anatomy
poorva
WhiteBloodCellsInflammation-2.pptxWhite Blood Cells & Inflammation
Srujana Rayalam DVM, PhD
Dept. of Pharmaceutical Sciences
PCOM-GA campus
PHAR 113G Anatomy, Physiology & Pathophysiology I
8/25/2020 4:02 PM
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Learning Objectives
Describe the main functions of white blood cells
Outline the different types of white blood cells & their key characteristics
Outline the production & maturation process for monocytes & lymphocytes
Describe how neutrophils & macrophages seek & destroy invading organisms
Outline the roles of resident macrophages in vulnerable tissue sites
Describe the sequence of events that occur in the inflammatory response to infection
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Mesmerizingly Creepy Handprint Shows We’re All Crawling With Bacteria
http://www.huffingtonpost.com/2015/06/08/bacteria-handprint-photo_n_7538912.html
Tasha Sturm, a microbiology tech at Cabrillo College, told The Huffington Post that she had her 8-year-old son make a handprint in a petri dish filled with agar jelly.
Next, she put the plate in her lab’s incubator. Warmed to body temperature and fed by agar jelly, the bacteria and fungus on her son’s hand grew into the cultures you see above.
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Components of blood and the relationship of blood to other body tissues
Six distinct types of white blood cells (WBC)
Size: all > than RBCs
All contain nuclei
Total WBC ≈ 7000 cells/μl (compared to 5x106 RBC)
WBC also found in lymphatic & other tissues
Neutrophils & lymphocytes most abundant
Basophils and plasma cells least abundant
Essentials of Anatomy and Physiology (5th edition)
Primary functions of WBCs
Six types: Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Plasma cells
These cells work together in two ways to prevent disease:
(1) by destroying invading bacteria or viruses by phagocytosis and
(2) by forming antibodies and sensitized lymphocytes, which may destroy or inactivate the invader
Characteristics of WBCs
Neutrophils, eosinophils & basophils have multi-lobed nuclei (polymorphonuclear)
Often called “granulocytes”
Granulocytes & monocytes formed in bone marrow
Responsible for inflammatory response
Monocytes must first migrate into tissues & mature into macrophages
Lymphocytes & plasma cells formed mostly in lymphoid tissue
Responsible for immunity
Plasma cells derived from B lymphocytes
Characteristics of WBCs…cont’d
Essentials of Anatomy and Physiology (5th edition)
| Type of White Blood Cells | % By Volume of WBC | Description | Function |
| Neutrophils | 60 – 70 % | Nucleus has many interconnected lobes; blue granules | Phagocytize and destory bacteria; most numerous WBC |
| Eosinophils | 2 – 4 % | Nucleus has bilobed nuclei; red or yellow granules containing digestive enzymes | Play a role in ending allergic reactions |
| Basophils | < 1 % | Bilobed nuclei hidden by large purple granules full of chemical mediators of inflammation | Function in inflammation medication; similar in function to mast cells |
| Lymphocytes (B Cells and T Cells) | 20 – 25 % | Dense, purple staining, round nucleus; little cytoplasm | the most important cells of the immune system; effective in fighting infectious organisms; act against a specific foreign molecule (antigen) |
| Monocytes | 4 – 8 % | Largest leukocyte; kidney shaped nucleus | Transform into macrophages; phagocytic cells |
Production & Maturation of White Blood Cells
All leukocytes are derived from multipotent hemopoietic stem cells in bone marrow
Granulocytes & monocytes produced exclusively in bone marrow (myeoloblastic lineage)
Some enter blood circulation; most stored in bone marrow
B & T lymphocytes produced mainly in lymphoid tissues (lymphoblastic lineage)
Most stored in lymphoid tissues
Guyton and Hall Textbook of Medical Physiology (12th edition)
Life span of WBCs
Granulocytes have short life span (hours in bloodstream; few days in tissues)
Many monocytes mature into resident macrophages after migration into tissue
Prolonged life span (months) in tissues
Lymphocytes cycle between lymph tissues & bloodstream
Essentials of Anatomy and Physiology (5th edition)
Neutrophils and Macrophages Defend Against Infections
Neutrophils and monocytes can squeeze through the pores of the blood capillaries by diapedesis
Guyton and Hall Textbook of Medical Physiology (12th edition)
Chemotaxis
Different chemical substances in the tissues cause both neutrophils and macrophages to move toward the source of the chemical.
