Chapter 41 Key Concepts 411 Animals Use Innate and Adaptive Mechanisms for Defense 412 Innate Defenses Are Nonspecific 413 Adaptive Defenses Are Specific 414 The Humoral Adaptive Response Involves Antibodies ID: 909830
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Slide1
Immunology: AnimalDefense Systems
Slide2Chapter 41 Key Concepts
41.1 Animals Use Innate and Adaptive Mechanisms for Defense41.2 Innate Defenses Are Nonspecific
41.3 Adaptive Defenses Are Specific
41.4 The Humoral Adaptive Response Involves Antibodies
Slide3Chapter 41 Key Concepts
41.5 The Cellular Adaptive Response Involves T Cells and Receptors41.6 Malfunctions in Immunity Can Be Harmful
Slide4Investigating Life: Vaccines and Immunity
What are the mechanisms and implications of long-lasting immunity?
Smallpox was eliminated by 1978 with the help of extensive vaccination programs—a stunning international success.
Yet many people today refuse to be vaccinated. This may harm other people: about 80% of the population must have the vaccine for “herd immunity” to be effective.
Slide5Key Concept 41.1 Focus Your LearningThe two general types of defense mechanisms are innate defenses and adaptive defenses.
Many animal groups have Toll-like receptors (TLRs) that participate in innate defense responses.All white blood cells originate from multipotent stem cells in the bone marrow.
Slide6Key Concept 41.1 Focus Your LearningIn mammals, the major immune system proteins include antibodies, MHC proteins, T cell receptors, and cytokines.
Slide741.1 Animals Use Innate and Adaptive Mechanisms for Defense
Animals have various means of defense against pathogens—organisms or viruses that cause disease.
Defense systems are based on the recognition of
self
(one’s own) and
nonself
(foreign) molecules.
Slide841.1 Animals Use Innate and Adaptive Mechanisms for Defense
Defensive responses have three phases:
Recognition phase
—
organism must discriminate between self and
nonself
Activation phase
—
mobilization of cells and molecules to fight invaderEffector phase—mobilized cells and molecules destroy invader
Slide941.1 Animals Use Innate and Adaptive Mechanisms for Defense
Two types of defense mechanisms:
Innate defenses
(nonspecific) act rapidly; include barriers such as skin, phagocytic cells, and toxins.
Adaptive defenses
are aimed at specific pathogens. Slow to develop and long-lasting (e.g., antibodies for a specific virus).
Slide1041.1 Animals Use Innate and Adaptive Mechanisms for Defense
All animals have innate defenses.
The Japanese horseshoe crab, which evolved 400 million years ago, relies only on innate defenses.
Barriers include physical, chemical, and biological mechanisms The horseshoe crab has a hard exoskeleton to protect from pathogen invaders.
Slide11In-Text Art, Ch. 41, p. 868 (1)
Slide1241.1 Animals Use Innate and Adaptive Mechanisms for Defense
Cells such as phagocytes (amoebocytes in the horseshoe crab) bind to microbial pathogens, ingest and destroy them.
Slide13In-Text Art, Ch. 41, p. 868 (2)
Slide1441.1 Animals Use Innate and Adaptive Mechanisms for Defense
Toxic molecules—horseshoe crab blood includes peptides that disrupt bacterial cell membranes, or bind to bacterial surfaces and cross-link them.
Slide15In-Text Art, Ch. 41, p. 868 (3)
Slide1641.1 Animals Use Innate and Adaptive Mechanisms for Defense
The recognition and activation phases of innate immunity evolved very early. Animals from humans to fruit flies have Toll-like receptors
(
TLRs
) that recognize nonself molecules called
pathogen-associated molecular patterns
(
PAMPs
).
Slide1741.1 Animals Use Innate and Adaptive Mechanisms for Defense
In vertebrates, TLRs recognize and bind to specific molecules found in broad classes of pathogens, such as bacterial cell wall components.
Binding triggers a signal transduction pathway that ends with expression of genes for anti-pathogen molecules.
Slide18Figure 41.1 Cell Signaling and Defense
Slide1941.1 Animals Use Innate and Adaptive Mechanisms for Defense
Mammals have both innate and adaptive defense systems—they work together as a coordinated system.Innate immunity is the first line of defense; adaptive defenses often require days or weeks to become effective.
Slide20Table 41.1 Innate and Adaptive Immune Responses to an Infection
Slide2141.1 Animals Use Innate and Adaptive Mechanisms for Defense
Components of mammalian defense systems are dispersed throughout the body.
