Chapter 22: The Lymphatic System Biology 142 A&P R.L. Brashear-Kaulfers

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Chapter 22 The Lymphatic SystemBiology 142
APR.L. Brashear-Kaulfers
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Pathogens

• Microscopic organisms that cause disease
• viruses
• bacteria
• fungi
• parasites
• Each attacks in a specific way

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The Lymphatic SystemProtects us against disease

• Lymphocytes
• Lymphatic system cells respond to
• environmental pathogens
• toxins
• abnormal body cells, such as cancers

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What is the difference between nonspecific and
specific defense, and the role of lymphocytes
in the immune response?
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Specific Defenses

• Lymphocytes
• part of the immune response
• Identify, attack, and develop immunity to a
  specific pathogen
• Immunity- The ability to resist infection and
  disease

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The Immune System

• All body cells and tissues involved in production
  of immunity
• not just lymphatic system

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Nonspecific Defenses

• Block or attack any potential infectious organism
• Cannot distinguish one attack from another

Immunity Nonspecific Defenses
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Organization of the Lymphatic System
What are the major components of the lymphatic
system and their functions?
Figure 221
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4 Parts of the Lymphatic System

• Lymph
• a fluid similar to plasma
• does not have plasma proteins
• Lymphatic vessels (lymphatics)
• network that carries lymph from peripheral
  tissues to the venous system
• Lymphoid tissues and lymphoid organs
• found throughout the body
• Lymphocytes, phagocytes, and other immune system
  cells

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Function of the Lymphatic System

• To produce, maintain, and distribute lymphocytes-
• Lymphocyte Production
• - Lymphocytes are produced
• in lymphoid tissues (e.g., tonsils)
• lymphoid organs (e.g., spleen, thymus)
• and in red bone marrow
• Lymphocytes Distribution
• detect problems
• travel into site of injury or infection

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Lymphocyte Circulation

• From blood to interstitial fluid (lymph) through
  capillaries
• Returns to venous blood through lymphatic vessels

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The Circulation of Fluids

• From blood plasma to lymph and back to the venous
  system
• Also transports hormones, nutrients, and waste
  products

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Lymphatic Vessels

• Are vessels that carry lymph
• Lymphatic system begins with smallest vessels
  lymphatic capillaries (terminal lymphatics)
• Lymphatic Capillaries-
• Differ from blood capillaries in 4 ways
• start as pockets rather than tubes
• have larger diameters
• have thinner walls
• flat or irregular in section

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Lymphatic Capillaries
Endothelial cells loosely bound together with
overlap Overlap acts as one-way valve allows
fluids, solutes, viruses, and bacteria to
enter prevents return to intercellular space
Figure 222
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Lacteals

• Are special lymphatic capillaries in small
  intestine
• Transport lipids from digestive tract

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Lymphatic Vessels and Valves
Figure 223
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Lymph Flow

• From lymphatic capillaries to larger lymphatic
  vessels containing one-way valves
• Lymphatic vessels travel with veins

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Lymphatic Ducts and the Venous System
Figure 224
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The Lymphatic System

• Is divided into
• 1) Superficial lymphatics - located in
• skin
• mucus membranes
• serous membranes lining body
• 2) Deep lymphatics- Are larger vessels that
  accompany deep arteries and veins

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Superficial and Deep Lymphatics

• Join to form large lymphatic trunks
• Trunks empty into 2 major collecting vessels
• thoracic duct
• right lymphatic duct

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The Inferior Thoracic Duct

• Collects lymph from
• left bronchiomediastinal trunk
• left subclavian trunk
• left jugular trunk
• Empties into left subclavian vein
• The Right Lymphatic Duct
• Collects lymph from
• right jugular trunk
• right subclavian trunk
• right bronchiomediastinal trunk
• Empties into right subclavian vein

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Lymphedema

• Blockage of lymph drainage from a limb
• Causes severe swelling
• Interferes with immune system function

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Why are lymphocytes important, and how are they
distributed in the body?

