Chapter 43

The Immune System

PowerPoint Lectures for Biology, Seventh Edition
Neil Campbell and Jane Reece

Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Overview: Reconnaissance, Recognition, and Response • An animal must defend itself
– From the many dangerous pathogens it may encounter in the environment

• Two major kinds of defense have evolved that counter these threats
– Innate immunity and acquired immunity

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• Innate immunity
– Is present before any exposure to pathogens and is effective from the time of birth – Involves nonspecific responses to pathogens

Figure 43.1
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3µm

• Acquired immunity, also called adaptive immunity
– Develops only after exposure to inducing agents such as microbes, toxins, or other foreign substances – Involves a very specific response to pathogens

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• A summary of innate and acquired immunity

INNATE IMMUNITY Rapid responses to a broad range of microbes

ACQUIRED IMMUNITY Slower responses to specific microbes

External defenses Skin Mucous membranes Invading microbes (pathogens) Secretions

Internal defenses Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Cell-mediated response (cytotoxic lymphocytes) Humoral response (antibodies)

Figure 43.2

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• Concept 43.1: Innate immunity provides broad defenses against infection • A pathogen that successfully breaks through an animal’s external defenses
– Soon encounters several innate cellular and chemical mechanisms that impede its attack on the body

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External Defenses • Intact skin and mucous membranes
– Form physical barriers that bar the entry of microorganisms and viruses

• Certain cells of the mucous membranes produce mucus
– A viscous fluid that traps microbes and other particles

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• In the trachea, ciliated epithelial cells
– Sweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungs 10µm

Figure 43.3
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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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Internal Cellular and Chemical Defenses • Internal cellular defenses
– Depend mainly on phagocytosis

• Phagocytes, types of white blood cells
– Ingest invading microorganisms – Initiate the inflammatory response

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Phagocytic Cells
• Phagocytes attach to their prey via surface receptors
– And engulf them, forming a vacuole that fuses with a lysosome
Microbes 1 Pseudopodia surround microbes. 2 Microbes are engulfed into cell.

MACROPHAGE

3 Vacuole containing microbes forms. Vacuole Lysosome containing enzymes 4 Vacuole and lysosome fuse. 5 Toxic compounds and lysosomal enzymes destroy microbes. 6 Microbial debris is released by exocytosis.

Figure 43.4
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• Macrophages, a specific type of phagocyte
– Can be found migrating through the body – Can be found in various organs of the lymphatic system

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• The lymphatic system
– Plays an active role in defending the body from pathogens
1 Interstitial fluid bathing the tissues, along with the white blood cells in it, continually enters lymphatic capillaries. Adenoid Tonsil 4 Lymphatic vessels return lymph to the blood via two large ducts that drain into veins near the shoulders. Interstitial fluid Lymphatic capillary 2 Fluid inside the lymphatic capillaries, called lymph, flows through lymphatic vessels throughout the body.

Lymph nodes

Blood capillary Tissue cells Lymphatic vessel 3 Within lymph nodes, microbes and foreign particles present in the circulating lymph encounter macrophages, dendritic cells, and lymphocytes, which carry out various defensive actions.

Spleen
Peyer’s patches (small intestine) Appendix

Lymphatic vessels

Figure 43.5
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Lymph node

Masses of lymphocytes and macrophages

Antimicrobial Proteins • Numerous proteins function in innate defense
– By attacking microbes directly of by impeding their reproduction

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• About 30 proteins make up the complement system
– Which can cause lysis of invading cells and help trigger inflammation

• Interferons
– Provide innate defense against viruses and help activate macrophages

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Inflammatory Response • In local inflammation, histamine and other chemicals released from injured cells
– Promote changes in blood vessels that allow more fluid, more phagocytes, and antimicrobial proteins to enter the tissues

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• Major events in the local inflammatory response
Pathogen Pin Blood clot

Macrophage Chemical signals Phagocytic cells Capillary

Blood clotting elements

Phagocytosis

Red blood cell
1 Chemical signals released by activated macrophages and mast cells at the injury site cause nearby capillaries to widen and become more permeable. 2 Fluid, antimicrobial proteins, and clotting elements move from the blood to the site. Clotting begins. 3 Chemokines released by various kinds of cells attract more phagocytic cells from the blood to the injury site. 4 Neutrophils and macrophages phagocytose pathogens and cell debris at the site, and the tissue heals.

