The Lymphatic System Lymphocyte and...

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© 2012 Pearson Education, Inc.

22 The Lymphatic System and Immunity

Lymph

Lymphocyte


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


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


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


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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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



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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•  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



•  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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•  Special Histiocytes

•  Microglia found in central nervous system

•  Kupffer cells found in liver sinusoids

•  Free Macrophages

•  Special free macrophages

•  Alveolar macrophages (phagocytic dust cells)



•  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



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


Secretion of Perforin

Perforin molecules

NK cell

Abnormal cell

Pores formed by perforin complex

Lysis of Abnormal Cell

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•  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



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.


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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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



•  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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•  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.


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


Complement Pathways

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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)



•  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



  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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  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


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


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 macrophages; stimulation of fibroblasts

Activation of specific defenses

Pathogen removal, clot erosion, scar tissue formation

Tissue Repair

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•  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



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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  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


22-4 Specific Defenses

•  Adaptive (Specific) Defenses

•  Specific resistance (immunity)

•  Responds to specific antigens

•  With coordinated action of T cells and B cells

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