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Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

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Page 1: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Immunology: Animal Defense Systems

31

Page 2: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Chapter 31 Immunology: Animal Defense Systems

Key Concepts

• 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

• 31.2 Innate Defenses Are Nonspecific

• 31.3 The Adaptive Immune Response Is Specific

Page 3: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Chapter 31 Immunology: Animal Defense Systems

Key Concepts

• 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

• 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

Page 4: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Chapter 31 Opening Question

How can a person survive an infection and be resistant to further infection?

Page 5: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

Animals have various means of defense against pathogens—agents that cause disease.

Two general types of defense mechanisms can provide immunity—the ability to avoid disease when invaded by a pathogen.

Page 6: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

Innate immunity—nonspecific, used against many organisms:

• Includes barriers, such as skin and molecules toxic to invaders, as first line of defense.

• Second line of innate defenses includes phagocytic cells, which ingest foreign cells and other particles.

• These defenses may be present all the time or activated rapidly.

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Concept 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

Adaptive immunity is specific:

• Distinguishes between substances produced by self and nonself.

• Involves antibody proteins and others that bind to and destroy pathogens.

• Slow to develop and long-lasting, found only in vertebrate animals.

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Table 31.1 Innate and Adaptive Immune Responses to an Infection

Page 9: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

Mammals have both kinds of defense systems—they work together as a coordinated system.

The main factors in immunity are specific cells and proteins.

These are produced in the blood and lymphoid tissues and circulate throughout the body

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Concept 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

White blood cells, or leukocytes, are suspended in the blood plasma.

Two kinds:

• Phagocytes (such as macrophages) are large cells that engulf pathogens and other substances by phagocytosis.

• Lymphocytes, which include B cells and T cells, are involved in adaptive immunity

Page 11: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Figure 31.1 White Blood Cells

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Concept 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

Cell–cell interactions in the mammalian defense system involve four key protein types:

• Antibodies—proteins that bind specifically to substances identified by the immune system

Antibodies are produced by B cells.

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Concept 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

• Major histocompatibility complex (MHC) proteins are found in two classes:

• MHC I proteins are found on most cell surfaces

• MHC II proteins are found on most immune system cells

MHC proteins are important self-identifying labels.

Page 14: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens

• T cell receptors are integral membrane proteins on T cells, recognize and bind nonself molecules on other cells

• Cytokines are soluble signaling proteins that bind to a cell’s surface receptors and alter that cell’s behavior

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Concept 31.2 Innate Defenses Are Nonspecific

Nonspecific defenses are general mechanisms—the first line of defense.

They are genetically programmed and “ready to go.”

In mammals, they include physical barriers as well as cellular and chemical defenses.

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Concept 31.2 Innate Defenses Are Nonspecific

• Skin is a primary nonspecific defense.

The physical barrier of the skin as well as the saltiness of the skin make it hard for bacteria to penetrate.

• Normal flora—the bacteria and fungi that usually live on body surfaces

They are part of the defense system because they compete with pathogens for nutrients and space.

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Figure 31.2 Innate Immunity

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Concept 31.2 Innate Defenses Are Nonspecific

• Mucus is secreted by mucous membranes. Mucus traps microorganisms so cilia can remove them.

Cilia continuously move the mucus plus debris up towards nose and mouth.

• Lysozyme, an enzyme that attacks bacterial cell walls, is found in tears, nasal mucus, and saliva.

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Concept 31.2 Innate Defenses Are Nonspecific

• Mucous membranes produce defensins, peptides with hydrophobic domains that are toxic to many pathogens.

Defensins insert themselves into the plasma membrane of the pathogen and make it permeable.

• Harsh conditions in the internal environment, such as extreme acidity, can also kill pathogens.

