54.0 Introduction

1. Body Armor Is Ineffective Against Microbes
1. Vertebrates Have Evolved a Variety of Defenses Against Invaders fig 54.1
2. Scientific research Seeks to Improve Our Defenses Against Infection

54.1 Many of the body's most effective defenses are nonspecific

1. Nonspecific Defense by the Skin
1. Vertebrates Employ a Multilevel Defense
1. First line of defense is nonspecific
1. Like walls and moats of medieval cities
2. Skin and mucous membranes block entry of invaders

2. Second line of defense uses cells that function like roaming patrols
1. Nonspecific defenses of chemicals and cells
2. Act rapidly with infection
3. Employ negative test that cannot be foiled by copycat foreign cells
4. All cells possess glycoproteins made by major histocompatibility complex (MHC)
1. Called MHC proteins or human leukocyte antigens (HLA)
2. Genes encoding MHC proteins are highly polymorphic
3. Different in each individual
4. Cells distinguish self from foreign cells, self vs. nonself recognition

3. Third line of defense is a positive test
1. Identifies molecules characteristic of foreign microbes, cancer cells
2. Cells possess surface receptor molecules that recognize non-self molecules

4. Skin is largest organ in human body fig 54.2

2. The Skin as a Barrier to Infection
1. Physically protects against microbe entry
2. Provides chemical defenses on surface
1. Oil and sweat glands make skin's surface acidic
2. Inhibits growth of microorganisms
3. Sweat contains lysozyme that digests bacterial cell walls

3. Prevents body water loss by evaporation
4. Composition of skin
1. Stratum corneum is outermost layer of epidermis
1. Constantly subjected to damage
2. Cells shed continuously
3. Replenished by stratum basale layer innermost layer of epidermis

2. Cells formed migrate to intermediate layer called stratum spinosum
1. Produce keratin during migration upward, makes skin tough and water resistant
2. Remain at outer surface about one moth before being replaced

3. Psoriasis: Chronic skin disorder, cells reach epidermis every 3 to 4 days

5. Lower skin layers provide support and insulation
1. Dermis is thicker than epidermis
1. Supports epidermis
2. Provides matrix for nerve endings, muscles, blood vessels
3. Wrinkling accompanying aging occurs here, leather produced from dermal layer

2. Subcutaneous tissue lies below dermis
1. Composed of adipose cells
2. Acts as shock absorber
3. Insulates body, conserves body heat
4. Thickness varies throughout body

3. Other External Surfaces
1. Alternate routes of entry for invaders
2. Digestive tract
1. Saliva contains lysozymes
2. Stomach produces digestive acids
3. Intestine produces protein-digesting enzymes

3. Respiratory tract
1. Cells in bronchi and bronchioles produce entrapping mucus, swept outward by cilia
2. Ciliated epithelial cells trap microbes, swept to glottis fig 54.3

2. Cells and Proteins that Kill Invading Microbes
1. Nonspecific Actions that Provide Defense when the Skin is Breached
1. Myriad of cell and chemical devices
2. Respond to any microbial attack, without determining identity of invader

2. Cells that Kill Invading Microbes
1. Macrophages are one type of phagocyte fig 54.4
1. Directly ingest individual bacteria
2. Bacterium pulled inside via phagocytosis
3. Vacuole with bacterium attacked by cell's lysosome with oxygen free radicals
4. Also ingest viruses, cell debris, dust particles
5. Circulate in extracellular fluid, other phagocytes in liver, spleen, bone marrow
6. Monocytes from blood respond to infection and transform into macrophages

2. Neutrophils are also phagocytic
1. White blood cells that directly ingest bacteria
2. Macrophages kill only one cell at a time, but kill many cells sequentially
3. Neutrophils release bleach-like chemicals that kill many invaders at once
4. Also kill selves in process

