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22 The Lymphatic System and Immunity
Lymph
Lymphocyte
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Medical Conditions Lymphomas : Malignant cancers consisting of abnormal
lymphocytes or lymphoid stem cells. (Hodgkin’s disease)
Splenomegaly : Enlargement of the spleen due to infection ( such as mononucleosis)
Hyposplenism : Results from a non functional or missing spleen. Individuals are more prone to bacterial infections.
Tonsillectomy : Removal of the tonsils.
Lymphadenopathy : Chronic or excessive enlargement of lymph nodes.
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Medical Conditions
Filariasis : Infections by a parasitic roundworm ( Wucheria bancrofti), transmitted via mosquitoes or black flies.
The adult worms form massive colonies in the lymph nodes and completely blocks drainage.
The result is an extreme form of lymphedema, with grossly distended and deformed limbs or external genitalia
This form of edema is knoiwn as elephantiasis.
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Medical Conditions
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22-2 Structures of Body Defenses
• The Lymphatic System and Body Defenses
• Body defenses provide resistance to fight infection, illness, and disease
• Two categories of defenses
1. Innate (nonspecific) defenses
2. Adaptive (specific) defenses
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22-2 Structures of Body Defenses
• Innate (Nonspecific) Defenses
• Always work the same way
• Against any type of invading agent
• Nonspecific resistance
• Adaptive (Specific) Defenses • Protect against specific pathogens • Depend on activities of lymphocytes
• Specific resistance (immunity) • Develops after exposure to environmental hazards
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22-3 Nonspecific Defenses
• Seven Major Categories of Innate (Nonspecific) Defenses 1. Physical barriers
2. Phagocytes 3. Immunological surveillance 4. Interferons 5. Complement
6. Inflammatory response
7. Fever
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Innate Defenses Physical barriers keep hazardous organisms and materials outside the body.
Phagocytes engulf pathogens and cell debris.
Immunological surveillance is the destruction of abnormal cells by NK cells in peripheral tissues.
Interferons are chemical messengers that coordinate the defenses against viral infections.
Duct of eccrine sweat gland Hair
Fixed macrophage Neutrophil
Free macrophage
Natural killer cell
Lysed abnormal cell
Eosinophil Monocyte
Secretions
Epithelium
Interferons released by activated lymphocytes, macrophages, or virus-infected cells
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Complement system consists of circulating proteins that assist antibodies in the destruction of pathogens.
is a localized, tissue-level response that tends to limit the spread of an injury or infection.
Inflammatory response
is an elevation of body temperature that accelerates tissue metabolism and the activity of defenses.
Fever
Mast cell
Complement
Lysed pathogen
Body temperature rises above 37.2ºC in response to pyrogens
1. Blood flow increased 2. Phagocytes activated 3. Capillary permeability increased
7. Adaptive defenses activated
4. Complement activated 5. Clotting reaction walls off region 6. Regional temperature increased
Innate Defenses
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22-3 Nonspecific Defenses
1. Physical Barriers • Outer layer of skin
• Hair
• Epithelial layers of internal passageways
• Secretions that flush away materials
• Sweat glands, mucus, and urine
• Secretions that kill or inhibit microorganisms
• Enzymes, antibodies, and stomach acid
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22-3 Nonspecific Defenses
2. Phagocytes : there are 2 classes
1. Microphages
• Neutrophils and eosinophils
• Leave the bloodstream
• Enter peripheral tissues to fight infections
2. Macrophages
• Large phagocytic cells derived from monocytes
• Distributed throughout body
• Make up monocyte–macrophage system (reticuloendothelial system)
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22-3 Nonspecific Defenses
• Activated Macrophages Respond to pathogens in several ways
• Engulf pathogen and destroy it with lysosomal enzymes
• Bind to pathogen so other cells can destroy it
• Destroy pathogen by releasing toxic chemicals into interstitial fluid
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22-3 Nonspecific Defenses
• Two Types of Macrophages
1. Fixed macrophages
• Also called histiocytes
• Stay in specific tissues or organs
• For example, dermis and bone marrow
2. Free macrophages
• Also called wandering macrophages
• Travel throughout body
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22-3 Nonspecific Defenses
• Special Histiocytes
• Microglia found in central nervous system
• Kupffer cells found in liver sinusoids
• Free Macrophages
• Special free macrophages
• Alveolar macrophages (phagocytic dust cells)
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22-3 Nonspecific Defenses
• Movement and Phagocytosis
• All macrophages:
• Move through capillary walls (emigration)
• Are attracted or repelled by chemicals in surrounding
fluids (chemotaxis)
• Phagocytosis begins:
• When phagocyte attaches to target (adhesion)
• And surrounds it with a vesicle
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(b)
Lysosome
Microbe adheres to phagocyte. Phagocyte forms pseudopods that eventually engulf the particle.
