Innate Immunity: Defenses Against Infection

Innate Immunity: Broad Defenses Against Infection

• Invading microbes must breach the external barriers of skin and mucous membranes.
• The skin and mucous membranes are the first line of defense.
• The second line of defense involves innate cellular and chemical mechanisms.
• Intact skin acts as a barrier that is difficult for bacteria or viruses to penetrate.
• Mucous membranes lining the digestive, respiratory, and genitourinary tracts also prevent microbe entry.
• Mucus traps microbes and other particles.
• Ciliated epithelial cells in the trachea sweep out mucus, preventing lung entry.
• Skin pH ranges from 3 to 5, preventing colonization by many microbes.
• Saliva, tears, and mucous secretions wash away microbes.
• These secretions contain antimicrobial proteins like lysozyme, which digests bacterial cell walls.
• The stomach's acidic environment destroys many microbes.
• Hepatitis A virus is an exception, surviving gastric acidity and entering via the digestive tract.

Phagocytic Cells and Antimicrobial Proteins

• Microbes that penetrate the first defense line face phagocytosis, the ingestion of invaders by white blood cells.
• Phagocytes attach to microbes via surface receptors not found on normal body cells.
• Phagocytes engulf microbes, forming a vacuole that fuses with a lysosome.
• Lysosomes contain nitric oxide and other toxic oxygen forms that act as antimicrobial agents.
• Lysozymes and other enzymes degrade microbial components.
• Some microbial adaptations evade phagocyte destruction
• Some bacterial capsules hide surface polysaccharides, preventing phagocyte attachment.
• Some bacteria resist digestion, growing and reproducing within phagocytes.
• Neutrophils make up 60–70% of white blood cells and are phagocytic.
• Damaged cells release chemical signals that attract neutrophils.
• Neutrophils enter infected tissues, engulfing and destroying microbes, but self-destruct within days.
• Monocytes, about 5% of leukocytes, migrate into tissues and develop into macrophages, large, long-lived phagocytes.
• Macrophages reside in tissues like lungs, liver, lymph nodes, and spleen, contacting infectious agents.
• Microbes in the blood get trapped in the spleen, while those in interstitial fluid flow into lymph nodes.
• Eosinophils contribute to defense against large parasites like blood flukes by discharging destructive enzymes.
• Dendritic cells ingest microbes and stimulate acquired immunity.
• Around 30 serum proteins form the complement system which is another set of antimicrobial agents,.
• These proteins are activated by microbe surfaces, leading to lysis.
• Interferons, secreted by virus-infected cells, defend against viral infection.
• Interferons induce neighboring cells to inhibit viral reproduction and limit cell-to-cell spread.
• Interferons produced against one virus may confer short-term resistance to unrelated viruses.
• One type of interferon activates phagocytes.
• Recombinant DNA technology is used to produce interferons for treating viral infections and cancer.

Inflammatory Response

• Tissue damage or microbe entry triggers a localized inflammatory response.
• Mast cells in connective tissues release histamine.
• Histamine causes dilation and increased permeability of nearby capillaries.
• Leukocytes and damaged tissue cells release prostaglandins, promoting blood flow.
• Increased blood supply leads to swelling, redness, and heat.
• Blood-engorged capillaries leak fluid, causing swelling.
• Increased blood flow delivers clotting elements to the injured area.
• Clotting begins repair and blocks microbe spread.
• Increased blood flow increases phagocyte migration from the blood into tissues.
• Chemokines secreted by cells, including endothelial cells and monocytes, attract phagocytes.
• The body mounts a systemic response to severe tissue damage or infection.
• Injured cells secrete chemicals, stimulating neutrophil release from bone marrow.
• White blood cell count may increase significantly within hours of initial inflammation during severe infection.
• Fever occurs when substances released by activated macrophages raise the body's temperature.
• Moderate fever facilitates phagocytosis and hastens tissue repair.
• Septic shock, an overwhelming systemic inflammatory response, is characterized by high fever and low blood pressure.
• Septic shock is a common cause of death in U.S. critical care units
• Local inflammation is essential for healing, but widespread inflammation is devastating.
• Natural killer (NK) cells destroy virus-infected and abnormal cells.
• NK cells attach to target cells and release chemicals that cause programmed cell death (apoptosis).
• The first line of defense, skin and mucous membranes, prevents microbes from entering the body.
• The second line of defense uses phagocytes, natural killer cells, inflammation, and antimicrobial proteins.
• Both lines of defense are nonspecific.
• Insects' hemolymph contains hemocytes which are the circulating cells.
• Some hemocytes phagocytose microbes, while others form capsules around large parasites.
• Some hemocytes secrete antimicrobial peptides.
• Invertebrates lack cells analogous to lymphocytes.
• Sponge cells distinguish self from nonself cells.
• Earthworm phagocytic cells show immunological memory.

