the lymphatic system and body defenses. adaptive defense system: third line of defense immune...
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The Lymphatic System and Body Defenses
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Adaptive Defense System: Third Line of DefenseImmune response is the immune system’s
response to a threatImmunology is the study of immunityAntibodies are proteins that protect from
pathogens
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Adaptive Defense System: Third Line of DefenseThree aspects of adaptive defense
Antigen specific—recognizes and acts against particular foreign substances
Systemic—not restricted to the initial infection site
Memory—recognizes and mounts a stronger attack on previously encountered pathogens
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Adaptive Defense System: Third Line of DefenseTypes of Immunity
Humoral immunity = antibody-mediated immunityProvided by antibodies present in body fluids
Cellular immunity = cell-mediated immunityTargets virus-infected cells, cancer cells, and cells of
foreign grafts
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Adaptive Defense System: Third Line of DefenseAntigens (nonself)
Any substance capable of exciting the immune system and provoking an immune response
Examples of common antigensForeign proteins (strongest)Nucleic acidsLarge carbohydratesSome lipidsPollen grainsMicroorganisms
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Adaptive Defense System: Third Line of DefenseSelf-antigens
Human cells have many surface proteinsOur immune cells do not attack our own
proteinsOur cells in another person’s body can
trigger an immune response because they are foreignRestricts donors for transplants
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Adaptive Defense System: Third Line of DefenseAllergies
Many small molecules (called haptens or incomplete antigens) are not antigenic, but link up with our own proteins
The immune system may recognize and respond to a protein-hapten combination
The immune response is harmful rather than protective because it attacks our own cells
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Adaptive Defense System: Third Line of DefenseCells of the adaptive defense system
Lymphocytes respond to specific antigensB lymphocytes (B cells)T lymphocytes (T cells)
Macrophages help lymphocytes
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Adaptive Defense System: Third Line of DefenseImmunocompetent—cell becomes capable
of responding to a specific antigen by binding to it
Cells of the adaptive defense system Lymphocytes
Originate from hemocytoblasts in the red bone marrow
B lymphocytes become immunocompetent in the bone marrow (remember B for Bone marrow)
T lymphocytes become immunocompetent in the thymus (remember T for Thymus)
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Lymphocyte Differentiation and Activation
Figure 12.11
Site of lymphocyte origin
KEY:
Site of antigen challenge and finaldifferentiation to mature B and T cells
Sites of development ofimmunocompetence as Bor T cells; primary lymphoid organs
Lymphocytes destined to become T cellsmigrate from bone marrow to the thymus and develop immunocompetence there.B cells develop immuno-competence inthe bone marrow.
After leaving the thymus or bone marrowas naive immunocompetent cells,lymphocytes “seed” the infectedconnective tissues (especially lymphoidtissue in the lymph nodes), where theantigen challenge occurs and thelymphocytes become fully activated.
Activated (mature) lymphocytes circulatecontinuously in the bloodstream andlymph, and throughout the lymphoidorgans of the body.
and
Bone marrow
Bone marrow
Lymph nodesand otherlymphoid tissues
ImmaturelymphocytesCirculation
in blood
Immunocompetent,but still naive,lymphocytesmigrate via blood
MatureimmunocompetentB and T cellsrecirculate inblood and lymph
Thymus
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Adaptive Defense System: Third Line of DefenseCells of the adaptive defense system
(continued)Macrophages
Arise from monocytesBecome widely distributed in lymphoid organsSecrete cytokines (proteins important in the immune
response)Tend to remain fixed in the lymphoid organs
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Functions of Cells and Molecules Involved in Immunity
Table 12.3 (2 of 2)
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Humoral (Antibody-Mediated) Immune ResponseB lymphocytes with specific receptors bind
to a specific antigenThe binding event activates the
lymphocyte to undergo clonal selectionA large number of clones are produced
(primary humoral response)
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Humoral Immune ResponseMost B cells become plasma cells
Produce antibodies to destroy antigensActivity lasts for 4 or 5 days
Some B cells become long-lived memory cells (secondary humoral response)
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Humoral Immune ResponseSecondary humoral responses
Memory cells are long-livedA second exposure causes a rapid responseThe secondary response is stronger and
longer lasting
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Figure 12.12
Humoral Immune ResponsePrimary Response(initial encounterwith antigen)
AntigenAntigen bindingto a receptor on aspecific B cell(lymphocyte)(B cells withnon-complementaryreceptors remaininactive)
Proliferation toform a cloneB lymphoblasts
Plasmacells
Secretedantibodymolecules
Clone of cellsidentical toancestral cells
Subsequent challengeby same antigen
MemoryB cell
MemoryB cells
Plasmacells
Secretedantibodymolecules
Secondary Response(can be years later)
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Figure 12.13
Humoral Immune Response
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Active ImmunityOccurs when B cells encounter antigens
and produce antibodiesActive immunity can be
Naturally acquired during bacterial and viral infections
Artificially acquired from vaccines
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Passive ImmunityOccurs when antibodies are obtained from
someone elseConferred naturally from a mother to her
fetus (naturally acquired)Conferred artificially from immune serum or
gamma globulin (artificially acquired)Immunological memory does not occurProtection provided by “borrowed
antibodies”
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Passive ImmunityMonoclonal antibodies
Antibodies prepared for clinical testing or diagnostic services
Produced from descendents of a single cell line
Examples of uses for monoclonal antibodiesDiagnosis of pregnancyTreatment after exposure to hepatitis and rabies
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Types of Acquired Immunity
Figure 12.14
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Antibodies (Immunoglobulins or Igs)Soluble proteins secreted by B cells
