Immunity to Infection

Size: px
Start display at page:

Download "Immunity to Infection"

Transcription

1 Anders Elm Pedersen, University of Copenhagen, Copenhagen, Denmark The immune system comprises innate and adaptive immune responses coordinated to prevent infection. Innate immune responses are early responses based on preformed cells and effector molecules with a limited repertoire of antigen receptors. In contrast, adaptive immune responses take several days to mount, but take advantage of a very large repertoire of antigen receptors and comprises memory. The immune system must constantly face pathogen invasion strategies and at the same time avoid destruction of non-infected host tissue. In the following review the role of the various components of the immune system and their role in immunity to infections is described. Infection versus Disease We are coexisting with a tremendous number of microorganisms such as bacteria, fungi, parasites and viruses. A number of these are strict pathogens that lead to lethal infectious disease, e.g. orthopoxvirus (smallpox) and Mycobacterium tuberculosis (tuberculosis), whereas others are microorganisms of the normal microbial flora that cause opportunistic infections only in an immunocompromised host (e.g. Candida infection in a patient with Human immunodeficiency virus (HIV)), or when the microorganism is transported to an unprotected site (e.g. bacteraemia caused by abdominal surgery). See also: Infections in the Immunocompromised Host; Microorganisms Thus, whether or not an infectious agent causes disease is a delicate balance between the genetic (e.g. X-linked agammaglobulinaemia) or acquired (e.g. patients with acquired immune deficiency syndrome (AIDS) or stressed, traumatized individuals) immune status of the host and the virulence of the pathogen (the ability of the microorganism to destroy immunological barriers and grow at the expense of host tissue). See also: Immunodeficiency Some pathogens cause disease by direct tissue destruction. Staphylococcus aureus produces the enzyme hyaluronidase, which promotes the spread of the bacteria by destroying connective tissue. In contrast, an organism such as Clostridium tetani does not cause significant local symptoms at the site of inoculation. Instead the muscle cramps known as tetanus are caused by a toxin secreted into the bloodstream. Many of the symptoms of infection are not related to the specific microorganism involved. In fact, symptoms such as fever, exanthema and tumour, rubor and dolor are caused by the host inflammatory response elicited by the microorganism. Indeed, some diseases are the result of an overvigorous immune response to an otherwise fairly harmless microorganism (e.g. acute hepatitis caused by hepatitis B virus). See also: Toxin Action: Molecular Mechanisms Nonspecific Resistance Most of the microorganisms in our environment never cross the epithelial barriers that cover the body surfaces. Introductory article. Infection versus Disease. Nonspecific Resistance Article Contents. Innate Immune Response: Humoral. Innate Immune Response: Cellular. Acquired Immune Response: Humoral (B Cells). Acquired Immune Response: Cellular (T Cells). Activation of the Most Appropriate Immune Response to a Given Infectious Agent. Pathological Sequelae of the Immune Response. Microbial Evasion from the Host Immune Response. Regional versus Central Immune Response doi: / a pub2 Epithelial surfaces function as a physical barrier. Likewise, mucosal epithelium expels most microorganisms simply by mucus secretion and ciliary action. The flushing action of saliva and urine also protects mucosal surfaces. See also: Skin: Immunological Defence Mechanisms Epithelial cells also secrete components that actively inhibit colonization with pathogenic microorganisms. For instance, free fatty acids produced in sebaceous glands together with lactic acid from perspiration and low ph make the skin a hostile environment to most bacteria. Also, many of the secreted body fluids (e.g. tears, mucus, saliva) contain microbicidal factors. For example, lysozyme, which cleaves the peptidoglycan layer of Gram-positive bacteria, induces bacterial lysis and lactoferrin (an iron-binding enzyme) competes with microorganisms for iron and thereby inhibit their growth. See also: Lysozyme Innate Immune Response: Humoral When a pathogen crosses the epithelial barrier despite the barrier function of the epithelial surface, the first counterstrike of the immune system is the innate immune response. This is composed of preexisting antimicrobial molecules and cells, and is actually capable of defeating most infections at an early stage. Only when innate host defence is overwhelmed, the induction of an adaptive immune response is required. The alternative pathway of complement Complement activation leading to opsonization and killing of pathogens can occur in three distinct ways. For example, the classical pathway is dependent on antibody bound to the surface of the pathogen. It therefore takes approximately 5 7 days to activate the complement system in this way the time needed for the adaptive immune system to mount an effective antibody response. In contrast, the alternative complement pathway is a component of the ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd. 1

