Chapt 43

Chapter 43
The Immune System

Overview: Reconnaissance, Recognition, and Response
An animal must defend itself from the many dangerous pathogens it may encounter
Two major kinds of defense have evolved: innate immunity and acquired immunity

Innate immunity is present before any exposure to pathogens and is effective from the time of birth
It involves nonspecific responses to pathogens
Innate immunity consists of external barriers plus internal cellular and chemical defenses
Key internal defenses are macrophages and other phagocytic cells

LE 43-1 3 µm

Acquired immunity, or adaptive immunity, develops after exposure to agents such as microbes, toxins, or other foreign substances
It involves a very specific response to pathogens
Recognition is by white blood cells called lymphocytes
Some lymphocytes produce antibodies; others destroy infected cells, cancer cells, or foreign tissue

LE 43-2 Invading microbes (pathogens) External defenses Skin Mucous membranes Secretions INNATE IMMUNITY Rapid responses to a broad range of microbes ACQUIRED IMMUNITY Slower responses to specific microbes Internal defenses Phagocytic cells Inflammatory response Humoral response (antibodies) Antimicrobial proteins Natural killer cells Cell-mediated response (cytotoxic lymphocytes)

Concept 43.1: Innate immunity provides broad defenses against infection
A pathogen that breaks through external defenses encounters innate cellular and chemical mechanisms that impede its attack
External Defenses
Skin and mucous membranes are physical barriers to entry of microorganisms and viruses
Mucous membrane cells produce mucus, a viscous fluid that traps microbes and other particles
In the trachea, ciliated epithelial cells sweep mucus and any entrapped microbes upward, preventing microbes from entering the lungs

LE 43-3 10 µm

Secretions of the skin and mucous membranes provide an environment hostile to microbes
Secretions give the skin a pH between 3 and 5, acidic enough to prevent colonization of many microbes
Skin secretions include proteins such as lysozyme, which digests bacterial cell walls

Internal Cellular and Chemical Defenses
Internal cellular defenses depend mainly on phagocytosis
White blood cells called phagocytes ingest microorganisms and initiate inflammation
Phagocytic Cells
Phagocytes attach to prey via surface receptors and engulf them, forming a vacuole that fuses with a lysosome

LE 43-4 Pseudopodia Microbes MACROPHAGE Lysosome containing enzymes Vacuole

Macrophages, a type of phagocyte, migrate through the body and are found in organs of the lymphatic system
The lymphatic system defends against pathogens

LE 43-5 Adenoid Tonsil Lymph nodes Peyer’s patches (small intestine) Spleen Appendix Lymphatic vessels Lymph node Masses of lymphocytes and macrophages Lymphatic vessel Blood capillary Tissue cells Lymphatic capillary Interstitial fluid

Antimicrobial Proteins
Proteins function in innate defense by attacking microbes directly or impeding their reproduction
About 30 proteins make up the complement system, which causes lysis of invading cells and helps trigger inflammation
Interferons provide innate defense against viruses and help activate macrophages

Inflammatory Response
In local inflammation, histamine and other chemicals released from injured cells promote changes in blood vessels
These changes allow more fluid, phagocytes, and antimicrobial proteins to enter tissues

LE 43-6 Pathogen Pin Chemical signals Capillary Phagocytic cells Macrophage Red blood cell Blood clotting elements Blood clot Phagocytosis

Natural Killer Cells
Natural killer (NK) cells attack virus-infected body cells and cancer cells
They trigger apoptosis in the cells they attack

Invertebrate Immune Mechanisms
Many invertebrates defend against infection by many of the same mechanisms in the vertebrate innate response

Concept 43.2: In acquired immunity, lymphocytes provide specific defenses against infection
Acquired immunity is the body’s second major kind of defense
An antigen is a foreign molecule that is recognized by lymphocytes and elicits a response from them
A lymphocyte recognizes and binds to a small portion of the antigen called an epitope

LE 43-7 Antigen- binding sites Epitopes (antigenic determinants) Antibody A Antibody B Antibody C Antigen

Antigen Recognition by Lymphocytes
Two main types of lymphocytes circulate in the blood of vertebrates: B lymphocytes (B cells) and T lymphocytes (T cells)
A single B cell or T cell has about 100,000 identical antigen receptors
All antigen receptors on a single cell recognize the same epitope

B Cell Receptors for Antigens
B cell receptors bind to specific, intact antigens
Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack transmembrane regions that anchor receptors in the plasma membrane
Video: T Cell Receptors

LE 43-8 Antigen- binding site Disulfide bridge Light chain V V C C C C V V Antigen- binding site Variable regions Constant regions Transmembrane region Antigen- binding site C V C V Plasma membrane T cell  chain  chain Disulfide bridge Cytoplasm of T cell A T cell receptor consists of one  chain and one  chain linked by a disulfide bridge. A B cell receptor consists of two identical heavy chains and two identical light chains linked by several disulfide bridges. Heavy chains Cytoplasm of B cell B cell

