Opportunities in Biology (1989) / Chapter Skim
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7. The Immune System and Infectious Diseases
7. The Immune System and Infectious Diseases
Pages 224-259
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From page 224... ...
The cells of the immune system are found in the blood and lymph, where they are in a recirculating pool, and in the spleen, lymph nodes, and lymphoid tissues associated with the gastrointestinal tract, the brochopulmonary tree, and mucosal surfaces. Lymphocytes and macrophages develop in the thymus and the bone marrow.
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From page 225... ...
B cells are the antecedents of antibodyproducing cells, whereas T cells have their major effects in regulating the level of activity of the immune system and in mediating cellular effecter mechanisms of immunity, such as destroying virus-infected cells and tumor cells. The study of the immune system has proven to be of great importance in efforts to understand and to regulate immune responses, both to enhance the system's protective actions against microbes and tumor cells and to control its actions in the development of autoimmune diseases and other disorders with immunological components.
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From page 226... ...
or for the variable regions of T-cell receptors (for T cells)
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From page 227... ...
, and of the related B- and T-cell receptors is important in its own right since they represent a majority of biological recognition systems. Antibody Molecules and B-Cell Receptors Are Proteins Called Immunoglobulins Although Ig exists in several distinct forms, termed classes, these molecules have a common structural organization consisting of a unit that is a dimer of a heavy (H)
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From page 228... ...
T-Cell Receptor Molecules Are Heterodirneric Ig-like Molecules Most T cells express receptors composed of a and ,3 chains; others express receptors composed of ~ and ~ chains. T-cell receptor polypeptide chains have amino acid sequence homologies to Ig H and L chains.
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From page 229... ...
B Lymphocytes B Cells Undergo an Ordered Set of Developmental Processes as They Develop from Hematopoietic Progenitor Cells The B lymphocytes are derived from precursors in hematopoietic tissue. These progenitor cells develop into pre-B cells, which lack membrane receptors and thus are insensitive to antigenic stimulation.
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From page 230... ...
Receptor Cross-Linkage Mediates B-Cell Activation B-cell activation in response to antigenic stimulation seems to follow one of two activation pathways; these alternatives may reflect the existence of two distinct types of antigenic substances. Many biologically important antigenic molecules (termed type II antigens)
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From page 231... ...
B-Cell Activation Can Also Occur Through Cognate T-Cell-B-Cell Interaction Many of the most important antigenic substances against which the immune system must respond have no more than one copy of any individual epitope. These molecules include proteins having many different epitopes but no repetitive elements.
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From page 232... ...
This H chain interacts with L chains to form a secretory protein rather than a membrane protein. An Important Differentiation Event in the Physiology of Antibody Production Is the "Switch" in Expression of Ig Class by B Cells As has been described, each Ig class seems to play a distinct role in the immune response.
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From page 233... ...
These T cells are generally referred to as killer cells. Killer T cells mainly recognize antigen in association with a different group of MHC molecules, class I molecules.
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From page 234... ...
The association of distinct human leukocyte antigen types with susceptibility to diseases such as non-insulin-dependent diabetes mellitus may reflect the capacity of complexes of antigen and specific MHC molecules to give rise to immune responses that destroy the tissues upon which such complexes appear.
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From page 235... ...
Tolerance induction in T cells would prevent cellular (T-cell mediated) immune responses against self-antigens and would also markedly diminish antibody responses against self-antigens since most antibody responses require some form of T-cell help.
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From page 236... ...