Phagocytic vesicle is fused with a lysosome.
Microbe in fused vesicle is killed and digested by lysosomal enzymes within the phagolysosome, leaving a residual body.
Indigestible and residual material is removed by exocytosis.
Phagocytic vesicle containing antigen (phagosome).
Residual body
Acid hydrolase enzymes
Phagolysosome 4
3
2
1
5
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22-3 Nonspecific Defenses
3. Immunological Surveillance • Is carried out by natural killer (NK) cells
• Activated NK Cells
1. Identify and attach to abnormal cell (nonselective)
2. Golgi apparatus in NK cell forms perforin vesicles
3. Vesicles release proteins called perforins (exocytosis)
4. Perforins create pores in plasma membrane of abnormal cell, resulting in lysis and death of the cell
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Recognition and Adhesion
NK cell Golgi apparatus
Abnormal cell
Realignment of Golgi apparatus
Action of NK-cells
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Secretion of Perforin
Perforin molecules
NK cell
Abnormal cell
Pores formed by perforin complex
Lysis of Abnormal Cell
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22-3 Nonspecific Defenses
• NK-cells also attack cancer cells and cells infected with viruses • Cancer cells
• With tumor-specific antigens
• Are identified as abnormal by NK cells
• Some cancer cells avoid NK cells (immunological escape)
• Viral infections
• Cells infected with viruses
• Present abnormal proteins on plasma membranes
• Allow NK cells to identify and destroy them
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22-3 Nonspecific Defenses
4. Interferons (IFN) • Cytokines are chemical messengers released by tissue cells that
act to coordinate local activities and can function as hormones to affect whole body
• Interferons are a type of cytokines released by activated lymphocytes and macrophages
• Genes that synthesize IFN are activated when a host cell is invaded by a virus
• Interferon molecules leave the infected cell and enter neighboring cells
• Interferon stimulates the neighboring cells to activate genes for PKR (an antiviral protein)
• PKR nonspecifically blocks viral reproduction in the neighboring cell
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Interferon (IFN)
Genes that synthesize IFN are activated when a host cell is invaded by a virus
Interferon molecules leave the infected cell and enter neighboring cells
Interferon stimulates the neighboring cells to activate genes for PKR (an antiviral protein)
PKR nonspecifically blocks viral reproduction in the neighboring cell.
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Alpha (α)-interferons are produced by cells infected with viruses. They attract and stimulate NK cells and enhance resistance to viral infection.
Beta (β)-interferons, secreted by fibroblasts, slow inflammation in a damaged area.
Gamma (γ)-interferons, secreted by T cells and NK cells, stimulate macrophage activity.
• Three Types of Interferons
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22-3 Nonspecific Defenses
5. Complement • Plasma contains 11 special complement (C) proteins
that form the complement system and ‘complements’ the action of antibodies
• Two pathways activate the complement system
1. Classical pathway
2. Alternative pathway
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22-3 Nonspecific Defenses
• The Classical Pathway • This is a Fast method and requires C1 to binds to antibody molecule
already attached attached to antigen on bacterial walls. It is thus directly linked to the immune system at work ( the antibodies).
• This activates C1 resulting in a cascade reaction among other complement proteins
• The Alternative Pathway • Is triggered by interaction among factors B, D, and P (properdin),
and polysaccharide molecules present on microorganisms
• It also involvess a cascade reaction but is is a slower mechanism
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22-3 Nonspecific Defenses
• Both pathways converge on C3 protein, which cleaves into C3a and C3b
• C3b initiates formation of a membrane attack complex (MAC) by joining five complement proteins, which create a large pore (channel) in the bacterial (or foreign cell) wall
• MAC thus causes cell lysis and also interferes with a cell’s ability to eject Ca2+
• C3b also causes opsonization ( enhances phagocytosis) , and C3a causes inflammation via enhancement of histamine release.
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The most rapid and effective activation of the complement system occurs through the classical pathway.
