Nonspecific Defenses Against Infection

1. Explain what is meant by nonspecific defense and list the nonspecific lines of defense in the vertebrate body. Nonspecific defense is a trait of innate immunity, they quickly recognize and respond to a broad range of microbes regardless of their precise identity. These nonspecific lines of defense include: External: Skin, Mucous membranes, Secretions Internal: Phagocytic Cells, Antimicrobial proteins, Inflammatory response, and Natural Killer Cells 2. Distinguish between: a. innate and acquired immunity Innate immunity: Is present before any exposure to pathogens and is effective from the time of birth. These defenses are largely nonspecific, and quickly recognize and respond to a broad range of microbes regardless of their precise identity. These nonspecific lines of defense include: External: Skin, Mucous membranes, Secretions Internal: Phagocytic Cells, Antimicrobial proteins, Inflammatory response, and Natural Killer Cells Acquired Immunity: develops only after exposure to inducing agents such as microbes, abnormal body cells, toxins or other foreign substances. They are highly specific, that is they can distinguish one inducing agent from another, even if they only differ slightly. This is achieved by white blood cells called LYMPHOCYTES, which produce two general types of immune responses. Humoral (antibodies) and Cell-mediated (cytotoxic lymphocytes) b. humoral and cell mediated response Humoral response: Cells derived from B lymphocytes secrete defensive proteins called ANTIBODIES that bind to microbes and mark them for elimination. Cell Mediated response: Cytotoxic lymphocytes directly destroy infected body cells, cancer cells and foreign tissue. 3. Explain how the physical barrier of skin is reinforced by chemical defenses. Intact skin is a barrier that can’t usually be penetrated. Coupled with the mucous membranes lining the digestive, respiratory and genitourinary tracts bar the entry of potentially harmful microbes. Certain cells in the mucus membrane produce MUCUS, a viscous fluid that traps microbes and other particles. Microbial colonization is also inhibited by the washing action of the mucous secretions of saliva and tears. Together they provide an environment hostile to microbes. Oil and Sweat glands give the skin a pH ranging from 3 to 5 which is acidic enough to prevent colonization of many microbes. Similarly the acidic environment of the stomach destroys most pathogens before they can enter the intestines. Secretions from the skin and mucus membanes also contain antimicrobial proteins. One such protein is LYSOZYME, an enzyme that digests the cell walls of many bacteria. Present in saliva, tears and mucus secretions. In addition microbes that penetrate the bodies external defenses must contend with the bodies internal mechanism of innate defense. These defenses primarily depend on PHAGOCYTOSIS. 4. Define phagocytosis. Name four types of phagocytic leukocytes. Phagocytosis: the ingestion of invading microorganisms by certain types of white blood cells generically referred to as PHAGOCYTES. These Phagocytes produce certain antimicrobial proteins and help initiate inflammation which can limit the spread of microbes in the body. Phases of Phagocytosis: 1) Phagocytes engulfs microbe 2) A vacuole is formed which fuses with a lysosome 3) Nitric oxide and toxic forms of oxygen poison the microbe 4) lysozyme degrades the microbial componets 4 types of phagocytic leukocytes: Neutrophils, macrophages, Eosinophils, dendritic cells Neutrophils: -Constitute about 60%-70% of all white blood cells. -Are attracted to and then enter infected tissue, ENGULFING and DESTROYING the microbes there -Tend to self destruct in the process of phagocytosis, avg. life span is only a few days Macrophages (big eaters): -Large, long lived cells develop from MONOCYTES -Constitute about 5% of circulating blood cells. -Circulate in the blood for a few hours before they migrate into tissues, where they become macrophages -Carrying out phagocytosis sets off internal signaling pathways that activate the macrophages, increasing their

Eosinophils: -have low phagocytic activity. 6.defensive abilities -Permanent residents in the spleen. It is characterized by high fever and low blood pressure. Other antimicrobial proteins include about 30 serum proteins that make up the COMPLEMENT SYSTEM. In addition to lysozyme. which allows enhanced blood flow. All of these help in repairing tissue damage and stopping the spread of infection. including how it is triggered. 10. such as a bacterium Macrophages have receptors that bind to polysaccharides present on the surface of bacterial cells but not on body cells. Describe the roles of antimicrobial proteins in innate immunity. 2) What causes the common signs of inflammation. secreting chemicals that stimulate the release of additional neutrophils from the bone marrow.1*** 1) Innate defenses are nonspecific. but critical to defense against multicellular parastic invaders (like blood fluke) -rather then engulfing. and other tissues of the lymphatic system. ***Concept Check 43. They are secreted by virus infected body cells and induce neighboring uninfected cells to produce other substances that inhibit viral reproduction. Explain how interferon limits cell-to-cell spread of viruses. How. by speeding up body reactions hasten the repair of tissues. do macrophages recognize an infectious agent. These vascular changes aid in delivering clotting factors. Substances on the surface of many microbes however can trigger a cascade of steps that activate the complement systems. Certain complacent proteins also help trigger inflammation or play a role in acquired defense. 