3. Natural killer cells do not attack microbes directly
1. Attack cells infected by microbes and especially viruses
2. Not phagocytic, create a pore in target cell membrane fig 54.5
3. Target cell absorbs water, swells and bursts fig 54.6
4. Also attack cancer cells, often before they form tumor

4. Killing cells distinguish self from nonself via self-identifying MHC proteins
1. Body cells that make self marker improperly are attacked by same cells
2. Resulting diseases called autoimmune diseases

3. Proteins that Kill Invading Microbes
1. Complement system
1. Named because it complements cellular defenses
2. Complex composed of about 20 circulating proteins
1. Proteins form membrane attack complex with bacteria or fungus cell wall
2. Forms pore in membrane, cell swells and bursts fig 54.7

3. Aggregation also triggered by antibodies binding to invaders
4. Augment other body defenses
1. Amplify inflammatory response by stimulating histamine release
2. Attract phagocytes to area of infection
3. Coat invading microbes to help macrophages stick more readily

2. Three major classes of interferons: Alpha, beta and gamma
1. Nearly all body cells make alpha and beta interferons
1. Polypeptides that act as messengers to protect other cells from viral infection
2. Viruses still penetrate, but unable to replicate and assemble new viruses

2. Gamma interferon only produced by particular lymphocytes and natural killer cells
1. Part of immune defense against infection and cancer

3. The Inflammatory Response
1. Localized, Nonspecific Reaction to Infection
1. Infected or injured cells release chemicals
1. Include histamine and prostaglandin
2. Promote dilation of blood vessels, increase local blood flow and temperature
3. Increase permeability of capillaries
1. Produces edema and tissue swelling
2. Allow phagocytes to migrate from blood to extracellular fluid
1. Neutrophils arrive first, make killing chemicals, produce pus
2. Macrophages follow engulfing remains of dead cells fig 54.8

2. Autoimmune diseases like arthritis cause inflammation without infection

2. The Temperature Response
1. Pyrogens are chemicals released by macrophages
1. Include interleukin-1
2. Carried by blood to brain

2. Induces fever: Increased body temperature
1. Active production of fever in lizards, they move to warm environment
2. Stimulates phagocytosis, reduces levels of iron in blood
3. Excessive fever may inactivate critical body enzymes

1. Characteristics of the Immune Response
1. Body Remembers Previous Encounters with Potential Invaders
1. Catching many diseases results in permanent immunity to each disease
2. Immune system provides mechanism for immunity and resisting infection

2. Terms Used in Describing Specific Immunity
1. Antigen
1. Molecule that provokes specific immune response
2. Large, complex molecules like proteins
3. Generally foreign to body, include bacteria and viruses
4. Large antigen may have several parts, each stimulates different immune response
5. Different parts called antigenic determinant sites, serves as different antigen
6. Particular lymphocytes have receptor proteins that recognize antigen
1. Direct immune response against antigen or cell carrying antigen
2. Failure in nonself recognition produces auto immune disease

2. Antibody
1. Protein produced by particular lymphocytes in response to antigen
2. Secreted into blood, body fluids to produce humoral immunity
3. Other lymphocytes do not produce antibodies, attack cells via cell-mediated immunity

3. Active immunity
1. Immunity caused by exposure to pathogen
2. Also called acquired immunity

4. Passive immunity
1. Immunity derived from antibodies produced by another individual
2. Antibodies from mother passed to fetus

3. Discovery of the Immune Response
1. Jenner and smallpox fig 54.9
1. Milkmaids rarely developed smallpox infections
2. Developed milder form called cowpox, conferred resistance to smallpox
3. First use of vaccination
4. Injecting harmless microbe to confer resistance to harmful one

2. Pasteur and fowl cholera
1. Isolated culture of organisms that would elicit disease in other fowl
2. Accidentally created weakened form of bacteria
3. Weakened culture caused minor symptoms and conferred immunity
4. Immune response reacted to foreign molecules on surface of bacteria