T Cell Receptors for Antigens and the Role of the MHC
Each T cell receptor consists of two different polypeptide chains
V V C C
T cells bind to antigen fragments that are bound to cell-surface proteins called MHC molecules
MHC molecules are so named because they are encoded by a family of genes called the major histocompatibility complex

Infected cells produce MHC molecules, which bind to antigen fragments and are transported to the cell surface, a process called antigen presentation
A nearby T cell can then detect the antigen fragment displayed on the cell’s surface
Depending on their source, peptide antigens are handled by different classes of MHC molecules
Class I MHC molecules are found on almost all nucleated cells of the body
They display peptide antigens to cytotoxic T cells

LE 43-9 Antigen- presenting cell Antigen fragment Class II MHC molecule T cell receptor Helper T cell Antigen fragment Class I MHC molecule T cell receptor Cytotoxic T cell Infected cell Microbe

Class II MHC molecules are located mainly on dendritic cells, macrophages, and B cells
They display antigens to helper T cells

Lymphocyte Development
Lymphocytes arise from stem cells in bone marrow
Newly formed lymphocytes are alike but later develop into B cells or T cells, depending on where they mature

LE 43-10 Lymphoid stem cell Bone marrow Thymus T cell Blood, lymph, and lymphoid tissues (lymph nodes, spleen, and others) B cell

Generation of Lymphocyte Diversity by Gene Rearrangement
Random, permanent gene rearrangement forms functional genes encoding the B or T cell antigen receptor chains

LE 43-11 DNA of undifferentiated B cell DNA of differentiated B cell pre-mRNA mRNA Cap Light-chain polypeptide Variable region Constant region B cell B cell receptor Translation Poly (A) RNA processing (removal of intron; addition of cap and poly (A) tail) Transcription of resulting permanently rearranged, functional gene Functional gene Deletion of DNA between a V segment and J segment and joining of the segments V 4 – V 39 V 1 V 2 V 3 V 40 V 1 V 2 V 3 J 5 C Intron J 5 Intron C J 4 J 3 J 2 J 1 V 3 J 5 Intron C V 3 J 5 C V C

Testing and Removal of Self-Reactive Lymphocytes
As B and T cells mature in the bone and thymus, their antigen receptors are tested for self-reactivity
Lymphocytes with receptors for antigens that are already in the body are destroyed by apoptosis or rendered nonfunctional

Clonal Selection of Lymphocytes
In a primary immune response, binding of antigen to a mature lymphocyte induces the lymphocyte’s proliferation and differentiation
This process is called clonal selection
Clonal selection of B cells generates a clone of short-lived activated effector cells and a clone of long-lived memory cells
Animation: Role of B Cells

LE 43-12 B cells that differ in antigen specificity Antigen molecules Antigen receptor Antibody molecules Clone of memory cells Clone of plasma cells

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

Concept 43.3: Humoral and cell-mediated immunity defend against different types of threats
Humoral immune response involves activation and clonal selection of B cells, resulting in production of secreted antibodies
Cell-mediated immune response involves activation and clonal selection of cytotoxic T cells

LE 43-14_3 First exposure to antigen Antigens engulfed and displayed by dendritic cells Activate Humoral immune response Cell-mediated immune response Helper T cell Active and memory helper T cells Gives rise to Antigens displayed by infected cells Activate Cytotoxic T cell Memory cytotoxic T cells Gives rise to Secreted cytokines activate Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues Activate Gives rise to Secrete antibodies that defend against pathogens and toxins in extracellular fluid Plasma cells Memory B cells B cells Intact antigens

Helper T Cells: A Response to Nearly All Antigens
A surface protein called CD4 binds the class II MHC molecule
This binding keeps the helper T cell joined to the antigen-presenting cell while activation occurs
Activated helper T cells secrete cytokines that stimulate other lymphocytes
Animation: Helper T Cells

LE 43-15 Dendritic cell Bacterium Peptide antigen Class II MHC molecule TCR CD4 Helper T cell B cell Cytokines Cytotoxic T cell Cell-mediated immunity (attack on infected cells) Humoral immunity (secretion of antibodies by plasma cells) Dendritic cell

Cytotoxic T Cells: A Response to Infected Cells and Cancer Cells
Cytotoxic T cells make CD8, a surface protein that greatly enhances interaction between a target cell and a cytotoxic T cell
Binding to a class I MHC complex on an infected cell activates a cytotoxic T cell and makes it an active killer
The activated cytotoxic T cell secretes proteins that destroy the infected target cell

Peptide antigen Target cell Class I MHC molecule TCR CD8 Granzymes Perforin Cytotoxic T cell Pore Apoptotic target cell Released cytotoxic T cell Cytotoxic T cell Cancer cell Antibody Classes The five major classes of antibodies, or immunoglobulins, differ in distribution and function

B Cells: A Response to Extracellular Pathogens
Activation of B cells is aided by cytokines and antigen binding to helper T cells
Clonal selection of B cells generates antibody-secreting plasma cells, the effector cells of humoral immunity