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In-Text Art, Ch. 31, p. 623 (1)

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Concept 31.2 Innate Defenses Are Nonspecific

Pathogens that do penetrate surfaces encounter more complex nonspecific second defenses:

• Activation of defensive cells

• Secretion of defensive proteins—complement and interferon proteins

Pathogenic cells, viruses, or fragments of invaders can be recognized by phagocytes, which then ingest them by phagocytosis.

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Concept 31.2 Innate Defenses Are Nonspecific

Natural killer cells—a type of lymphocyte that can detect virus-infected cells and some tumor cells:

• Can initiate apoptosis in these cells

• Can interact with the specific defense mechanisms and lyse cells labeled by antibodies

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Concept 31.2 Innate Defenses Are Nonspecific

Vertebrate blood has antimicrobial proteins that make up the complement system.

Proteins act in a cascade—each protein activates the next.

Provide three types of defense:

• Attach to microbes and mark them for phagocytes to engulf

• Activate inflammation response and attract phagocytes to site of infection

• Lyse invading cells

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Concept 31.2 Innate Defenses Are Nonspecific

Interferons are signaling molecules produced by cells infected by a pathogen.

Interferons increase resistance of neighboring cells to the pathogen by:

• Binding to receptors on noninfected cell membranes—stimulate a signaling pathway that inhibits viral reproduction

• Stimulating cells to hydrolyze pathogen’s proteins to peptides

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Concept 31.2 Innate Defenses Are Nonspecific

Inflammation is a coordinated response to injury—it isolates damage, recruits cells against pathogens, and promotes healing.

Mast cells are cells adhering to skin and organ linings; release chemical signals:

• Tumor necrosis factor—cytokine that kills target cells and activates immune cells

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Concept 31.2 Innate Defenses Are Nonspecific

• Prostaglandins—initiate inflammation in nearby tissues, dilate blood vessels and interact with nerve endings, increasing sensitivity to pain

• Histamine—amino acid derivative that increases permeability of blood vessels so white blood cells can act on tissues

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Concept 31.2 Innate Defenses Are Nonspecific

Symptoms of inflammation: Redness, swelling, heat, pain, result from dilation of blood vessels in the area.

Phagocytes enter the area and engulf pathogens and dead cells.

Cytokines may signal the brain to produce fever—toxic to some pathogens.

Pus is a mixture of leaked fluid and dead cells.

Platelets appear near a wound to promote healing.

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Concept 31.2 Innate Defenses Are Nonspecific

The inflammation response may be too strong:

• In an allergic reaction, a nonself molecule that is normally harmless binds to mast cells, causing the release of histamine and subsequent inflammation.

• In autoimmune diseases, the immune system fails to distinguish between self and nonself, and attacks tissues in the organism’s own body.

• In sepsis, the inflammation due to a bacterial infection does not remain local.

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Figure 31.3 Interactions of Cells and Chemical Signals Result in Inflammation

Page 30: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.3 The Adaptive Immune Response Is Specific

Scientists discovered that a factor that develops in blood serum in response to a toxin is an example of adaptive immunity that is specific to the toxin.

Passive immunity is the development of immunity from antibodies received from another individual.

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Figure 31.4 The Discovery of Specific Immunity (Part 1)

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Figure 31.4 The Discovery of Specific Immunity (Part 2)

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Concept 31.3 The Adaptive Immune Response Is Specific

Adaptive immunity has four key features:

• Specific—focuses on antigens that are present

• Diverse—responds to novel pathogens

• Distinguishes self from nonself, prevents destruction of self cells

• Has immunological memory, to respond to a later exposure to a pathogen

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Concept 31.3 The Adaptive Immune Response Is Specific

Specificity—lymphocytes are crucial:

T cell receptors and antibodies bind to specific nonself molecules (antigens).

Specific sites on the antigens are called antigenic determinants, or epitopes.

Page 35: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.3 The Adaptive Immune Response Is Specific

An antigenic determinant is a specific portion of a large molecule.

A single antigenic molecule can have multiple, different antigenic determinants.

The host responds to an antigen’s presence with highly specific defenses using T cell receptors and antibodies.

