assgnmt 1

1. Indicate to which branch(es) of the immune system the following statements apply, using H for the humoral branch and CM for the cell-mediated branch. Some statements may apply to both branches. a. Involves class I MHC molecules CM b. Responds to viral infection H & CM c. Involves T helper cells H & CM d. Involves processed antigen CM e. Most likely responds following an organ transplant CM f. Involves T cytotoxic cells CM g. Involves B cells H h. Involves T cells H & CM i. Responds to extracellular bacterial infection H j. Involves secreted antibody H k. Kills virus-infected self-cells CM 2. Specific immunity exhibits four characteristic attributes, which are mediated by lymphocytes. List these four attributes and briefly explain how they arise. 1. Antigenic Specificity 2. Diversity 3. Immunologic Memory 4. Self/nonself recognition The antigenic specificity of the immune system permits it to distinguish subtle differences among antigens. Antibodies can distinguish between two protein molecules that differ in only a single amino acid. The immune system is capable of generating tremendous diversity in its recognition molecules, allowing it to recognize billions of unique structures on foreign antigens. Once the immune system has recognized and responded to an antigen, it exhibits immunologic memory; that is, a second encounter with the same antigen induces a heightened state of immune reactivity. Because of this attribute, the immune system can confer life-long immunity to many infectious agents after an initial encounter. Finally, the immune system normally responds only to foreign antigens, indicating that it is capable of self/nonself recognition. The ability of the immune system to distinguish self from nonself and respond only to nonself molecules is essential, for, as described below, the outcome of an inappropriate response to self molecules can be fatal. 3. Adaptive immunity has evolved in vertebrates but they have also retained innate immunity. What would be the disadvantages of having only an adaptive immune system? Comment on how possession of both types of immunity enhances protection against infection. Adaptive immunity is triggered when an infection eludes the innate defense mechanisms and generates a threshold dose of antigen. This antigen then initiates an adaptive immune response, which becomes effective only after several days. The time is required for antigen- specific T cells and B cells to locate their specific foreign antigen, to proliferate, and to differentiate into armed effector cells. in my opinion, if adaptive immunity were to be engaged as quickly as innate immunity, the response would be very fast and vigorous and hypersensitivity like reaction may occur. 4. Innate and adaptive immunity act in cooperative and interdependent ways to protect the host. Discuss the collaboration of these two forms of immunity. Innate and adaptive immunity operate in cooperative and interdependent ways. The activation of innate immune responses produces signals that stimulate and direct subsequent adaptive immune responses. Cooperate to give complete response against pathogens. ex) phagocytic cell (that takes up foreign material and processes it to form peptide antigens that are presented by the phagocyte). The presented antigens stimulate T-cells that either provide help to B-cells for production of antibody or stimulate cytotoxic T-cells to provide protection against infected or cancerous cells. In addn., the phagocytic cells take part in inflammation, producing cytokines that attract T and B cells to the site. Name three features of a secondary immune response that distinguish it from a primary immune response. Secondary immune response occurs as a result of second and subsequent exposure of the same antigen while primary immune response occurs as a result of primary contact with an antigen. In secondary immune response, the responding cell is memory cell, while in primary immune response, the responding cell is naïve B-cell and T-cell In secondary immune response, lag phase is shorter (1-3 days) due to the presence of memory cell while in primary immune response, lag phase is often longer (4-7 days), sometimes as long as weeks or months Compare and contrast the four types of antigen-binding molecules used by the immune system—antibodies, T-cell receptors, class I MHC molecules, and class II MHC molecules—in terms of the following characteristics: a. Specificity for antigen b. Cellular expression c. Types of antigen recognized (a) Both antibodies and T-cell receptors display fine specificity for antigen; very small modifications in an antigen can prohibit its binding to its corresponding antibody or T-cell receptor. MHC molecules do not possess such fine specificity, and a variety of unrelated peptide antigens can be bound by the same MHC molecule. (b) Antibodies are expressed only by the cells of the B-cell lineage; T-cell receptors are expressed by the cells of the T-cell lineage; class I MHC molecules are expressed by virtually all nucleated cells; class II MHC molecules are expressed only by specialized cells that function as antigen-presenting cells (e.g., B cells, macrophages, and dendritic cells). (c) Antibodies can bind to protein or polysaccharide antigens; T-cell receptors recognize only peptides associated with MHC molecules; MHC molecules bind only to processed peptides. Fill in the blanks in the following statements with the most appropriate terms: a. macrophages, B cells, and Dendritic cells all function as antigen presenting