2. Evolution of the Immune System
1. All Organisms have Mechanisms to Protect Selves from Invaders
1. Bacterial cells produce restriction endonucleases that degrade viral DNA
2. More difficult problem faced by multicellular organisms, invaders not pure DNA

2. Invertebrates
1. Employ negative test against invaders
1. All body cells possess cell surface proteins that identify "self"
2. Cells lacking self protein are destroyed
3. Employ negative test to recognize foreign cells and invaders
4. Does not protect against "copycat" invaders with markers resembling self marker

2. Immune defense first recognized in examination of starfish larva attacked by thorn
1. Metchnikoff in 1882
2. Found cells attempting to engulf thorn
3. Discovery known as cellular immune response
4. Ehrlich worked on elucidating humoral immune response

3. Common Elements of Immune Response Shared by Invertebrates and Vertebrates
1. Phagocytes
1. Cells that attack invading microbes
2. Travel through circulatory system or circulating fluid in body cavity
3. In sponges, phagocytic cells present in spaces between cells

2. Distinguishing self from nonself
1. Evolved early in history of life
2. Sponges attack grafts from other sponges, as do insects and starfish
3. Invertebrates do not show evidence of immunological memory
4. Antibody-based humoral defense evolved in vertebrates

3. Complement
1. Invertebrates lack complement itself
2. Many arthropods have analogous defense called prophenoloxidase (proPO) system
1. ProPO defense activated by cascade of enzyme reactions
2. Last reaction converts inactive proPO to active enzyme phenyloxidase
3. Phenyloxidase kills microbes and helps encapsulate foreign objects

4. Lymphocytes
1. Lacking in invertebrates
2. Annelids, other invertebrates have lymphocyte-like cells, evolutionary precursors

5. Antibodies
1. Invertebrates have lectin proteins, forerunners of antibodies
2. Lectins tag invading microorganisms, enhance phagocytosis
3. All proteins in group have recognition structure called Ig fold
4. Ig fold evolved as self-recognition molecule in early metazoans
5. Many insects have immunoglobins
1. Bind to microbial surfaces
2. Promote destruction by phagocytes

4. Vertebrates fig 54.11
1. Lampreys have an immune system based on lymphocytes
1. Earliest record of vertebrate system
2. Lack distinct populations of B and T cells

2. Early jawed fishes and sharks have immune response similar to mammals'
1. Cellular response carried out by T cell lymphocytes
2. Antibody-mediated humoral response carried out by B cells
3. Possess thymus that produces T cells
4. Possess spleen with multitudes of B cells
5. Amino acid sequences of antibodies very similar

3. Notable difference: Antibody-encoding genes arrayed differently

3. The Cells of the Vertebrate Immune System tbl 54.1
1. Immune System Not Localized Within a Single Body Organ
1. Composed of individual leukocytes, white blood cells
2. Several kinds
1. Phagocyte cells: Neutrophils, eosinophils, basophils, monocytes
2. Lymphocytes: T cells and B cells are not phagocytic
1. Cell-mediated response via T cells
2. Humoral response via B cells

2. T Cells
1. Arise from bone marrow stem cells and travel to thymus
1. Develop ability to identify invaders via surface antigens
2. Different T cells recognize different antigens

2. Four kinds of T cells
1. Inducer T cells: Oversee development of T cells in thymus
2. Helper T cells (T_H): Initiate immune response
3. Cytotoxic T cells (T_C): Lyse cells infected with viruses
4. Suppressor T cells: Terminate immune response

3. B Cells
1. Arise from and mature in bone marrow, do not travel to thymus
1. Complete maturation in marrow, circulate in blood and lymph
2. Individual cells specialized to recognize specific antigens

2. Antigen initiates rapid division of specific B cell
1. B cell progeny differentiate into plasma cells and memory cells
2. Plasma cells produce antibody proteins that flag antigens
3. Flagged cells are marked for destruction

4. Active Immunity Through Clonal Selection
1. B and T cells have receptors on surface that bind to specific antigens
1. Antigen must encounter lymphocyte with correct receptor to evoke immune response
2. Only a few B or T cells have right receptor first time antigen is encountered

