blood and immunity · the normal bone marrow cells by the non-functional leukemic cells. frequent...
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Leucocyte(WBC)
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Introduction Crucial in the body’s defense against
pathogens
These are complete cells, with a nucleus and organelles
They lack Hb so they are colorless
They are formed partially in the bone marrow and partially in the lymph tissue
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Types of Leucocytes Granulocytes
Granules in their cytoplasm which can be stained
Biologically active substances involved in inflammatory and allergic reactions.
Neutrophils, Eosinophil, and Basophils
Agranulocytes
Lack visible cytoplasmic granules
Lymphocytes and Monocytes
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Leucocytes
Granulocytes
Eosinophil1-6 %
Basophil0-1%
Neutrophil40-75%
Agranulocytes
Monocytes2-10%
Lymphocytes 20-40%
Polymorphonuclear WBC
How to remember WBC ranking? Never Let Monkeys Eat Bananas
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Types of LeucocytesGranulocytes
Agranulocytes
Neutrophil Eosinophil Basophil
Monocyte Lymphocyte
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Leukocyte Levels In The Blood Normal levels =4,000 to 11,000 cells/mm3
Abnormal leukocyte levels Leucocytosis
Above 11,000 leukocytes/mm3
Generally indicates an infection
Leucopenia Abnormally low leukocyte level < 4000/mm3
Commonly caused by certain drugs
Leukemia Abnormally high (~>80,000) and immature
leucocytes.
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Leucocytosis VSLeukemoid reaction VS
Leukemia
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Leukopoiesis
Genesis of WBC.
The granulocytes and monocytes are formed only in the bone marrow.
Lymphocytes and plasma cells are produced mainly in the various lymphogenous tissues—especially the lymph glands, spleen, thymus,
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Myeloblast
Lymphoblast
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Myeloblast
promyelocyte
Young neutrophil metamyelocyte
Neutrophil myelocyte
Band neutrophil metamyelocyte
neutrophil
Basophil myelocyte
Eosinophilmyelocyte
Eosinophilmetamyelocyte
eosinophil basophil
monoblast
promonocyte
monocyte
Lymphoblast
prolymphocyte
lymphocyte
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NeutrophilSize:10-14 µm in diam.Nucleus:
1. Multilobed (1-6 lobes) therefore called polymorphnuclear leucocytes.
2. Young cell have single horse shoe shaped nucleus.
average half-life in the circulation is 6 hours
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Neutrophil4 types of granules are present1. Primary/ Azurophilic granules:
Contains :
myeloperoxidase, (produces HOCl for killing
bacteria).
acid hydrolases, which can digest bacteria,
elastase, proteinase, α-1 antitrypsin
Antimicrobial proteins like cathepsin-G,
Defensins- α, β
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2. Secondary /peroxidase negative granules:more numerous. Contain
Lactoferrin-antibacterial
Gelatinase, lysozyme- microbicidal, Vit B12
binding protein &
Components of enzyme system that produce free radicals like H2O2, which kills the microbes.
Substances that facilitates chemotaxis.
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3. Tertiary granules: Gelatinase, alkaline phosphatase and cytochrome-b
4. Secretory Granules: secretory vesicles contain CD3, phospholipase and tyrosine kinase
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Functions of Neutrophil Functions:1. Phagocytosis:2. Reaction of inflammation: release
leukotrienes, prostaglandins, thromboxanes
3. Febrile Response: They contain fever producing substance, endogenous pyrogen which is an important mediator of febrile response to bacterial pyrogens
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Steps of phagocytosisSteps of Phagocytosis: 1. Margination2. Diapedesis3. Chemotaxis4. Recognition and
attachment(Opsonization)5. Engulfment and creation of phagosome6. Fusion of phagosome with lysosome7. Destruction and digestion8. Residual body Exocytosis
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Margination: Cytokines cause increased level of selectins
and intercellular adhesion molecule-1 (ICAM-1) on the surface of endothelial cells.
These adhesion molecules bind to complementary molecules/receptors on the neutrophil, causing it to adhere to the wall of the capil.lary or venule
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Diapedesis Cytokines cause the intercellular
attachments between the endothelial cells of the capillaries and small venulesto loosen,
Neutrophils crawl through these openings directly from the blood into the tissue spaces.
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A single neutrophil can usually phagocytize 3 to 20 bacteria before the neutrophil becomes inactivated and dies.
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Neutrophillic Killing of Bacteria
the killing effect results from powerful oxidizing agents formed in peroxisome of neutrophils.
These oxidizing agents include large quantities of superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl ions (OH−), which are lethal to most bacteria, even in small quantities
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Variation In Neutrophil Count:
A. Physiological1)After Exercise,2)After injection of epinephrine, 3)Pregnancy, menstruation,
parturition & lactation,4)Newborn,
B. Pathological1)Acute pyogenic (pus
forming) bacterial infections,
2) Acute Rheumatic feverGout
3)Following tissue destruction,
i) Burns ii) After hemorrhage, iii) poisoning by lead,
mercury,
Neutrophilia: ↑ in neutrophils>8000/mm3
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Neutropenia: ↓ In Neutrophils < 1500/mm3 Typhoid fever Viral infection Malaria Aplasia of bone marrow
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Eosinophils The eosinophils normally constitute about 2
percent of all the blood leukocytes.
Size:10-14 µm in diam. (2%)Nucleus:
1. Usually (85%) cells ‘bilobed’.
2. Lobes are connected with one another by chromatin threads thus producing spectacle appearance.
3. Remaining 15% cells have trilobed nucleus.
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Granules1. Coarse, stain bright brick red with
acidic (eosin) dye.
