The Lymphatic System and Immunity Chapter 21 Lecture Notes

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The Lymphatic System and ImmunityChapter 21
Lecture Notes

• to accompany
• Anatomy and Physiology From Science to Life
• textbook by
• Gail Jenkins, Christopher Kemnitz, Gerard Tortora

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Chapter Overview

• 21.1 Lymphatic System
• 21.2 One-way Lymphatic Flow
• 21.3 Lymphatic Organs
• 21.4 Nonspecific Resistance
• 21.5 Specific Defenses
• 21.6 Cell-mediated Immunity
• 21.7 Antibody-mediated Immunity
• 21.8 Complement System
• 21.9 Immunization

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Essential Terms

• pathogen
• disease-producing microbes
• resistance
• ability to defend against damage or disease
• susceptibility
• lack of resistance
• nonspecific resistance/innate defenses
• provide immediate and general protection
• specific resistance/immunity
• develops in response to particular invader

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Introduction

• Lymphatic System and Immunity
• Circulates body fluids and defends against
  disease-causing agents
• Innate defenses and immunity protect against
  general and specific damage or disease
• Lymphatic system is closely related to
  cardiovascular and digestive systems

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Concept 21.1Lymphatic System
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Lymphatic System

• Vessels and fluid that transport various
  substances
• Help maintain fluid homeostasis
• Tissues contain stem cells that develop into
  various types of blood cells
• Helps defend body against disease-causing agents
• Lymph
• Located within lymphatic vessels and tissue

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Figure 21.1
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Lymphatic Tissue

• Specialized reticular connective tissue
• Lymphocytes
• B cells
• T cells

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Functions of Lymphatic Tissue

• Drain excess interstitial fluid
• Transport dietary lipids
• Carry out immune responses

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Concept 21.2 One-way Lymphatic Flow
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Lymphatic Vessels

• Lymphatic capillaries
• Tiny and located between cells
• Closed at one end
• Lymphatic vessels
• Thinner walls than veins
• More valves than veins
• Lymphatic nodes
• Lymph flows through masses of B and T cells

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Figure 21.2
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Lymphatic capillaries

• Larger diameter than blood capillaries
• Overlapping endothelial cells
• Pressure from interstitial fluid causes cells to
  separate allowing fluid in
• Pressure within vessels causes cells to press
  closer together preventing outflow of lymph
• Anchoring filaments

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Lymph Trunks

• Lymph trunks
• Union of vessels exiting most proximal chain of
  lymph nodes
• Meet at one of two main ducts
• Principal Trunks
• Lumbar
• Intestinal
• Bronchomediastinal
• Subclavian
• Jugular

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Figure 21.3
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Thoracic Duct

• Also left lymphatic duct
• Cisterna chyli
• Receives from intestinal and right and left
  lumbar trunks
• Drains lymph to venous blood at junction of left
  internal jugular and left subclavian veins

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Drainage into Thoracic Duct

• Lumbar trunks
• Lower limbs, pelvis, kidneys, adrenal glands,
  deep lymphatic vessels of abdominal wall
• Intestinal trunk
• Stomach, intestines, pancreas, spleen, and liver
• Left jugular
• Left side of head and neck
• Left subclavian trunk
• Upper left limb
• Left bronchomediastinal trunk
• Left side of parts of anterior thoracic wall,
  anterior abdominal wall, diaphragm, left lung,
  and left side of heart

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Right Lymphatic Duct

• Drains into venous blood at junction of right
  internal jugular and right subclavian veins
• Drainage
• Right jugular trunk
• Right side of head and neck
• Right subclavian trunk
• Right upper limb
• Right bronchomediastinal trunk
• Right side of thorax, right lung, right side of
  heart, and liver
• Lymph flow sequence

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Lymph Flow

• Skeletal muscle pump
• Respiratory pump

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Figure 21.4
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Concept 21.3 Lymphatic Organs
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Lymphatic Organs

• Widely distributed
• Two classifications based on function
• Primary lymphatic organs
• Immunocompetent
• Red bone marrow
• Thymus
• Secondary lymphatic organs and tissues
• Immune response
• Lymph nodes
• Spleen
• Lymphatic nodules lack capsule