Activation and Cascade C3b Attachment (classical pathway)
C3b Attachment (alternate pathway)
The classical pathway ends with the conversion of an inactive C3 to an activated C3b that attaches to the cell wall.
The attached C1 protein then acts as an enzyme, catalyzing a series of reactions involving other complement proteins.
C3b
C3b C3b
C3 C2
C1
C1 attachment
Classical Pathway
Antibody Binding and C1 Attachment Antibody binding
Antibodies
Bacterial cell wall
C4
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The alternative pathway is important in the defense against bacteria, some parasites, and virus-infected cells.
Alternative Pathway
C3
C3b
The alternative pathway begins when several complement proteins, notably properdin, interact in the plasma. This interaction can be triggered by exposure to foreign materials, such as the capsule of a bacterium. The end result is the attachment of an activated C3b protein to the bacterial cell wall.
Properdin Factor B Factor D
Bacterial cell wall
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Complement Pathways
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22-3 Nonspecific Defenses
6. Inflammation • Also called inflammatory response
• A localized response
• Triggered by any stimulus that kills cells or injures tissue
Cardinal Signs and Symptoms of inflammation
• Swelling (tumor)
• Redness (rubor)
• Heat (calor)
• Pain (dolor)
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22-3 Nonspecific Defenses
• Three Effects of Inflammation
1. Temporary repair and barrier against pathogens
2. Retards spread of pathogens into surrounding areas
3. Mobilization of local and systemic defenses
• And facilitation of repairs (regeneration)
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Begins with a flood of inflammatory chemicals released into the extracellular fluid
Inflammatory mediators: Kinins, prostaglandins (PGs), complement, and
cytokines
Released by injured tissue, phagocytes, lymphocytes, and mast cells
Cause local small blood vessels to dilate, resulting in hyperemia
Inflammation Response
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Inflammation Response
Chemicals liberated by the inflammatory response increase the permeability of local capillaries
Exudate—fluid containing proteins, clotting factors, and antibodies
Exudate seeps into tissue spaces causing local edema (swelling), which contributes to the sensation of pain
The surge of protein-rich fluids into tissue spaces (edema)
Helps dilute harmful substances
Brings in large quantities of oxygen and nutrients needed for repair
Allows entry of clotting proteins, which prevents the spread of bacteria
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Inflammation Response
Phagocytotic response has four main phases: Leukocytosis – neutrophils are released from the bone
marrow in response to leukocytosis-inducing factors released by injured cells
Margination – neutrophils cling to the walls of capillaries in the injured area
Diapedesis – neutrophils squeeze through capillary walls and begin phagocytosis
Chemotaxis – inflammatory chemicals attract neutrophils to the injury site
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Neutrophils enter blood from bone marrow
Endothelium Basement membrane Capillary wall
Margination Diapedesis
Positive chemotaxis
Inflammatory chemicals diffusing from the inflamed site act as chemotactic agents
Innate defenses Internal defenses
1 2
3
4
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Tissue Damage
Mast Cell Activation
Chemical change in interstitial fluid
Release of histamine and heparin from mast cells
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Redness, Swelling, Warmth, and Pain Phagocyte Attraction
Attraction of phagocytes, especially neutrophils
Release of cytokines
Dilation of blood vessels, increased blood flow, increased vessel permeability
Clot formation (temporary repair)
Removal of debris by neutrophils and macro- phages; stimulation of fibroblasts
Activation of specific defenses
Pathogen removal, clot erosion, scar tissue formation
Tissue Repair
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22-3 Nonspecific Defenses
• Products of Inflammation • Necrosis
• Local tissue destruction in area of injury
• Pus • Mixture of debris and necrotic tissue
• Abscess • Pus accumulated in an enclosed space
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22-3 Nonspecific Defenses
7. Fever
• A maintained body temperature above 37°C (99°F)
• Pyrogens • Any material that causes the hypothalamus to raise
body temperature • Circulating pathogens, toxins, or antibody complexes
• Some leukocytes and macrophages also release cytokines that act as pyrogens (called endogenous pyrogens e.g. interleukin-1).
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22-3 Nonspecific Defenses
High fevers are dangerous because they can denature enzymes
Moderate fever can be beneficial, as it causes:
The liver and spleen to sequester iron and zinc (needed by microorganisms)
An increase in the metabolic rate, which speeds up tissue repair
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22-4 Specific Defenses
• Adaptive (Specific) Defenses
• Specific resistance (immunity)
• Responds to specific antigens
• With coordinated action of T cells and B cells