• Lymphocytes
• Make up 2030 of circulating leukocytes
• Most are stored, not circulating

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3 Classes of Circulating Lymphocytes

• T cells thymus-dependent
• Make up 80 of circulating lymphocytes
• 2. B cells bonemarrow derived
• Make up 1015 of circulating lymphocytes
• Differentiate into plasma cells- Produce and
  secrete antibodies (immunoglobin proteins)
• 3. NK cells
• natural killer cells

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3 Main Types of T Cells

• Cytotoxic T cells-Attack cells infected by
  viruses
• Produce cell-mediated immunity
• 2. Helper T cells- Stimulate function of T cells
  and B cells
• 3. Suppressor T cells-Inhibit function of T
  cells and B cells

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Regulatory T Cells

• Are helper and suppressor T cells
• Control sensitivity of immune response
• Other T Cells
• Inflammatory T cells
• Suppressor and inducer T cells

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Antigens

• Targets which identify any pathogen or foreign
  compound
• Immunoglobin Proteins (Igs)
• Also called antibodies (Ab)
• The binding of a specific antibody to its
  specific target antigen initiates
  antibody-mediated immunity
• - A chain of events which destroys the target
  compound or organism

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Natural Killer (NK) Cells

• Also called large granular lymphocytes
• Make up 510 of circulating lymphocytes
• Responsible for immunological surveillance
• Attack
• foreign cells
• virus-infected cells
• cancer cells

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Lymphocyte Distribution

• Tissues maintain different T cell and B cell
  populations
• Lymphocytes wander through tissues
• enter blood vessels or lymphatics for transport
• can survive many years

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Production and Distribution of Lymphocytes
Figure 225
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Lymphopoiesis

• Lymphocyte production involves
• bone marrow
• thymus
• peripheral lymphoid tissues
• Hemocytoblasts In bone marrow, divide into 2
  types of lymphoid stem cells

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Lymphoid Stem Cells

• Group 1
• remain in bone marrow
• produce B cells and natural killer cells
• Group 2
• migrate to thymus
• produce T cells in environment isolated by
  blood-thymus barrier

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T Cells and B Cells

• Migrate throughout the body
• to defend peripheral tissues
• Retain their ability to divide
• is essential to immune system function

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Differentiation

• B cells differentiate
• with exposure to hormone interleukin-7
• T cells differentiate
• with exposure to several thymic hormones
• Interleukin-7 - A cytokine produced by stromal
  cells in bone marrow

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What are the structures and functions of
lymphoid tissues and organs?Lymphoid Tissues
Connective tissues dominated by lymphocytes
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Lymphoid Nodules
Figure 226
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Lymphoid Nodule

• Areolar tissue with densely packed lymphocytes
• Germinal center contains dividing lymphocytes

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Distribution of Lymphoid Nodules

• Lymph nodes
• Spleen
• Respiratory tract (tonsils)
• Along digestive and urinary tracts

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Mucosa-Associated Lymphoid Tissue (MALT)

• Lymphoid tissues associated with the digestive
  system
• aggregated lymphoid nodules
• clustered deep to intestinal epithelial lining
• Appendix
• mass of fused lymphoid nodules

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The 5 Tonsils

• In wall of pharynx
• left and right palatine tonsils
• pharyngeal tonsil (adenoid)
• 2 lingual tonsils

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Lymphoid Organs

• Lymph nodes
• Thymus
• Spleen
• Are separated from surrounding tissues
• By a fibrous connective-tissue capsule

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Lymph Nodes

• Range from 125 mm diameter

Figure 227
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Afferent Lymphatic Vessels

• Carry lymph
• from peripheral tissues to lymph node
• Efferent Lymphatic Vessels
• Leave lymph node at hilus
• Carry lymph to venous circulation

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Lymph from Afferent Lymphatics

• Flows through lymph node in a network of sinuses
• From subcapsular sinus
• contains macrophages and dendritic cells
• Through outer cortex
• contains B cells within germinal centers
• Through deep cortex
• dominated by T cells
• Through the core (medulla)
• contains B cells and plasma cells
• organized into medullary cords
• Into hilus and efferent lymphatics

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Lymph Node

• A filter
• purifies lymph before return to venous
  circulation
• Removes
• debris
• pathogens
• 99 of antigens

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Antigen Presentation

• First step in immune response
• Extracted antigens are presented to
  lymphocytes
• or attached to dendritic cells to stimulate
  lymphocytes

