the body’s defenses ch. 43 ap biology ms. haut. nonspecific immunity first line of defense –...

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The Body’s Defenses The Body’s Defenses Ch. 43 AP Biology Ms. Haut

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The Body’s DefensesThe Body’s Defenses

Ch. 43

AP Biology

Ms. Haut

Nonspecific ImmunityNonspecific Immunity

First line of defense– Skin—barrier – Mucous membranes—trap microbes– Secretions—tears, saliva, and mucus contain

antimicrobial proteins (lysozyme)

In the trachea, ciliated epithelial cells– Sweep mucus and any entrapped microbes

upward, preventing the microbes from entering the lungs

Figure 43.3

10m

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Secretions of the skin and mucous membranes– Provide an environment that is often hostile to

microbes

Secretions from the skin– Give the skin a pH between 3 and 5, which is acidic

enough to prevent colonization of many microbes– Also include proteins such as lysozyme, an enzyme

that digests the cell walls of many bacteria

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Nonspecific ImmunityNonspecific Immunity

Second line of defense limits spread of invaders– Phagocytic white blood cells—ingest invading

organisms– Antimicrobial proteins– Inflammatory response – Natural killer cells

Internal Cellular and Chemical Internal Cellular and Chemical DefensesDefenses

Internal cellular defenses– Depend mainly on phagocytosis

Phagocytes, types of white blood cells– Neutrophils, Monocytes, Macrophages,

Eosinophils, Natural killer (NK) cells– Ingest invading microorganisms– Initiate the inflammatory response

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Phagocytic CellsPhagocytic Cells

Phagocytes attach to their prey via surface receptors

– And engulf them, forming a vacuole that fuses with a lysosome

Figure 43.4

Pseudopodiasurroundmicrobes.

1

Microbesare engulfedinto cell.

2

Vacuolecontainingmicrobesforms.

3

Vacuoleand lysosomefuse.

4

Toxiccompoundsand lysosomalenzymesdestroy microbes.

5

Microbialdebris isreleased byexocytosis.

6

Microbes

MACROPHAGE

Vacuole Lysosomecontainingenzymes

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The lymphatic system– Plays an active role in defending the body

from pathogens

Adenoid

Tonsil

Lymphnodes

Spleen

Peyer’s patches(small intestine)

Appendix

Lymphaticvessels

Masses oflymphocytes andmacrophages

Tissuecells

Lymphaticvessel

Bloodcapillary

LymphaticcapillaryInterstitial

fluid

Lymphnode

Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries.

1

Figure 43.5

Fluid inside thelymphatic capillaries,called lymph, flowsthrough lymphaticvessels throughoutthe body.

2

Within lymph nodes,microbes and foreignparticles present in the circulating lymphencounter macro-phages, dendritic cells, and lymphocytes, which carry out various defensive actions.

3

Lymphatic vesselsreturn lymph to theblood via two large

ducts that drain intoveins near the

shoulders.

4

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Inflammatory ResponseInflammatory Response

Histamine and Prostaglandins are released by white blood cells in response to tissue damage– Trigger dilation and increased permeability of nearby

capillaries– Increased blood flow delivers clotting factors to the injury

(marks beginning of repair process/blocks spread of microbes) Phagocytic cells migrate to injury in response to chemokines Pus—the accumulation of dead phagocytic cells and fluid leaked

from capillaries

Natural Killer CellsNatural Killer Cells

Natural killer (NK) cells– Patrol the body and attack virus-infected body

cells and cancer cells– Trigger apoptosis in the cells they attack

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Acquired ImmunityAcquired Immunity

Third line of defense– Lymphocytes

Arise from stem cells in the bone marrow

– B and T Lymphocytes Circulate in blood and concentrated in spleen, lymph nodes,

and lymph tissues Recognize and respond to specific microbes and foreign

particles (antigens)

– Antibodies Proteins secreted by B lymphocytes in response to an antigen Interact specifically with the shape of the antigen

Antigen-binding sitesAntibody A

Antigen

Antibody BAntibody C

Epitopes(antigenicdeterminants)

An antigen is any foreign molecule– That is specifically recognized by lymphocytes

and elicits a response from them

A lymphocyte actually recognizes and binds– To just a small, accessible portion of the

antigen called an epitope

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Antigen Recognition by Antigen Recognition by LymphocytesLymphocytes

The vertebrate body is populated by two main types of lymphocytes– B lymphocytes (B cells) and T lymphocytes (T cells)– Which circulate through the blood

The plasma membranes of both B cells and T cells– Have about 100,000 antigen receptor that all recognize the

same epitope

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B Cell Receptors for AntigensB Cell Receptors for Antigens

B cell receptors– Bind to specific,

intact antigens– Are often called

membrane antibodies or membrane immunoglobulins

Figure 43.8a

Antigen-bindingsite

Antigen-binding site

Disulfidebridge

Lightchain

Heavy chains

Cytoplasm of B cell

V

A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges.