8. Injured cells put out a call for reinforcements. Explain what occurs during the condition known as septic shock. lymph nodes. and phagocytic cells to the tissue of the affected region. Describe the inflammation response. Explain how the action of natural killer cells differs from the action of phagocytes. swelling and heat. Damage to tissue by physical injury or the entry of pathogens leads to the release of chemical signals that trigger a the localized INFLAMMATORY RESPONSE. Describe the factors that influence phagocytosis during the inflammation response. Dendritic Cells: -can ingest microbes like macrophages do -primary role is to stimulate the development of acquired immunity. antimicrobial proteins. and how do these changes help protect the body against infection Vessel dilation. MAST CELLS found in connective tissues release HISTOMINE(one of the most active chemicals) that triggers dialation and increased permeability of nearby capillaries. then. Moderate fevers may facilitate phagocytosis and. In the absence of an infection. Leading to lysis(bursting) of invading cells. 9. Certain bacterial infections can induce an overwhelming systemic inflammatory response. redness. eosionphils position themselves against the parasites body and then discharge destructive enzymes that damage the invader. Two types of interferon (a & B) provide innate defense against viral infections. and increase vessel permeability result in the common signs of inflammation. When injured. Surface receptors on the NK cell recognize general features on the surface of its targets. these proteins are inactive. the NK cell releases chemicals that lead to the death of the striken cell by APOPTOSIS. 5. Once it is attached to a virus infected cell or cancer cell. 3) State two ways in which the innate defenses of insects (invertebrates) and vertebrates are similar. – Histamine released from mast cells in connective tissue – Prostaglandins released from activated macrophages increases blood flow to injured area – Blood-filled capillaries leak blood causing redness and swelling – Enhanced blood flow and vessel permeability help deliver antimicrobial proteins and blood clotting elements • Blood clotting begins the healing and isolates the microbe – Activated complement proteins modulate release of histamine or chemoattractants for macrophages – Chemokines direct phagocyte migration and stiumlate production antimicrobial compounds 7. . or programmed cell death.

each lymphocyte displays specifically for a particular epitope on an antigen and defends against that antigen or a small set of closely related antigens. In this stage B cells generate antibody secreting effecter B cells. A single antigen usually has several different epitopes. Antibodies: are released during the Humoral response and are secreted by B lymphocytes. they are either destroyed by apoptosis or rendered nonfunctional.The exoskeleton of insects provides an external barrier similar to the skin and mucous membranes of vertebrates. that is they all recognize the same epitope. Explain why the antigen receptors of lymphocytes are tested for self-reactivity during development. The other clone consists of MEMORY CELLS. by binding to specific receptors. Antigens: is any foreign molecule that is specifically recognized by lymphocytes and elicits a response from them. If they are. If an individual is exposed again to the same antigen. Describe the mechanism of clonal selection. which form the antigen binding site. Primary immune response is a result of the first time a body is exposed to a certain antigen. Each person has about 1 million different B cells and 10 million different T cells. The immune systems capacity to generate secondary immune responses called IMMUNOLOGICAL MEMORY . This is SECONDARY IMMUNE RESPONSE 18. In other words. but later develop into T cells or B cells depending on WHERE they continue their maturation. Phagocytic cells and antimicrobial proteins also contribute to innate defenses in both insects and vertebrates. and all the receptors on a single cell are identical. This cloning results in 2 type of cells. 12. Failure to eliminate them and maintain SELF TOLERENCE can lead to autoimmune diseases. Explain how B lymphocytes and T lymphocytes recognize specific antigens B cells and T cells recognize antigens by means of antigen specific receptors embedded in their plasma membranes. the response is faster and of greater magnitude and more prolonged. Thus their antigen receptors are tested for potential self reactivity. and bind to microbes and mark them for elimination. accessible portion of an antigen called an EPITOPE. Explain how the particular structure of a lymphocyte’s antigen binding site forms during development. Explain the role of recombinase in generating the staggering variability of lymphocytes. a developing lymphocyte may end up with antigen receptors that are specific for some of the bodies own molecules. long lived cells bearing receptors specific for the same inducing antigen. selectively activates a tiny fraction of cells from the bodys diverse pool of lymphocytes. and selected T cells are activated in their effecter forms. 