2 innate immune system and is activated spontaneously. This occurs because the protein C3 is constantly cleaved to yield C3b in the plasma. C3b, in turn, attaches to host or pathogen cells. Host cells, however, are protected against the final assembly of complement, because they express protective proteins such as decay-accelerating factor and membrane cofactor of proteolysis. Most pathogens lack such proteins, and factor P is allowed to bind and stabilize the components of complement on the surface of the pathogen. Eventually, the terminal complement components are activated and the pathogen is lysed. See also: Complement; Complement: Alternative Pathway Interferons Human cells have evolved a special strategy to avoid spread of viral infection. Double-stranded ribonucleic acid (RNA), which is made during the infectious cycle of most viruses, induces the synthesis of interferon (IFN)a and IFNb. These interferons in turn inhibit protein synthesis in local host cells and thereby inhibit viral replication. This is promoted by binding of the interferons to receptors on neighbouring cells followed by induction of intracellular enzymes that degrade viral RNA and inhibit protein synthesis, in part by inactivating the eukaryotic protein synthesis initiation factor, eif-2. Interferons also stimulate an increase in proteasome activity and expression of major histocompatibility complex (MHC) class I molecules, thereby increasing the processing and presentation of viral antigens which increase the chance of recognition and killing from cytotoxic CD8 T cells (see later). See also: Interferons; Major Histocompatibility Complex (MHC) Innate Immune Response: Cellular Whereas preformed effector molecules act immediately on the pathogen, most cellular responses require a few hours to respond to a pathogen. Macrophages derived from circulating monocytes are important in coordinating this early induced immune response. They are found in great numbers in connective tissue, and in the lung, liver and spleen. These macrophages express, on their surface, several receptors for so-called microbial-associated molecular patterns. An important group of such receptors are the Toll-like receptors (TLR) of which about 10 have been described to date. For example, bacterial lipopolysaccharide (LPS), which is part of the capsule of Gram-negative bacteria, is bound to TLR-4 dimer+cd14 on the macrophage. Phagocytosis of the pathogen is often enough to defeat an infection. However, the interaction between antigen and the TLR on the macrophage leads secretion of cytokines that are pivotal in the induction of additional immune responses if necessary. See also: Lipopolysaccharides; Macrophages The effects of these cytokines (interleukin (IL)-1, IL-6, IL-8, IL-12 and tumour necrosis factor (TNF)a) are local as well as systemic. Local effects include initiation of an acute inflammatory response characterized by pain, redness, heat and swelling. This is in part initiated by TNFa, which increases vascular permeability to allow the entry of additional immunoglobulin, complement and cells at the site of infection and to increase fluid drainage to lymph nodes. Most cytokines are also involved in the activation and attraction of additional cells of the immune system, such as neutrophils, lymphocytes and natural killer (NK) cells. See also: Cytokines; Tumour Necrosis Factors The systemic effects of cytokines include the induction of the acute-phase response and fever. The acute-phase response is initiated when IL-1, IL-6 and TNFa reach hepatocytes. The liver increases the secretion of acute phase proteins into the blood plasma and suppresses the secretion of other plasma proteins. C-reactive protein and mannosebinding protein are among the proteins secreted by the liver during the acute-phase response. These proteins share the ability to bind specific conserved antigens on fungal and bacterial cell walls and to activate components of the complement system. This, in turn, facilitates the removal of pathogens by phagocytes, or causes lysis of the pathogen. Neutrophil granulocytes make up the first wave of cells that cross the permeable vasculature at the site of inflammation. Lymphocyte function-associated antigen-1 (LFA-1) binds intercellular adhesion molecule 1 (ICAM-1) on activated endothelial cells and induces diapedesis of the neutrophil across the endothelial cells. The neutrophil is then attracted to the infectious site by chemokines and act as very potent phagocytic effector cells. They are often recruited in massive numbers and die a few days after they entered the inflamed tissue. Some viruses are capable of blocking the synthesis and transport of MHC class I molecules (Figure 1) to the cell surface. This makes infected cells susceptible to killing by natural killer (NK) cells which kill cells that lack expression of MHC class I molecules on the cell surface. The activity of NK cells is greatly amplified during an infection when exposed to IFNa, IFNb and IL-12. Particular infections with herpes viruses and Listeria monocytogenes are known to be susceptible to NK cell activity. Also, NK cell activation might be important for the subsequent direction of the adaptive immune response, since they secrete large amounts of IFNg, which induces a T H 1 response. See also: Immune Defence: Microbial Interference; Natural Killer (NK) Cells Acquired Immune Response: Humoral (B Cells) The fundamental difference between the innate and the adaptive immune systems is the diversity and the capacity for memory. Recognition mechanisms in the innate immune system are limited to conserved epitopes of pathogens and take generations to develop. This is due to the fact 2 ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd.

3 Innate immune response Cells in antiviral state IFNα Virus-infected cells NK cell Killing of virus-infected cells Adaptive immune response Bacteria Virus Macrophage phagocytosing pathogens Antigen uptake Activation of macrophage CD4 T H 1 cell Epithelial barrier Dendritic cell Migration to regional lymph node Neutrophils MHC-I CD8 T cell CD28 B7 B7 IL-2 IFNγ IL-2 CD28 IFNγ Cell-mediated immune response MHC-II Antigen-presenting cell CD4 T H 0 cell IL-2 IL-4 CD4 T H 2 cell Antibody secretion MHC-II CD40L CD40 Humoral immune response Plasma cell Naive B cell Figure 1 Innate and adaptive immune responses. Macrophages, neutrophils and natural killer cells are attracted to the site of pathogen entry. Dendritic cells take up antigen and migrate to regional lymph nodes. Here antigen presentation to T cells take place, and these differentiate into helper T cells (T H 1orT H 2 CD4 T cells) and cytotoxic T cells (CD8 T cells). Activation of B cells and immunoglobulin production are also initiated. that only receptor molecules encoded by germline deoxyribonucleic acid (DNA) can be employed in innate immunity. In contrast, adaptive immunity has evolved the potential for an enormous diversity, because germline DNA can be recombined whenever necessary to encode new antigen receptors, such as immunoglobulin and the T cell antigen receptor (). At the same time, adaptive immunity includes the potential for memory. See also: B Lymphocytes; Epitopes; Immunity: Humoral and Cellular Initiation of the adaptive immune response requires the activation of T cells. This is performed by antigen-presenting cells (APCs) such as macrophages, B cells and in particular dendritic cells (DCs) that are known as professional APCs. DCs take up antigen at the site of infection, process it, present it on MHC molecules and transport it to the regional lymph node where presentation to T cells occurs. Other kinds of DCs are specialized to store whole antigens on the surface and in this way present it to B cells in the lymph nodes. See also: Antigen-presenting Cells; Dendritic Cells (T-lymphocyte Stimulating); T Lymphocytes: Helpers Activation of B cells Circulating B cells express immunoglobulin (Ig) M molecules on the cell surface, the so-called B-cell antigen receptor (BCR). When antigen is bound to a specific B cell, the sigm: antigen complex is internalized by endocytosis and the B cell is activated to secrete IgM. In turn, fragments of antigen are bound to MHC class II molecules (Figure 2) and transported to the cytoplasmic membrane. This enables recognition by T helper cells and is important for the production of immunglobulins with higher affinity and specificity than IgM. When the B cell receives a T-cell signal in addition to ligation of the BCR, the B cell in the germinal centre of a lymph node can undergo extensive proliferation and somatic hypermutation. The result of this is the production of high-affinity IgG and the differentiation of B cells into plasma and memory cells. See also: B Lymphocytes; B Lymphocytes: Receptors; Clathrin-coated Vesicles and Receptor-mediated Endocytosis; Germinal Centres; Lymphocytes: Recirculation; T-lymphocyte Activation ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd. 3