2. Clonal selection
1. Binding of receptor and antigen stimulates cell division
2. Produces clone of identical cells

3. Primary immune response fig 54.12
1. First encounter to specific antigen, few cells to mount response
2. Immune response is relatively weak

4. Secondary immune response fig 54.13
1. Primary response may involve B plasma cells that secrete antibodies
2. Some B cells become memory cells
3. Development of clone of memory cells enables next response to be swifter, stronger

5. Memory cells can survive for decades
1. Example: Can't contract measles a second time
2. Also provides effectiveness of vaccines

6. Diseases caused by viruses with mutating protein coats are harder to defeat
1. Genetic change causes new strains to appear yearly
2. Not recognized by memory cells of previous infections

1. The Humoral Immune Response
1. B Cell Lymphocytes Produce and Secrete Antibodies
1. Circulating in body fluids, blood, lymph, extracellular fluid
1. Term humoral refers to fluids

2. B cell divides in response to antigen exposure fig 54.14
1. Plasma cells are short-lived antibody factories
2. Memory cells are long-lived protectors

2. Antibodies Are Immunoglobulin Proteins
1. Immunoglobulins (Ig) divided into subclasses based on structure and function
1. IgM
1. First antibody secreted in primary response
2. Serve as receptors on lymphocyte surface
3. Promote agglutination reactions, cause antigen particles to stick together

2. IgG
1. Major form of antibody secreted in secondary response
2. Major antibody in blood plasma

3. IgD
1. Serve as receptors for antigens on B cell surface
2. Other function unknown

4. IgA
1. External form secreted in saliva and milk

5. IgE
1. Promotes release of histamines
2. Produces symptoms of allergic response

2. Each B cell has 100,000 IgM or IgD receptors on surface
1. T cells bind only to antigens presented by certain cells
2. B cells bind to free antigens
1. Provokes primary response in which IgM antibodies are secreted
2. Stimulates cell division and clonal expansion

3. With subsequent exposure plasma cells secrete IgG class antibodies
1. Produce vast amounts even though short lived
2. Antibodies constitute 20% of weight of total proteins in blood

4. IgG antibody production peaks after three weeks fig 54.15

3. IgM (and IgG) antibodies bind to cell, cause aggregation of complement proteins
1. Complement produces pore that pierces cell membrane of infected cell fig 54.16
2. Water enters cell, causes it to burst

4. IgG antibodies bind to antigens on cell and serve as markers
1. Stimulate phagocytosis by macrophages
2. Some complement proteins attract phagocytic cells
3. Activation of complement accompanied by increase in phagocytosis

5. Antibodies don't kill invaders directly
1. Cause destruction by activating complement system
2. Target pathogen for attack by phagocytes

2. Antibodies
1. Structure of Antibodies
1. Composed of two short, light chains and two long, heavy chains fig 54.17
2. Chains held together by disulfide bonds, forming Y-shaped molecule fig 54.18
3. Specificity resides in arms of Y
1. Variable amino acid regions located on arms
2. Amino acid sequence of stem by constant within a class of antibodies

4. Most sequence variation lies in terminal half of each arm
1. Six hypervariable segments, three in light and three in heavy chain
2. Form cleft that serves as binding site for antigen
3. Both arms have same cleft, binds same antigen

5. Antibodies may have identical clefts and bind to same antigen
1. May be different in stem portion of antibody molecule
2. Stem formed by "constant" regions of heavy chain
3. Five classes of heavy chains: IgM, IgG, IgA, IgD, IgE

6. IgE antibodies bind to mast cells
1. Heavy chain stems insert into receptors on mast cell plasma membrane
2. Create B cell receptors on mast cell surface
3. Cells encounter specific antigen, initiate inflammatory response, release histamine
4. Increases vasodilation, capillary permeability
5. Lymphocytes, macrophages and complement proteins reach site more readily