13. 20. --Lymphocytes that migrate from bone marrow to the THYMUS(a gland in the thoracic cavity above the heart) develop into T cells --Lymphocytes that remain in the bone marrow and complete maturation become B cells --The variable regions at the tip of each antigen receptor chain. 15.000 of these ANTIGEN RECEPTORS. Compare the structures and functions of cytotoxic T cells and helper T cells. all specific for and dedicated to eliminating that antigen. Distinguish between antigen and epitope. Thus can respond to an enormous number of different antigen receptor chains. A single B or T cell bears about 100. account for the diversity of lymphocytes. Distinguish between primary and secondary immune responses. A lymphocyte actually recognizes and binds to just a small. One clone consist of a larger number of short lived EFFECTOR CELLS that combat the same antigen. each capable of inducing a response from lymphocytes that recognize that epitope. How Specific Immunity Arises 11. depends on the clones of long lived T and B memory cells generated following initial exposure to an antigen. 19. Distinguish between effector cells and memory cells. this relatively small number of selected cells gives rise to clones of thousands of cells. 17. --Newly formed lymphocytes are all alike. 16. 14. each with a particular antigen binding specificity. Describe the cellular basis for immunological memory. Because the rearrangements of antigen receptor genes are random. called PLASMA CELLS. Distinguish between antigens and antibodies. Clonal Selection: Each antigen. Class 1 MHC molecules displaying bound peptide antigens are recongnized by CYTOTOXIC T Cells . Predict the consequences that would occur if such testing did not take place.

How does this process demonstrate both the specificity and memory of acquired immunity. 21. Explain how cytotoxic T cells and natural killer cells defend against tumors. Distinguish between humoral immunity and cell-mediated immunity. In these cells class 2 MHC bind peptides derived from foreign materials that been internalized and fragmented through phagocytosis or endocytosis. variable V regions constant C regions. thereby promoting cell mediated and humoral responses. macorphages and B cells known as Antigen presenting cells displayed internalized antigens to T HELPER CELLS. The T cell receptor binds with an MHC molecule peptide antigen complex. This interaction helps keep the helper T cell and the antigen presenting cell joined while activation of the helper T cell proceeds. disulfide bridges.2*** 1) Draw a B cell receptor. resulting in production of secreted antibodies that circulate in the blood and lymph Cell Mediated Immunity: involves the activation and clonal selection of cytotoxic T cells. macrophages and B cells. Transmembrane region. respectively. Class 2 MHC: are made by just a few cell types. 25. bind peptides derived from foreign antigens that been synthesized within the cell. 40 V X 5 J = 200 possible light chains. --Dendritic cells are particularly effective in presenting antigens to naïve helper T cells. 23. When a helper T cell encounters and recognizes a class II MHC molecule-antigen complex on an antigen present cell. --Macrophages play the key role in initiating a secondary immune response by presenting antigens to memory helper T cells --B cells primarily present antigens to helper T cells in the course of the humoral response. Immune Responses 22. Acquired immunity includes two branches. Memory: the large number of memory B cells generated respond more rapidly to the same antigen the next time it enters the body. Each antigen binding site is fromed from a region on a light chain and heavy chain. ***Concept Check 43. The number of possible random combinations is 200 ligh chains X 8. a secreted antibody lacks a transmembrane region and cytoplasmic tail. and greatly enchances the interaction between a target cell and a cytotoxic cell. of which there are 27. Both Are Surface Proteins CD4 is present on most helper T cells. Describe the roles of helper T lymphocytes in both humoral and cell-mediated immunity. dendritic cells are important in triggering a primary immune response. and label the following light chaings. Binding of CD8 to the side of a class I MHC molecule helps keep the two cells in contact during activation of the cytotoxic T cell. Humoral Immunity: involves the activation and clonal selection of B cells. 51 V X 6 J X 27 D = 8. T cell receptors bind small fragments of antigens that are complexed with class I or class II mHC molecules on the surface of infected body cells or antigen presenting cells. How many different antigen binding specificities can be generated given random V-J and VDJ arrangements. antigen binding sites.262 heavy chains = 1.8a. and binds the class II MHC molecule. 24. the helper T cell proliferates and differentiates into a clone of activated helper T cells and memory helper T cells. --Activated helper T cells secrete several different cytokines that stimulate other lymphocytes. 