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Lymphoid Functions

• Lymphoid tissues and lymph nodes
• distributed to monitor peripheral infections
• respond before infections reach vital organs of
  trunk

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Lymph Nodes of Gut, Trachea, Lungs, and Thoracic
Duct

• Protect against pathogens in digestive and
  respiratory systems
• Lymph Glands
• Large lymph nodes at groin and base of neck
• Swell in response to inflammation

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Lymphadenopathy

• Chronic or excessive enlargement of lymph nodes
  may indicate infections, endocrine disorders, or
  cancer

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The Thymus
Figure 228
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The Thymus

• Located in mediastinum
• Deteriorates after puberty
• diminishing effectiveness of immune system
• Divisions of the Thymus Thymus is divided into 2
  thymic lobes
• Septa divide lobes into smaller lobules

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A Thymic Lobule

• Contains a dense outer cortex
• And a pale central medulla
• Thymus Hormones
• Thymosins
• Promote development of lymphocytes

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Lymphocytes

• Divide in the cortex
• T cells migrate into medulla
• Mature T cells leave thymus by medullary blood
  vessels

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Reticular Epithelial Cells in the Cortex

• Surround lymphocytes in cortex
• Maintain blood-thymus barrier
• Secrete thymic hormones that stimulate
• stem cell divisions
• T cell differentiation

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Reticular Epithelial Cells in the Medulla

• Form concentric layers (Hassalls corpuscles)
• The medulla has no bloodthymus barrier
• T cells can enter or leave bloodstream

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The Spleen
Figure 229
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3 Functions of the Spleen

• Removal of abnormal blood cells and other blood
  components by phagocytosis
• Storage of iron recycled from red blood cells
• Initiation of immune responses by B cells and T
  cells
• in response to antigens in circulating blood

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Structure of the Spleen

• Attached to stomach by gastrosplenic ligament
• Contacts diaphragm and left kidney
• Splenic veins, arteries, and lymphatic vessels
• communicate with spleen at hilus

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Structure of the Spleen

• Inside fibrous capsule
• Red pulp contains many red blood cells
• Contains elements of circulating blood plus
  fixed free macrophages
• White pulp resembles lymphoid nodules

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Trabecular Arteries

• Branch and radiate toward capsule
• Finer branches surrounded by white pulp
• Capillaries discharge red blood cells into red
  pulp

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Splenic Circulation

• Blood passes through
• network of reticular fibers
• Then enters large sinusoids (lined by
  macrophages)
• which empty into trabecular veins

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Spleen Function

• Phagocytes and other lymphocytes in spleen
• identify and attack damaged and infected cells
• in circulating blood

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Body Defenses

• Provide resistance to fight infection, illness,
  and disease
• 2 categories of defenses
• nonspecific defenses Always work the same way ,
  against any type of invading agent
• specific defenses Protect against specific
  pathogens
• Depend on activities of lymphocytes
• Specific resistance (immunity)
• develops after exposure to environmental hazards

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7 Types of Nonspecific Resistance

• Physical barriers
• Phagocytic cells
• Immunological surveillance
• Interferons
• Complement
• Inflammation
• Fever

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Nonspecific and Specific Defenses

• Operate together to provide resistance to
  infection and disease

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The 7 Nonspecific Defenses
Figure 2210
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The 7 Nonspecific Defenses

• Physical Barriers -Keep hazardous materials
  outside the body
• Phagocytes -Attack and remove dangerous
  microorganisms
• Immunological Surveillance -Constantly monitors
  normal tissues
• with natural killer cells (NK cells)
• Interferons -Trigger production of antiviral
  proteins in normal cells
• Antiviral proteins
• do not kill viruses
• block replication in cell

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The 7 Nonspecific Defenses

• Complement (C) Proteins -Form the complement
  system
• Complements action of antibodies
• Inflammation -Triggers a complex inflammatory
  response
• Fever -A high body temperature
• increases body metabolism
• accelerates defenses
• inhibits some viruses and bacteria

Immunity Complement
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What are the components and mechanisms of each
nonspecific defense?
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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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2 Classes of Phagocytes