4 MHC class I molecule MHC class II molecule NK cell Empty MHC-I molecule Antigenic protein KIR Inhibition of NK cell MHC-I molecule with peptide Primed CD8 T cell TAP transporter CD8 Initiation of cytotoxicity Cell surface Endoplasmatic reticulum Antigenic peptides Internalization of extracellular antigen Endoplasmatic reticulum Empty MHC-II molecule CD4 T cell CD4 Cell surface Fusion of vesicles containing antigenic peptide with vesicles containing MHC-II molecules Proteasome Intracellular antigen Figure 2 Major histocompatibility complex molecules. MHC class I molecules present peptides derived from intracellular antigens to CD8 T cells. Also the presence of MHC-I molecules on the cell surface prevents attack by natural killer cells. In contrast, MHC class II molecules present peptides from extracellular antigens and present these to CD4 T cells. Antibodies of different isotypes have different effector functions The different immunoglobulin isotypes exert different effector functions in the humoral immune response. IgM is the first antibody produced during an immune response and comprises 5 10% of the total immunoglobulin pool. This antibody is produced before the B cell undergoes somatic hypermutation and is therefore of low affinity. However, IgM forms pentameric molecules, and the many antigen-binding sites confer high avidity instead. Because of the large size of the pentamers, IgM is primarily found in the blood. Here it provides first-line immunity against bacteria with cell wall polysaccharides because IgM promotes effective bacteriolysis through activation of the classical complement system. See also: Antibody Classes; Somatic Hypermutation in Antibody Evolution B cells undergo somatic hypermutation in germinal centres of lymph nodes and switch to IgG production. The benefit of this process is the high affinity of the IgG molecule and the initiation of various effector functions by the Fc domain of the antibody. IgG is a monomeric molecule which readily diffuses out of the bloodstream into the tissues. It comprises approximately 85% of the immunoglobulin pool and is involved in processes such as neutralization of bacterial toxins and viruses. In particular, IgG1 is involved in a process called opsonization. When antibody is bound to a pathogen, such as a bacterium or parasite, the Fc domain is recognized by various effector cells such as macrophages and neutrophils which then generate toxic products and initiate phagocytosis. If the pathogen is coated with IgG1 or IgG3, it can also be destroyed by antibody-dependent cell-mediated cytotoxicity (ADCC). In this process, NK cells bearing the Fc receptor FcgRIII (CD16) bind the Fc domain, and this triggers a cytotoxic attack that destroys the target. See also: Antibodydependent Cell-mediated Cytotoxicity (ADCC); Fc Receptors; Immunoglobulin Gene Rearrangements; Phagocytosis: Enhancement IgA exists both as a serum immunoglobulin and as a secretory immunoglobulin (siga). siga binds to a receptor on epithelial cells and is transported across the epithelial barrier into, for example, intestinal and respiratory secretions, saliva and tears. Here it prevents attachment of bacteria or toxins to the epithelial cells and is thus a major component of mucosal immunity. IgE comprises less than 1% of the total immunoglobulin pool. It is important in infections with large parasites such as helminths, where eosinophils recognize the Fc domain of IgE bound to the parasite and release toxic proteins such as major basic protein. See also: Immunity to Parasitic Worms Memory in the humoral immune response The benefit of the adaptive immune response is the induction of memory and thereby potential lifelong immunity. 4 ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd.