7. IgA antibodies present in secretions
1. Include milk, mucous and saliva
2. Antibodies in milk may confer immune protection to nursing infants

2. Antibody Diversity
1. Mechanism for recognizing millions of different antigens
1. Chromosomes contain only a few hundred receptor-encoding genes
2. Can generate 106 to 109 different antibody molecules

2. Somatic rearrangement
1. Millions of receptor genes not inherited at conception
2. Receptor genes are not single nucleotide sequences
3. Assembled by combining three or four DNA segments
4. Chromosomal sites composed of a cluster of similar sequences fig 54.19

3. Generation of additional sequences by somatic mutation
1. Segments joined off register, shifts reading frame during translation
2. Random mistakes occur during DNA replication in formation of clones

4. Variability in humans
1. Heavy chain sequences = 16,000 combinations
2. Light chains sequences = 1200 combinations
3. 16,000 x 1,200 = 19 million different possible antibodies

5. All effects produce 200 million mathematical combinations
6. T cells are as diverse as B cells, subject to similar somatic rearrangements, mutations

3. Immunological Tolerance
1. Mature animal does not respond to its own tissue as foreign
1. Acceptance of self cells

2. Embryo can respond to both foreign and self molecules
1. Looses ability to respond to self as development proceeds
2. Foreign tissue introduced before immune system develops is not recognized as foreign

3. Immunological tolerance has two explanations
1. Clonal deletion
1. Maturation of hemopoietic stem cells in embryo, fetus or newborn
2. Receptors for self antigens are eliminated

2. Clonal suppression
3. Receptors for antigens are suppressed

4. Spontaneous breakdown of tolerance causes B and/or T cells to recognize own antigens
1. Myasthenia gravis: Antibodies against muscle ACh receptors, causes paralysis

3. Antibodies in Medical Diagnosis
1. Blood Typing
1. Blood type indicates class of antigens found on surface of red blood cell
1. Types must be matched between donors and recipients in blood transfusions

2. Several groups, major group called ABO system
1. Type A: Only A antigens
2. Type B: Only B antigens
3. Type AB: Both A and B antigens
4. Type O: Neither A or B antigen

3. Body is tolerant of own blood cell antigens
1. Type A person doesn't produce anti-A antibodies

4. Cross production of antibodies to antigens
1. Type A does make antibodies to B antigens
2. Type B makes antibodies to A antigens
3. May result from antibodies to certain bacteria cross reacting with A or B antigens
4. Type AB develop tolerance to both antigens, produce neither antibody
5. Type O don't develop tolerance to either, produce both antibodies

5. Test of compatibility on a glass slide fig 54.20
1. Type A blood mixed with serum from type B
2. Anti-A antibodies in serum cause type A cells to agglutinate

6. Blood matched prior to transfusions
1. Clumping in blood vessels causes inflammation and organ damage

7. Rh factor
1. Second group of antigens associated with red blood cells
1. Rh positive persons posses antigens
2. Rh negative persons lack antigens

2. Rh negative is recessive to Rh positive, fewer people are Rh negative
3. Factor is important when Rh– mothers give birth to Rh+ babies
1. Fetal and maternal blood normally separated across placenta
2. Rh– mother not exposed to Rh antigen of fetus during pregnancy
3. Exposure may occur at birth, mother's blood becomes sensitized
4. Mother produces anti-Rh antibodies

4. Antibodies can cross placenta during subsequent pregnancy
1. Causes hemolysis of Rh+ red blood cells of fetus
2. Causes erythroblastosis fetalis (hemolytic disease of the newborn)

5. Can be prevented by injecting Rh– mother with antibodies against Rh
1. Must be done within 72 hours of the birth of each Rh+ baby
2. Passive immunization, injected antibodies inactivate Rh antigens
3. Prevent mother from becoming actively immunized to antigens