• Microphages neutrophils and eosinophils
• Leave the bloodstream
• Enter peripheral tissues to fight infections
• Macrophages large phagocytic cells derived from
  monocytes
• Distributed throughout body
• Make up monocytemacrophage 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

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2 Types of Macrophages

• Fixed macrophages - also called histocytes
  Microglia
• found in central nervous system
• Kupffer cells
• found in liver sinusoids
• Stay in specific tissues or organs
• e.g., dermis and bone marrow
• Free macrophages -Travel through blood stream
• Special free macrophages
• alveolar macrophages (phagocytic dust cells)

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3 Functional Characteristics of Free Macrophages
and Microphages

• 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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Natural Killer Cell Function
Immunological Surveillance is carried out by
Natural killer (NK) cells
Figure 2211
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NK Cell Function

• Identifies and attaches to abnormal cell
  (non-selective)
• Golgi apparatus in NK cell
• forms perforin vesicles
• Vesicles release perforin (exocytosis)
• Perforin lyses abnormal cell membrane

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NK Cells attack cancer cells and cells
infected with viruses

• 1) Cancer Cells -with tumor specific antigens
• are identified as abnormal by NK cells
• some cancer cells avoid NK cells (immunological
  escape)
• 2) Viral Infections Cells infected with
  viruses
• present abnormal proteins on cell membranes
• allow NK cells to identify and destroy them

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Interferons

• Proteins (cytokines) released by activated
  lymphocytes and macrophages-
• Cytokines - Chemical messengers released by
  tissue cells
• to coordinate local activities
• to act as hormones to affect whole body

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3 Types of Interferons

• Alpha interferons
• produced by leukocytes
• stimulate NK cells
• Beta interferons
• secreted by fibroblasts
• slow inflammation
• Gamma interferons
• secreted by T cells and NK cells
• stimulate macrophage activity

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Complement Activation
Complement Plasma contains 11 special complement
(C) proteins that complement antibody action
Figure 2212
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Complement Activation

• Complements work together in cascades
• 2 pathways activate the complement system
• classical pathway
• alternative pathway

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The Classical Pathway

• Fast method
• C1 binds to antibody molecule attached to antigen
  (bacterium)
• Bound protein acts as enzyme
• catalyzes chain reaction

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The Alternative Pathway

• Slow method
• Exposed to antigen
• factor P (properdin)
• factor B
• and factor D interact in plasma
• Both pathways end with
• conversion of inactive complement protein (C3)
• to active form (C3b)

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4 Effects of Complement Activation

• Stimulation of inflammation
• Attraction of phagocytes
• Enhancement of phagocytosis by opsonization
• complements working with antibodies (opsonins)
• Destruction of target cell membranes
• 5 complement proteins join to form membrane
  attack complex (MAC)

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Inflammation

• Also called inflammatory response
• A localized response
• Triggered by any stimulus that kills cells or
  injures tissue

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Cardinal Signs and Symptoms

• Swelling (tumor)
• Redness (rubor)
• Heat (calor)
• Pain (dolor)

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3 Effects of Inflammation

• Temporary repair and barrier against pathogens
• Retards spread of pathogens into surrounding
  areas
• Mobilization of local and systemic defenses
• and facilitation of repairs (regeneration)

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Inflammation and Tissue Repair
Figure 2213
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Inflammation and Tissue Repair

• Injured cells release
• prostaglandins
• proteins
• potassium ions
• Changes interstitial environment and stimulates
  mast cells
• Mast cells release
• histamine (increases capillary permeability)
• heparin (inhibits clotting

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Inflammation and Tissue Repair

• Increased blood flow
• raises local temperature
• causes area to swell, redden, and become painful
• Blood clot forms around damaged area, isolating
  it
• Complements
• break down bacteria
• attract phagocytes

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Inflammation and Tissue Repair

• Activated neutrophils attack debris and bacteria
• Phagocytes and foreign proteins
• activate bodys specific defense system
• Macrophages clean up pathogens and cell debris
• Fibroblasts form scar tissue

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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

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Fever - A maintained body temperature above 37C
(99F)

• Pyrogens - Any material that causes the
  hypothalamus to raise body temperature
• circulating pathogens, toxins, or antibody
  complexes
• Endogenous Pyrogens Interleukin-1 (IL-1)
• pyrogen released by active macrophages
• a cytokine