some of the bacterial or viral toxins,
degenerative products of the inflamed tissues
several reaction products of the “complement complex” and
several reaction products caused by plasma clotting in the inflamed area
Guyton and Hall Textbook of Medical Physiology (12th edition)
Phagocytosis & Oxidative Burst
Primary mechanism for destruction of invading organisms is “phagocytosis”
Neutrophils and macrophages surround organism with multiple pseudopodia & engulf into phagocytic vesicle
Merger of phagocytic vesicle with lysosome initiates digestion of organism
Macrophages have much greater capacity for phagocytosis than neutrophils
Guyton and Hall Textbook of Medical Physiology (12th edition)
Organism must be recognized as “foreign” to initiate phagocytosis
Targeted by “opsonization” with antibody & complement fragment
Phagocytosis & Oxidative Burst…cont’d
Generation of oxygen free radicals (“oxidative burst”) provides secondary mechanism
Bactericidal agents kill most bacteria even when the lysosomal enzymes fail to digest them
Some bacteria like tuberculosis bacillus have coats that are resistant to lysosomal digestion → responsible for many of the chronic diseases
Superoxide, hydrogen peroxide & hydroxyl radicals generated in nutrient – limited environment in the phagolysosome
Phagocyte oxidase – important enzyme in phagosome
Oxygen free radicals have strong bactericidal action
Guyton and Hall Textbook of Medical Physiology (12th edition)
Monocyte-Macrophage Cell System (Reticuloendothelial System)
Monocytes, mobile macrophages, fixed tissue macrophages (resident), and a few specialized endothelial cells in the bone marrow, spleen, and lymph nodes → reticuloendothelial system.
Macrophages become attached within tissue & remain for prolonged period
Abundant in tissues vulnerable to infection
Skin – Langerhans cells
Lung – alveolar macrophages
Liver – Kupffer cells
GI tract – intestinal and colonic macrophages
Resident macrophages also present abundantly in spleen and lymph nodes
Guyton and Hall Textbook of Medical Physiology (12th edition)
Monocytes and Macrophages
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Macrophages…cont’d
Classically activated M1 macrophage
inflammatory
Alternatively activated M2 macrophage
anti-inflammatory
helps in tissue repair
Basic Immunology: Functions and Disorders of the Immune System; Fourth Edition; Abul K. Abbas et al.,
Inflammation
Inflammation is characterized by:
vasodilation of the local blood vessels, with consequent excess local blood flow
increased permeability of the capillaries, allowing leakage of large quantities of fluid into the interstitial spaces
clotting of the fluid in the interstitial spaces because of increased amounts of fibrinogen and other proteins leaking from the capillaries
migration of large numbers of granulocytes and monocytes into the tissue and
swelling of the tissue cells
Guyton and Hall Textbook of Medical Physiology (12th edition)
Infection or tissue injury (trauma, chemicals, heat etc) → release of chemotactic substances → inflammation
Inflammation..cont'd
Many different substances contribute in triggering events
Histamine
Leukotrienes
Complement fragments
Cytokines
Macrophage and Neutrophil Responses During Inflammation
Resident macrophages
provide 1st line of defense against infection
Respond rapidly (-1 hour) & initiate phagocytosis of invading organism
the first effect is rapid enlargement of these cells
Neutrophil migration into tissue
Provides 2nd line of defense
Attracted by chemotactic factors & inflammatory cytokines (e.g., TNFα, IL-1)
↑ expression of adhesion molecules
Margination
Diapedesis and chemotaxis
Neutrophils also rapidly mobilized from bone marrow
Marked rise in neutrophil count in blood (“neutrophilia”) after infection
Count may rise from 4,000–5,000 cells/μl to 15,000–25,000 cells/μl
Monocyte migration into tissue & maturation to macrophages
3rd line of defense
Slow process due to small number of circulating monocytes & need to mature
Macrophages ultimately play dominant role & trigger immune response
Bone marrow produces more granulocytes & monocytes
4th line of defense
significant lag time (3–4 days) for this response
series of colony stimulating factors (GM-CSF, G-CSF & M-CSF) play main role
Eosinophils
Eosinophils have minor role in combating bacterial & viral infection
More important role against parasite infection
Major basic protein – larvicidal effects on helminths
Kill parasites with hydrolytic enzymes & oxygen free radicals
Also accumulate in tissues during allergic reactions
Basophils
Basophils contribute to inflammatory response
Release histamine, bradykinin, serotonin & heparin
Triggered by abundance of IgE antibodies on these cells
Play predominant role in many allergic reactions
Mast cells (similar to basophils, but resident in tissues) have similar action
Mast cells
Derived from bone marrow precursor cells
Reside in tissues adjacent to blood vessels
Express a high-affinity receptor for Fc fragment of IgE
Contain numerous mediator-filled granules
Mast cell cytoplasmic granules
Histamine (dilation of small blood vessels, increase of vascular permeability, contraction of smooth muscles)
Proteases (cause a damage to the tissues)
Cytokines: Interleukins and TNFa
Growth factors: TGF- β, VEGF
Eicosanoids: LTC4- leukotrienes (stimulate prolonged smooth muscle contraction), PGD2- prostaglandins (cause vascular dilation)
Summary
Functions and types of white blood cells
Production & maturation of monocytes & lymphocytes
Phagocytosis by neutrophils & macrophages
Roles of resident macrophages
Sequence of events that occur in the inflammatory response to infection