Figure 43.6
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Natural 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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Invertebrate Immune Mechanisms • Many invertebrates defend themselves from infection
– By many of the same mechanisms in the vertebrate innate response

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• Concept 43.2: In acquired immunity, lymphocytes provide specific defenses against infection • Acquired immunity
– Is the body’s second major kind of defense – Involves the activity of lymphocytes

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• 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
Antibody A Antigenbinding sites Epitopes (antigenic determinants)

Antigen

Antibody B Figure 43.7

Antibody C

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Antigen Recognition by Lymphocytes • 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 Antigens
• B cell receptors
– Bind to specific, intact antigens – Are often called membrane antibodies or membrane immunoglobulins
Antigenbinding site Antigenbinding site

V V

V
V

Disulfide bridge

Light chain

Variable regions Constant regions Transmembrane region

C

C

C C

Heavy chains B cell Cytoplasm of B cell

Plasma membrane

Figure 43.8a

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

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T Cell Receptors for Antigens and the Role of the MHC

• Each T cell receptor
– Consists of two different polypeptide chains
AntigenBinding site Variable regions V Constant regions Transmembrane region C V C

Plasma membrane

α chain

β chain T cell

Disulfide bridge Cytoplasm of T cell

Figure 43.8b

(b) A T cell receptor consists of one α chain and one β chain linked by a disulfide bridge.

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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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• Depending on their source
– Peptide antigens are handled by different classes of MHC molecules

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• Class I MHC molecules, found on almost all nucleated cells of the body
– Display peptide antigens to cytotoxic T cells
Infected cell Antigen fragment 1 Class I MHC molecule T cell receptor 2 2 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection. 1 A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface.

Figure 43.9a

(a) Cytotoxic T cell

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• Class II MHC molecules, located mainly on dendritic cells, macrophages, and B cells
– Display antigens to helper T cells AntigenMicrobe 1 A fragment of foreign protein (antigen) inside the cell associates with an MHC molecule and is transported to the cell surface. 2 presenting cell Antigen fragment

1 Class II MHC molecule T cell receptor

2 The combination of MHC molecule and antigen is recognized by a T cell, alerting it to the infection.

Figure 43.9b
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(b)

Helper T cell

Lymphocyte Development • Lymphocytes
– Arise from stem cells in the bone marrow

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• Newly formed lymphocytes are all alike
– But they later develop into B cells or T cells, depending on where they continue their maturation
Bone marrow Lymphoid stem cell Thymus

B cell

T cell

Figure 43.10

Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others)

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Generation of Lymphocyte Diversity by Gene Rearrangement • Early in development, random, permanent gene rearrangement
– Forms functional genes encoding the B or T cell antigen receptor chains

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• Immunoglobulin gene rearrangement
V4–V39 DNA of undifferentiated B cell V1 V2 V3 V40 J1 J2 J3 J4 J5 Intron C

1 Deletion of DNA between a V segment
DNA of differentiated B cell V1 V2 V3 J5 Intron C

and J segment and joining of the segments

2 Transcription of resulting permanently rearranged, functional gene pre-mRNA V3 J5 Intron C

3 RNA processing (removal of intron; addition of cap and poly (A) tail) mRNA Cap V3 J5 C Poly (A) 4 Translation Light-chain polypeptide V C B cell B cell receptor

Figure 43.11

Variable Constant region region

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Testing and Removal of Self-Reactive Lymphocytes • As B and T cells are maturing in the bone and thymus
– Their antigen receptors are tested for possible self-reactivity

• Lymphocytes bearing receptors for antigens already present in the body
– Are destroyed by apoptosis or rendered nonfunctional

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Clonal Selection of Lymphocytes • 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
B cells that differ in antigen specificity Antigen molecules Antigen molecules bind to the antigen receptors of only one of the three B cells shown.

Antigen receptor

The selected B cell proliferates, forming a clone of identical cells bearing receptors for the selecting antigen. Some proliferating cells develop into long-lived memory cells that can respond rapidly upon subsequent exposure to the same antigen. Some proliferating cells develop into short-lived plasma cells that secrete antibodies specific for the antigen.

Antibody molecules Clone of memory cells Clone of plasma cells

Figure 43.12
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• In the secondary immune response
– Memory cells facilitate a faster, more efficient response
1 Day 1: First 3 Day 28: 2 Primary exposure to Second exposure response to antigen A to antigen A; first antigen A exposure to produces antiantigen B bodies to A 104 Antibody concentration (arbitrary units) 103 4 Secondary response to antigen A produces antibodies to A; primary response to antigen B produces antibodies to B

102 101 100

Antibodies to A

Antibodies to B

Figure 43.13

0

7

14

21

28

35

42

49

56

Time (days)

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• Concept 43.3: Humoral and cell-mediated immunity defend against different types of threats • Acquired 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
Humoral immune response Cell-mediated immune response First exposure to antigen