cells. b. Antigen-presenting cells deliver a co-stimulatory/activated signal to TH cells. c. Only antigen-presenting cells express class II MHC molecules, whereas nearly all cells express class I MHC molecules. d. Exogenous antigens are internalized by antigen-presenting cells, degraded in the phagosome, endosome, and displayed with class II MHC molecules on the cell surface. e. Endogenous antigens are produced in altered self-cells, degraded in the polysome , and displayed with class I MHC molecules on the cell surface. Briefly describe the three major events in the inflammatory response. vasodilation, an increase in capillary permeability, and influx of phagocytes a. Vasodilation—an increase in the diameter of blood vessels—of nearby capillaries occurs as the vessels that carry blood away from the affected area constrict, resulting in engorgement of the capillary network. The engorged capillaries are responsible for tissue redness (erythema) and an increase in tissue temperature. b. An increase in capillary permeability facilitates an influx of fluid and cells from the engorged capillaries into the tissue. The fluid that accumulates (exudate) has a much higher protein content than fluid normally released from the vasculature. Accumulation of exudate contributes to tissue swelling (edema). c. Influx of phagocytes from the capillaries into the tissues isfacilitated by the increased permeability of the capillaries. The emigration of phagocytes is a multistepprocess that includes adherence of the cells to the endothelial wall of the blood vessels (margination), followed by their emigration between the capillaryendothelial cells into the tissue (diapedesis or extravasation), and, finally, their migration through the tissue to the site of the invasion (chemotaxis). As phagocytic cells accumulate at the site and begin to phagocytose bacteria, they release lytic enzymes, which can damage nearby healthy cells. The accumulation of dead cells, digested material, and fluid forms a substance called pus. a. Vasodilation—an increase in the diameter of blood vessels—of nearby capillaries occurs as the vessels that carry blood away from the affected area constrict, resulting in engorgement of the capillary network. The engorged capillaries are responsible for tissue redness (erythema) and an increase in tissue temperature. b. An increase in capillary permeability facilitates an influx of fluid and cells from the engorged capillaries into the tissue. The fluid that accumulates (exudate) has a much higher protein content than fluid normally released from the vasculature. Accumulation of exudate contributes to tissue swelling (edema). c. Influx of phagocytes from the capillaries into the tissues isfacilitated by the increased permeability of the capillaries. The emigration of phagocytes is a multistepprocess that includes adherence of the cells to the endothelial wall of the blood vessels (margination), followed by their emigration between the capillaryendothelial cells into the tissue (diapedesis or extravasation), and, finally, their migration through the tissue to the site of the invasion (chemotaxis). As phagocytic cells accumulate at the site and begin to phagocytose bacteria, they release lytic enzymes, which can damage nearby healthy cells. The accumulation of dead cells, digested material, and fluid forms a substance called pus. The T cell is said to be self-MHC restricted. What does this mean? They can recognize only antigen that is associated with class I or II MHC molecules Preparations enriched in hematopoietic stem cells are useful for research and clinical practice. In the method for enriching hematopoietic stem cells, why is it necessary to use lethally irradiated mice to demonstrate enrichment? The lethally irradiated mice serve as an assay system for multipotent HSCs, since only mice injected with these stem cells are able to reconstitute their hematopoietic systems and survive. As HSCs are successively enriched in a preparation, the total number of cells that must be injected to restore hematopoiesis and thus enable survival decreases At what age does the thymus reach its maximal size? B a. During the first year of life b. Teenage years (puberty) c. Between 40 and 50 years of age d. After 70 years of age Explain why each of the following statements is false. All TH cells express CD4 and recognize only antigen associated with class II MHC molecules. CD4+ cells that recognize class II MHC molecules functional as TH cells, whereas CD8+ cells that recognize class I MHC molecules functional as TC cells. However, some functional TH cells express CD8 and are class I restricted, and some functional Tc cells express CD4 and are class II restricted. But these are exceptions to the general pattern The pluripotent stem cell is one of the most abundant cell types in the bone marrow. the bone marrow contains few pluripotent stem cells, they constitute only about 0.05% of all bone-marrow cells Activation of macrophages increases their expression of class I MHC molecules, making the cells present antigen more effectively. TH cells recognize ag associated with class II MHC molecules Lymphoid follicles are present only in the spleen and lymph nodes. organized lymphoid follicles are also present in the tonsils, peyer's patches, and other mucosal-associated tissue (peripheral organ) Infection has no influence on the rate of hematopoiesis. in response to infection, TH cells and macrophages are activated and secrete various cytokines that induce increased hematopoietic