Lymphoid tissues include thymus, bone marrow, spleen, and lymph nodes.
Blood and lymph are complex systems with both defensive and nondefensive functions. Both consist of liquids in which cells are suspended.
Slide22Figure 41.2 The Human Lymphatic System
Slide2341.1 Animals Use Innate and Adaptive Mechanisms for Defense
Blood plasma contains ions, small solutes, soluble proteins, red and white blood cells, and platelets.
Red cells remain in the circulatory system, but white cells and platelets are also in the lymph.
All blood cells originate from multipotent stem cells in the bone marrow.
Slide2441.1 Animals Use Innate and Adaptive Mechanisms for Defense
Lymph: Fluid derived from blood and other tissues. From tissues, lymph moves into lymph system vessels.
Lymph vessels join and eventually form the thoracic duct, which joins the circulatory system at a major vein near the heart.
Slide2541.1 Animals Use Innate and Adaptive Mechanisms for Defense
Lymph nodes occur at many sites along the lymph vessels
.
They contain
lymphocytes
, a type of white blood cell.
As lymph passes through the nodes, lymphocytes initiate an immune response if foreign cells or molecules are detected.
Slide2641.1 Animals Use Innate and Adaptive Mechanisms for DefenseWhite blood cells (leukocytes):
Lymphocytes—T cells and B cells; not phagocytic.Phagocytes—phagocytic white cells.There are many types with specialized functions (e.g., granulocytes have vesicles containing defensive enzymes).
Slide27Figure 41.3 White Blood Cells (Part 1)
Slide28Figure 41.3 White Blood Cells (Part 2)
Slide2941.1 Animals Use Innate and Adaptive Mechanisms for Defense
Cell-cell interactions involve four key protein types:
Antibodies
—produced by B cells and bind specifically to substances identified as
nonself
.
Molecules that bind antibodies are called
antigens
.
Slide3041.1 Animals Use Innate and Adaptive Mechanisms for Defense
Major histocompatibility complex (MHC
) proteins display antigens on the surface of self cells.
T cells can then recognize the antigens.
Also function as important self-identifying labels.
Slide3141.1 Animals Use Innate and Adaptive Mechanisms for Defense
T cell receptors are integral membrane proteins on T cells; they recognize and bind antigens presented by MHC proteins on other cells.
Cytokines
are soluble signaling proteins that bind to a cell’s surface receptors and alter that cell’s behavior.
Slide32Key Concept 41.1 Learning OutcomesCompare various types of defense mechanisms.Describe the role of the Toll-like receptor (
TLR) pathway in innate immunity.Infer what types of immune-related molecules and genes a particular animal would have.
Slide33Key Concept 41.2 Focus Your LearningInnate immunity is applied to any potential harmful invader.
Physical barriers, such as skin, are the first line of innate defense.Inflammation involves recruitment of cells and defensive molecules to an area damaged by a pathogen or other injury.
Slide3441.2 Innate Defenses Are Nonspecific
Innate defenses are mechanisms to stop pathogens from invading or quickly eliminate those that do.
They are genetically programmed and “ready to go.”
Slide3541.2 Innate Defenses Are Nonspecific
Skin is the first line of innate defense.
Physical barrier
: Bacteria can rarely penetrate healthy unbroken skin.
Saltiness and dryness of skin
: Not hospitable to bacteria growth.
Presence of normal flora
: Bacteria and fungi that normally live on skin compete with pathogens for space and nutrients.
Slide36Figure 41.4 Innate Immunity
Slide3741.2 Innate Defenses Are Nonspecific
If a pathogen lands inside nose or an internal organ:
Mucus
in the nose, respiratory, digestive, and urogenital systems traps microorganisms.
Cilia continuously move the mucus and its trapped debris away.
Slide3841.2 Innate Defenses Are Nonspecific
Lysozyme, made by mucous membranes, attacks bacterial cell walls and causes them to burst (lyse).
Defensins
, made by mucous membranes, are peptides with hydrophobic domains that insert into pathogen cell membranes and make them permeable.
Slide3941.2 Innate Defenses Are Nonspecific
Harsh internal environments can kill pathogens—(e.g., the stomach contains hydrochloric acid and proteases).
Slide4041.2 Innate Defenses Are Nonspecific
Complement and interferon proteins are produced in response to pathogens.
Vertebrate blood has over 20 different proteins that make up the antimicrobial
complement system
.
Activated by both innate and adaptive defense responses.