LE 43-17 Macrophage Class II MHC molecule Bacterium Peptide antigen CD4 TCR Helper T cell Activated helper T cell Cytokines Clone of memory B cells Endoplasmic reticulum of plasma cell Clone of plasma cells Secreted antibody molecules B cell +

J chain IgM (pentamer) Promotes neutralization and agglutination of antigens; very effective in complement activation (see Figure 43.19) First lg class produced after initial exposure to antigen; then its concentration in the blood declines IgG (monomer) Promotes opsonization, neutralization, and agglutination of antigens; less effective in complement activation than lgM (see Figure 43.19) Only lg class that crosses placenta, thus conferring passive immunity on fetus Most abundant lg class in blood; also present in tissue fluids

IgA (dimer) Provides localized defense of mucous membranes by agglutination and neutralization of antigens (see Figure 43.19) J chain Secretory component Presence in breast milk confers passive immunity on nursing infant Present in secretions such as tears, saliva, mucus, and breast milk IgE (monomer) Triggers release from mast cells and basophils of histamine and other chemicals that cause allergic reactions (see Figure 43.20) IgD (monomer) Present primarily on surface of naive B cells that have not been exposed to antigens Transmembrane region Acts as antigen receptor in antigen-stimulated proliferation and differentiation of B cells (clonal selection)

Antibody-Mediated Disposal of Antigens
The binding of antibodies to antigens is also the basis of antigen-disposal mechanisms
Microbes are eliminated by phagocytosis and complement-mediated lysis
Animation: Antibodies

LE 43-19 Viral neutralization (blocks binding to host and opsonization increases phagocytosis) Agglutination of antigen-bearing particles, such as microbes Precipitation of soluble antigens Activation of complement system and pore formation Binding of antibodies to antigens inactivates antigens by Bacteria Soluble antigens MAC Complement proteins Foreign cell Pore Virus Bacterium Enhances Phagocytosis Macrophage Cell lysis Leads to

Active and Passive Immunization
Active immunity develops naturally in response to an infection
It can also develop following immunization, also called vaccination
In immunization, a nonpathogenic form of a microbe or part of a microbe elicits an immune response to an immunological memory

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

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

Blood Groups and Transfusions
Antigens on red blood cells determine whether a person has type A, B, AB, or O blood
Antibodies to nonself blood types exist in the body
Transfusion with incompatible blood leads to destruction of the transfused cells
Recipient-donor combinations can be fatal or safe

A red blood cell antigen called the Rh factor creates difficulties when an Rh-negative mother carries successive Rh-positive fetuses

Tissue and Organ Transplants
MHC molecules stimulate rejection of tissue grafts and organ transplants
Chances of successful transplantation increase if donor and recipient MHC tissue types are well matched
Immunosuppressive drugs facilitate transplantation
Lymphocytes in bone marrow transplants may cause a graft versus host reaction in recipients

Concept 43.5: Exaggerated, self-directed, or diminished immune responses can cause disease
If the delicate balance of the immune system is disrupted, effects range from minor to often fatal
Allergies
Allergies are exaggerated (hypersensitive) responses to antigens called allergens
In localized allergies such as hay fever, IgE antibodies produced after first exposure to an allergen attach to receptors on mast cells

The next time the allergen enters the body, it binds to mast cell–associated IgE molecules
Mast cells release histamine and other mediators that cause vascular changes leading to typical allergy symptoms
An acute allergic response can lead to anaphylactic shock, a life-threatening reaction that can occur within seconds of allergen exposure

LE 43-20 IgE Allergen Granule Mast cell Histamine

Autoimmune Diseases
In individuals with autoimmune diseases, the immune system loses tolerance for self and turns against certain molecules of the body
Rheumatoid arthritis is an autoimmune disease leading to damage and inflammation of joints

Other examples of autoimmune diseases:
Systemic lupus erythematosus
Multiple sclerosis
Insulin-dependent diabetes

Immunodeficiency Diseases
Inborn or primary immunodeficiency results from hereditary or congenital defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses
Acquired or secondary immunodeficiency results from exposure to chemical and biological agents
Inborn (Primary) Immunodeficiencies
In severe combined immunodeficiency (SCID), both the humoral and cell-mediated branches of acquired immunity fail to function
Acquired (Secondary) Immunodeficiencies
Acquired immunodeficiencies range from temporary states to chronic diseases

Acquired Immunodeficiency Syndrome (AIDS)
People with AIDS are highly susceptible to opportunistic infections and cancers that take advantage of an immune system in collapse
Because AIDS arises from loss of helper T cells, it impairs both the humoral and cell-mediated immune responses
The loss of helper T cells results from infection by the human immunodeficiency virus (HIV)
Animation: HIV Reproductive Cycle

LE 43-22 1 µm

The spread of HIV is a worldwide problem
The best approach for slowing this spread is education about practices that transmit the virus

Chapt 43

by many87 on Oct 19, 2010

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Chapt 43 — Presentation Transcript