5 When the individual is challenged with the pathogen a second time, specific antibody is already present and can prevent the pathogen from entering the epithelial surfaces. Also, an already immunized host does not need to wait for the adaptive immune response to be primed, and the reactivation of the adaptive immune system during a second exposure to antigen is much faster than the primary immune response and the affinity of the antibody increases with each challenge to a pathogen. See also: Immunological Memory Acquired Immune Response: Cellular (T Cells) T cells are pivotal in the activation and control of the adaptive immune response. The production of T cells takes place in the bone marrow, where after they undergo positive and negative selection in the thymus and then start circulating in the lymph and bloodstream as naïve CD4 and CD8 T cells. As with naïve B cells, these T cells must encounter antigen to proliferate and differentiate. Hence, CD8 T cells become CD8 cytotoxic T cells. CD4 T cells are Thelper (T H ) cells and can differentiate into either T H 1 cells, which are involved in the activation of macrophages, or T H 2 cells, which activate B cells to produce antibody (Figure 1). As a part of the adaptive immune system, T cells have the capability of memory function. See also: T Lymphocytes: Cytotoxic; T Lymphocytes: Helpers Antigen presentation to T cells Macrophages and B cells are able to present antigen to T cells. However, dendritic cells are by far the most effective cells in this event, and are also called professional APCs because they upon activation upregulate an abundance of costimulatory molecules which is needed for effective priming of T cells. DCs take up antigen by pinocytosis and phagocytosis, process it and present it to T cells as peptide antigens in combination with MHC molecules. Antigen uptake and activation of DCs take place in the periphery, where they are activated by inflammatory cytokines and binding of microbial-associated molecular patterns to TLR. The activation also leads to induction of chemokine receptors necessary for the migration through lymph vessels to the lymph node, where activation of T cells take place (Figure 1). See also: Antigen Presentation to Lymphocytes; Dendritic Cells (T-lymphocyte Stimulating); Lymph Nodes; T Lymphocyte Responses: Development All T cells express the. The recognizes MHC molecules in combination with the relevant antigen on the surface of either the APC or the target cell. CD8 on CD8 T cells restricts this binding to MHC class I molecules, whereas CD4 on CD4 T cells restricts the binding to MHC class II molecules (Figure 2), which is only present on APCs. However, for the T cell to be activated, the APC must express B7 molecules, which bind the costimulatory molecule CD28 on the T cell. This process, called priming, is therefore most efficient when dendritic cells are involved. In contrast, after priming, the armed effector T cells and memory cells can respond to target cells expressing the relevant MHC molecules, without colligation of CD28. See also: Major Histocompatibility Complex: Interaction with Peptides; T-cell Receptors Major histocompatibility complex molecules MHC class I molecules are expressed on the cell surface of all nucleated cells and consist of a heavy chain noncovalently bound to b 2 -microglobulin and a peptide. These molecules are specialized in presenting antigens from intracellular pathogens, such as viruses, to CD8 T cells. Cellular proteins are constantly renewed. Old proteins are then degraded by proteolytic enzymes called proteasomes. Some of the resulting peptide fragments are transported to the endoplasmic reticulum by transporters associated with antigen processing (TAPs). Here peptide, b 2 -microglobulin and heavy chain assemble and the fully folded MHC class I molecule is transported to the cell surface (Figure 2). During a viral infection, viral peptides dominate and will bind to the MHC class I molecule. See also: Antigen Processing; Major Histocompatibility Complex: Human The MHC class II molecule consists of an a and a b subunit and, like the MHC class I, binds an antigenic peptide. However, MHC class II molecules are expressed only on APCs, and present exogenously derived peptides. Antigen is taken up into intracellular vesicles of the APCs and degraded by the low ph in lysosomes. Somewhere along the route of intravesicular transport, the vesicle containing antigen fragments fuses with a vesicle containing newly synthesized MHC class II molecule. This allows the MHC class II molecule to bind an antigenic peptide and be transported to the cell surface, so making recognition by CD4 T cells possible (Figure 2). See also: Major Histocompatibility Complex: Interaction with Peptides CD4Tcells When a naive CD4 T cell responds to a peptide: MHC class II complex, it initiates an autocrine secretion of IL-2, begins to proliferate and can either become a T H 1oraT H 2 cell, depending on the infectious agent and the cytokines produced by the innate immune response. This step in T-cell differentiation determines whether a humoral or a cell-mediated immune response will predominate. T H 1 cells are specialized in the activation of macrophages. As a part of the innate immune response, macrophages engulf pathogens and present antigenic peptides in combination with MHC class II molecules. When recognizing the antigen presenting macrophage, T H 1 cells secrete cytokines such as IFNg, granulocyte macrophage colony-stimulating factor ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd. 5

6 (GM CSF) and TNF, which activate the infected macrophage to increase the production of antibacterial agents such as nitric oxide and oxygen radicals. In contrast, T H 2 cells are specialized for B-cell activation. The B cell internalizes antigen through sig, and the antigenic peptides are presented in combination with MHC class II molecules. In turn, T H 2 cells binds the CD40 molecule at the surface of the antigen bearing B cell and start to secrete cytokines such as IL-4, IL-5 and IL-6, which stimulate B-cell proliferation and differentiation (Figure 1) and thus a humoral immune response. In addition to T H 1oraT H 2 cells, it has recently been demonstrated that a third subset of CD4+ T cells exist, namely the T H 17 cell which secretes high amounts of IL-17. These cells are now known to be important in chronic infections or chronic autoimmune diseases. See also: Macrophages; T Lymphocytes: Helpers Not all CD4 T cells are effector cells. Also, regulatory cells exist that are known to dampen immune responses or prevent activation of autoreactive T cells in the periphery. Here, natural occurring CD4+CD25+ regulatory T cells have attracted much attention and are the best studied subset of regulatory T cells. CD8Tcells Cytotoxic CD8 T cells are pivotal in the destruction of virally infected cells. When a primed CD8 T cell recognizes a viral peptide in combination with a MHC class I molecule, it starts secreting perforin and granzymes. Perforin is inserted into the membrane of the infected target cell and promotes cell lysis, whereas the granzymes activate intracellular proapoptotic enzymes known as caspases in the target cell. In addition, many CD8 T cells express Fas ligand on their surface. If the target cell expresses Fas, it will initiate an additional cascade of proapoptotic molecules and die by programmed cell death (apoptosis). See also: Immunological Cytotoxic Factors; T Lymphocytes: Cytotoxic Activation of the Most Appropriate Immune Response to a Given Infectious Agent Infectious agents can be divided into intracellular or extracellular bacteria, fungi, viruses and parasites and elicit different kinds of immune response (Table 1). Again, the differentiation of CD4 T cells into either T H 1orT H 2 cells is pivotal in the induction of either a primarily humoral or a primarily cell-mediated immune response. Intracellular bacteria such as mycobacteria evade the immune system by hiding inside macrophages. In this case a cell-mediated immune response is the best choice, since the bacteria are protected from antibody. Activated T H 1 cells enhance the ability of macrophages to kill the mycobacteria. Similar, intracellular parasites are best defeated by a T H 1 response. A special mechanism in the immune response to intracellular bacteria is the formation of a granuloma formed by giant and epithelioid cells. See also: Immune Mechanisms Against Intracellular Pathogens In contrast, extracellular bacteria are best defeated by antibody in combination with complement activation, ADCC and phagocytosis of the opsonized pathogen. Thus, extracellular bacteria usually elicit a humoral immune response with the predominance of T H 2 cells. See also: Immune Mechanisms Against Extracellular Pathogens The nature of the pathogen itself actually tends to determine the outcome of the adaptive immune response. Macrophages and dendritic cells are stimulated in the early phase of the infection by microbial-associated molecular patterns to produce various cytokines. In turn, the combination of these cytokines influences the differentiation of T cells and thus the induction of either a cell-mediated or a humoral immune response. It has been shown that some bacteria (e.g. Listeria) stimulate macrophages to secrete IL-12, which in turn commits the CD4 T cell to differentiate into T H 1 cells. Also, the cytokines that commit this differentiation inhibit the differentiation of CD4 cells into T H 2 Table 1 Immune responses to infectious agents Extracellular bacteria Intracellular bacteria Viruses Fungi Parasites Neutrophils Eosinophils Macrophages Natural killer cells CD8 T cells CD4 T H 1 cells IgM IgG IgA IgE Complement Note:T H, T helper; Ig, immunoglobulin. ++, very important component in the defence to the pathogen; +, important;, less important. 6 ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd.

