The Lymphatic System and Body Defenses

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

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

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

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

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

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

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

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)

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

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

Functions of Cells and Molecules Involved in Immunity

Table 12.3 (2 of 2)

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)

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)

Humoral Immune ResponseSecondary humoral responses

Memory cells are long-livedA second exposure causes a rapid responseThe secondary response is stronger and

longer lasting

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)

Figure 12.13

Humoral Immune Response

Active ImmunityOccurs when B cells encounter antigens

and produce antibodiesActive immunity can be

Naturally acquired during bacterial and viral infections

Artificially acquired from vaccines

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”

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

Types of Acquired Immunity

Figure 12.14

Antibodies (Immunoglobulins or Igs)Soluble proteins secreted by B cells

(plasma cells)Carried in blood plasmaCapable of binding specifically to an

antigen

Figure 12.15a

Antibodies (Immunoglobulins or Igs)

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

Antibody Structure

Figure 12.15b

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

Table 12.2

Immunoglobin Classes

AntibodiesAntibody function

Antibodies inactivate antigens in a number of waysComplement fixationNeutralizationAgglutinationPrecipitation

Antibody Function

Figure 12.16

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

Cellular (Cell-Mediated) Immune Response

Figure 12.17

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

Cellular (Cell-Mediated) Immune Response

Figure 12.18

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

Functions of Cells and Molecules

Involved in Immunity

Table 12.3 (1 of 2)

Functions of Cells and Molecules

Involved in Immunity

Table 12.3 (2 of 2)

Figure 12.19

Summary of Adaptive Immune Response

Figure 12.19 (1 of 2)

Summary of Adaptive Immune Response

Figure 12.19 (2 of 2)

Summary of Adaptive Immune Response

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

Organ Transplants and RejectionAutografts and isografts are ideal donorsXenografts are never successfulAllografts are more successful with a closer

tissue match

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

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

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

Disorders of Immunity: ImmunodeficienciesProduction or function of immune cells or

complement is abnormalMay be congenital or acquiredIncludes AIDS (Acquired Immune Deficiency

Syndrome)

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

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

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

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

Self Tolerance BreakdownCross-reaction of antibodies produced

against foreign antigens with self-antigensRheumatic fever

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