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Forms of Immunity
Figure 2214
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Specific Defenses

• Specific resistance (immunity)
• responds to specific antigens
• with coordinated action of T cells and B cells

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T Cells

• Provide cell-mediated immunity
• Defends against abnormal cells and pathogens
  inside cells

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B Cells

• Provide antibody-mediated immunity
• Defends against antigens and pathogens in body
  fluids

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Forms of Immunity

• 1) Innate Immunity
• present at birth
• 2) Acquired Immunity
• after birth
• Active
• antibodies develop after exposure to antigen
• Passive
• antibodies are transferred from another source

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Active Immunity

• Naturally acquired
• through environmental exposure to pathogens
• Induced
• through vaccines containing pathogens

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Passive Immunity

• Naturally acquired
• antibodies acquired from the mother
• Induced
• by an injection of antibodies

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4 Properties of Immunity

• Specificity- Each T or B cell
• responds only to a specific antigen, ignores all
  others
• Versatility-The body produces many types of
  lymphocytes
• each fights a different type of antigen (Ag)
• active lymphocyte clones itself to fight specific
  Ag
• Memory-Some active lymphocytes (memory cells)
• stay in circulation
• provide immunity against new exposure
• Tolerance- Immune system ignores normal
  antigens

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What are the differences between cell-mediated
(cellular) immunity and antibody-mediated
(humoral) immunity?
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The Immune Response
Figure 2215 (Navigator)
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The Immune Response

• 2 main divisions
• cell mediated immunity (T cells)
• antibody mediated immunity (B cells)

Immunity Cell-Mediated Immunity
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What are the types of T cells and their
functions in the immune response?
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What are the types of T cells and their
functions in the immune response?

• 1) Cytotoxic T Cells also called Tc cells
• Attack cells infected by viruses
• Responsible for cell-mediated immunity
• 2) Helper T Cells also called Th cells
• Stimulate function of T cells and B cells
• 3) Suppressor T Cells also called Ts cells
• Inhibit function of T cells and B cells

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Antigens and MHC Proteins
Antigens and MHC Proteins
PLAY
Figure 2216a (Navigator)
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Antigen Recognition

• T cells only recognize antigens that are bound to
  glycoproteins in cell membranes

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Antigen Presentation
Figure 2216b
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MHC Proteins

• The membrane glycoproteins that bind to antigens
• Genetically coded in chromosome 6
• the major histocompatibility complex (MHC)
• differs among individuals

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2 Classes of MHC Proteins

• Class I found in membranes of all nucleated
  cells
• Pick up small peptides in cell and carry them to
  the surface
• T cells ignore normal peptides
• abnormal peptides or viral proteins activate T
  cells to destroy cell
• Class II found in membranes of
  antigen-presenting cells (APCs)
• found in lymphocytes Antigenic fragments
• from antigenic processing of pathogens
• bind to Class II proteins
• inserted in cell membrane to stimulate T cells

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Antigen-Presenting Cells (APCs)

• Responsible for activating T cells against
  foreign cells and proteins
• Phagocytic APCs
• Free and fixed macrophages
• in connective tissues
• Kupffer cells
• of the liver
• Microglia
• in the CNS

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Pinocytic APCs

• Langerhans cells
• in the skin
• Dendritic cells
• in lymph nodes and spleen

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What are the mechanisms of T cell activation and
the differentiation of the major classes of T
cells?
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An Overview of the Immune Response
Figure 2215 (Navigator)
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Antigen Recognition

• Inactive T cell receptors
• recognize Class I or Class II MHC proteins
• recognize a specific antigen
• Binding occurs when MHC protein matches antigen

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CD Markers

• Also called cluster of differentiation markers
• in T cell membranes
• molecular mechanism of antigen recognition
• more than 70 types
• designated by an identifying number
• CD3 Receptor Complex
• Found in all T cells

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CD8 Markers

• Found on cytotoxic T cells and suppressor T cells
• Respond to antigens on Class I MHC proteins
• CD4 Markers
• Found on helper T cells
• Respond to antigens on Class II MHC proteins
• CD8 or CD4 Markers - Bind to CD3 receptor complex
• Prepare cell for activation