7 cells, and vice versa. Interestingly, the balanced secretion of cytokines also determines the predominance of effector cell or regulatory T-cell activation. For example, a combination of TGFb and IL-6 secretion from APCs induces T H 17 effector cells and at the same time turns off the function of CD4+CD25+ regulatory T cells. See also: Cytokines; Immune Mechanisms Against Intracellular Pathogens The MHC affinity and avidity of the antigen influences CD4 T-cell differentiation. In general, antigenic peptides that are in abundance and cause a strong :MHC class II interaction stimulate a cell-mediated immune response, whereas antigenic peptides that are less likely to produce strong :MHC class II interactions stimulate a humoral immune response. Viral infections produce a mixed T H 1 and T H 2 response, but the T H 1 response often dominates. CD8 T cells are pivotal in controlling viral infections because they destroy the viral reservoir contained in infected cells. Pathological Sequelae of the Immune Response TNFa is a striking example of the balance between lifesaving actions and wasting, disastrous effects of the immune system. On the one hand, TNFa causes the activation of endothelial cells, necessary to allow sufficient leucocytes and lymphocytes to enter the site of infection and remove the pathogen. On the other, if TNFa is secreted in excess into the bloodstream, as seen in sepsis with Gram-negative bacteria, systemic oedema follows and the patient may go into shock. Eventually, disseminated intravascular coagulation, multiple organ failure and death ensue. Paradoxically, the fatal outcome is not so much due to bacteria in the bloodstream as to the devastating effect of the systemic TNFa production by the immune system. See also: Septicaemic Shock; Tumour Necrosis Factors Several other examples of such overreaction of the immune system exist and can be divided into the categories of type I IV hypersensitivities. See also: Hypersensitivity: Immunological Type I hypersensitivity is caused by IgE. The Fc domain of this immunoglobulin is bound to mast cells. When IgE is crosslinked by an antigen, reactions such as vasodilatation, chemotaxis and smooth muscle contraction occur because of the release of cytokines, histamine, proteases, prostaglandins, etc. This is an important event in the acute inflammatory response. However, when exaggerated, asthmatic episodes and even anaphylactic shock may ensue because of vasodilatation. The most dramatic example of this is the rupture of a hydatid cyst caused by larvae of Echinococcus granulosus. Because of previous sensitization with IgE, the sudden release of large amounts of antigen causes an acute anaphylactic shock. See also: Hypersensitivity: Anaphylactic (Type I) Type II hypersensitivity is caused by antibody that binds specific cell surface molecules. Autoantibodies are actually produced during a number of infections, but they rarely do any harm. However, a classical example of disease is the pancarditis sometimes observed after a streptococcal infection. In this case, group A b-haemolytic streptococci express an antigen that is also expressed in the myocardium. See also: Autoimmune Disease: Pathogenesis; Hypersensitivity: Antibody-mediated Cytotoxic (Type II) Type III hypersensitivity is the result of deposition of circulating immune complexes. When large amounts of antigen exist in the blood, the antigen eventually forms complexes with antibodies and is deposited in capillaries and connective tissue. Here, the immune complexes activate the classical complement pathway and attract a number of inflammatory cells. Again, streptococcal infection is an example of postinfective allergic reactions, here in the form of the acute glomerulonephritis sometimes observed 2 3 weeks following infection. See also: Antigen Antibody Complexes; Hypersensitivity: Immune Complex Mediated (Type III) Type IV hypersensitivity is also known as cell-mediated hypersensitivity and includes the formation of granuloma and delayed-type hypersensitivity responses with the involvement of CD4 T cells, CD8 T cells and macrophages. Immune responses involving these cells often cause tissue damage, which leads to fibrosis and calcification. See also: Hypersensitivity: T Lymphocyte-mediated (Type IV) Microbial Evasion from the Host Immune Response The human immune system today is the result of millions of years of coevolution with pathogens. Similarly, in order to survive, pathogens must constantly evolve new strategies to escape from the immune response. Many bacteria and viruses have a tremendous capacity for mutation. For instance, the influenza virus constantly introduces new point mutations in the genes encoding the surface proteins, haemagglutinin and neuraminidase. This process is termed antigenic drift and underlies the influenza epidemics seen every 2 3 years, when the mutated virus is no longer recognized by the immune response elicited by the previous virus strain. See also: Antigenic Variation in Microbial Evasion of Immune Responses, Immune Response: Evasion and Subversion by Pathogens; Influenza Viruses The parasites known as African trypanosomes have evolved such antigen variation to virtuosity. The parasite is covered by a variant surface glycoprotein. Although only one variant is expressed on the surface, the genome actually encodes about 1000 variants of the protein. When antibodies are raised against the first variant, a few parasites have already begun expressing a new variant. The parasite is therefore rarely cleared by the immune system. See also: Trypanosomiases; Trypanosoma Many viruses have evolved a number of advanced strategies for interference with antigen presentation which have only recently been discovered. For instance, the E3 protein ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd. 7