Acquired Immunity: Lymphocytes and Specific Defenses

• Lymphocytes are the key cells of acquired immunity and the body’s second major kind of defense.
• Macrophages and dendritic cells secrete cytokines, activating lymphocytes and other immune cells.
• Innate and acquired defenses interact and cooperate.
• Antigens are foreign molecules that elicit a response from lymphocytes.
• Most antigens are large molecules such as proteins or polysaccharides.
• Antigens are cell-associated molecules that protrude from the surface of pathogens or transplanted cells.
• Lymphocytes recognize and bind to a small portion of an antigen called an epitope.
• Lymphocytes provide the specificity and diversity of the immune system.
• B lymphocytes (B cells) and T lymphocytes (T cells) are the two main types of lymphocytes.
• Both circulate throughout the blood and lymph and are concentrated in the spleen, lymph nodes, and other lymphatic tissue.
• B and T cells recognize antigens by means of antigen-specific receptors embedded in their plasma membranes.
• A single B or T cell bears about 100,000 identical antigen receptors.
• Lymphocytes display specificity for a particular epitope on an antigen.
• Each B cell receptor is a Y-shaped molecule with two identical heavy chains and two identical light chains linked by disulfide bridges.
• The transmembrane region anchors the receptor in the cell’s plasma membrane.
• Light- and heavy-chain variable (V) regions at the tips of the Y vary from one B cell to another.
• Constant (C) regions do not vary from cell to cell.
• Each B cell receptor has two identical antigen-binding sites formed from part of a heavy-chain V region and part of a light-chain V region.
• The interaction between an antigen-binding site and its corresponding antigen is stabilized by multiple noncovalent bonds.
• Secreted antibodies, or immunoglobulins, are similar to B cell receptors but lack transmembrane regions.
• B cell receptors are often called membrane antibodies or membrane immunoglobulins.
• Each T cell receptor consists of two polypeptide chains: an alpha chain and a beta chain, linked by a disulfide bridge.
• A transmembrane region anchors the molecule in the cell’s plasma membrane.
• Alpha and beta chain variable (V) regions form a single antigen-binding site at the tip of the molecule.
• Constant (C) regions make up the remainder of the molecule.
• T cell receptors recognize and bind antigens with the same specificity as B cell receptors.
• Receptors on B cells recognize intact antigens, the receptors on T cells recognize small fragments of antigens that are bound to normal cell-surface proteins called MHC molecules.
• MHC molecules are encoded by the major histocompatibility complex (MHC).
• As a newly synthesized MHC molecule moves toward the plasma membrane, it binds with a fragment of antigen within the cell and brings it to the cell surface, a process called antigen presentation.
• There are two ways in which foreign antigens can end up inside cells of the body.
• Peptide antigens are handled by a different class of MHC molecule and recognized by a particular subgroup of T cells.
• Class I MHC molecules, found on almost all nucleated cells of the body, bind peptides derived from foreign antigens synthesized within the cell.
• Any body cell that becomes infected or cancerous can display such peptide antigens by virtue of its class I MHC molecules.
• Class I MHC molecules displaying bound peptide antigens are recognized by cytotoxic T cells which are a subgroup of T cells.
• Class II MHC molecules are made by dendritic cells, macrophages, and B cells.
• Class II MHC molecules bind peptides derived from foreign materials that have been internalized and fragmented by phagocytosis.
• Each vertebrate species has numerous different alleles for each class I and class II MHC gene, producing the most polymorphic proteins known.
• Most people are heterozygous for every one of our MHC genes.
• It is unlikely that any two people, except identical twins, will have the same set of MHC molecules.
• The MHC provides a biochemical fingerprint unique to each individual marking body cells as “self.”
• Lymphocyte development gives rise to an immune system that distinguishes self from nonself.
• Lymphocytes originate from pluripotent stem cells in the bone marrow or liver of a developing fetus.
• Early lymphocytes are all alike, but they later develop into T cells or B cells, depending on where they continue their maturation.
• Lymphocytes migrate from the bone marrow to the thymus which is where they develop into T cells.
• Lymphocytes mature in the bone marrow and become B cells.
• Variable regions at the tip of each antigen receptor chain, which form the antigen-binding site, account for the diversity of lymphocytes.
• Each person has a million different B cells and 10 million different T cells, each with a specific antigen-binding ability.
• Unique genes that encode the antigen receptor chains are at the core of lymphocyte diversity.
• Genes for the light chain of the B cell receptor and for the alpha and beta chains of the T cell receptor undergo similar rearrangements, but we will consider only the gene coding for the light chain of the B cell receptor.
• Immunoglobulin light-chain gene contains a series of 40 variable (V) gene segments separated by a long stretch of DNA from 5 joining (J) gene segments.
• Recombinase enzymes link one V gene segment to one J gene segment, forming a single exon.
• Recombinase acts randomly and can link any one of 40 V gene segments to any one of 5 J gene segments.
• The light-chain gene can create 200 possible gene products (40 V × 5 J).
• The light chains combine randomly with the heavy chains that are similarly produced.
• Random rearrangements of antigen receptor genes may produce antigen receptors that are specific for the body’s own molecules.
• As B and T cells mature, their antigen receptors are tested for potential self-reactivity.
• Lymphocytes bearing receptors specific for molecules present in the body are either destroyed by apoptosis or rendered nonfunctional.
• Failure to do this can lead to autoimmune diseases such as multiple sclerosis.
• Microorganisms only interact with lymphocytes bearing receptors specific for its various of antigenic molecules out of repertoire of B cells and T cells.
• A lymphocyte is “selected” when it encounters a microbe with epitopes matching its receptors.
• Selection activates the lymphocyte, stimulating it to divide and differentiate, and eventually to produce two clones of cells.
• One clone consists of a large number of effector cells, short-lived cells that combat the same antigen.
• The other clone consists of memory cells, long-lived cells bearing receptors for the same antigen.
• This antigen-driven cloning of lymphocytes is called clonal selection and is fundamental to acquired immunity.
• Each antigen, by binding selectively to specific receptors, activates a tiny fraction of cells from the body’s diverse pool of lymphocytes.
• This small number of selected cells gives rise to clones of thousands of cells, all specific for and dedicated to eliminating that antigen.
• The selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to an antigen is the primary immune response.
• About 10 to 17 days are required from the initial exposure for the maximum effector cell response.
• Selected B cells and T cells generate antibody-producing effector B cells called plasma cells, and effector T cells, respectively.
• During this response, a stricken individual may become ill, but symptoms of the illness diminish and disappear as antibodies and effector T cells clear the antigen from the body.
• A second exposure to the same antigen at some later time elicits the secondary immune response.
• The secondary response is faster (only 2 to 7 days), of greater magnitude, and more prolonged.
• The antibodies produced in the secondary response tend to have greater affinity for the antigen.
• The immune system’s capacity to generate secondary immune responses is called immunological memory.
• Immunological memory is based not only on effector cells, but also on clones of long-lived T and B memory cells.
• These memory cells proliferate and differentiate rapidly when they later contact the same antigen.