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Concept 31.3 The Adaptive Immune Response Is Specific

Diversity:

The immune system must respond to a wide variety of pathogens by activating specific lymphocytes from a pool.

Diversity is generated primarily by DNA changes—chromosomal rearrangements and other mutations.

The adaptive immune system is “predeveloped”—all of the machinery available to respond to an immense diversity of antigens is already there, even before the antigens are encountered.

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Concept 31.3 The Adaptive Immune Response Is Specific

Antigen binding “selects” a particular B or T cell for proliferation.

A particular lymphocyte is selected via binding and activation, and then it proliferates to generate a clone—called clonal selection for this mechanism of producing an immune response.

Page 38: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Figure 31.5 Clonal Selection in B Cells

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Concept 31.3 The Adaptive Immune Response Is Specific

Normally, the body is tolerant of its own molecules; develops during early B and T cell differentiation.

Clonal deletion—Any immature B and T cells that show the potential to mount an immune response to self antigens undergo apoptosis.

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Concept 31.3 The Adaptive Immune Response Is Specific

A failure of clonal deletion—autoimmunity.

In diseases such as systemic lupus erythematosis (SLE) or Hashimoto’s thyroiditis, immune cells mount a response against normal tissues.

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Concept 31.3 The Adaptive Immune Response Is Specific

Immunological memory—the immune system “remembers” a pathogen after the first encounter.

Primary immune response—when antigen is first encountered, “naïve” lymphocytes proliferate to produce two types of cells— effector and memory cells.

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Concept 31.3 The Adaptive Immune Response Is Specific

Effector cells carry out the attack. Effector B cells (plasma cells) secrete antibodies. Effector T cells secrete cytokines and other molecules.

Memory cells are long-lived cells that can divide on short notice to produce effector and more memory cells.

Memory B and T cells may survive for decades.

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Concept 31.3 The Adaptive Immune Response Is Specific

Secondary immune response—when antigen is encountered again, memory cells proliferate and launch an army of plasma cells and effector T cells.

Vaccinations trigger a primary immune response to prepare the body for a quicker, secondary response, if it encounters the pathogen again.

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Concept 31.3 The Adaptive Immune Response Is Specific

The adaptive immune response involves three phases:

• Recognition phase—the organism discriminates between self and nonself to detect a pathogen.

• Activation phase—the recognition event leads to a mobilization of cells and molecules to fight the invader.

• Effector phase—the mobilized cells and molecules destroy the invader.

Page 45: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Figure 31.6 The Adaptive Immune System (Part 1)

Page 46: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Figure 31.6 The Adaptive Immune System (Part 2)

Page 47: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.3 The Adaptive Immune Response Is Specific

The three phases can occur in either of two types of response: the humoral immune response and the cellular immune response.

Humoral immune response involves B cells that make antibodies.

Cytotoxic T (TC) cells are the workhorses of the cellular immune response.

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Concept 31.3 The Adaptive Immune Response Is Specific

A key event is the exposure or presentation of the antigen to the immune system.

In humoral immunity, this occurs when an antigen binds to a B cell that has an antibody specific to that antigen.

In cellular immunity, an antigen is inserted into the membrane of an antigen-presenting cell.

The antigen is recognized by a T-helper (TH) cell, with a specific T cell receptor protein.

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Concept 31.3 The Adaptive Immune Response Is Specific

Antigen binding readies a B cell for division.

Antigen fragments bind to the MHC complex and are presented on the B cell surface.

A specific TH cell binds and stimulates the B cell to divide and form a clone.

In the cellular immune response, TH cell binding to the antigen-presenting cell causes cytokine release.

Cytokines stimulate TC cells with the same T cell receptor to divide.