2. Monoclonal Antibodies fig 54.21
1. Antibodies are commercially prepared for medical diagnosis and research
1. Early production by purifying antigen and injecting it into animals
2. Antigen has many antigen determinant sites, antibodies thus polyclonal
3. Stimulate development of different B cell clones, with different specificities
4. Decreases sensitivity to a particular antigenic site
5. Resulted in cross-reaction with closely related antigens

2. Production of monoclonal antibodies
1. Exhibit specificity to only one antigenic determinant
1. Animal injected with antigen, later killed
2. B lymphocytes obtained from spleen, placed in thousands of incubation vessels

2. Cells die unless hybridized with cancerous multiple myeloma cells
1. Fusion produces hybrid that divides and makes clone called hybridoma
2. Each hybridoma secretes large amounts of identical, monoclonal antibodies
3. Thousands of hybridomas tested
4. Single one that produces desired antibody cultured, rest discarded

3. Resulted in development of more sensitive clinical laboratory tests
1. Modern pregnancy test use particles covered with monoclonal antibodies fig 54.22
1. Antibodies are against pregnancy hormone hCG antigen
2. Particles mixed with sample containing antigen
3. Antigen-antibody reaction causes visible agglutination of particles

1. The Role of MHC Proteins in T Cell Function
1. Cell Surface Proteins Play Role in Immune Response tbl 54.2
1. MHC proteins serve as self labels
1. MHC-I present on every nucleated cell
2. MHC-II present on macrophages, B cells and CD4⁺T cells
3. MHC-II cells work together, markers permit recognition of one another

2. Human MHC proteins specified by highly polymorphic genes
3. Rare for two persons to have same allele combinations, same mix of MHC proteins
4. MHC protein self/nonself recognition critical for function of T cells
1. T cells cannot bind to free antibodies like B cells do
2. Bind only to antigens presented on cell surface
3. T cells only recognize antigens associated with MHC proteins

5. Cells called antigen-presenting cells
1. Cytotoxic T lymphocytes interact with antigens presented with MHC-I proteins
1. Act to destroy infected cells

2. Helper T lymphocytes interact with antigens presented with MHC-II proteins

2. Coreceptors Associated with Proteins of T Cell Receptors
1. Coreceptor CD8 associated with cytotoxic T cell receptor
1. Cells shown as CD8⁺
2. CD8 coreceptor only interacts with MHC-I of infected cell

2. Coreceptor CD4 associated with helper T cell receptor
1. Cells indicated as CD4⁺
2. CD4 only interacts with MHC-II proteins of another cell

3. Process associated with invasion by foreign particle
1. Particle taken up by macrophages by phagocytosis, partly digested
2. Particle provides foreign antigens that move to surface of cell membrane
3. Foreign antigens form complex with MHC-II proteins
4. Complex required for interaction with receptors on surface of helper T cells
5. Macrophages present antigens to helper T cells, begin their activation fig 54.24

2. The Cell-Mediated Immune Response
1. Complex Series of Steps Associated with T Cells and Antigens
1. Helper T cell presented with foreign antigen and MHC proteins
2. Involves secretion of autocrine regulatory molecules
1. Generally called cytokines
2. Are lymphokines if secreted by lymphocytes

2. Cytokines
1. Named by association with biological activity
1. Example: B cell-stimulating factor
2. Names can be misleading, one cytokine may have multiple actions

2. Interleukin used to describe cytokine with known amino acid sequence
1. Interleukin-1: Secreted by macrophages, can activate T cell system
2. Interleukin-4: Secreted by T cells, required for clone development of B cells
3. Interleukin-2: Released by helper T cells, activates cytotoxic T lymphocytes

3. Cell Interactions in the T Cell Response
1. Macrophages process foreign antigens, secrete interleukin-1
1. Stimulates cell division, proliferation of T cells

2. Helper T cells activated by antigens of macrophages
1. Secrete two cytokines: macrophage colony-stimulating factor, gamma interferon
2. Also secrete interleukin-2, stimulates proliferation of cytotoxic T cells and B cells