Humoral and Cell-Mediated Immunity

• The immune system can mount a humoral response or a cell-mediated response to antigens.
• Humoral immunity involves B cell activation and clonal selection which results in the production of circulating antibodies.
• Circulating antibodies defend mainly against free bacteria, toxins, and viruses in the body fluids.
• Cell-mediated immunity destroys certain target cells through the activation and clonal selection of cytotoxic T lymphocytes
• Humoral and cell-mediated immune responses are linked by cell-signaling interactions
• Helper T lymphocytes function in both humoral and cell-mediated immunity.
• When a helper T cell recognizes a class II MHC molecule-antigen complex on an antigen-presenting cell, the helper T cell proliferates and differentiates into a clone of activated helper T cells and memory helper T cells.
• A surface protein called CD4 binds the side of the class II MHC molecule.
• CD4 interaction helps keep the helper T cell and the antigen-presenting cell joined while activation of the helper T cell proceeds.
• Activated helper T cells secrete cytokines that stimulate other lymphocytes, thereby promoting cell-mediated and humoral responses.
• Dendritic cells are important in triggering a primary immune response.
• They capture antigens, migrate to the lymphoid tissues, and present antigens, via class II MHC molecules, to helper T cells.
• Macrophages present antigens to memory helper T cells, while B cells primarily present antigens to helper T cells in the course of the humoral response.