Slide4141.2 Innate Defenses Are Nonspecific
Complement proteins act in a cascade:
Attach to microbes and mark them for phagocytes to engulf.
Activate inflammatory response and attract phagocytes to site of infection.
Lyse invading cells.
Slide4241.2 Innate Defenses Are Nonspecific
Interferons are signaling molecules that increase resistance of neighboring cells to a pathogen.
They are a class of cytokines; particularly important in defense against viruses.
They bind to uninfected cells, stimulating a signaling pathway that inhibits viral reproduction.
Slide4341.2 Innate Defenses Are Nonspecific
Phagocytes travel in lymph and blood, and may move out of vessels and into tissues.
Phagocytes engulf foreign cells, viruses, and fragments.
Defensins
, nitric oxide, and reactive oxygen intermediates inside the phagocyte kill the pathogens.
Slide44In-Text Art, Ch. 41, p. 872
Slide4541.2 Innate Defenses Are Nonspecific
Natural killer cells: Lymphocytes that can distinguish virus-infected cells and some tumor cells from normal cells.
Can initiate apoptosis in these cells
Can interact with adaptive defense mechanisms and lyse cells labeled by antibodies
Slide4641.2 Innate Defenses Are Nonspecific
Dendritic cells: Phagocytes that act as messengers between innate and adaptive immune systems.Engulf pathogens and fragments of virus-infected cells, digest them, and “present” the antigenic fragments on its surface
Also secrete signals that activate cells of the adaptive immune system
Slide4741.2 Innate Defenses Are Nonspecific
Inflammation is a response to injury or infection.
It isolates damaged areas to stop the spread, recruits cells and molecules to the area to kill invaders, and promotes healing.
Slide4841.2 Innate Defenses Are Nonspecific
Mast cells are the first responders; adhere to skin and organ linings and release chemical signals:
Tumor necrosis factor
—cytokine that kills target cells and activates immune cells.
Slide4941.2 Innate Defenses Are Nonspecific
Prostaglandins—dilate blood vessels and interact with nerve endings; responsible for pain.
Histamine
—amino acid derivative that dilates blood vessels and leads to itching and rashes in allergic reactions.
Slide5041.2 Innate Defenses Are Nonspecific
The redness and heat of inflammation result from dilation and leakiness of blood vessels in the affected area.
Histamine and other signals attract phagocytes; they engulf invaders and dead cells.
Phagocytes produce cytokines, which can signal the brain to produce fever.
Slide51Figure 41.5 Interactions of Cells and Chemical Signals Result in Inflammation (Part 1)
Slide52Figure 41.5 Interactions of Cells and Chemical Signals Result in Inflammation (Part 2)
Slide53Figure 41.5 Interactions of Cells and Chemical Signals Result in Inflammation (Part 3)
Slide5441.2 Innate Defenses Are Nonspecific
Increased body temperature accelerates lymphocyte production and phagocytosis; also inhibits growth of some pathogens.
After inflammation, pus may accumulate
—
leaked fluid and dead cells; it is gradually consumed by macrophages.
Slide55Key Concept 41.2 Learning Outcomes
Summarize the roles of physical barriers, chemical defenses, and cellular defenses in innate immunity.Explain how the innate defense system defends against a pathogen.
List the steps in the inflammatory response.
Slide56Key Concept 41.3 Focus Your Learning
The humoral and cellular immune responses work simultaneously and cooperatively.Memory cells, the key to immunological memory, retain the capacity to divide to produce effector and more memory cells.
Vaccinations initiate a primary immune response, generating memory cells without causing illness.
Slide5741.3 Adaptive Defenses Are Specific
The adaptive immune system has four key traits:
Specificity
Ability to distinguish self from
nonself
Diversity
—
response to a wide variety of
nonself moleculesImmunological memory
Slide5841.3 Adaptive Defenses Are Specific
Specificity
T cell receptors and antibodies bind to specific
nonself
molecules (antigens).
Specific sites on the antigens are called
antigenic determinants
or
epitopes.
Slide59In-Text Art, Ch. 41, p. 874
Slide6041.3 Adaptive Defenses Are Specific
An antigenic determinant is a specific portion of a large molecule.
Most antigens are proteins or polysaccharides; there can be multiple antigens on an invading bacterium.
One antigenic molecule can have multiple, different antigenic determinants.
Slide6141.3 Adaptive Defenses Are Specific
The host responds to an antigen’s presence with highly specific defenses using T cell receptors and antibodies.
Each T cell and each antibody is specific for a single antigenic determinant.