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Costimulation

• For T cell to be activated, it must be
  costimulated
• by binding to stimulating cell at second site
• which confirms the first signal

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2 Classes of CD8 T Cells

• Activated by exposure to antigens on MHC
  proteins
• one responds quickly
• producing cytotoxic T cells and memory T cells
• the other responds slowly
• producing suppressor T cells

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Activation of Cytotoxic T Cells
Also called killer T cells Seek out and
immediately destroy target cells
Figure 2217 (Navigator)
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Actions of Cytotoxic T Cells

• Release perforin
• to destroy antigenic cell membrane
• Secrete poisonous lymphotoxin
• to destroy target cell
• Activate genes in target cell
• that cause cell to die

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Slow Response

• Can take up to 2 days from time of first exposure
  to an antigen, for cytotoxic T cells to reach
  effective levels

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Memory Tc Cells

• Produced with cytotoxic T cells
• Stay in circulation
• Immediately form cytotoxic T cells
• if same antigen appears again

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Suppressor T Cells

• Secrete suppression factors
• Inhibit responses of T and B cells
• After initial immune response
• Limit immune reaction to single stimulus

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Activation of Helper T Cells
Helper T Cells - Activated CD4 T cells divide
into active helper T cells secrete cytokines
memory T cells remain in reserve
Figure 2218
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4 Functions of Cytokines

• Stimulate T cell divisions
• produce memory T cells
• accelerate cytotoxic T cell maturation
• Attract and stimulate macrophages
• Attract and stimulate NK cells
• Promote activation of B cells

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Pathways of T Cell Activation
Figure 2219
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KEY CONCEPT

• Cell-mediated immunity involves close physical
  contact between activated Tc cells and foreign,
  abnormal or infected cells
• T cell activation usually involves
• antigen presentation by phagocytic cell
• costimulation by cytokines from active phagocytes
  
• Tc cells may destroy target cells through local
  release of cytokines, lymphotoxins, or perforin

130
What are the mechanisms of B cell activation and
the differentiation of plasma cells and memory B
cells?
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B Cells

• Responsible for antibody-mediated immunity
• Attack antigens by producing specific antibodies
• Millions of populations, each with different
  antibody molecules

Immunity Antibody-Mediated Immunity
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B Cell Sensitization

• Corresponding antigens in interstitial fluids
  bind to B cell receptors
• B cell prepares for activation
• Preparation process is sensitization

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B Cell Sensitization and Activation
During sensitization, antigens are taken into
the B cell, processed, reappear on surface,
bound to Class II MHC protein
PLAY
Figure 2220 (Navigator)
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Helper T Cells

• Sensitized B cell is prepared for activation, but
  needs helper T cell activated by same antigen
• B Cell Activation
• Helper T cell binds to MHC complex
• secretes cytokines that promote B cell activation
  and division

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B Cell Division

• Activated B cell divides into
• plasma cells -Synthesize and secrete antibodies
  into interstitial fluid
• Memory B cells- Like memory T cells remain in
  reserve to respond to next infection

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Antibody Structure
What is the structure of an antibody, and what
types of antibodies are found in body fluids and
secretions
Figure 2221a, b
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Antibody Structure

• 2 parallel pairs of polypeptide chains
• 1 pair of heavy chains
• 1 pair of light chains
• Each chain contains
• constant segments
• variable segments-Determine specificity of
  antibody molecule

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5 Heavy-Chain Constant Segments

• Determine 5 types of antibodies
• IgG
• IgE
• IgD
• IgM
• IgA

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Binding Sites

• Free tips of 2 variable segments
• form antigen binding sites of antibody molecule
• which bind to antigenic determinant sites of
  antigen molecule

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Antibody Function

• AntigenAntibody Complex An antibody bound to
  an antigen

Figure 2221c, d
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A Complete Antigen

• Has 2 antigenic determinant sites
• Binds to both of antigen binding sites of
  variable segments of antibody
• Exposure to a complete antigen leads to
• B cell sensitization
• immune response

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A Hapten

• Also called partial antigen
• Must attach to a carrier molecule to act as a
  complete antigen
• Dangers of Haptens
• Antibodies produced attack both hapten and
  carrier molecule
• If carrier is normal
• antibody attacks normal cells
• e.g., penicillin allergy