Cell-Mediated and Humoral Response

• Cytotoxic T cells kill cancer cells and cells infected by viruses and other intracellular pathogens in the cell-mediated response,.
• Fragments of nonself proteins synthesized in target cells associate with class I MHC molecules and are displayed on the cell surface, where they can be recognized by cytotoxic T cells.
• This interaction is enhanced by the T surface protein CD8.
• When a cytotoxic T cell is activated by specific contacts with class I MHC-antigen complexes on an infected cell, the activated cytotoxic T cell differentiates into an active killer, which kills its target cell—primarily by secreting proteins that act on the bound cell.
• The death of the infected cell deprives the pathogen of a place to reproduce while also exposing it to circulating antibodies, which mark it for disposal.
• Once activated, cytotoxic T cells kill other cells infected with the same pathogen.
• Cytotoxic T cells defend against malignant tumors because tumor cells carry distinctive molecules not found on normal cells.
• Class I MHC molecules on a tumor cell present fragments of tumor antigens to cytotoxic T cells.
• Cancers and viruses reduce the amount of class I MHC protein on affected cells to avoid detection by cytotoxic T cells.
• Natural killer cells are a backup defense and part of the nonspecific defenses, which lyse virus-infected and cancer cells.
• B cells make antibodies against extracellular pathogens in the humoral response.
• The activation of B cells is aided by cytokines secreted by helper T cells activated by the same antigen.
• These B cells proliferate and differentiate into a clone of antibody-secreting plasma cells and a clone of memory B cells.
• When antigen first binds to receptors on the surface of a B cell, the cell takes in a few of the foreign molecules by receptor-mediated endocytosis.
• The B cell then presents antigen fragments to a helper B cell.
• T-dependent antigens require the participation of helper T cells in order to trigger a humoral immune response by B cells.
• T-independent antigens include polysaccharides of many bacterial capsules and the proteins of the bacterial flagella.
• These antigens bind simultaneously to a number of membrane antibodies on the B cell surface, stimulating the B cell to generate antibody-secreting plasma cells without the help of cytokines.
• A T-independent antigens generates a weaker response than T-dependent antigens and generates no memory cells.
• Any given humoral response stimulates a variety of different B cells, with each giving rise to a clone of thousands of plasma cells.
• Each plasma cell is estimated to secrete about 2,000 antibody molecules per second over the cell’s 4- to 5-day life span.
• A secreted antibody lacks a transmembrane region that would anchor it to a plasma membrane, but has the same general Y-shaped structure as a B cell receptor.
• Antigens that elicit a humoral immune response are typically the protein and polysaccharide surface components of microbes, incompatible transplanted tissues, or incompatible transfused cells.
• In some humans, the proteins of foreign substances such as pollen or bee venom act as antigens that induce an allergic, or hypersensitive, humoral response.
• Antibodies are immunoglobins (Igs).
• There are five major types of heavy-chain constant regions which determine the five major classes of antibodies.
• IgM and IgA exist primarily as polymers of the basic antibody molecule: IgM as a pentamer and IgA as a dimmer.
• IgG, IgE, and IgD exist exclusively as monomers.
• Antibody specificity and antigen-antibody binding has been applied in laboratory research, clinical diagnosis, and disease treatment.
• Polyclonal antibodies are the products of many different clones of B cells, each specific for a different epitope.
• Monoclonal antibodies are prepared from a single clone of B cells grown in culture which are specific for the same epitope on an antigen.
• Toxin-linked monoclonal antibodies search and destroy tumor cells.
• Viral neutralization occurs as antibodies bind to proteins on the surface of a virus, blocking the virus’s ability to infect a host cell.
• Opsonization occurs as bound antibodies enhance macrophage attachment to and phagocytosis of the microbes.
• Antibody-mediated agglutination of bacteria or viruses effectively neutralizes and opsonizes the microbes.
• Each antibody molecule has at least two antigen-binding sites make agglutination possible.
• IgM can link together five or more viruses or bacteria and these large complexes are readily phagocytosed by macrophages.
• In precipitation, the cross-linking of soluble antigen molecules forms immobile precipitates that are disposed of by phagocytosis.
• The complement system participates in the antibody-mediated disposal of microbes and transplanted body cells.
• The pathway begins when IgM or IgG antibodies bind to a pathogen
• The first complement component links two bound antibodies and is activated, initiating the cascade.
• Complement proteins generate a membrane attack complex (MAC) in the bacterial membrane, resulting in cell lysis.
• Whether activated as part of innate or acquired defenses, the complement cascade results in the lysis of microbes and produces activated complement proteins that promote inflammation or stimulate phagocytosis.