Antigenic determinants are referred to simply as “antigens.”
Slide6241.3 Adaptive Defenses Are Specific
Distinguishing self from nonself
Every cell in the body has many different antigens; the immune system must be able to recognize them all and not attack them.
Slide6341.3 Adaptive Defenses Are Specific
Diversity
The immune system must respond to a wide variety of pathogens.
Each pathogen may exist in many different varieties or strains.
Humans can respond specifically to about 10 million different antigens.
Slide6441.3 Adaptive Defenses Are Specific
Immunological memory
After one response to a pathogen, the immune system “remembers” the pathogen and can respond more quickly and powerfully if that pathogen invades again.
Slide6541.3 Adaptive Defenses Are Specific
Macrophages and dendritic cells activate the adaptive immune system.After ingestion of a pathogen or infected cell, phagocytes display fragments of the pathogen (antigens) on their surface.
Antigen presentation
is one way the innate immune system communicates with the adaptive immune system.
Slide6641.3 Adaptive Defenses Are Specific
Macrophages and dendritic cells then migrate to lymph nodes, where they present antigen to immature (previously unexposed) T cells.They also secrete cytokines and other signals that stimulate activation and differentiation of the T cells.
Slide6741.3 Adaptive Defenses Are Specific
Adaptive immune system has two types of responses:
Humoral immune response
—relies on
B cells
making antibodies
Cellular immune response
—relies on
cytotoxic T (Tc) cellsThe two responses operate simultaneously and cooperatively.
Slide6841.3 Adaptive Defenses Are SpecificBoth types of adaptive immune responses occur in three phases:
Recognition phase: The antigen on the surface of the antigen-presenting cell is recognized by a T-helper (TH) cell bearing a T cell receptor protein that is specific for the antigen.
Binding initiates the activation phase.
Slide6941.3 Adaptive Defenses Are Specific
Activation phase: When the TH cell recognizes an antigen on an antigen-presenting cell, it releases cytokines that stimulate B cells and T
C
cells to divide.
Results in clones of the B cells and T
C
cells.
Slide7041.3 Adaptive Defenses Are SpecificEffector phase
: B cell clones produce antibodies that bind to pathogen or infected cells.The bound antibodies attract phagocytes and complement proteins. In cellular immunity, TC clones bind to infected cells and destroy them.
Slide71Figure 41.6 The Adaptive Immune System
Slide7241.3 Adaptive Defenses Are Specific
For adaptive immunity, the body must generate a vast diversity of lymphocytes.
Diversity is generated by DNA changes just after B and T cells are formed.
There are millions of different kinds of both B and T cells.
The response machinery for a huge diversity of antigens is already present before they are encountered.
Slide7341.3 Adaptive Defenses Are Specific
Clonal selection
Antigens presented on antigen-presenting cells, particularly dendritic cells, trigger the selection of specific lymphocytes for that antigen.
Antigen binding “selects” a particular B or T cell for proliferation.
Slide74Figure 41.7 Clonal Selection in B Cells (Part 1)
Slide75Figure 41.7 Clonal Selection in B Cells (Part 2)
Slide7641.3 Adaptive Defenses Are Specific
Clonal deletion helps distinguish self from nonself.
During early differentiation, any immature B or T cell that shows potential to mount an immune response against self antigens undergoes programmed cell death (apoptosis).
Slide7741.3 Adaptive Defenses Are Specific
Immunological memory: An activated lymphocyte produces two kinds of daughter cells:
Effector cells
attack the antigen
Effector B cells (
plasma cells
) secrete antibodies; effector T cells secrete cytokines and other molecules that destroy
nonself
cells.
Slide7841.3 Adaptive Defenses Are Specific
Memory cells are
long-lived cells that can divide on short notice to produce effector cells and more memory cells.
Memory B and T cells may survive in the body for decades, rarely dividing.
Slide7941.3 Adaptive Defenses Are Specific
Primary immune response
When antigen is first encountered, previously unexposed lymphocytes that recognize the antigen proliferate to produce clones of effector and memory cells.
Slide8041.3 Adaptive Defenses Are Specific
Secondary immune response
When antigen is encountered again, memory cells proliferate and launch an army of plasma cells and effector T cells.
Response is much more rapid and powerful.
Slide8141.3 Adaptive Defenses Are Specific
Because of immunological memory, exposure to many diseases provides natural immunity.
Vaccination
provides artificial immunity by introducing an antigen in a form that does not cause disease.