143
5 Classes of Antibodies
Table 221
144
5 Classes of Antibodies

• Also called immunoglobins (Igs)
• Are found in body fluids
• Are determined by constant segments
• Have no effect on antibody specificity

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7 Functions of AntigenAntibody Complexes

• Neutralization of antigen binding sites
• Precipitation and agglutination
• formation of immune complex
• Activation of complement
• Attraction of phagocytes
• Opsonization
• increasing phagocyte efficiency
• Stimulation of inflammation
• Prevention of bacterial and viral adhesion

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KEY CONCEPT

• Antibody-mediated immunity involves the
  production of specific antibodies by plasma cells
  derived from activated B cells
• B cell activation usually involves
• antigen recognition, through binding to surface
  antibodies, costimulation by a Th cell
• Antibodies produced by active plasma cells bind
  to target antigen and
• inhibit its activity or destroy it
• remove it from solution
• promote its phagocytosis by other defense cells

147
Primary and Secondary Responses

• Occur in both cell-mediated and antibody-mediated
  immunity

Figure 2222
148
Primary and Secondary Responses to Antigen
Exposure

• First exposure
• produces initial response (Primary)
• Next exposure
• triggers secondary response
• more extensive and prolonged
• memory cells already primed

149
The Primary Response

• Takes time to develop
• Antigens activate B cells
• Plasma cells differentiate
• Antibody titer slowly rises
• Peak response
• can take 2 weeks to develop
• declines rapidly
• IgM
• is produced faster than IgG
• is less effective

150
The Secondary Response

• Activates memory B cells
• at lower antigen concentrations than original B
  cells
• secrete antibodies in massive qualities
• Effects of Memory B Cell Activation
• IgG
• rises very high and very quickly
• can remain elevated for extended time
• IgM
• production is also quicker
• slightly extended

151
KEY CONCEPT

• Immunization produces a primary response to a
  specific antigen under controlled conditions
• If the same antigen appears at a later date, it
  triggers a powerful secondary response that is
  usually sufficient to prevent infection and
  disease

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Summary of the Immune Response

• Specific and nonspecific defenses

Figure 2223
153
Body Responses to Bacterial Infection
Figure 2224
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Combined Immune System Responses
Figure 2225
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Combined Responses to Bacterial Infection

• Neutrophils and NK cells begin killing bacteria
• Cytokines draw phagocytes to area
• Antigen presentation activates
• helper T cells
• cytotoxic T cells
• B cells activate and differentiate
• Plasma cells increase antibody levels

156
Combined Responses to Viral Infection

• Similar to bacterial infection
• But cytotoxic T cells and NK cells are activated
  by contact with virus-infected cells

157
Summary Cells of the Immune System
Table 222
158
KEY CONCEPT

• Viruses replicate inside cells, whereas bacteria
  may live independently
• Antibodies (and administered antibiotics) work
  outside cells, so are primarily effective against
  bacteria rather than viruses
• Antibiotics cannot fight the common cold or flu
• T cells, NK cells, and interferons are the
  primary defense against viral infection

159
What is the origin, development, activation, and
regulation of normal resistance to disease?
160
Immune System Development

• Fetus can produce immune response or
  immunological competence
• after exposure to antigen
• at about 34 months

161
Development of Immunological Competence

• Fetal thymus cells migrate to tissues that form T
  cells
• Liver and bone marrow produce B cells
• 4-month fetus produces IgM antibodies

162
Before Birth

• Maternal IgG antibodies
• pass through placenta
• provide passive immunity to fetus
• After Birth
• Mothers milk provides IgA antibodies
• while passive immunity is lost

163
Normal Resistance

• Infant produces IgG antibodies through exposure
  to antigens
• Antibody, B-cell, and T-cell levels slowly rise
  to adult levels
• about age 12

164
Hormones of the Immune System
Table 223
165
6 Groups of Hormonal Cytokines

• Interleukins
• Interferons
• Tumor necrosis factors
• Chemicals that regulate phagocytic activities
• Colony stimulating factors
• Miscellaneous cytokines

166
What are the origins of autoimmune disorders,
immunodeficiency diseases, and allergies, and
what are some examples of each?
167
Immune Disorders