Immunity and Immunization

• Immunity can be achieved naturally or artificially.
• Immunity conferred by recovering from an infectious disease is called active immunity because it depends on the response of the infected person’s own immune system.
• Active immunity can be acquired naturally or artificially by immunization ( vaccination).
• Vaccines include inactivated bacterial toxins, killed microbes, parts of microbes, viable but weakened microbes, and genes encoding microbial proteins.
• These agents can act as antigens, stimulating an immune response and producing immunological memory.
• A vaccinated person who encounters the actual pathogen will have the same quick secondary response based on memory cells as a person who has had the disease.
• Routine immunization of infants and children has reduced the incidence of infectious diseases and led to the eradication of smallpox.
• Not all infectious agents are easily managed by vaccination.
• The emergence of new strains of pathogens complicates vaccine development against some microbes, such as the parasite that causes malaria.
• Antibodies can be transferred from one individual to another, providing passive immunity.
• Passive immunity occurs naturally when IgG antibodies cross the placenta to the fetus or when IgA antibodies are passed from mother to nursing infant.
• Passive immunity persists as long as these antibodies last, a few weeks to a few months.
• This protects the infant from infections until the baby’s own immune system has matured.
• Passive immunity can be transferred artificially by injecting antibodies into another animal, conferring short-term, but immediate, protection.
• A person bitten by a rabid animal may be injected with antibodies against rabies virus since passive immunization is the immediate defense until active immunization of the longer-term defense can work.

Immune System and Tissue Transplantation

• The immune system attacks cells from other individuals as well as attacking pathogens.
• A skin graft from one person to a nonidentical individual will be destroyed by immune responses.
• The structure of the placenta allows to a pregnant woman to not reject the fetus as a foreign body.
• Immune reactions from individuals with incompatible blood types is a potential problem with blood transfusions.
• An individual with type A blood has A antigens on the surface of red blood cells.
• B antigens are found on type B red blood cells.
• AB antigens are found on type AB red blood cells.
• Type O red blood cells have neither antigen
• A person with type A blood has antibodies to the B antigen, even without prior exposure to type B blood.
• Antibodies arise in response to bacteria that have epitopes similar to blood antigens.
• An individual with type A blood does not make antibodies to A-like bacterial epitopes, because these are considered self.
• If a person with type A blood receives type B blood, the preexisting anti-B antibodies will induce a transfusion reaction.
• Blood group antigens are polysaccharides, inducing T-independent responses, which elicit no memory cells.
• Responses are like a primary response, generating IgM anti-blood-group antibodies, not IgG.
• IgM antibodies do not cross the placenta, protecting a developing fetus.
• The Rh factor can cause mother-fetus problems because antibodies produced for it are IgG.
• A mother who is Rh-negative has a fetus that is Rh-positive, having inherited the factor from the father causing any small amounts of fetal blood to cross the placenta and cause the mother to mount a humoral response against the Rh factor.
• Danger occurs in subsequent Rh-positive pregnancies, when the mother’s Rh-specific memory B cells produce IgG antibodies that can cross the placenta and destroy the red blood cells of the fetus.
• To prevent this, the mother is injected with anti-Rh antibodies, which is passively immunizing to eliminate the Rh antigen, after delivering her first Rh-positive baby,
• The donor and recipient MHC of tissue should be matched as closely as possible in order to minimize rejection.
• Siblings usually provide the closest tissue-type match.
• Medicines are used to suppress the immune response to the transplant.
• This leaves the recipient more susceptible to infection and cancer during the course of treatment.
• Selective drugs, suppress helper T cell activation without crippling nonspecific defense or T-independent humoral responses, which greatly improved the success of organ transplants.
• Recipient irradiation typically treats prior to bone marrow transplants, eliminating all abnormal cells and leaving little chance of graft rejection.
• The donated marrow may react against the recipient, producing graft versus host reaction, unless well matched.