It initiates a primary immune response, generating memory cells.
Slide82In-Text Art, Ch. 41, p. 876
Slide8341.3 Adaptive Defenses Are Specific
Mutation can result in the pathogen’s antigens changing over time, and a vaccination may become ineffective.This happens with influenza virus—new strains appear every year and a new vaccine must be made.
Slide8441.3 Adaptive Defenses Are Specific
Recent findings: Memory cells can last a long time and help in a response to new, related antigens.
Memory cells are making antibodies that bind to the first strain of flu and to later ones as well.
This may lead to a vaccine that is broadly effective and obviates the need to develop new ones.
Slide85Investigating Life: What Are the Mechanisms and Implications of Long-Lasting Immunity?
Hypothesis: Exposure to new strains of flu stimulates antibody production against strains to which an individual was exposed previously.
Slide86Investigating Life: What Are the Mechanisms and Implications of Long-Lasting Immunity?
Method:
As part of a larger study, blood samples were taken from 40 people who had been exposed to 3 major flu outbreaks.
The blood was tested for antibodies every year from 1987 to 2008.
Slide87Investigating Life: What Are the Mechanisms and Implications of Long-Lasting Immunity?, Experiment
Slide88Investigating Life: What Are the Mechanisms and Implications of Long-Lasting Immunity?
Conclusion:
People exposed to flu virus develop long-lasting memory cells that make antibodies that have broad specificity to other flu strains.
Slide89Key Concept 41.3 Learning Outcomes
Distinguish between the recognition, activation, and effector phases in adaptive immunity.Make and explain inferences regarding rates of infection in the context of immunological memory.
Summarize how vaccines provide long-lasting immunity to pathogens.
Slide90Key Concept 41.4 Focus Your Learning
Antibody proteins are immunoglobulins with four polypeptide chains—two identical light chains and two identical heavy chains, each with constant and variable regions.IgG is the most common of the five classes of immunoglobulins.
DNA rearrangements and other mutations generate the diversity of immunoglobulins.
Slide9141.4 The Humoral Adaptive Response Involves Antibodies
B cells are the basis for the humoral immune response:
A B cell begins with a receptor protein specific to an antigen.
If an antigen binds to the receptor, the B cell presents the antigen to a T
H
cell with a receptor that recognizes the antigen.
Slide9241.4 The Humoral Adaptive Response Involves Antibodies
The TH cell then secretes cytokines that stimulate the B cell to divide and give rise to a clone of plasma cells, plus memory cells.The plasma cells secrete antibodies into the blood stream—up to 2,000 molecules per second!
Slide9341.4 The Humoral Adaptive Response Involves Antibodies
Antibodies belong to a protein class called immunoglobulins.
All are tetramers with 2 identical light chains and 2 identical heavy chains, held together by disulfide bonds.
Each polypeptide chain has a constant region and a variable region.
Slide94Figure 41.8 The Structure of an Immunoglobulin (Part 1)
Slide95Figure 41.8 The Structure of an Immunoglobulin (Part 2)
Slide9641.4 The Humoral Adaptive Response Involves Antibodies
Constant region: Determines the class of antibody—the function and destination.
Variable regions
: Specific for each immunoglobulin; the 3D structure is responsible for antibody specificity.
Immunoglobulins are bivalent—they can bind two antigen molecules.
Slide9741.4 The Humoral Adaptive Response Involves Antibodies
Antigens have multiple epitopes, so large complexes form that are easy targets for phagocytes.
Slide98In-Text Art, Ch. 41, p. 879
Slide9941.4 The Humoral Adaptive Response Involves Antibodies
Five classes of antibodies are determined by the constant regions of the heavy chains.
IgG is most abundant; made in greatest amounts during a secondary immune response.
Slide100Table 41.2 Antibody Classes
Slide10141.4 The Humoral Adaptive Response Involves Antibodies
Some IgG bind to antigens, then attach to macrophages via the heavy chain.
Slide102In-Text Art, Ch. 41, p. 880
Slide10341.4 The Humoral Adaptive Response Involves Antibodies
Immunoglobulin diversity results from DNA rearrangements and other mutations.
Each mature B cell makes only one specific antibody to a specific epitope.
It would be impossible to have a gene for every epitope.
Slide10441.4 The Humoral Adaptive Response Involves Antibodies
The genome of B cells has multiple different coding regions for each domain of the immunoglobulin.Diversity is generated by putting together different combinations of these regions.