(a)

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

B cell

V

V

C

C C

C

V

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T Cell Receptors for Antigens T Cell Receptors for Antigens and the Role of the MHCand the Role of the MHC

Each T cell receptor– Consists of

two different polypeptide chains

Antigen-Binding site

chain

Disulfide bridge

chain

T cell

A T cell receptor consists of one chain and one chain linked by a disulfide bridge.

(b)

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

Cytoplasm of T cell

Figure 43.8b

V V

C C

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T cells bind to small fragments of antigens– That are bound to normal cell-surface proteins

called MHC molecules

MHC molecules– Are encoded by a family of genes called the

major histocompatibility complex

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Infected cells produce MHC molecules– Which bind to antigen fragments and then are

transported to the cell surface in a process called antigen presentation

A nearby T cell– Can then detect the antigen fragment displayed

on the cell’s surface

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Self-ToleranceSelf-Tolerance

Lymphocyte development gives rise to an immune system that distinguishes between self and non-self– Inability to recognize self leads to autoimmune diseases

Lymphocytes recognize cell surface glycoproteins encoded by a family of genes called the major histocompatibility complex (MHC)– Class I MHC molecules on all nucleated cells– Class II MHC molecules restricted to macrophages, B

cells, activated T cells, and cells of the interior thymus

Figure 43.9a

Infected cell

Antigenfragment

Class I MHCmolecule

T cellreceptor

(a) Cytotoxic T cell

A fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.

1

The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.

2

1

2

Class I MHC molecules, found on almost all nucleated cells of the body– Display peptide antigens to cytotoxic T cells

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Class II MHC molecules, located mainly on dendritic cells, macrophages, and B cells– Display antigens to helper T cells

1

2

Figure 43.9b

Microbe Antigen-presentingcell

Antigenfragment

Class II MHCmolecule

T cellreceptor

Helper T cell

A fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.

1

The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.

2

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Clonal Selection of Clonal Selection of LymphocytesLymphocytes

In a primary immune response– Binding of antigen to a mature lymphocyte

induces the lymphocyte’s proliferation and differentiation, a process called clonal selection

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Clonal selection of B cells– Generates a clone of short-lived activated effector

cells and a clone of long-lived memory cells

Figure 43.12

Antigen molecules

Antigenreceptor

B cells thatdiffer inantigenspecificity

Antibodymolecules

Clone of memory cells Clone of plasma cells

Antigen moleculesbind to the antigenreceptors of only oneof the three B cellsshown.

The selected B cellproliferates, forminga clone of identicalcells bearingreceptors for theselecting antigen.

Some proliferatingcells develop intoshort-lived plasmacells that secreteantibodies specificfor the antigen.

Some proliferating cellsdevelop into long-livedmemory cells that canrespond rapidly uponsubsequent exposureto the same antigen.

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In the secondary immune response– Memory cells facilitate a faster, more efficient

response

An

tibo

dy

con

cen

tra

tion

(arb

itra

ry u

nits

)

104

103

102

101

100

0 7 14 21 28 35 42 49 56

Time (days)Figure 43.13

Antibodiesto A

Antibodiesto B

Primaryresponse toantigen Aproduces anti-bodies to A

2Day 1: First exposure toantigen A

1 Day 28: Second exposureto antigen A; firstexposure to antigen B

3 Secondary response to anti-gen A produces antibodiesto A; primary response to anti-gen B produces antibodies to B

4

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Acquired immunity includes two branchesAcquired immunity includes two branches

The humoral immune response involves the activation and clonal selection of B cells, resulting in the production of secreted antibodies

The cell-mediated immune response involves the activation and clonal selection of cytotoxic T cells

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The roles of the major participants in the acquired immune response

Figure 43.14

Humoral immune response Cell-mediated immune response

First exposure to antigen

Intact antigensAntigens engulfed and

displayed by dendritic cellsAntigens displayed

by infected cells

Activate Activate Activate

Gives rise to Gives rise to Gives rise to

B cellHelperT cell

CytotoxicT cell

Plasmacells

MemoryB cells

Active and memory helperT cells

Memory cytotoxic

T cells

Active cytotoxic

T cells

Secrete antibodies that defend againstpathogens and toxins in extracellular fluid

Defend against infected cells, cancer cells, and transplanted tissues

Secretedcytokinesactivate

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Helper T Cells: A Response to Helper T Cells: A Response to Nearly All AntigensNearly All Antigens

Helper T cells produce CD4, a surface protein– That enhances their binding to class II MHC

molecule–antigen complexes on antigen-presenting cells

Activation of the helper T cell then occursActivated helper T cells

– Secrete several different cytokines that stimulate other lymphocytes

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The role of helper T cells in acquired immunity

Figure 43.15

After a dendritic cell engulfs and degrades a bacterium, it displays bacterial antigen fragments (peptides) complexed with a class II MHC molecule on the cell surface. A specific helper T cell binds to the displayed complex via its TCR with the aid of CD4. This interaction promotes secretion of cytokines by the dendritic cell.

