which destroy/digest bacteria
release defensin proteins that act like antibiotics
release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria
Basophil Function
Involved in inflammatory and allergy reactions
Leave capillaries (diapedesis) & enter tissues
Release heparin, histamine & serotonin
heighten the inflammatory response and account for hypersensitivity (allergic) reaction
Heparin is a potent anti-coagulant that does not allow clotting within vessels
Eosinophil Function
Leave capillaries to enter tissue fluid
Attack parasitic worms
Release histaminase
slows down inflammation caused by basophils
Phagocytize antibody-antigen complexes
Monocyte Function
Take longer to get to site of infection, but arrive in larger numbers
Become wandering macrophages, once they leave the capillaries
Destroy microbes and clean up dead tissue following an infection
Lymphocyte Functions
B cells
destroy bacteria and their toxins
turn into plasma cells that produce and release antibodies
T cells
attack viruses, fungi, transplanted organs, cancer cells
Natural killer cells (NKC)
attack many different microbes & some tumor cells
destroy foreign invaders by direct attack
Differential WBC Count
Detection of deviations iormal ranges of circulating WBCs
indicates immune response to infection, poisoning, leukemia, chemotherapy, parasites, or allergens
Normal WBC counts:
Neutrophils: 60-70% (up if bacterial infection)
Lymphocyte: 20-25% (up if viral infection)
Monocytes: 3 – 8 % (up if fungal/viral infection)
Eosinophil: 2 – 4 % (up if parasite or allergy reaction)
Basophil: < 1% (up if allergy reaction)
Blood Types
Agglutinogens – surface antigens on cells
Presence or absence of surface antigens determines Blood Type
Composed of glycoproteins & glycolipids
Antigens: A, B and Rh (D)
Agglutinins – antibodies in the plasma
Cross-reactions occur when antigens meet antibodies
ABO Blood Groups
Based on 2 glycolipid isoantigens called A and B found on the surface of RBCs
display only antigen A — Blood Type A
display only antigen B — Blood Type B
display both antigens A & B — Blood Type AB
display neither antigen — Blood Type O
Plasma contains isoantibodies or agglutinins to the A or B antigens not found in your blood
Anti-A antibody reacts with antigen A
Anti-B antibody reacts with antigen B
Blood Type Testing
RH blood groups
Antigen was discovered in blood of Rhesus monkey
People with Rh isoantigens on RBC surface are Rh+
Normal plasma contains no anti-Rh antibodies
Antibodies develop only in Rh– blood type & only after exposure to the antigen
Transfusion reaction upon 2nd exposure to the antigen results in hemolysis of the Rh+ RBCs
HDN
Rh negative mom and Rh+ fetus will have mixing of blood at birth
Mom’s body creates Rh antibodies unless she receives a RhoGam shot soon after first delivery, miscarriage or abortion
In 2nd child, Hemolytic Disease of the Newborn may develop causing hemolysis of the fetal RBCs
Universal Donors and Recipients
People with type AB+ blood called “universal recipients” since have no antibodies in plasma
AB+ blood cells contain all three surface antigens (A, B & D).
Hence, their immune system will not make antibodies to those markers.
Only true if cross match the blood for other antigens
People with type O– blood cell called “universal donors” since they have no antigens on their cells
O– RBCs have no surface antigens.
RBCs are “naked” and remain undetected by recipient immune systems.