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Thymus

• Two lobes separated by capsule of connective
  tissue
• Trabeculae separate lobes into lobules
• Cortex
• Types of cells in cortex
• T cells, dendritic, and macrophages
• Epithelial cells
• Produce thymic hormones
• Medulla
• T cells more mature
• Thymic (Hassalls) corpuscles
• Thymus begins to atrophy at puberty
• Populates secondary lymphatic organs and tissues
  with T cells

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Figure 21.5a
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Figure 21.5b
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Figure 21.5c
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Lymph Nodes

• Along lymphatic vessels and scattered throughout
  the body
• Groups near surface regions of
• Cervical area
• Axillary
• Inguinal
• Capsule with trabeculae
• Inner network of reticular fibers and fibroblasts

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Figure 21.6a
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Figure 21.6b
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Figure 21.6c
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Lymph Nodes

• Outer cortex
• Lymphatic nodules of B cells
• Germinal center
• Plasma cells and memory B cell formation
• Memory B cells
• Have memory of specific antigens
• Inner cortex
• T cells and dendritic cells
• Medulla
• B cells, plasma cells, and macrophages
• Reticular fiber and cell network

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Flow Through Lymph Nodes

• Lymph flows one-way through node
• Afferent lymphatic vessels
• Valves direct lymph into node
• Sinuses
• Subcapsular sinus
• Trabecular sinuses
• Medullary sinuses
• Efferent lymphatic vessels
• Valves direct lymph, antibodies, and activated T
  cells out of node
• Hilus

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Spleen

• Largest mass of lymphatic tissue
• Hilus
• Passage for splenic artery, splenic vein and
  efferent lymphatic vessels
• White pulp
• Lymphocytes and macrophages
• Central arteries
• Red pulp
• Venous sinuses
• Splenic cords
• RBCs, macrophages, lymphocytes, plasma cells,
  and granulocytes

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Functions of Spleen

• Macrophage removal of damaged blood cells and
  platelets
• Storage of platelets
• Hemopoiesis of fetus

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Figure 21.7
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Lymphatic Nodules

• Not surrounded by capsule
• MALT (mucosa-associated lymphatic tissue)
• Most solitary but some large aggregates of
  nodules
• Peyers patches
• Tonsils
• Pharyngeal tonsil / adenoid
• Palatine tonsils
• Lingual tonsils

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Concept 21.4 Nonspecific Resistance
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Nonspecific Resistance

• Present at birth
• Immediate protection against variety of pathogens
  and foreign substances
• First line of defense
• Skin and mucous membranes
• Physical and chemical
• Second line of defense
• Antimicrobial proteins, natural killer cells and
  phagocytes, inflammation, and fever

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First Line of Defense

• Epidermis
• Mucous membranes
• Mucous
• Cilia
• Lacrimal apparatus of eyes
• Saliva
• Urine flow
• Vaginal secretions
• Defecation and vomiting
• Sebum
• Perspiration
• Lysozyme
• Gastric juice

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Second Line of Defense

• Antimicrobial proteins
• Interferons (IFNs)
• Antivirals that prevent replication of virus
• Complement system
• Enhance immune reactions
• Transferrins
• Inhibit bacterial growth by reducing available
  iron

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Second Line of Defense

• Natural killer (NK) cells
• 5 10 of lymphocytes
• In spleen, lymph nodes and red bone marrow
• Attack body cells displaying abnormal plasma
  membrane proteins
• Perforin perforates cell membranes
• Granzymes destroy cell proteins
• Phagocytes
• Phagocytosis
• Neutrophils
• Macrophages
• Develop from monocytes
• Wandering
• Fixed

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Second Line of Defense

• 5 phases of phagocytosis
• Chemotaxis
• Adherence
• Ingestion
• Pseudopods
• Phagosome
• Digestion
• Phagolysosome
• Killing
• Residual bodies

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Figure 21.8a
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Figure 21.8b
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Second Line of Defense

• Inflammation
• Redness
• Pain
• Heat
• Swelling
• Stages of response
• Vasodilation and increased permeability of blood
  vessels
• Emigration of phagocytes
• Tissue repair

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Figure 21.9
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Second Line of Defense

• Substances that contribute to inflammatory
  response
• Histamine
• Kinins
• Prostaglandins (PGs)
• Leukotrines (LTs)
• Complement
• Pain symptom of inflammation
• Clotting may also occur