236 OPPORTUNITIES IN BIOLOGY ~:~ORGAN~:~TRANSPLANT:~I ION:: :~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ .~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~: :~ ~ :~ ~ :~ ~ ~ ~ ~ ~ ~ ~ :::::: :~:~Transpl:antation~ of keys: for then t:reatm:e~nt~:~of :~chron~ ~:~renal disease ~ ~: ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ :~ ~: ~ ~ ~ :~ ~: ~,~ ~ If: :~ ~ ~ :~:~has~b~com~:~an almost~rotrtine therapy.: TI ransplantation~1s~:~:~bein~g:~:~lncre~s-~:~ ~:inq9 Frigid for fur: fu~nition~of~:bone~ Go: Heart liver ~a~:~:~lung. I: : :: :::: :: :: : :~ ~ :::::: :::: ~ :: ::: : ::: : :: : ::: ::: :: i: :::: i: : ::: : ::: : : ::~::: :: : : ~ ~ :::: ~ : i:::: :::: :: ~ ::~ : ~:::~: : ::: ~ ~ : :: ::: i:: : ~ :~:~in~tli~e~experime~ntal:~t:ran~splan~tion~6f :~other~organs ~notably:~the~:~ : :s~ncre~ic islets ~indicites~:th:at~the field~o{:~clink~al~transpkini32ion~will~co~n-~ :~:~:tibue~to~:~expar~.~ ~ Surgical :~thchniques ~have~:~advanced~rem~arkably: ~:allowing~:~:~: ~ :: :: i: : ~ :: :~::: ::: : i: ~ :::::::: :: ::: i: ~ :~ i: ~ : ~:<~:~sshil~pe:~doFm~ancQ~often~heroicoperabons.~me:~maJor~bb~iQr~tQ ::: ~:~l~term~f~ion~of~ornan~and ~:tissue~:~howeve~r :~:~:~is~im~n,~u~nological~:~:~ reaction Of he :fore~gn~organ~ by:the:~host,~and, ~in~the~:~case~ of: ~:bon~e marrow :~: gram ~of~th:~:reaction~:Of~th:e grafted~tissu~ against:~the~host (g~raf~vers~:us~hobt~:~::: ~ ~ ~ ~ ~ t ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ :~;~:~disiase)
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From page 237... ...
This process may be a major factor in the development of pathogenic autoantibodies. T Cells Are Activated by Signals from a Receptor Complex and the Expression of IL-2 Receptors The membrane receptors through which T cells recognize antigen associated with class I or class II MHC molecules are composed of two distinct chains, which are Ig-like in that they bear sequence homology to Ig and have a generally Ig-like structural organization.
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From page 238... ...
The recognition of the antigenic complex on the surface of the target cell activates the killer cell, which in turn sets in motion the process that destroys the target cells. Although controversy still exists on this subject, T-cell-mediated cytotoxicity seems to involve killer-cell production of substances called porins, which polymerize, integrate into the target-cell membrane, and cause cell lysis.
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From page 239... ...
~ patient.: immunity, mainly against arising tumor cells, but possibly also against infectious agents. Regulation of the Immune Response Immune Responses Are Subject to Both Positive and Negative Regulatory Control A key example of regulatory control is the action of T lymphocytes as helper cells in antibody responses.
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From page 240... ...
Suppressor mechanisms may also limit immune responses to tumor cells and thus diminish the effectiveness of the immunological control of tumor cell growth. A particularly intriguing mechanism through which immune responses may be regulated involves the "immunological network," which is based on the capacity of antibodies and receptors to recognize one another.
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From page 241... ...
Hypersensitivity, Inflammation, and Phagocytosis The Study of the Cellular and Chemical Mechanisms of Inflammation and Phagocytosis Is Crucial to the Development of Anti-inflammatory Drugs A common feature of the cellular response to foreign agents is a local inflammatory response. Inflammation that occurs as a result of immune responses is often referred to as hypersensitivity.
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From page 242... ...
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From page 243... ...
Phagocytic cells have other means of destroying ingested microorganisms, including a complex enzyme system for generating toxic oxygen products, including hydrogen peroxide and hydroxyl radicals. In addition, these cells produce hypochlorous acid, hypochlorite, and chlorine, which oxidize and halo
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From page 244... ...
, elaboration of toxins, and penetration of host cells. For viruses, virulence factors include the capacity to spread, replication in cells, survival in tissue fluids, interaction with proteases and host-cell receptors, and resistance to host defense (macrophages, T cells, and interferon)
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From page 245... ...
The Chemical Nature of Some Bacterial Adhesins and Their Corresponding Receptors on Host Tissues Is Known A large number of studies performed during the past decade have established that many bacteria have surface structures that bind to specific macromolecules on host cells in a lock-and-key (or induced-fit) fashion analogous to the combina
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From page 246... ...
1. Bacterial surface lectins can bind to the carbohydrates on the surface of animal cells.
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From page 247... ...