activity. The induced hematopoiesis expands the population of WBCs that can fight the infection. Follicular dendritic cells can process and present antigen to T lymphocytes. unlike other types of dendritic cells, follicular dendritic cells do not express class II MHC molecules and thus do not fn as ag presenting cells for TH cell activation. These cells, which are present only in lymph follicles, can trap circulating ab-ag complexes, this ability is thought to facilitate B-cell activation and the development of memory B cells All lymphoid cells have antigen-specific receptors on their membrane. B and T lymphocytes have antigen binding receptors, but a small population of lymphoid cells, called null cells, does not All vertebrates generate B lymphocytes in bone marrow. although many animals, such as humans and mice, generate B cells in bone marrow, others, such as some ruminants and birds, do not What do nude mice and humans with DiGeorge’s syndrome have in common? Both have a congenital defect that prevents development of the thymus. Both lack circulating T cells and cannot mount cell-mediated immune responses Some microorganisms are classified as intracellular pathogens. Define this term and explain why the immune response to these pathogens differs from that to other extracellular pathogens. After phagocytosis by macrophages, most bacteria and fungi are destroyed and broken down, the resulting ag peptides are displayed along with class II MHC molecules on the cell surface, where they can induce TH cell activation and subsequent ab (humoral) response. In contrast, intracellular bacteria and fungi have various mechanisms for surviving in macrophages after phagocytosis. These bacteria thus do not induce an ab response. 15. The T and B cells that differentiate from hematopoietic stem cells recognize as self the bodies in which they differentiate. Suppose a woman donates HSCs to a genetically unrelated man whose hematopoietic system was totally destroyed by a combination of radiation and chemotherapy. Suppose further that, although most of the donor HSCs differentiate into hematopoietic cells, some differentiate into cells of the pancreas, liver, and heart. Decide which of the following outcomes is likely and justify your choice. C a. The T cells from the donor HSCs do not attack the pancreatic, heart, and liver cells that arose from donor cells, but mount a GVH response against all of the other host cells. b. The T cells from the donor HSCs mount a GVH response against all of the host cells. c. The T cells from the donor HSCs attack the pancreatic, heart, and liver cells that arose from donor cells, but fail to mount a GVH response against all of the other host cells. d. The T cells from the donor HSCs do not attack the pancreatic, heart, and liver cells that arose from donor cells and fail to mount a GVH response against all of the other host cells. I think that the T cells that arise from the donor HSCs will not attack the pancreatic, heart, and liver cells that arose from donor cells and fail to mount a GVH response against all of the other host cells. Although the donor and the patient are not genetically related, allogenic HSCTs work if the donor and recipient are HLA matches, which may or may not be applicable since there are not any leukocytes of the recipient to match, due to his cancer treatment. Furthermore, there should also be no Graft-versus-host (GVH) response, as the HSCs have differentiated into cells of the pancreas, liver, and heart, which suggests that they have joined, and not attacked, the recipient's tissues. If the HSCs were causing GVHD they would have attacked the tissues of the recipient, not built them up. Also, the donor HSCs differentiate in an environment that contains antigens characteristic of both the host and the donor, so they would have a tolerance to the cells and tissues of both. Thus, this hypothetical situation produced a successful outcome. List the primary lymphoid organs and summarize their functions in the immune response. Bone marrow (bursa of fabricius in birds) > functions as site for B-cell maturation Thymus > functions as site for T cell maturation 17. Indicate whether each of the following statements about the spleen is true or false. If you think a statement is false, explain why. a. It filters antigens out of the blood. TRUE b. The marginal zone is rich in T cells, and the periarteriolar lymphoid sheath (PALS) is rich in B cells. FALSE Marginal zone is rich in B Cells, & PALS is rich in T cells) c. It contains germinal centers. TRUE d. It functions to remove old and defective red blood cells. TRUE e. Lymphatic vessels draining the tissue spaces enter the spleen. FALSE the spleen is not supplied with afferent lymphatics f. Lymph node but not spleen function is affected by a knockout of the Ikaros gene. FALSE IN ADDN TO BEING ESSENTIAL FOR THE FORMATION OF NK CELLS, IKAROS IS ALSO ESSENTIAL FOR THE FORMATION OF T AND B CELLS. THEREFORE, ITS KNOCKOUT WOULD PREVENT LYMPH NODES AS SERVING AS SITES FOR THE GENERATION OF ADAPTIVE IMMUNE RESPONSES 18. For each type of cell indicated (a–m), select the most appropriate description (1–13) listed below. Each description may be used once, more than once, or not at all. Cell Types Common myeloid progenitor cells Monocytes Eosinophils Dendritic cells Natural killer (NK) cells Lymphoid dendritic cell Mast cells Neutrophils M cells Bone-marrow stromal cells Lymphocytes Myeloid dendritic cell Hematopoietic stem cell Descriptions Major cell type presenting antigen to TH cells D,L