Intact antigens Activate

Antigens engulfed and displayed by dendritic cells Activate Secreted cytokines activate

Antigens displayed by infected cells Activate

B cell

Helper T cell

Cytotoxic T cell

Gives rise to

Gives rise to

Gives rise to

Plasma cells

Memory B cells

Active and memory helper T cells

Memory cytotoxic T cells

Active cytotoxic T cells

Figure 43.14

Secrete antibodies that defend against pathogens and toxins in extracellular fluid

Defend against infected cells, cancer cells, and transplanted tissues

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Helper T Cells: A Response to Nearly All Antigens • Helper T cells produce CD4, a surface protein
– That enhances their binding to class II MHC molecule–antigen complexes on antigenpresenting cells

• Activation of the helper T cell then occurs

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• Activated helper T cells
– Secrete several different cytokines that stimulate other lymphocytes

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• The role of helper T cells in acquired immunity
1 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. Dendritic cell Bacterium Cytotoxic T cell Peptide antigen Class II MHC molecule TCR 2 1 CD4 Dendritic cell Cytokines 2 Proliferation of the T cell, stimulated by cytokines from both the dendritic cell and the T cell itself, gives rise to a clone of activated helper T cells (not shown), all with receptors for the same MHC–antigen complex. 3 Helper T cell Cell-mediated immunity (attack on infected cells) Humoral immunity (secretion of antibodies by plasma cells)

B cell
3 The cells in this clone secrete other cytokines that help activate B cells and cytotoxic T cells.

Figure 43.15
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Cytotoxic T Cells: A Response to Infected 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

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• 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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• The activated cytotoxic T cell
– Secretes proteins that destroy the infected target cell 2 The activated T cell releases perforin 1 A specific cytotoxic T cell binds to a 3 The granzymes initiate apoptosis within the
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. Cytotoxic T cell Perforin molecules, which form pores in the target cell membrane, and proteolytic enzymes (granzymes), which enter the target cell by endocytosis. target cells, leading to fragmentation of the nucleus, release of small apoptotic bodies, and eventual cell death. The released cytotoxic T cell can attack other target cells.

Released cytotoxic T cell Cancer cell

Granzymes 1 TCR Class I MHC molecule CD8 2 Pore 3

Apoptotic target cell

Target cell

Peptide antigen

Figure 43.16
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Cytotoxic T cell

B Cells: A Response to Extracellular Pathogens • Activation of B cells
– Is aided by cytokines and antigen binding to helper T cells

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• The clonal selection of B cells
– Generates antibody-secreting plasma cells, the effector cells of humoral immunity

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1 After a macrophage engulfs and degrades

2

a bacterium, it displays a peptide antigen complexed with a class II MHC molecule. A helper T cell that recognizes the displayed complex is activated with the aid of cytokines secreted from the macrophage, forming a clone of activated helper T cells (not shown).

A B cell that has taken up and degraded the same bacterium displays class II MHC–peptide antigen complexes. An activated helper T cell bearing receptors specific for the displayed antigen binds to the B cell. This interaction, with the aid of cytokines from the T cell, activates the B cell.

3 The activated B cell proliferates

and differentiates into memory B cells and antibody-secreting plasma cells. The secreted antibodies are specific for the same bacterial antigen that initiated the response.

Bacterium Macrophage Peptide antigen Class II MHC molecule
1

B cell
2 3

Clone of plasma cells

Secreted antibody molecules

TCR

CD4 Cytokines

Endoplasmic reticulum of plasma cell

Helper T cell

Activated helper T cell

Clone of memory B cells

Figure 43.17
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Antibody Classes • The five major classes of antibodies, or immunoglobulins
– Differ in their distributions and functions within the body

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• The five classes of immunoglobulins
IgM (pentamer) First Ig class produced after initial exposure to antigen; then its concentration in the blood declines Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19) Most abundant Ig class in blood; also present in tissue fluids Only Ig class that crosses placenta, thus conferring passive immunity on fetus Promotes opsonization, neutralization, and agglutination of antigens; less effective in complement activation than IgM (see Figure 43.19) IgA (dimer) Secretory component J chain Present in secretions such as tears, saliva, mucus, and breast milk Provides localized defense of mucous membranes by agglutination and neutralization of antigens (see Figure 43.19) Presence in breast milk confers passive immunity on nursing infant IgE (monomer) Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions (see Figure 43.20) J chain

IgG (monomer)

IgD (monomer)

Present primarily on surface of naive B cells that have not been exposed to antigens Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection)

Figure 43.18

Transmembrane region

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Antibody-Mediated Disposal of Antigens • The binding of antibodies to antigens
– Is also the basis of several antigen disposal mechanisms – Leads to elimination of microbes by phagocytosis and complement-mediated lysis