2) What is the major difference in the types of antigens bound by B cell receptors and T cell receptors B cell receptors bind intact extracellular antigens present on the surface of microbes or free in body fluids. HUMORAL and CELL MEDIATED immunity. Specificity: Only B cells with receptors that bind to the antigen are selected to proliferate and differentiate into plasma cells secreting antibodies specific for the antigen and memory B cells bearing receptors specific for the same antigen. which directly destroy certain target cells. Compare the production and functions of class I MHC and class II MHC molecules.65 X 10^6 possible antigen binding specificities.Class 2 MHC molecules including Dendritic. CD8 is present on most cytotoxic T cells. Describe the functions of the proteins CD4 and CD8.12. and cytoplasmic tails. .262 possible heavy chains. Class I MHC: found on almost all nucleated cells of the body. mainly dendritic cells. heavy chains. 4) A light chain immunoglobulin gene consists of 40 V gene segments and 5 J gene segments and a heavy chain gene consists of 51 V gene segments and 6 J gene segments and another set of gene segments D. 3) Consider the process of clonal selection of B cells show in Figure 43. How does the structure of a secreted antibody differ? See figure 43.

Explain how antibodies interact with antigens. and agglutination. opsonization. and (b) assist in the destruction and elimination of antigens. 26. Active Immunity also can develop following immunization often called vaccination. Immunity in Health and Disease 33. Due to clonal selection.Because tumor cells carry distinctive molecules(tumor antigens) not found on normal body cells. Instead the transferred antibodies are poised to immediately help . certain types of cancer are treated with tumor specific monoclonal antibodies bound to toxin molecules. 31. 27. These are all Antigen disposal mechanisms. Explain why macrophages are regarded as the main antigen-presenting cells in the primary response but memory B cells are the main antigen-presenting cells in the secondary response. selectively attaching to an killing tumor cells. monoclonal antibodies are particularly useful for tagging specific molecules. Class I MHC molecules on a tumor cell display fragments of tumor antigens to cytotoxic T cells. during secondary response the long lived clones of memory B cells produce clones of themselves to fight the antigen faster. Diagram and label the structure of an antibody and explain how this structure allows antibodies to (a) recognize and bind to antigens. all of which are identical and specific for the same epitope on an antigen. Distinguish between active and passive immunity and describe examples of each. Distinguish between the variable (V) and constant (C) regions of an antibody molecule. In a process called OPSONIZATION. Agglutination is possible because each antibody molecule has at least two antigen binding sites that can bind to identical epitopes on separate bacterial cells or virus particles linking them together. the bound antibodies enhance macrophage attachment to the microbes and thus increase phagocytosis. Macrophages are the main antigen presenting cells in the primary response because it is the first time the body is exposed to the antigen. Describe the production and uses of monoclonal antibodies. 32. The toxin linked antibodies carry out a precise search and destroy mission. See figure 43. Distinguish between T-dependent antigens and T-independent antigens. In both basic research and medical applications. Constant (C): the remainder of the molecule is made up of constant (c) whose amino acid sequences vary little from cell to cell.18 30. this is also the basis of several antigen disposal mechanisms. they are identified as foreign by the immune system. For example. Similarly antibodies may bind to a pathogenic bacterium. Smallpox) Immunity can also be conferred by transferring antibodies from an individual who is immune to a particular infectious agent to someone who is not. This Vaccination induce an immediate immune response and long lasting immunological memory(thanks to memory cells) (Ex. Some antigens however can evoke a B cell response without involvement of helper T cells. Antibody mediated AGGLUTINATION (clumping) of bacteria or viruses forms aggregates that can be readily phagocytosed by macrophages. can induce apoptosis in virus infected and cancer cells. thereby blocking the virus’s ability to infect a host cell. 28. The body secretes various effecter cells including plasma cells. NK cells as part of the body’s non specific innate defenses. Antibodies bind to antigens(to mark for elimination). which mark and eventually destroy the antigens. Antigens that induce antibody production only with assistance from helper T cells are known as T DEPENDENT ANTIGENS. coating much of the bacterial surface. Compare the processes of neutralization. Immunity conferred by natural exposure to an infectious agent is called ACITVE IMMUNITY because it depends on the action of a person’s own lymphocytes and the resulting memory cells specific fro the invading pathogen. The simplest VIRAL NEUTRALIZATION antibodies bind to certain proteins on the surface of a virus. Variable (V): Are at the tips of the Y(in b cells) are light and heavy chain variable (v) named because their amino acid sequences vary extensively from one b cell to anoter. This Is called PASSIVE IMMUNITY. 29. Monoclonal antibodies are prepared from a single clone of B cells grown in culture. because it does not result from the action of the recipients own B and T cells. There are T INDEPENDENT ANTIGENS and include the polysaccharides of many bacterial capsules and the proteins that make up bacterial flagella.