Slide10541.4 The Humoral Adaptive Response Involves Antibodies
Each gene encoding an immunoglobulin is a “supergene” made by recombination of clusters of smaller genes.There are hundreds of immunoglobulin genes located in separate clusters.
Slide106Figure 41.9 Supergene
Slide10741.4 The Humoral Adaptive Response Involves 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.
Slide108Figure 41.10 Heavy-Chain Gene Recombination and RNA Splicing
Slide10941.4 The Humoral Adaptive Response Involves Antibodies
Each B cell precursor assembles two supergenes—one for the light chain, one for the heavy chain.
Genes for the light chains are made in a similar way, with an equally large amount of diversity.
Light and heavy chain diversity together yield about 324 million possibilities.
Slide11041.4 The Humoral Adaptive Response Involves Antibodies
Mutations generate even more diversity.
Imprecise recombination can create frame-shift mutations, nucleotides can be added before splicing, and immunoglobulin genes have high spontaneous mutation rates.
Once the B cell’s specificity has been determined, it cannot change.
Slide11141.4 The Humoral Adaptive Response Involves Antibodies
Once pre-transcriptional processing is completed, a supergene is transcribed and translated to produce an immunoglobulin light or heavy chain.
These combine to form an active immunoglobulin protein.
Slide11241.4 The Humoral Adaptive Response Involves Antibodies
Class switching
B cells can make only one type of antibody at a time, but can change the class of antibody they make.
Early B cells produce IgM molecules—the receptors that recognize the specific antigens. The constant region of the heavy chain is encoded by the μ gene.
Slide11341.4 The Humoral Adaptive Response Involves Antibodies
If B cell becomes a plasma cell, a deletion occurs in the DNA, resulting in an antibody with a different constant region of the heavy chain.
The antibody still has the same variable regions, and thus the same specificity—but a different function.
Slide114Key Concept 41.4 Learning Outcomes
Compare the antigen-binding site of an antibody with other molecules such as enzymes that bind other molecules.Describe the roles of molecules such as immunoglobulins in humoral immunity and of T cell receptors in cellular immunity.
Compare the diversity of specific antibodies in an individual with the diversity of other biological molecules.
Slide115Key Concept 41.5 Focus Your Learning
In the effector phase of the humoral response, T-helper (TH) cells activate previously unexposed B cells with the same specificity to produce antibodies.
Regulatory T cells (
Tregs
), which recognize self antigens, help ensure that the immune system does not attack self cells and molecules indiscriminately.
Slide116Key Concept 41.5 Focus Your Learning
Two classes of effector T cells (cytotoxic T cells and T-helper cells) are involved in the cellular adaptive response.
Diversity in MHC molecules is very high in humans.
Slide11741.5 The Cellular Adaptive Response Involves T Cells and Receptors
The cellular immune response involves two types of effector T cells:
T-helper cells (T
H
)
Cytotoxic T cells (T
C
)
They work with MHC proteins, which present antigens on cell surfaces.
Slide11841.5 The Cellular Adaptive Response Involves T Cells and Receptors
T cells have specific membrane receptors that are glycoproteins with two polypeptide chains.
Each chain is encoded by a different gene and has constant and variable regions.
T cell receptors bind only to antigens displayed by an MHC protein on the surface of a target cell.
Slide119Figure 41.11 A T Cell Receptor
Slide12041.5 The Cellular Adaptive Response Involves T Cells and Receptors
When a T cell is activated, it proliferates. Its descendants form clones of two types of effector cells:
Cytotoxic T cells
(
T
C
) recognize virus-infected or mutated cells and kill them by lysis.
T-helper cells
(TH) assist both humoral and cellular responses.
Slide12141.5 The Cellular Adaptive Response Involves T Cells and Receptors
Major histocompatibility complex (MHC) proteins form complexes with antigens on cell surfaces and assist with recognition by the T cells.
MHC proteins are cell membrane glycoproteins.
Slide12241.5 The Cellular Adaptive Response Involves T Cells and Receptors
Two classes of MHC proteins:
Class I MHC
present antigens to T
C
cells are present on every cell.
Viral protein fragments are complexed with MHC I; T
C
cells with appropriate receptors then bind to the complex.TC cells also have a surface protein, CD8, that binds to MHC I.
Slide12341.5 The Cellular Adaptive Response Involves T Cells and Receptors
Class II MHC are on B cells, macrophages, and dendritic cells; they present antigens to TH
cells.
When these cells ingest a
nonself
antigen, fragments bind to MHC II and are carried to the membrane and presented to T
H
cells.