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• Antibody-mediated mechanisms of antigen disposal
Binding of antibodies to antigens inactivates antigens by

Viral neutralization (blocks binding to host) and opsonization (increases phagocytosis) Virus

Agglutination of antigen-bearing particles, such as microbes Bacteria

Precipitation of soluble antigens

Activation of complement system and pore formation Complement proteins

MAC

Pore Bacterium Soluble antigens Foreign cell

Enhances Phagocytosis

Leads to Cell lysis

Figure 43.19

Macrophage

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Active and Passive Immunization • Active immunity
– Develops naturally in response to an infection – Can also develop following immunization, also called vaccination

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• In immunization
– A nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory for that microbe

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• Passive immunity, which provides immediate, short-term protection
– Is conferred naturally when IgG crosses the placenta from mother to fetus or when IgA passes from mother to infant in breast milk – Can be conferred artificially by injecting antibodies into a nonimmune person

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• Concept 43.4: The immune system’s ability to distinguish self from nonself limits tissue transplantation • The immune system
– Can wage war against cells from other individuals

• Transplanted tissues
– Are usually destroyed by the recipient’s immune system
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Blood Groups and Transfusions • Certain antigens on red blood cells
– Determine whether a person has type A, B, AB, or O blood

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• Antibodies to nonself blood types
– Already exist in the body

• Transfusion with incompatible blood
– Leads to destruction of the transfused cells

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• Recipient-donor combinations
– Can be fatal or safe

Table 43.1

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• Another red blood cell antigen, the Rh factor
– Creates difficulties when an Rh-negative mother carries successive Rh-positive fetuses

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Tissue and Organ Transplants • MHC molecules
– Are responsible for stimulating the rejection of tissue grafts and organ transplants

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• The chances of successful transplantation are increased
– If the donor and recipient MHC tissue types are well matched – If the recipient is given immunosuppressive drugs

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• Lymphocytes in bone marrow transplants
– May cause a graft versus host reaction in recipients

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• Concept 43.5: Exaggerated, self-directed, or diminished immune responses can cause disease • If the delicate balance of the immune system is disrupted
– The effects on the individual can range from minor to often fatal consequences

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Allergies • Allergies are exaggerated (hypersensitive) responses
– To certain antigens called allergens

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• In localized allergies such as hay fever
– IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells

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• The next time the allergen enters the body
– It binds to mast cell–associated IgE molecules

• The mast cells then release histamine and other mediators
– That cause vascular changes and typical symptoms

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• The allergic response
IgE Allergen 1 Histamine 3 2

Granule Mast cell 1 IgE antibodies produced in 2 On subsequent exposure to the 3 Degranulation of the cell, triggered by cross-linking of response to initial exposure same allergen, IgE molecules adjacent IgE molecules, to an allergen bind to attached to a mast cell recogreleases histamine and other receptors or mast cells. nize and bind the allergen. chemicals, leading to allergy symptoms.

Figure 43.20

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• An acute allergic response sometimes leads to anaphylactic shock
– A whole-body, life-threatening reaction that can occur within seconds of exposure to an allergen

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Autoimmune Diseases • In individuals with autoimmune diseases
– The immune system loses tolerance for self and turns against certain molecules of the body

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• Rheumatoid arthritis
– Is an autoimmune disease that leads to damage and painful inflammation of the cartilage and bone of joints

Figure 43.21
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• Other examples of autoimmune diseases include
– Systemic lupus erythematosus – Multiple sclerosis – Insulin-dependent diabetes

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Immunodeficiency Diseases • An inborn or primary immunodeficiency
– Results from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses

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• An acquired or secondary immunodeficiency
– Results from exposure to various chemical and biological agents

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Inborn (Primary) Immunodeficiencies • In severe combined immunodeficiency (SCID)
– Both the humoral and cell-mediated branches of acquired immunity fail to function

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Acquired (Secondary) Immunodeficiencies • Acquired immunodeficiencies
– Range from temporary states to chronic diseases

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Stress and the Immune System • Growing evidence shows
– That physical and emotional stress can harm immunity

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• Acquired Immunodeficiency Syndrome (AIDS) • People with AIDS
– Are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse

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• Because AIDS arises from the loss of helper T cells
– Both humoral and cell-mediated immune responses are impaired

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• The loss of helper T cells
– Results from infection by the human immunodeficiency virus (HIV)

Figure 43.22
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1µm

• The spread of HIV
– Has become a worldwide problem

• The best approach for slowing the spread of HIV
– Is educating people about the practices that transmit the virus

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