***Concept Check 43. including the roles of IgE. there is a danger of a graft versus host reaction. 35. B) antigens and related bacterial epitopes are polysaccharides. packed cells should be used. Histamine release causes dilation and increase permeability of small blood vessels and lead to the typical symptoms sneezing.4*** 1) Explain why a person who has type AB blood is considered a universal blood recipient. Describe the potential problem of Rh incompatibility between a mother and her unborn fetus and explain what precautionary measures may be taken. cytotoxic T cell and B cell An activated helper T cell secretes cytokines that promote activation of both cytotoxic T cells and B cells. 34. 37. once it is activated by antigens and cytokines: helper T cells. since the donor serum(fluid part of the blood) would contain antibodies to A and to B. but persists only as long as the transferred antibodies last. In the case of donated type O blood. 38. which could react with the recipients red blood cells. An autograft will not trigger a rejection reaction. If small amounts of fetal bloo cross the placenta. the introduction of antigen. Why is this reaction particular to a bone marrow transplant The danger of the graft rejecting the host arises because transplanted bone marrow contains lymphocytes that could react against components of the recipients body. Someone who is actively immunized may be immune to that antigen for life. type B blood. . and histamine. An Rh-negative mother who carries an Rh positive fetus can be dangerous. the child would be unable to produce antibodies against extracelluar bacteria. type AB blood. These IgE cells can induce mast cells to release histamine and other inflammatory agents. 3) Severely burned patients generally must receive numerous skin grafts. as a protein antigen induces immune responses in which memory cells are generated. or type O blood-that is they are universal recipients. runny nose. What is the advantage of using skin from an unburned part of a patients own body rather then from another person. 4) Explain why passive immunization provides short term protection from an infection. The most common allergies involve antibodies of the IgE class. (ex. the moth mother mounts a humoral response against the Rh factor. Such polysaccharide antigens induce immune responses in which no memory cells are generated. Without cytotoxic T cells or helper T cells to help activate them.3*** 1) Describe the main role of each of the following cell types.destroy any microbes for which they are specific. tearing eyes and smooth muscle contractions. they can safely receive type A blood. whereas active immunization provides long-term protection Passive immunization the transfer of antibodies from one individual to another is protective only as long as the antibody molecules last. Explain how the immune response to Rh factor differs from the response to A and B blood antigens. Active immunization. An activated B cell differentiates into plasma cells that secret antibodies 2) What cells and functions would be deficient in a child born without a thymus? A child lacking a thymus would have no functional T cells. To prevent this the mother is injected with anti Rh antibodies around the 7th month and again just after delivering an Rh positive baby. Rh factor. Allergies are exaggerated (hypersensitive) responses to certain antigens called allergens. Without helper T cells to help activate B cells. An activated cytotoxic T cell kills infected cells and tumor cells by apoptosis. Blood group (A. 36. mast cells. Rabies) ***Concept Check 43. Describe an allergic reaction. induces an immune response in the recipient that can lead to the generation of long lived memory cells. Later exposure of these memory cells to the Rh factor leads to production of anti-Rh antibodies that are IgG. It provides immediate protection. the childs immune system would be unable to kill virus infected cells 3) Discuss how antibodies help protect us from infection or the effects of infection Antibodies bound to viruses can block their attachment to potential host cells (viral neutralization) coating of bacteria or other particles by antibodies bound to surface antigens increases their phagocytosis by macrophages (opsonization) Antibodies bound to antigens on bacterial cells also can activate a cascade of complement proteins leading to lysis of the bacteria (complement activation) Cross linking of antigens on many bacterial cells or viruses by binding of multiple antibody molecules can lead to formation of large clumps (agglutination) which are then phagocytosed. Because individuals with type AB blood do not produce antibodies against either the A or the B antigens. 2) In bone marrow transplantation.