Proliferation of the T cell, stimulatedby cytokines from both the dendritic cell and the T cell itself, gives rise toa clone of activated helper T cells(not shown), all with receptors for thesame MHC–antigen complex.

The cells in this clonesecrete other cytokines that help activate B cellsand cytotoxic T cells.

Cell-mediatedimmunity(attack on

infected cells)

Humoralimmunity

(secretion ofantibodies byplasma cells)

Dendriticcell

Dendriticcell

Bacterium

Peptide antigen

Class II MHCmolecule

TCR

CD4

Helper T cell

Cytokines

Cytotoxic T cell

B cell

1

2 3

1

2 3

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Cytotoxic T Cells: A Response to Cytotoxic T Cells: A Response to Infected Cells and Cancer CellsInfected Cells and Cancer Cells Cytotoxic T cells make CD8

– A surface protein that greatly enhances the interaction between a target cell and a cytotoxic T cell

Cytotoxic T cells– Bind to infected cells, cancer cells, and transplanted

tissues Binding to a class I MHC complex on an infected

body cell– Activates a cytotoxic T cell and differentiates it into

an active killer

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Cytotoxic T cell

Perforin

Granzymes

CD8TCR

Class I MHCmolecule

Targetcell Peptide

antigen

Pore

ReleasedcytotoxicT cell

Apoptotictarget cell

Cancercell

CytotoxicT cell

A specific cytotoxic T cell binds to a class I MHC–antigen complex on a target cell via its TCR with the aid of CD8. This interaction, along with cytokines from helper T cells, leads to the activation of the cytotoxic cell.

1 The activated T cell releases perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis.

2 The granzymes initiate apoptosis within the target cells, leading to fragmentation of thenucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells.

3

1

2

3

Figure 43.16

The activated cytotoxic T cell– Secretes proteins that destroy the infected target

cell

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Active ImmunityActive Immunity

Depends on response of the infected person’s own immune system

Can be acquired artificially by immunization– Inactivated or killed, or attenuated microbes, or

parts of microbes are made into vaccines and injected into an organism

– Unable to cause disease, but can act as antigen to stimulate immune response and formation of memory cells

Passive ImmunityPassive Immunity

Occurs naturally when antibodies of a pregnant woman cross the placenta to her fetus

Antibodies also passed from mother to nursing infant in breast milk– Colostrum—early secretions of milk

Provides protection from infections until baby’s own immune system matures

The allergic responseThe allergic response Hypersensitive response to certain environmental antigens

(allergens) Symptoms: sneezing, runny nose, tearing eyes, smooth

muscle contractions can lead to breathing difficulty

Figure 43.20

IgE antibodies produced in response to initial exposure to an allergen bind to receptors or mast cells.

1 On subsequent exposure to the same allergen, IgE molecules attached to a mast cell recog-nize and bind the allergen.

2 Degranulation of the cell,triggered by cross-linking of adjacent IgE molecules, releases histamine and other chemicals, leading to allergysymptoms.

3

1

2

3

Allergen

IgE

Histamine

GranuleMast cell

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Autoimmune DiseasesAutoimmune DiseasesImmune system loses tolerance for self and

turns against certain molecules of the body– Lupus erythrematosus—immune system

generates antibodies against all sorts of molecules including histones and DNA released by normal cell breakdown

Characterized by skin rashes, fever, arthritis, and kidney dysfunction

– Rheumatoid arthritis—leads to damage and painful inflammation of the cartilage and bone of joints

Figure 43.21

Immunodeficiency DiseasesImmunodeficiency Diseases

Inborn genetic disease– Bone marrow transplants used to supply

functional lymphocytes– Gene therapy—remove own cells, provide

functional gene, and return to bodyImmune dysfunction later in life

– Certain cancers can suppress immune system Hodgkin’s disease—damages lymphatic system

– Can be caused by a virus—HIV leads to AIDS

Acquired Acquired Immunodeficiency Immunodeficiency Syndrome (AIDS)Syndrome (AIDS)

Caused by the direct and indirect destruction of CD4-bearing T cells

Stages of HIV InfectionStages of HIV Infection