(plasma cells)Carried in blood plasmaCapable of binding specifically to an
antigen
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Figure 12.15a
Antibodies (Immunoglobulins or Igs)
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AntibodiesAntibody structure
Four amino acid chains linked by disulfide bonds
Two identical amino acid chains are linked to form a heavy chain
The other two identical chains are light chains
Specific antigen-binding sites are present
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Antibody Structure
Figure 12.15b
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AntibodiesAntibody classes
Antibodies of each class have slightly different roles
Five major immunoglobulin classes (MADGE)IgM—can fix complementIgA—found mainly in mucusIgD—important in activation of B cellIgG—can cross the placental barrier and fix
complementIgE—involved in allergies
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Table 12.2
Immunoglobin Classes
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AntibodiesAntibody function
Antibodies inactivate antigens in a number of waysComplement fixationNeutralizationAgglutinationPrecipitation
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Antibody Function
Figure 12.16
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Cellular (Cell-Mediated) Immune ResponseAntigens must be presented by
macrophages to an immunocompetent T cell (antigen presentation)
T cells must recognize nonself and self (double recognition)
After antigen binding, clones form as with B cells, but different classes of cells are produced
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Cellular (Cell-Mediated) Immune Response
Figure 12.17
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Cellular (Cell-Mediated) Immune ResponseT cell clones
Cytotoxic (killer) T cellsSpecialize in killing infected cellsInsert a toxic chemical (perforin)
Helper T cellsRecruit other cells to fight the invadersInteract directly with B cells
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Cellular (Cell-Mediated) Immune Response
Figure 12.18
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Cellular (Cell-Mediated) Immune ResponseT cell clones (continued)
Regulatory T cellsRelease chemicals to suppress the activity of T and
B cellsStop the immune response to prevent uncontrolled
activityA few members of each clone are memory
cells
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Functions of Cells and Molecules
Involved in Immunity
Table 12.3 (1 of 2)
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Functions of Cells and Molecules
Involved in Immunity
Table 12.3 (2 of 2)
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Figure 12.19
Summary of Adaptive Immune Response
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Figure 12.19 (1 of 2)
Summary of Adaptive Immune Response
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Figure 12.19 (2 of 2)
Summary of Adaptive Immune Response
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Organ Transplants and RejectionMajor types of grafts
Autografts—tissue transplanted from one site to another on the same person
Isografts—tissue grafts from an identical person (identical twin)
Allografts—tissue taken from an unrelated person
Xenografts—tissue taken from a different animal species
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Organ Transplants and RejectionAutografts and isografts are ideal donorsXenografts are never successfulAllografts are more successful with a closer
tissue match
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Disorders of Immunity: Allergies (Hypersensitivity)Abnormal, vigorous immune responsesTypes of allergies
Immediate hypersensitivityTriggered by release of histamine from IgE binding
to mast cellsReactions begin within seconds of contact with
allergenAnaphylactic shock—dangerous, systemic response
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Disorders of Immunity: Allergies (Hypersensitivity)Types of allergies (continued)
Delayed hypersensitivityTriggered by the release of lymphokines from
activated helper T cellsSymptoms usually appear 1–3 days after contact
with antigen
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Allergy Mechanisms
Figure 12.20
Antigen (allergen)invades body
Plasma cellsproduce largeamounts of classIgE antibodiesagainst allergen
Mast cell withfixed IgEantibodies
Granulescontaininghistamine
IgE
IgE antibodiesattach to mastcells in bodytissues (and tocirculatingbasophils)
Sensitization stage
More ofsame allergeninvades body
Allergenbinding to IgEon mast cellstriggers release ofhistamine (andother chemicals)
Histamine causes blood vessels to dilate andbecome leaky, which promotes edema;stimulates release of large amounts of mucus;and causes smooth muscles to contract
Subsequent(secondary)responses
Antigen
Histamine
Mast cellgranules releasecontents afterantigen bindswith IgEantibodies
Outpouringof fluid fromcapillaries
Release ofmucus
Constriction ofbronchioles
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Disorders of Immunity: ImmunodeficienciesProduction or function of immune cells or
complement is abnormalMay be congenital or acquiredIncludes AIDS (Acquired Immune Deficiency
Syndrome)
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Disorders of Immunity: Autoimmune DiseasesThe immune system does not distinguish
between self and nonselfThe body produces antibodies and
sensitized T lymphocytes that attack its own tissues
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Disorders of Immunity: Autoimmune DiseasesExamples of autoimmune diseases
Multiple sclerosis—white matter of brain and spinal cord are destroyed
Myasthenia gravis—impairs communication between nerves and skeletal muscles
Type I diabetes mellitus—destroys pancreatic beta cells that produce insulin
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Disorders of Immunity: Autoimmune DiseasesExamples of autoimmune diseases
Rheumatoid arthritis—destroys jointsSystemic lupus erythematosus (SLE)
Affects kidney, heart, lung and skinGlomerulonephritis—impairment of renal
function
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Self Tolerance BreakdownInefficient lymphocyte programmingAppearance of self-proteins in the
circulation that have not been exposed to the immune systemEggsSpermEye lensProteins in the thyroid gland
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Self Tolerance BreakdownCross-reaction of antibodies produced
against foreign antigens with self-antigensRheumatic fever
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Developmental Aspects of the Lymphatic System and Body DefensesExcept for thymus and spleen, the
lymphoid organs are poorly developed before birth
A newborn has no functioning lymphocytes at birth, only passive immunity from the mother
If lymphatics are removed or lost, severe edema results, but vessels grow back in time