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Concept 31.3 The Adaptive Immune Response Is Specific

The result of activation is the formation of two clones of cells:

• A clone of B cells that can produce antibodies specific for the antigen

• A clone of TC cells that express a T cell receptor that can bind to any cell expressing the antigen on its surface

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Concept 31.3 The Adaptive Immune Response Is Specific

In the effector phase, B clone cells produce antibodies that bind to free antigen— results in inactivation and destruction of the antigen.

TC clone cells bind to cells bearing the antigen and destroy them.

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

B cells are the basis of the humoral immune response.

A “naïve” B cell expresses a receptor protein specific for an antigen on its cell surface.

The cell is activated by antigen-binding and after TH cell stimulation will give rise to clones of plasma and memory cells.

Plasma cells secrete antibodies into the blood stream.

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

A B cell can also be stimulated to divide by a TH cell binding to the exposed antigen on the B cell surface.

The specific TH cell may come from a clone that was activated by the cellular immune response.

Interaction between B cells and TH cells provides a connection between the cellular and humoral systems.

The TH cell bound to the B cell secretes cytokines that stimulate the B cell to divide.

Page 54: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

Antibodies, or immunoglobulins, all contain a tetramer of four polypeptides.

In each molecule are two light chains and two heavy chains, held together by disulfide bonds.

Each polypeptide chain has a constant region and a variable region.

Page 55: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Figure 31.7 The Structure of an Immunoglobulin (Part 1)

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Figure 31.7 The Structure of an Immunoglobulin (Part 2)

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

The amino acid sequence of the constant region determines the general structure and function (the class) of an immunoglobulin.

The amino acid sequence of the variable region is different for each specific immunoglobulin—responsible for antibody specificity.

Two antigen-binding sites on an immunoglobulin are identical—bivalent.

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In-Text Art, Ch. 31, p. 630

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

Five classes of immunoglobulins (Ig) differ in function and in the type of heavy chain:

• IgG is secreted by B cells and constitutes about 80 percent of circulating antibodies.

• IgD is the cell surface receptor on a B cell.

• IgM is the initial surface and circulating antibody released by a B cell.

• IgA protects mucosa on epithelia exposed to the environment.

• IgE binds to mast cells and is involved with inflammation.

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

Each mature B cell can produce only one specific antibody with a specific amino acid sequence.

The B cell genome:

• Has a number of different coding regions for each domain of an immunoglobulin

• Diversity is generated by putting together different combinations of these regions.

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

Each gene encoding an immunoglobulin is actually a supergene assembled from a cluster of smaller genes.

Every cell has hundreds of immunoglobulin genes that could participate in synthesis of both variable and constant regions.

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Figure 31.8 Heavy-Chain Genes

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

During B cell development the genes are cut out and rearranged. One gene from each cluster is chosen randomly for joining, others are deleted.

A unique supergene is assembled.

Result—enormous diversity of specific antibodies.

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Figure 31.9 Heavy-Chain Gene Recombination and RNA Splicing

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

Each B cell precursor assembles two supergenes—one for the light chain, one for the heavy chain.

Genes for the light chains are on separate chromosomes; they are made in a similar way, with an equally large amount of diversity possible.

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

Other mechanisms for diversity:

• When DNA is rearranged, errors can occur during recombination, creating new codons—imprecise recombination

• Before DNA is rejoined, terminal transferase adds nucleotides, creating insertion mutations

• High spontaneous mutation rate

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Concept 31.4 The Adaptive Humoral Immune Response Involves Specific Antibodies

Antibodies can act as receptors on the cell surface.

They can also be secreted from B cells into the blood:

• Some bind to the antigen expressed on surface of a pathogen.

• If antigen is free in the bloodstream, antibodies may use cross-linking function to form large complexes to be destroyed by phagocytes.

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

Cellular immune response involves two types of effector T cells:

• T-helper cells (TH)

• Cytotoxic T cells (TC)

Major histocompatibility proteins (MHC) proteins are also involved.