Phagocytic cells important in the body’s defense against parasitic organisms B, H Give rise to red blood cells M, A An antigen-presenting cell derived from monocytes that is not phagocytic L Generally first cells to arrive at site of inflammation H Secrete colony-stimulating factors (CSFs) J, K Give rise to thymocytes M, Circulating blood cells that differentiate into macrophages in the tissues B An antigen-presenting cell that arises from the same precursor as a T cell but not the same as a macrophage F Cells that are important in sampling antigens of the intestinal lumen I Nonphagocytic granulocytic cells that release various pharmacologically active substances G White blood cells that migrate into the tissues and play an important role in the development of allergies G These cells sometimes recognize their targets with the aid of an antigen-specific cell-surface receptor and sometimes by mechanisms that resemble those of natural killer cells. – NK-T cell 19. For each of the following situations, indicate which type(s) of lymphocyte(s), if any, would be expected to proliferate rapidly in lymph nodes and where in the nodes they would do so. a. Normal mouse immunized with a soluble protein antigen. b CELL proliferation in cortex and t cell proliferation in medulla, b cell can bind the soluble antigen while tcell couldnt b. Normal mouse with a viral infection. B&T cell c. Neonatally thymectomized mouse immunized with a protein antigen. B cell will increase, t cell will not d. Neonatally thymectomized mouse immunized with the thymus-independent antigen bacterial lipopolysaccharide (LPS), which does not require the aid of TH cells to activate B cells. B cell will proliferate Indicate whether each of the following statements is true or false. If you think a statement is false, explain why. Most antigens induce a response from more than one clone. true A large protein antigen generally can combine with many different antibody molecules. true A hapten can stimulate antibody formation but cannot combine with antibody molecules. False: a hapten cannot stimulate an immune response unless it is conjugated with a larger protein carrier. However, the hapten can combine with pre-formed antibody specific for the hapten MHC genes play a major role in determining the degree of immune responsiveness to an antigen. true T-cell epitopes tend to be accessible amino acid residues that can combine with the T-cell receptor. False: A tell cell can recognize only peptides that have been processed and presented by MHC molecules. These epitopes tend to be internal peptides. Many B-cell epitopes are nonsequential amino acids brought together by the tertiary conformation of a protein antigen. true Both TH and TC cells recognize antigen that has been processed and presented with an MHC molecule. true Each MHC molecule binds a unique peptide. true All antigens are also immunogens. False: immunogloblulins are capable of stimulating a specific immune response; antigens are capable of combining specifically with antibodies or T-Cell receptors induced during an immune response. Although all immunogens exhibit antigenicity, some antigens do not exhibit immunogenicity Antibodies can bind hydrophilic or hydrophobic compounds, but T-cell receptors can only bind peptide-MHC complexes. true What would be the likely outcome of each of the developments indicated below. Please be as specific as you can. An individual is born with a mutation in C-reactive protein that enables it to recognize phospholipids in both bacterial and mammalian cell membranes. A group of mice in which the CD1 family has been “knocked out” are immunized with Mycobacterium tuberculosis. Spleen cells from these mice are isolated and divided into two batches. One batch is treated with a lipid extract of the bacteria and a second batch is treated with a protein derived from the bacteria known as purified protein derivative (PPD). No T cell activation, Two vaccines are described below. Would you expect either or both of them to activate TC cells? Explain your answer. B A UV-inactivated (“killed”) viral preparation that has retained its antigenic properties but cannot replicate. Only proliferate b cell An attenuated viral preparation that has low virulence but can still replicate within host cells. ??b???tc???????????? For each pair of antigens listed below, indicate which is likely to be more immunogenic. Explain your answer. a. Native bovine serum albumin (BSA) Heat-denatured BSA Native BSA: heat denaturation is likely to destroy B cell epitopes in a globular protein, although T-CEll epitopes are generally stable to heat b. Hen egg-white lysozyme (HEL) Hen collagen HEL: The immunogenicity of an antigen generally is related to its foreignness to the animal exposed. However, collagen and some other proteins highly conserved throughout evolution exhibit little foreignness across diverse species and thus often are weak antigens. c. A protein with a molecular weight of 30,000 A protein with a molecular weight of 150,000 150,000 MW protein: Other things being equal, larger proteins are more immunogenic than smaller. d. BSA in Freund’s complete adjuvant BSA in Freund’s incomplete adjuvant BSA in complete Freund's adjuvant will be more immunogenic because mycobacteria included in the complete adjuvant have components that stimulate a wide range of cell types via their PRRs and thus will involve these cells in response against the BSA. Incomplete adjuvant lacks the added mycobacteria and will not provide the broad stimulus seen with complete.