Carbohydrate-Lectin Interactions Play a Central Role in the Mutual Recognition Between Many Bacteria and Host Cells One must be cautious in drawing general conclusions about the significance of lectin-carbohydrate interactions in viva on the basis of in vitro studies alone. It is not unlikely that the physiological environment influences the orientation and relative accessibility of the sugar moieties in the oligosaccharides involved in the interactions in vitro; a change in orientation theoretically would markedly affect not only the affinity but also the specificity of the bacteria-host-cell interaction.
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From page 248... ...
The receptor now seems to be fibronectin, a ubiquitous glycoprotein present on the surface of many host cells including oral epithelial cells. Binding of lipoteichoic acid to fibronectin occurs at a site on the glycoprotein that specifically binds fatty acid residues with a binding affinity two orders of magnitude higher than the binding of lipotichoic acid to fatty-acid binding sites of serum albumin.
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From page 249... ...
Spread through the blood can be rapid and can result in generalized infection. A Number of Pathogenic Bacterial Species Can Penetrate and Grow Intracellularly Within Host Cells Intracellular bacteria resist host immune mechanisms essentially by hiding within host cells.
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From page 250... ...
The exact neural pathway and the microbial determinants remain undefined. For neurotropic reoviruses, the viral attachment protein is responsible for allowing the neurotropic strain to enter peripheral nerves, whereupon subsequent movement takes place in the fast axonal transport system (see Chapter 4~.
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From page 251... ...
Interactions of Viruses with the Host Cell Viruses Exist Either as an Extracellular Virion Particle or as Intracellular Forms Undergoing Replication For inactivation of a virus, the infectious virus particle must be neutralized by antibodies or its replication must be inhibited within the host cell. To be therapeutically useful, any agent that inhibits replication must specifically affect a viral replication process and not the host cell.
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From page 252... ...
Herpes simplex virus may even utilize preexisting nuclear sites of cell DNA synthesis as sites for assembly of viral DNA replication complexes. Such perturbations of the host cell may lead to the gross pathological changes in the cell known as cytopathic effect.
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From page 253... ...
One of these regions is highly homologous to the soluble human protein thrombospondin, which cross-links host cells. Other Determinants of Tissue Tropisms Include Tissue-Specif id Host Enzymes and Regulatory Factors The cleavage of viral glycoproteins from an inactive precursor form to an active product is an important determinant of pathogenicity for myxovirus and paramyxovirus.
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From page 254... ...
The host response itself may lead to pathological outcomes, which may be relatively nonspecific (as when proteases are released from macrophages in an inflammatory response that subsequently results in injury to normal cells) or may result in specific injury from cellular immune responses or the action of antibodies.
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From page 255... ...
This response, clasically resulting in redness, swelling, pain, and loss of function, may damage the host more than the replicating microbe. The early inflammatory response has both cellular components (macrophages and natural killer cells)
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From page 256... ...
Hybridizatio:n experi:ments ~ with these clones: show~d :that ~:prion protei:n: ~mRNA~ was ~ndt :found exclu-~ : sively in::scrapie-inf~ctdd~ animals, but::: occorred to the same~ e~ctent:in t:he : tissues of un:inf~ted animals. :Thus, th~e relationship of:the prion protein: gene and Rs expressed protein to the infectious agents of scrapie and other; : : spongiforrn encephalopathie:s is as yet uncertain.
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From page 257... ...
Autoimmune responses have recently been identified for viral and bacterial antigens. In such cases, the host responds not only to the microbial antigen but also to normal host components.
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From page 258... ...
for Months to Years Plasmodium malariae, one of the four human malarial parasites, can persist in the bloodstream for the life of the host, reinvading new red cells every Free days. The adult schistosome, a trematode, lives in venules for many years, copulating and laying eggs that spread the infection and trigger the disease.
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From page 259... ...
Equally, the central role of the immune system in resistance to infectious diseases, in the elimination of tumor cells, and in the pathogenesis of many chronic disease makes it an obvious target for clinical efforts. During the next decade, substantial emphasis needs to be placed on developing a quantitative understanding of the contribution of the various components of the immune system to the function of that system in humans and other animals, both in normal situations and in various disease states.
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