Page 69: Immunology: Animal Defense Systems 31. Chapter 31 Immunology: Animal Defense Systems Key Concepts 31.1 Animals Use Innate and Adaptive Mechanisms to Defend

Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

T cells have specific membrane receptors—glycoproteins, with two polypeptide chains.

Each chain is encoded by a different gene—has distinct regions with constant and variable amino acid sequences.

T cell receptors can bind a piece or fragment of an antigen, on the surface of an antigen-presenting cell.

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Figure 31.10 A T Cell Receptor

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

TH and TC cells respond differently to antigen-binding.

TH binding results in activation of the cellular immune response.

TC binding results in the death of the cell carrying the antigen.

MHC proteins form complexes with antigens on cell surfaces and assist with recognition by the T cells, so that the appropriate type of T cell binds.

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

MHC proteins are plasma membrane glycoproteins. Two types present antigens to T lymphocytes:

• Class I MHC proteins are present on the surface of every nucleated cell. They present antigens to TC cells.

• Class II MHC proteins are on surfaces of macrophages, B cells, and dendritic cells—present antigens to TH cells.

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Figure 31.11 Macrophages Are Antigen-Presenting Cells

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

People can have very different MHC genotypes due to many possible combinations of alleles.

MHC proteins are “self” markers.

For antigen presentation, MHC I and MHC II proteins have an antigen binding site, which holds a polypeptide fragment.

T cell receptor recognizes not just the antigenic fragment, but the fragment bound to MHC I or II.

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Table 31.2 The Interaction between T Cells and Antigen-Presenting Cells

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

Activation of a TC cell results in the production of a clone of TC cells with the specific T cell receptor.

These TC cells bind to cells carrying the antigen–MHC I protein complex.

When bound, the TC cells do two things to eliminate the antigen-carrying cell:

• They produce perforin, which lyses the bound target cell.

• They stimulate apoptosis in the target cell.

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In-Text Art, Ch. 31, p. 634

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

Regulatory T cells (Tregs) are a third class that regulates the immune response.

Tregs recognize self antigens—when activated they release the cytokine interleukin 10.

This blocks T cell activation and leads to apoptosis of TC and TH cells bound to the same antigen.

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Figure 31.12 Tregs and Tolerance

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

The importance of Tregs is mediating tolerance to “self” antigens. Two lines of evidence for role of Tregs:

• If Tregs are destroyed experimentally in the thymus, the immune system mounts strong responses to self antigens (autoimmunity).

• A mutation in a gene critical to Treg function results in a disease IPEX—causes fatal immune responses.

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

Immune deficiency disorders can be inherited or acquired.

T or B cells may never form, or B cells lose their ability to give rise to plasma cells—the affected individual lacks a major line of defense against pathogens.

Acquired immune deficiency syndrome (AIDS) results from infection by human immunodeficiency virus (HIV).

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

HIV initially infects TH cells, macrophages, and antigen-presenting dendritic cells.

At first there is an immune response and TH cells are activated—but are later killed by both HIV and by lysis by TC cells.

Numbers of TH cells decline after infection.

However, the HIV-infected cells activate the humoral immune system and symptoms abate.

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Figure 31.13 The Course of an HIV Infection

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

During the dormant period, people with HIV feel fine.

Eventually more TH cells are destroyed and the person is susceptible to opportunistic infections:

• Kaposi’s sarcoma, a rare skin cancer caused by a herpes virus

• Pneumonia caused by fungus Pneumocystis jirovecii

• Lymphoma tumors caused by Epstein-Barr virus

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Concept 31.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors

Drug treatments for HIV are focused on inhibiting processes necessary for viral entry, assembly, and replication.

Combinations of such drugs result in long-term survival. Unfortunately, like many medical treatments, HIV drugs are not available to all who need them.

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Answer to Opening Question

Infection is met by the body in one way that protects it from immediate harm and by another that produces antibodies to protect against a future infection.

Antibody production is a slower response, but once in place forms an immunological memory.

Vaccines are an application of this response.

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Figure 31.14 Vaccination