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Second Line of Defense

• Emigration of phagocytes
• Neutrophils emigrate to site of inflammation
• Phagocytosis then death of neutrophil
• Macrophages more competent at phagocytosis
• Pus
• Fever elevated body temperature
• Resetting of hypothalmic thermostat
• Intensifies effects of IFNs
• Inhibits microbe growth
• Speeds up body reactions for repair

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Table 21.1 pt 1
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Table 21.1 pt 2
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Concept 21.5 Specific Defenses
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Specific Resistance or Immunity

• Defense against a particular type of invader
• Antigens (Ags)
• Foreign and provoke response
• Specificity for particular foreign bodies
• Self from non-self
• Memory for previously encountered Ags
• Provokes more rapid and vigorous response
• Immune system

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Maturation of T and B Cells

• Immunocompetence the ability to carry out
  immune response
• Cells develop from pluripotent stem cells of red
  bone marrow
• B cells develop in red bone marrow through life
• T cells mature in thymus
• Antigen receptors
• Able to recognize specific antigens
• CD4 or CD8

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Figure 21.10
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Types of Immune Response

• Cell-mediated immune responses
• CD8 T cells into cytoxic T cells
• Antibody-mediated immune responses
• B cells to plasma cells
• Secrete antibodies (Abs) or immunoglobulins
• Type of response depends on type of invader
• Many pathogens provoke both types

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Types of Immune Response

• Cell-mediated
• Intracellular pathogens
• Cancer cells
• Foreign tissue transplants

• Antibody-mediated
• Antigens in body fluids
• Extracellular pathogens (bacteria)

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Antigens and Antigen Receptors

• Immunogenicity
• Ability to provoke immune response by
• Stimulation production of specific antibodies
• Proliferation of specific T cells
• Antigen antibody generator
• Reactivity
• Ability of antigen to react specifically with
  antibodies or cells it has provoked
• Epitope / antigenic determinants
• Small part of a large antigen which acts as
  trigger for immune response

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Figure 21.11
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Antigens and Antigen Receptors

• Antigen route after successfully bypassing
  nonspecific defenses
• Through blood stream
• Trapped in the spleen
• Penetrate the skin
• Enter lymphatic vessels and lodge in nodes
• Through mucous membranes
• Trapped by MALT

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Chemical Nature of Antigens

• Large complex macromolecules
• Not large repetitive subunit molecules
  (polysaccharides)
• Hapten
• Smaller substance with reactivity but lacks
  immunogenicity
• Able to stimulate response only if attached to
  larger carrier molecule
• Autoimmune disorder

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Major Histocompatibility Complex Antigens

• In plasma membrane of body cells
• MHC
• Unique except identical twins
• Help T cells recognize foreign antigens
• Antigen Processing
• B cells able to bind in fluids without
  presentation requirements
• T cells
• Fragments with MHC complex antigen-MHC complex
• Antigen presentation

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Exogenous Antigens

• Antigens from outside the body
• APCs antigen presenting cells
• Macrophages, B cells, and dendritic cells
• Processing and presenting exogenous antigen
• Phagocytosis of antigen
• Digestion of antigen into peptide fragments
• Synthesis of MHC molecules
• Fusion of vesicles
• Binding of Peptide fragments to MHC molecules
• Insertion of antigen-MHC complex into plasma
  membrane

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Figure 21.12
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Endogenous Antigens

• Synthesized in the body cells
• Antigen fragment-MHC complex
• Movement to plasma membrane
• Cell signals for immune system to respond

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Concept 21.6 Cell-mediated Immunity
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Cell-mediated Immunity

• Activation of T cells by specific antigen
• Proliferation and differentiation
• Clone of effector cells
• Elimination of intruder
• TCRs T cell receptors
• Millions of cells with specific receptors
• Recognize and bind to antigen-MHC complexes
• CD4 and CD8 proteins maintain binding
• First signal

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Cell-mediated Immunity

• Second signal
• Costimulation
• Interleukin-2 (IL-2) cytokine
• Ignition TCR
• First signal
• Gear shift costimulation
• Second signal

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Cell-mediated Immunity

• Activation
• Proliferation
• Differentiation
• Clone
• All the above occur in secondary lymphatic tissue
  and organs

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Figure 21.13
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Types of T Cells

• Helper T cells / CD4 T cells
• CD4
• Secrete cytokines IL-2
• Positive feedback loop
• Cytotoxic T cells / CD8 T cells
• CD8
• Release cytotoxic substances
• Recognize foreign antigen-MHC complex on
• Cells infected by microbes
• Tissue transplant cells
• Some tumor cells