• Autoimmune disorders- A malfunction of system
  that recognizes and ignores normal antigens
• Activated B cells make autoantibodies against
  body cells
• Immunodeficiency disease-
• Thyroiditis
• Rheumatoid arthritis
• Insulin-dependent diabetes mellitus
• Allergies -

168
Immunodeficiency Diseases

• Problems with embryological development of
  lymphoid tissues
• can result in severe combined immunodeficiency
  disease (SCID)
• Viral infections such as HIV
• can result in AIDS
• Immunosuppressive drugs or radiation treatments
• can lead to complete immunological failure

169
Allergies

• Inappropriate or excessive immune responses to
  antigens
• Allergens
• antigens that trigger allergic reactions

170
4 Categories of Allergic Reactions

• Type I
• immediate hypersensitivity
• Type II
• cytotoxic reactions
• Type III
• immune complex disorders
• Type IV
• delayed hypersensitivity

171
Type I Allergy (1)

• Also called immediate hypersensitivity
• A rapid and severe response to the presence of an
  antigen
• Most commonly recognized type of allergy
• Includes allergic rhinitis (environmental
  allergies)
• Sensitization leads to
• production of large quantities of IgE antibodies
• distributed throughout the body
• Second exposure leads to
• massive inflammation of affected tissues

172
Type I Allergy (2)

• Severity of reaction depends on
• individual sensitivity
• locations involved
• Allergens in blood stream may cause anaphylaxis

173
Anaphylaxis

• Can be fatal
• Affects cells throughout body
• Changes capillary permeability
• produce swelling (hives) on skin
• Smooth muscles of respiratory system contract
• make breathing difficult
• Peripheral vasodilatation
• can cause circulatory collapse (anaphylactic
  shock)

174
Antihistamine Drugs

• Block histamine released by MAST cells
• Can relive mild symptoms of immediate
  hypersensitivity

175
Stress and the Immune Response

• Glucocorticoids
• secreted to limit immune response
• long-term secretion (chronic stress)
• inhibits immune response
• lowers resistance to disease

176
Functions of Glucocorticoids

• Depression of the inflammatory response
• Reduction in abundance and activity of phagocytes
• Inhibition of interleukin secretion

177
Aging and the Immune Response

• Immune system deteriorates with age, increasing
  vulnerability to infections and cancer

178
4 Effects of Aging on Immune Response

• Thymic hormone production
• greatly reduced
• T cells
• become less responsive to antigens
• Fewer T cells reduce responsiveness of B cells
• Immune surveillance against tumor cells declines

179
Integration with Other Systems
Nervous and Endocrine Systems Interact with
thymic hormones Adjust sensitivity of immune
Figure 2227
180
Disorders of the Lymphatic System

• 3 categories affect immune response
• disorders resulting from
• an insufficient immune response
• an inappropriate immune response
• an excessive immune response

181
SUMMARY (1)

• Divisions of the lymphatic system
• lymphatic vessels (lymphatics)
• lymph
• lymphoid tissues and organs
• Types of lymphocytes
• T cells
• B cells
• NK cells
• Lymphoid tissues and organs
• Nodules nodes
• MALT thymus
• spleen

182
SUMMARY (2)

• 7 nonspecific defenses
• physical barriers
• phagocytes
• immunological surveillance
• interferons
• complement
• inflammation
• fever

183
SUMMARY (3)

• Specific defenses
• cell-mediated immunity
• antibody mediated immunity
• Forms of immunity
• innate or acquired
• active or passive
• Properties of immunity
• specificity, versatility, memory, andtolerance

184
SUMMARY (4)

• T cells and cell-mediated immunity
• antigen presentation
• MHCs and APCs
• antigen recognition
• CD8 T cell activation
• CD4 T cell activation

185
SUMMARY (5)

• B cells and antibody-mediated immunity
• sensitization
• plasma cells and memory B cells
• antibody structure
• antigenantibody complex
• 5 classes of immunoglobins

186
SUMMARY (6)

• Primary and secondary responses to antigen
  exposure
• Hormones and the immune system
• interleukins, interferons, TNFs, and CSFs
• Immune disorders
• Effects of aging on the immune response