TH cells also have a surface protein CD4 that binds to MHC II.
Slide124Figure 41.12 Macrophages Are Antigen-Presenting Cells
Slide12541.5 The Cellular Adaptive Response Involves T Cells and Receptors
Humans have six genetic loci for MHC proteins, each with hundreds of alleles.With so many possible allele combinations, different people are very likely to have different MHC genotypes.
This is why it can be difficult to find a good “match” for organ donations.
Slide126Table 41.3 The Interaction between T Cells and Antigen-Presenting Cells
Slide12741.5 The Cellular Adaptive Response Involves T Cells and Receptors
TH cells and MHC II contribute to the humoral immune response.
Activation phase (in lymphoid tissue): T
H
cell binds to antigen-presenting cell and releases cytokines
—
the T
H
cell proliferates, forms a clone.Effector phase: TH cells activate unexposed B cells with the same specificity to produce antibodies.
Slide12841.5 The Cellular Adaptive Response Involves T Cells and Receptors
B cells are also antigen-presenting cells—they take up antigens bound to surface receptors by endocytosis, then display fragments on MHC II proteins.
A T
H
cell binds to the antigen-MHC II complex and releases cytokines that cause B cells to produce a clone of plasma cells, which secrete antibodies.
Slide129Figure 41.13 Phases of the Humoral
and Cellular Immune Responses (Part 1)
Slide13041.5 The Cellular Adaptive Response Involves T Cells and Receptors
TC cells and MHC I contribute to the cellular immune response.
Activation phase: A virus-infected or mutated cell displays peptide fragments bound to MHC I. T
C
cell recognizes and binds to the complex and proliferates.
Effector phase: T
C
clones recognize other infected cells, bind to them, and initiate lysis.
Slide131Figure 41.13 Phases of the Humoral and Cellular Immune Responses (Part 2)
Slide13241.5 The Cellular Adaptive Response Involves T Cells and Receptors
TC cells produce perforin, which lyses target cells.
T
C
cells also bind to a receptor (
Fas
) on target cells that initiates apoptosis.
T
C cells recognize self MHC proteins complexed with foreign or altered fragments and help rid the body of its own infected cells.
Slide13341.5 The Cellular Adaptive Response Involves T Cells and Receptors
Regulatory T cells (Tregs
) recognize self antigens.
When activated they secrete cytokines, which block activation of T cells that are bound to the same antigen-presenting cell.
Slide134Figure 41.14 Tregs and Tolerance
Slide135Key Concept 41.5 Learning Outcomes
Summarize the role of MHC proteins in the humoral immune response.Provide reasonable speculation regarding how drugs could generate
immunosupression
by targeting T-helper cells, and predict the side effects of these drugs.
Slide136Key Concept 41.5 Learning Outcomes
Describe how Tregs suppress the cellular and humoral immune systems.
Predict consequences of inappropriate levels of activity of
Tregs
.
Slide137Key Concept 41.6 Focus Your Learning
Allergic reactions, which can be immediate or delayed, result from an over-stimulation of the immune response.
Allergies can be treated by desensitization.
Autoimmunity occurs when T cells bind to antigen–MHC complexes that carry self antigens.
Slide138Key Concept 41.6 Focus Your Learning
The study of HIV has led to the development of treatments for HIV.
Slide13941.6 Malfunctions in Immunity Can Be Harmful
Allergic reactions occur when the immune system overreacts or is hypersensitive to an antigen.
The antigen may not be a danger, but the immune system produces inflammation and other symptoms that can cause serious illness or even death.
Slide14041.6 Malfunctions in Immunity Can Be Harmful
Immediate hypersensitivity: When exposed to an allergen (antigen) in food, pollen, insect venom etc., large amounts of
IgE
are produced.
The
IgE
constant end binds to mast cells and basophils.
If allergen exposure occurs again, large amounts of histamine are released.
Slide141Figure 41.15 An Allergic Reaction (Part 1)
Slide142Figure 41.15 An Allergic Reaction (Part 2)
Slide14341.6 Malfunctions in Immunity Can Be Harmful
Histamine produce symptoms such as inflammation, blood vessel dilation, difficulty in breathing.
It can be treated with antihistamines.
It is unknown why some people produce IgE in response to certain allergens.
Slide14441.6 Malfunctions in Immunity Can Be Harmful
Allergy to pollen can be treated by desensitization—small amounts of allergen are injected under the skin to stimulate IgG, but not IgE
, production.
The next exposure causes IgG to bind to the allergen, before
IgE
does.