2. Granules do not cover the nucleus.
3. The granules contain: histaminase, lysozymes & Major Basic Protein (MBP)
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Eosinophil Function1. Mild Phagocytosis: less motile than
neutrophils
2. Parasitic infestations: Major Basic Protein- Larvicidal Eosinophil Cationic Protein- bactericidal &
major destroyer of helminths. Eosinophil Peroxidase – destruction of
helminths, bacteria & tumour cells
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3. Allergic reaction: bronchial asthma & hay fever The mast cells and basophils release an
eosinophil chemotactic factor that causes eosinophil to migrate toward the inflamed allergic tissue.
Removing inflammation inducing substance like bradykinin, histamine
inhibit mast cell degranulation phagocytose & destroy Ag-Ab complexes
Specially abundant in the mucosa of respiratory tracts, GIT, urinary tract, where they provide mucosal
immunity
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Variation In Eosinophil Count
Eosinophilia: ↑ in eosinophilsCauses are:-1)Allergic conditions e.g.
bronchial asthma, hay fever, filariasis
2) Parasitic infestation, trichinosis & schistosomiasise.g. worms (hookworm, roundworm & tapeworm),
3) Skin disease like utricaria.
Eosinopenia: ↓ in eosinophilsCauses are:-1) ACTH & steroid therapy2) Stressful conditions, & 3) Acute pyogenic infections
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Basophils Size:10-14 µm in diam. Nucleus:
irregular bilobed shaped & its boundary is not clear because of overcrowding with coarse granules.
Granules: coarse, stain deep purple/blue Plenty, completely fill the cell &
overload the nucleus Contain:
heparin, histamine & 5HT.
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Basophils function1. Mild phagocytosis2. Role in allergic reaction: Basophils release histamine, bradykinin, slow
reacting substance of anaphylaxis (SRS-A) & serotonin (5HT).
These substances cause local vascular & tissue reactions that cause many allergic manifestations.
3. Liberates heparin which Acts as anticoagulant & keeps blood in fluid
state. Activates the enzyme lipoprotein lipase which
removes fat particles from the blood after fatty meal
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Variation in basophil count
Basophilia: ↑ in basophil count >100/mm3Causes are:- Viral infections, e.g. influenza,
small pox & chicken pox Allergic diseases Chronic myeloid leukemia.
Basopenia: ↓ in basophil countCauses are:-► Corticosteroid therapy, ► Drug induced reactions & ► Acute pyogenic infections
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Monocytes
Size: Largest WBC 18-20 µm.Nucleus:
Is large single, eccentric in position (present on one side of the cell).
It is kidney shaped
Granules:Sometimes may contain fine purple dust like granules called Azur granules
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Function of monocyte1. Role in phagocytosis:
These are powerful phagocytes & capable of phagocytosis as many as 100 bacteria. They also have ability to engulf large particles such as RBCs & malarial parasites.
2. Role in tumor immunity: kill tumor cells after sensitization by lymphocytes, play a key role in the lymphocyte – mediated immunity.
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2. Synthesis of Biological Substances: Interleukin1 TNF-α, lysosomes, Proteases and Acid hydrolases
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Leucopenia Condition where bone marrow produces very few
WBCs, This condition leaves the body unprotected
against many bacteria and other agents that might invade the tissues.
Cause: Irradiation of the body by x-rays or gamma
rays, or exposure to drugs and chemicals that contain
benzene or anthracene nuclei,
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Effect of Leucopenia The human body lives in symbiosis with many
bacteria. Any decrease in the number of WBCs immediately
allows invasion of adjacent tissues by bacteria that are already present.
Within 2 days after the bone marrow stops producing WBCs, ulcers may appear in the mouth and colon, or some form of severe respiratory infection might develop.
Without treatment death often occur in less than a week
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Leukemias
Uncontrolled production of WBCs caused by cancerous mutation of a myelogenous or lymphogenous cell is called leukemia.
Characterized by greatly increased numbers of abnormal or undifferentiated WBCs.
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Classification of Leukemia The lymphocytic leukemias are caused by
cancerous production of lymphoid cells.
Myelogenous leukemia, begins by cancerous production of young myelogenous cells in the bone marrow and then spreads throughout the body.
Depending on the onset of disease it is also classified as Acute Leukemia or Chronic Leukemia
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Cell Type
Lymphocyticleukemia
Myelogenousleukemia
("nonlymphocytic")
Acute
Acute lymphoblastic
leukemia(ALL)
Acute Myelogenous
leukemia(AML)
Chronic
Chronic lymphocytic
leukemia(CLL)
Chronic myelogenous
leukemia(CML)
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Lymphocytic Leukemia
Myelogenous Leukemia
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the more undifferentiated the cell, the more severe is the leukemia, often leading to death within a few months if untreated.
Leukemic cells, especially the very undifferentiated cells, are usually nonfunctional for providing normal protection against infection.
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Effects of Leukemia on the Body
Metastatic growth of leukemic cells in abnormal areas of the body.
spread to the spleen, lymph nodes, liver, and other vascular regions
Leukemic cells from the bone marrow may reproduce so greatly that they invade the surrounding bone, causing pain and, eventually, a tendency for bones to fracture easily.
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Thrombocytopenia and Anemia – displacement of the normal bone marrow cells by the non-functional leukemic cells.
Frequent infection as leukemic cells are immature to carry out immune functions.
The leukemic tissues reproduce new cells so rapidly that tremendous demands are made on the body reserves .
Tis metabolic starvation if continued long enough, alone is sufficient to cause death.