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Types of T Cells

• Memory T cells
• Remain in system after response is finished
• Allow for
• Quicker and
• More vigorous
• Second response to same antigen

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Elimination of Invaders

• Cytotoxic T cells
• Leave secondary lymphatic tissues and organs to
  kill infected target cells
• Virus-infected
• Cancerous
• Transplanted
• Can only kill cells with specific antigens to
  match their receptors

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Figure 21.14
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Elimination of Invaders

• One method
• Granzymes
• Released into cell and triggers apoptosis
• Second method
• Perforin and granulysin
• Perforations of plasma membrane result in
  cytolysis
• Granulysin perforates microbe
• Lymphotoxin destroys DNA of target cell
• Gamma-interferon to attract and activate
  phagocytes

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Concept 21.7 Antibody-mediated Immunity
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Antibody-mediated Immunity

• Response of B cells
• Remain in nodes, spleen or nodules
• Secrete antibodies which circulate in lymphatic
  fluid and blood

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Activation, Proliferation, and Differentiation of
B Cells

• Antigen binds to B-cell receptor
• Intake of antigen for protein digestion
• Peptide antigen-MHC complex
• Recognition by helper T cells
• T cells produce interleukins to costimulate and
  activate B cells
• B cells then
• Proliferate and differentiate into plasma cells
• Release antibodies

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Figure 21.15
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Activation, Proliferation, and Differentiation of
B Cells

• Antibody-secreting plasma cells
• Secrete antibodies for 4 or 5 days
• Cells die
• Some remain as memory B cells
• Each particular clone able to secrete only one
  type of antibody

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Antibodies

• Able to combine specifically with antigen which
  served as trigger
• Antibody Structure

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Antibody / Innumoglobulin Structure

• Igs immunoglobulins
• Group of proteins called globulins
• Four polypeptide chains
• Heavy (H) chains
• Light (L) chains
• Connected by S-S (disulfide) bonds
• Hinge region connected midregion of heavy
  chains
• Either T or Y shape
• Variable (V) region varies for each different
  antibody
• Antigen-binding site
• Bivalent able to bind two epitopes of antigen

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Figure 21.16a
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Figure 21.16b
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Antibody / Innumoglobulin Structure

• Constant (C) region
• Similar to the class of antibody
• Signals type of antigen-antibody response
• Five classes of antibodies
• IgG
• IgA
• IgM
• IgD
• IgE

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Table 21.2
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Antibody Actions

• Neutralizing antigen
• Immobilizing bacteria
• Agglutinating and precipitating antigen
• Activating complement
• Enhancing phagocytosis

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Concept 21.8 Complement System
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Complement System

• Defensive system of over 30 proteins
• Liver produces the proteins
• Circulated in blood plasma and tissues
• Cause cascade reactions
• Destroy microbes by causing
• Phagocytosis
• Cytolysis
• Inflammation
• Preventing excessive tissue damage

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Complement System

• Designation
• Upper case C
• Numbered according to order of discovery
• C1 through C9
• Lower case letter denotes active protein
• C3a or C3b

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Complement System Activation

• Classical Pathway
• Antibody binds to antigen (microbe)
• Alternative pathway
• No antibodies involved
• C3 triggered by interaction of lipid-cabohydrate
  complex on surface of microbes and factors B, D,
  and P
• Lectin pathway
• Proteins (lectins) produced by liver after
  digestion of microbes
• Lectins activate C3

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Figure 21.17
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Complement System

• C3 to C3a and C3b
• C3b binds to microbe, phagocytes bind to C3b
• Opsonization attachment of phagocyte to microbe
• E8 and C9 help form Membrane attack complex
• Cytolysis
• C3a and C5a bind to mast cells release
  histamine
• Inflammation
• Chemotaxis

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Table 21.4
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Concept 21.9 Immunization
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Immunization

• Hallmark Memory for specific antigens that have
  triggered immune responses in the past
• Due to presence of long-lasting antibodies
• Long-lived lymphocytes from antigen-stimulated B
  and T cells
• Second immune response is quicker and more
  intense than first encounter
• Antibody titer amount of antibodies in blood
  plasma

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Figure 21.18
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Immunity

• Primary response
• Secondary response
• Response to microbial invasion
• Immunological memory
• Basis for immunization by vaccination

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Table 21.3
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End Chapter 23