Desensitization does not work with food allergies because
IgE
response is so strong, a tiny amount of allergen provokes it.
Slide14541.6 Malfunctions in Immunity Can Be Harmful
Delayed hypersensitivity begins hours after exposure to the allergen.
The antigen is taken up by antigen-presenting cells and a T cell response is initiated. Cytokines cause inflammation and rash.
Example: Poison ivy rash
Slide14641.6 Malfunctions in Immunity Can Be Harmful
Autoimmunity: Errors in T cell selection result in T cells that bind to self antigen-MHC complexes.
Autoimmunity may result from:
Failure of negative deletion
Molecular mimicry—self antigens have components that resemble
nonself
and are recognized by T cells
Slide14741.6 Malfunctions in Immunity Can Be Harmful
Some autoimmune diseases:Systemic
lupus
erythematosis
(
SLE
)—antibodies to cellular components, including DNA and nuclear components.Results in large circulating antibody-antigen complexes that become stuck in tissues, causing inflammation.
Slide14841.6 Malfunctions in Immunity Can Be Harmful
Rheumatoid arthritis—T cell response to self antigens cannot be shut down, possibly due to low CTLA4 activity (a protein that blocks T cells from reacting to self antigens). Results in joint inflammation.
Hashimoto’s thyroiditis—
immune cells attack thyroid tissue.
Slide14941.6 Malfunctions in Immunity Can Be Harmful
Insulin-dependent diabetes mellitus (type I) occurs most often in children.
Caused by an immune reaction against proteins in the pancreatic cells that make insulin.
Insulin-producing cells are destroyed and insulin must be taken daily.
Slide15041.6 Malfunctions in Immunity Can Be Harmful
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 is unable to mount an adaptive immune response.
Slide15141.6 Malfunctions in Immunity Can Be Harmful
TH cells are crucial to both humoral and cellular responses.
T
H
cells are the target of
human immunodeficiency virus
(
HIV
), the retrovirus that results in (AIDS) acquired immune deficiency syndrome.
Slide15241.6 Malfunctions in Immunity Can Be Harmful
HIV can be transmitted by bodily fluids containing the virus (blood, semen, vaginal fluid, or breast milk).
The recipient tissue is blood (by transfusion) or mucous membranes (the mucus contains many lymphocytes).
Slide15341.6 Malfunctions in Immunity Can Be Harmful
HIV initially infects TH cells, macrophages, and antigen-presenting dendritic cells.
At first there is an immune response and T
H
cells are activated—but T
H
cells are later killed by HIV and lysed by T
C
cells.TH cell numbers decline after the first month.
Slide15441.6 Malfunctions in Immunity Can Be Harmful
Meanwhile, HIV production activates the humoral immune system.
HIV infection reaches a low, steady state level—the “set point.”
Set point level varies in individuals and determines rate of progression of the disease.
Slide155Figure 41.16 The Course of an HIV Infection
Slide15641.6 Malfunctions in Immunity Can Be Harmful
Gradually, TH cells are destroyed, and the person is susceptible to many infections.
Opportunistic infections:
Kaposi’s sarcoma, a rare skin cancer caused by a herpes virus
Pneumonia caused by the fungus
Pneumocystis
jirovecii
Lymphoma tumors caused by Epstein-Barr virus
Slide15741.6 Malfunctions in Immunity Can Be Harmful
Drug treatments for HIV are focused on inhibiting viral proteins, such as:
Reverse transcriptase—catalyzes synthesis of cDNA from viral RNA
Vital protease—cuts large viral protein into final active protein
Treatment with combinations of drugs has been very successful.
Slide158Key Concept 41.6 Learning Outcomes
Summarize the responses made during immediate hypersensitivity.Describe how desensitization can be used to minimize allergic reactions.
Summarize the hypotheses that explain how autoimmunity can occur.
Outline experiments to test the effectiveness of an HIV vaccine.
Slide159Investigating Life: Vaccines and Immunity
Vaccines have been spectacularly successful at inducing lasting immunity and even eradicating diseases when enough people are vaccinated.
Why do people refuse vaccines?
What are the mechanisms and implications of long-lasting immunity?
Slide160Investigating Life: Vaccines and Immunity
There seem to be several reasons:Complacency
—
some diseases such as measles are no longer visible threats.
Some people believe that vaccines are unsafe. The internet is full of these claims.
False alarms have led people to dismiss vaccination advisories
(e.g., swine flu).
Some people are suspicious of government programs in general.