8 of adenovirus type 2 can form complexes with MHC molecules, thereby preventing correct glycosylation and transport to the cell surface. Also, proteins of viruses such as Herpes simplex virus (HSV) and Cytomegalovirus (CMV) have been shown to inhibit the function of TAP transporters (Figure 2), thus interfering with the binding of antigenic peptides to MHC class I molecules. See also: Adenoviruses; Immune Defence: Microbial Interference The ultimate counterstrike against the immune system is observed with HIV. By depleting CD4 cells, the virus not only inhibits the immune response against the virus itself, but also against a number of opportunistic pathogens, such as Candida, mycobacteria, Pneumocystis carinii and CMV. This is actually what causes the death of the patient with AIDS. See also: AIDS: Clinical Manifestations Regional versus Central Immune Response Most effector systems of the immune response take place in direct proximity to the pathogen. Granulocytes, macrophages and lymphocytes are attracted to the site of infection by chemotaxis, and the priming of T cells and antibody production take place in the regional lymph nodes. See also: Lymph Nodes; Lymphoid System Very early in the immune response, several cytokines, including IL-1, IL-6 and TNF, are produced that trigger central reactions to the infection. As mentioned earlier, production of acute-phase proteins by the liver is an effective way to increase the capacity of the innate immune response. Several of these cytokines also bind to receptors in the central nervous system. Thus, IL-1 both acts as a pyrogen, regulating the hypothalamus to increase body temperature, and also stimulates increased adrenocorticotrophic hormone (ACTH) secretion. Although poorly understood, the effect of fever might be to destabilize some pathogens. For instance, many viruses (including HSV) stop replicating at temperatures above 378C. The increase in ACTH secretion leads to increasing plasma cortisol levels, which influences the conversion of protein to glucose, which is crucial in fasting individuals including those suffering from serious infections. In addition, cortisol has a number of anti-inflammatory functions, probably involved in limiting tissue damage during the inflammatory response. See also: Acute-phase Proteins Further Reading Cresswell P (1995) Assembly transport and function of MHC class II molecules. Annual Review of Immunology 12: Janeway CA and Travers P (2005) Immunobiology, 6th edn. New York: Garland. Murray PR, Rosenthal KS, Kobayashi GS and Pfaller MA (1998) Medical Microbiology, 3rd edn. St Louis, MO: Mosby Yearbook. Paul WE (2003) Fundamental Immunology, 5th edn. New York: Lippincott-Raven. Ploegh HL (1998) Viral strategies of immune evasion. Science 280: ENCYCLOPEDIA OF LIFE SCIENCES & 2007, John Wiley & Sons, Ltd.

CELL BIOLOGY - CLUTCH CH THE IMMUNE SYSTEM.

CELL BIOLOGY - CLUTCH CH THE IMMUNE SYSTEM. !! www.clutchprep.com CONCEPT: OVERVIEW OF HOST DEFENSES The human body contains three lines of against infectious agents (pathogens) 1. Mechanical and chemical boundaries (part of the innate immune system)

More information

All animals have innate immunity, a defense active immediately upon infection Vertebrates also have adaptive immunity

All animals have innate immunity, a defense active immediately upon infection Vertebrates also have adaptive immunity 1 2 3 4 5 6 7 8 9 The Immune System All animals have innate immunity, a defense active immediately upon infection Vertebrates also have adaptive immunity Figure 43.2 In innate immunity, recognition and

More information

Adaptive Immunity: Humoral Immune Responses

Adaptive Immunity: Humoral Immune Responses MICR2209 Adaptive Immunity: Humoral Immune Responses Dr Allison Imrie 1 Synopsis: In this lecture we will review the different mechanisms which constitute the humoral immune response, and examine the antibody

More information

Medical Virology Immunology. Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University

Medical Virology Immunology. Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University Medical Virology Immunology Dr. Sameer Naji, MB, BCh, PhD (UK) Head of Basic Medical Sciences Dept. Faculty of Medicine The Hashemite University Human blood cells Phases of immune responses Microbe Naïve

More information

The Immune System. These are classified as the Innate and Adaptive Immune Responses. Innate Immunity

The Immune System. These are classified as the Innate and Adaptive Immune Responses. Innate Immunity The Immune System Biological mechanisms that defend an organism must be 1. triggered by a stimulus upon injury or pathogen attack 2. able to counteract the injury or invasion 3. able to recognise foreign

More information

Overview of the Lymphoid System

Overview of the Lymphoid System Overview of the Lymphoid System The Lymphoid System Protects us against disease Lymphoid system cells respond to Environmental pathogens Toxins Abnormal body cells, such as cancers Overview of the Lymphoid