3. Cytotoxic cells only destroy infected cells if antigen displayed with MHC-II fig 54.24
4. Interactions among different cell types spreads
1. Helper T cells promote humoral response of B cells
2. Foreign antigen attaches to immunoglobulin receptors on B cells
3. B cells present antigen with MHC-II proteins to helper T cells
4. Stimulates proliferation of B cells
5. Causes conversion to plasma cells, secretion of antibodies

5. Helper T cells needed for cell-mediated and humoral responses fig 54.25

4. T Cells in Transplant Rejection and Surveillance Against Cancer
1. Cytotoxic t cells attack foreign versions of MHC-I
2. Immune system attacks transplanted tissue, causes graft rejection
1. Closer relatedness increases similarities of MHC proteins
2. More likely to tolerate each other's tissues
3. Relatives sought for kidney transplants

3. Cyclosporin inhibits graft rejection, inactivates cytotoxic T cells
4. Immunological surveillance against cancer
1. Developing tumors reveal surface antigens
2. Stimulate destruction of tumor cells
3. Tumor antigens activate immune system
4. Initiate attack by cytotoxic T cells and natural killer cells fig 54.26
5. proposed role of immune system in fighting cancer

5. Human interferon produced by bacteria available to treat cancer
1. Useful in treating certain forms of cancer
2. Include lymphomas, renal carcinoma, melanoma, Kaposi's sarcoma, breast cancer

6. Interleukin-2 (IL-2) genetically engineered, available for therapy
1. Activates cytotoxic T cells, B cells
2. Lymphocytes removed, treated with IL-2, returned to patient

1. T Cell Destruction: AIDS
1. Defeat Immune System by Attacking It Directly
1. Inactivate CD4⁺ T cells
1. CD4⁺ cells include helper T cells and inducer T cells
2. Immune unable to mount response to any foreign antigen

2. Mode of operation of retrovirus that causes AIDS
1. Acquired immune deficiency syndrome = AIDS
2. Virus is human immunodeficiency virus (HIV)
3. Recognizes CD4 coreceptors associated with these T cells

2. AIDS Attacks Immune System in Three Ways
1. HIV-infected cells die after releasing replicated viruses
1. Viruses infect other CD4⁺ T cells
2. Eventually all CD4⁺ calls are destroyed fig 54.27
3. CD4⁺ cells normally comprise 60-80% of circulating T cells
4. Decrease to near nothing in AIDS patients fig 54.28

2. HIV causes infected CD4⁺ cells to secrete suppressing factor
1. Blocks other T cells from responding to HIV antigen

3. HIV may block transcription of MHC genes
1. Hinder recognition and destruction of infected CD4⁺ cells
2. Protect cells from remaining actions of immune system

4. Destroys defense against infection, causes death from common diseases or cancers
1. Although new disease, it is one of most serious in human history
2. Disease is fatal but not highly communicable
1. Transmitted via infected blood fluids
2. Not all exposed individuals develop disease
3. Infected individuals do not live for more than a few year

3. Trying to develop a vaccine using vaccinia virus or harmless strain

5. Treatment slows progression of disease
1. Include drugs like AZT that inhibits activity of reverse transcriptase
2. Virus cannot produce DNA from Rna
3. New drugs recently available inhibit protease needed for viral assembly
4. Treatment may include combinations of drugs to lower HIV levels

6. Still attempting to develop vaccine

2. Antigen Shifting
1. Second Way Pathogens Attempt to Defeat Immune System
1. Mutate frequently to vary nature of surface antigens
2. Occurs in viruses that cause influenza
3. Exhibited by trypanosomes: Protists that cause sleeping sickness
1. Possess thousands of versions of gene that codes for coat protein
2. Genes lack individual promoters, are not transcribed
3. Promotor located within a transposable element that jumps at random
4. Coat changes frequently, cannot mount immunological defense