List three autoimmune disorders and describe possible mechanisms of autoimmunity. The loss of helper T cells results from the infection by HIV. that have low levels of CD4. The co-receptor for HIV normally functions as a chemokine receptor. Drugs that block the degranulation response prevent the release of inflammatory agents and hence the symptoms they cause. Note strategies that can reduce a person’s risk of infection. Hormones secreted by the adrenal glands during stress affect the numbers of white blood cells and may suppress the immune system in other ways. Unprotected sex and sharing of needles are the most common forms. If a persons chemokine receptors are faulty. HIV requires CD4 and a co-receptor. Explain this finding. such as semen or blood from person to person. Explain how HIV is transmitted and describe its incidence throughout the world. 43.5*** 1) How would a macrophage deficiency likely affect a persons innate and acquired defenses A person with a macrophage deficiency would have frequent infections. Transmission of HIV requires the transfer of body fluids containing infected cells. One co-receptor called fusin is present on all the cell types infected by HIV. The virus also infects other cell types such as macrophages and brain cells. To enter a host cell. The main receptor for HIV on helper T cells is the cell’s CD4 molecule. Describe the infectious agent that causes AIDS and explain how it enters a susceptible cell. HIV gains entry into cells by making use of three proteins that participate in normal immune responses. In addition to CD4. Is this disease best classified as an immunodeficiency disease. Likewise in the nervous systems. while a different co receptor is present only on marcophages and helper T cells. 41. which cause typical allergy symptoms. Explain why these drugs are effective in treating allergies such as Hay Fever. some neurotransmitters secreted when we are relaxed and happy may enhance immunity. HIV entry requires a second cell surface protein. Healthy immune function appears to depend on both the endocrine system and the nervous system. 40. antibodies bind to and block acetylcholine receptors at neuromuscular junctions. In some individuals the immune system loses tolerance for self and turns against cetain molecules of the body causing one of the many autoimmune diseases. HIV cannot use them for entry into cells. This would be due to poor innate responses. AIDS arises from the loss of helper T cells. arthritis and insulin dependent diabetes. both humoral and cell mediated immune responses are impaired. . 40 million people worldwide are living with HIV/AIDS.39. an auto-immune disease or an allergic disease? Explain Myasthenia gravis is considered an autoimmune disease because the immune system produces antibodies against self molecules 4) People who are nonfunction chemokine receptors because of genetic mutations are immune to HIV infection. releasing histamine and other inflammatory agents. Binding of antigens by IgE molecules attached to mast cells induces degranulation of these cells. Explain how general health and mental well-being might affect the immune system. The best approach for slowing the spread of HIV is to educate people about the practices that transmit the virus such as using a dirty needle or unprotected sex. preventing muscle contraction. a co-receptor. ***Concept Check 43. 2) Many anti allergy medications block response by mast cells. These include Lupus. 42. particularly diminished phagocytosis and inflammation and poor acquired responses because of the role of macrophages in presenting antigens to helper T cells. 3) In myasthenia gravis.