More information

محاضرة مناعت مدرس المادة :ا.م. هدى عبدالهادي علي النصراوي Immunity to Infectious Diseases

محاضرة مناعت مدرس المادة :ا.م. هدى عبدالهادي علي النصراوي Immunity to Infectious Diseases محاضرة مناعت مدرس المادة :ا.م. هدى عبدالهادي علي النصراوي Immunity to Infectious Diseases Immunity to infection depends on a combination of innate mechanisms (phagocytosis, complement, etc.) and antigen

More information

The Immune System: Innate and Adaptive Body Defenses Outline PART 1: INNATE DEFENSES 21.1 Surface barriers act as the first line of defense to keep

The Immune System: Innate and Adaptive Body Defenses Outline PART 1: INNATE DEFENSES 21.1 Surface barriers act as the first line of defense to keep The Immune System: Innate and Adaptive Body Defenses Outline PART 1: INNATE DEFENSES 21.1 Surface barriers act as the first line of defense to keep invaders out of the body (pp. 772 773; Fig. 21.1; Table

More information

The Immune System All animals have innate immunity, a defense active immediately

The Immune System All animals have innate immunity, a defense active immediately The Immune System All animals have innate immunity, a defense active immediately upon infection Vertebrates also have adaptive immunity Figure 43.2 INNATE IMMUNITY (all animals) Recognition of traits shared

More information

The Adaptive Immune Responses

The Adaptive Immune Responses The Adaptive Immune Responses The two arms of the immune responses are; 1) the cell mediated, and 2) the humoral responses. In this chapter we will discuss the two responses in detail and we will start

More information

ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY

ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY ACTIVATION OF T LYMPHOCYTES AND CELL MEDIATED IMMUNITY The recognition of specific antigen by naïve T cell induces its own activation and effector phases. T helper cells recognize peptide antigens through

More information

Physiology Unit 3. ADAPTIVE IMMUNITY The Specific Immune Response

Physiology Unit 3. ADAPTIVE IMMUNITY The Specific Immune Response Physiology Unit 3 ADAPTIVE IMMUNITY The Specific Immune Response In Physiology Today The Adaptive Arm of the Immune System Specific Immune Response Internal defense against a specific pathogen Acquired

More information

11/25/2017. THE IMMUNE SYSTEM Chapter 43 IMMUNITY INNATE IMMUNITY EXAMPLE IN INSECTS BARRIER DEFENSES INNATE IMMUNITY OF VERTEBRATES

11/25/2017. THE IMMUNE SYSTEM Chapter 43 IMMUNITY INNATE IMMUNITY EXAMPLE IN INSECTS BARRIER DEFENSES INNATE IMMUNITY OF VERTEBRATES THE IMMUNE SYSTEM Chapter 43 IMMUNITY INNATE IMMUNITY EXAMPLE IN INSECTS Exoskeleton made of chitin forms the first barrier to pathogens Digestive system is protected by a chitin-based barrier and lysozyme,

More information

Defense mechanism against pathogens

Defense mechanism against pathogens Defense mechanism against pathogens Immune System What is immune system? Cells and organs within an animal s body that contribute to immune defenses against pathogens ( ) Bacteria -Major entry points ;open

More information

Blood and Immune system Acquired Immunity

Blood and Immune system Acquired Immunity Blood and Immune system Acquired Immunity Immunity Acquired (Adaptive) Immunity Defensive mechanisms include : 1) Innate immunity (Natural or Non specific) 2) Acquired immunity (Adaptive or Specific) Cell-mediated

More information

Immunobiology 7. The Humoral Immune Response

Immunobiology 7. The Humoral Immune Response Janeway Murphy Travers Walport Immunobiology 7 Chapter 9 The Humoral Immune Response Copyright Garland Science 2008 Tim Worbs Institute of Immunology Hannover Medical School 1 The course of a typical antibody

More information

Immune system. Aims. Immune system. Lymphatic organs. Inflammation. Natural immune system. Adaptive immune system

Immune system. Aims. Immune system. Lymphatic organs. Inflammation. Natural immune system. Adaptive immune system Aims Immune system Lymphatic organs Inflammation Natural immune system Adaptive immune system Major histocompatibility complex (MHC) Disorders of the immune system 1 2 Immune system Lymphoid organs Immune

More information

Third line of Defense

Third line of Defense Chapter 15 Specific Immunity and Immunization Topics -3 rd of Defense - B cells - T cells - Specific Immunities Third line of Defense Specific immunity is a complex interaction of immune cells (leukocytes)

More information

Chapter 17B: Adaptive Immunity Part II

Chapter 17B: Adaptive Immunity Part II Chapter 17B: Adaptive Immunity Part II 1. Cell-Mediated Immune Response 2. Humoral Immune Response 3. Antibodies 1. The Cell-Mediated Immune Response Basic Steps of Cell-Mediated IR 1 2a CD4 + MHC cl.

More information

ANATOMY OF THE IMMUNE SYSTEM

ANATOMY OF THE IMMUNE SYSTEM Immunity Learning objectives Explain what triggers an immune response and where in the body the immune response occurs. Understand how the immune system handles exogenous and endogenous antigen differently.

More information

Topics. Humoral Immune Response Part II Accessory cells Fc Receptors Opsonization and killing mechanisms of phagocytes NK, mast, eosynophils

Topics. Humoral Immune Response Part II Accessory cells Fc Receptors Opsonization and killing mechanisms of phagocytes NK, mast, eosynophils Topics Humoral Immune Response Part II Accessory cells Fc Receptors Opsonization and killing mechanisms of phagocytes NK, mast, eosynophils Immune regulation Idiotypic network 2/15/2005 MICR 415 / 515

More information

The Immune System is the Third Line of Defense Against Infection. Components of Human Immune System

The Immune System is the Third Line of Defense Against Infection. Components of Human Immune System Chapter 17: Specific Host Defenses: The Immune Response The Immune Response Immunity: Free from burden. Ability of an organism to recognize and defend itself against specific pathogens or antigens. Immune

More information

Chapter 1. Chapter 1 Concepts. MCMP422 Immunology and Biologics Immunology is important personally and professionally!