2. How Malaria Hides from the Immune System
1. Protozoa parasite Plasmodium falciparum causes malaria
1. Kills 1 million people mostly children
2. Parasites enter red blood cells, consume hemoglobin
3. Parasite causes production of attachment knobs on cell surface
4. Prevents damaged cells from traveling to spleen for destruction

2. Immune system brings infection under control
1. Small number of parasites change knob proteins to new unrecognized form
2. Starts new wave of infection

3. Antigen-shifting defense recently determined
1. 6% of parasites DNA devoted to encoding block of 150 var genes
2. Genes shifted on and off in multiple combinations
3. Each cell division alters pattern of var gene expression 2%

3. DNA Vaccines May Get Around Antigen Shifting
1. Most vaccines associated with pathogen surface proteins
1. Vaccination triggers immune response
2. Vaccinated person contains B cells in blood to remember pathogen for future infections

2. Antigen shifting changes pathogens, B cells no longer recognize them
3. DNA vaccine makes use of killer T cells rather than B cells
1. Pathogens recognized by B cells, signal production of antibodies
2. Pathogens inside cells are protected from antibodies
3. Killer cells can only attack if pathogen proteins displayed on outside of cells
4. Only occurs if cell contains live version of pathogen
5. Vaccination with live vaccine may cause disease

4. DNA vaccines avoid risk of live pathogen vaccines
1. Contain plasmid with gene for critical internal protein that does not change
2. Plasmid injected, gene transcribed but not incorporated into host DNA
3. Fragment of pathogen protein stuck on to cell membrane
4. Cell thus marked for destruction
5. In later infections immune system responds rapidly

3. Autoimmunity and Allergy
1. Autoimmune Diseases
1. Produced when immune system fails to recognize self antigens
1. Results in activation of autoreactive T cells, production of autoantibodies by B cells
2. Causes inflammation and organ damage

2. Over 40 known autoimmune diseases affect 5-7% of population, most are female
3. Result from variety of mechanisms
1. Self antigen may be hidden from immune system, later treated as foreign
1. Hashimoto's disease: Protein normally trapped in thyroid triggers destruction of thyroid
2. Systemic lupus erythematosus: Antibodies made to nucleoproteins

4. Immune system suppressed to alleviate symptom of disease
1. Use corticosteroids, including hydrocortisone
2. Nonsteroidal anti inflammatory drugs like aspirin

2. Allergy
1. Used interchangeably with hypersensitivity
2. Abnormal immune response to antigens called allergens
1. Immediate hypersensitivity
1. Due to abnormal B cell response to allergen
2. Response occurs in seconds to minutes

2. Delayed hypersensitivity
1. Abnormal T cell response
2. Produces symptoms with 48 hours of exposure to allergen

3. Symptoms and actions of immediate hypersensitivity fig 54.30
1. Allergic rhinitis, conjunctivitis, allergic asthma, atopic dermatitis
2. Result from production of IgE antibodies instead of IgG antibodies
3. IgE antibodies do not circulate in blood, attach to tissue mast cells and basophils
4. With second exposure allergen binds to antibodies on mast cells and basophils
5. Stimulates cells to produce histamine, causes symptoms

4. Allergens that cause immediate hypersensitivity
1. Include foods, bee stings, pollen grains
2. Most common is seasonal hay fever, often caused by ragweed fig 54.31a
3. Other common source is the dust mite fig 54.31b
1. Shows as chronic allergy to dust or feathers
2. Mite eats skin scales shed from body
3. Allergens from mite feces, not body of mite

5. Allergies are generally mild, but some may be life threatening
1. Include allergies to peanuts, penicillin
2. Excessive release of histamines cause anaphylactic shock, fall in blood pressure

6. Time response for delayed hypersensitivity due to T cell association
1. Best example is contact dermatitis from poison ivy, oak or sumac
2. Symptoms caused by secretion of lymphokines
3. Little benefit derived from treatment with antihistamines
4. Treat best with corticosteroids