The Body’s Defenses Ch. 43 AP Biology Ms. Haut. Nonspecific Immunity First line of defense –...
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Transcript of The Body’s Defenses Ch. 43 AP Biology Ms. Haut. Nonspecific Immunity First line of defense –...
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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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
(b)Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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