Immune Response Malfunctions

• Malfunctions of the immune system can produce allergies, autoimmune and immunodeficiency diseases.
• Allergies are hypersensitive responses to environmental antigens.
• Allergies are evolutionary remnants of the immune system’s response to parasitic worms.
• Common allergies involve IgE class antibodies.
• Hay fever occurs when plasma cells secrete IgE specific for pollen allergens.
• IgE antibodies attach to mast cells in connective tissue, without binding to the pollen.
• When pollen enters the body, they attach to IgE on mast cells, cross-linking adjacent antibody molecules, triggering the mast cell to release histamines and inflammatory agents.
• High levels of histamines cause dilation and increased permeability of small blood vessels leading to allergy symptoms: sneezing, runny nose, tearing eyes, and smooth muscle contractions that can result in breathing difficulty.
• Antihistamines diminish allergy symptoms by blocking histamine receptors.
• Anaphylactic shock is an acute allergic response to injected or ingested allergens, a life-threatening reaction.
• Anaphylactic shock occurs as widespread mast cell degranulation triggers abrupt dilation of peripheral blood vessels, causing a precipitous drop in blood pressure which cause trigger death within minutes.
• People with anaphylactic shock carry syringes with epinephrine, which counteracts the allergic response.
• Autoimmune diseases arise when the immune system loses tolerance for self and turns against certain molecules of the body
• In systemic lupus erythematosus (lupus), the immune system generates antibodies against self-molecules, including histones and DNA.
• Lupus is characterized by skin rashes, fever, arthritis, and kidney dysfunction.
• Rheumatoid arthritis leads to damage and painful inflammation of the cartilage and bone of joints.
• The insulin-producing beta cells of the pancreas are the targets of autoimmune cytotoxic T cells in insulin-dependent diabetes mellitus.
• Multiple sclerosis (MS) is the most common chronic neurological disease in developed countries.
• In MS, T cells reactive against myelin infiltrate the central nervous system and destroy the myelin sheath that surrounds some neurons which leads to neurological abnormalities.
• Autoimmune disease likely arises from some failure in immune regulation, perhaps linked with particular MHC alleles.
• Immunodeficiency diseases comprise when the function of either the humoral or cell-mediated immune defense is compromised.
• Genetic or developmental defects in the immune system can cause inborn or primary immunodeficiency.
• Acquired or secondary immunodeficiency happens when an immunodeficiency defect in the immune system develops later in life, following exposure to a chemical or biological agent
• Severe combined immunodeficiency (SCID) comprises when both branches of the immune system fail to function and requires bone marrow transplant.
• Immunodeficiency may also develop later in life.
• Cancers such as Hodgkin’s disease, which damages the lymphatic system suppress the immune system.
• AIDS is another acquired immune deficiency.
• Hormones secreted by the adrenal glands during stress affect the number of white blood cells and may suppress the immune system in other ways.
• Some neurotransmitters secreted when we are relaxed and happy may enhance immunity.
• Physiological evidence also points to an immune system–nervous system link based on neurotransmitter receptors on the surfaces of lymphocytes and a network of nerve fibers that penetrates deep into the thymus.

Acquired Immunodeficiency Syndrome (AIDS)

• In 1981, medical community saw increased rates of Kaposi’s sarcoma, a cancer of the skin and blood vessels, and pneumonia.
• Pneumocystis carinii, signals a new threat to humans, later known as acquired immunodeficiency syndrome, or AIDS.
• People with AIDS are susceptible to opportunistic diseases.
• AIDS impairs both humoral and cell-mediated immune responses by the loss of helper T cells.
• Human immunodeficiency virus (HIV) was identified as the causative agent of AIDS in 1983.
• HIV gains entry into cells by making use of proteins that participate in normal immune responses.
• The main receptor for HIV on helper T cells is the cell’s CD4 molecule.
• HIV requires a second cell-surface protein, a coreceptor, in addition to CD4.
• Once inside the cell, the HIV RNA is reverse-transcribed, and the product DNA is integrated into the host cell’s genome.
• The viral genome can direct the production of new viral particles.
• The death of helper T cells in HIV infection is due to the damaging effects of viral reproduction, coupled with inappropriately timed apoptosis triggered by the virus.
• HIV infection cannot be cured, but certain drugs slow HIV reproduction and the progression to AIDS.
• These drugs are very expensive and not available to all infected people, especially in developing countries.
• The mutational changes that occur with each round of virus reproduction can generate drug-resistant strains of HIV.
• Transmission of HIV requires the transfer of body fluids containing infected cells, such as semen or blood, from person to person.
• he best approach for slowing the spread of HIV is educating people about the practices that lead to transmission, such as using dirty needles or having unprotected intercourse.