Chapter 1. Chapter 1 Concepts. MCMP422 Immunology and Biologics Immunology is important personally and professionally! MCMP422 Immunology and Biologics Immunology is important personally and professionally! Learn the language - use the glossary and index RNR - Reading, Note taking, Reviewing All materials in Chapters 1-3

More information

I. Lines of Defense Pathogen: Table 1: Types of Immune Mechanisms. Table 2: Innate Immunity: First Lines of Defense

I. Lines of Defense Pathogen: Table 1: Types of Immune Mechanisms. Table 2: Innate Immunity: First Lines of Defense I. Lines of Defense Pathogen: Table 1: Types of Immune Mechanisms Table 2: Innate Immunity: First Lines of Defense Innate Immunity involves nonspecific physical & chemical barriers that are adapted for

More information

Structure and Function of Antigen Recognition Molecules

Structure and Function of Antigen Recognition Molecules MICR2209 Structure and Function of Antigen Recognition Molecules Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will examine the major receptors used by cells of the innate and

More information

WHY IS THIS IMPORTANT?

WHY IS THIS IMPORTANT? CHAPTER 16 THE ADAPTIVE IMMUNE RESPONSE WHY IS THIS IMPORTANT? The adaptive immune system protects us from many infections The adaptive immune system has memory so we are not infected by the same pathogen

More information

Adaptive Immunity: Specific Defenses of the Host

Adaptive Immunity: Specific Defenses of the Host 17 Adaptive Immunity: Specific Defenses of the Host SLOs Differentiate between innate and adaptive immunity, and humoral and cellular immunity. Define antigen, epitope, and hapten. Explain the function

More information

Body Defense Mechanisms

Body Defense Mechanisms BIOLOGY OF HUMANS Concepts, Applications, and Issues Fifth Edition Judith Goodenough Betty McGuire 13 Body Defense Mechanisms Lecture Presentation Anne Gasc Hawaii Pacific University and University of

More information

Disease causing organisms Resistance Immunity

Disease causing organisms Resistance Immunity Part 1 Disease causing organisms Resistance Immunity Bacteria Most common pathogens Anthrax Cholera Staphylococcus epidermidis bacteria Bacterial diseases Tuberculosis Cholera Bubonic Plague Tetanus Effects

More information

Innate vs Adaptive Response

Innate vs Adaptive Response General Immunology Innate vs Adaptive Response Innate- non-specific (4 types of barriers) anatomic- ato mechanical ca (skin), ph, mucous, normal flora Physiologic- temperature, ph, chemicals (lysozyme,

More information

1. Lymphatic vessels recover about of the fluid filtered by capillaries. A. ~1% C. ~25% E. ~85% B. ~10% D. ~50%

1. Lymphatic vessels recover about of the fluid filtered by capillaries. A. ~1% C. ~25% E. ~85% B. ~10% D. ~50% BIOL2030 Huaman A&P II -- Exam 3 -- XXXX -- Form A Name: 1. Lymphatic vessels recover about of the fluid filtered by capillaries. A. ~1% C. ~25% E. ~85% B. ~10% D. ~50% 2. Special lymphatic vessels called

More information

There are 2 major lines of defense: Non-specific (Innate Immunity) and. Specific. (Adaptive Immunity) Photo of macrophage cell

There are 2 major lines of defense: Non-specific (Innate Immunity) and. Specific. (Adaptive Immunity) Photo of macrophage cell There are 2 major lines of defense: Non-specific (Innate Immunity) and Specific (Adaptive Immunity) Photo of macrophage cell Development of the Immune System ery pl neu mφ nk CD8 + CTL CD4 + thy TH1 mye

More information

Immunology. T-Lymphocytes. 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters,

Immunology. T-Lymphocytes. 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters, Immunology T-Lymphocytes 16. Oktober 2014, Ruhr-Universität Bochum Karin Peters, karin.peters@rub.de The role of T-effector cells in the immune response against microbes cellular immunity humoral immunity

More information

Cell Mediated Immunity CELL MEDIATED IMMUNITY. Basic Elements of Cell Mediated Immunity (CMI) Antibody-dependent cell-mediated cytotoxicity (ADCC)

Cell Mediated Immunity CELL MEDIATED IMMUNITY. Basic Elements of Cell Mediated Immunity (CMI) Antibody-dependent cell-mediated cytotoxicity (ADCC) Chapter 16 CELL MEDIATED IMMUNITY Cell Mediated Immunity Also known as Cellular Immunity or CMI The effector phase T cells Specificity for immune recognition reactions TH provide cytokines CTLs do the

More information

Diseases-causing agents, pathogens, can produce infections within the body.

Diseases-causing agents, pathogens, can produce infections within the body. BIO 212: ANATOMY & PHYSIOLOGY II 1 CHAPTER 16 Lecture: Dr. Lawrence G. Altman www.lawrencegaltman.com Some illustrations are courtesy of McGraw-Hill. LYMPHATIC and IMMUNE Systems Body Defenses Against

More information

Third line of Defense. Topic 8 Specific Immunity (adaptive) (18) 3 rd Line = Prophylaxis via Immunization!

Third line of Defense. Topic 8 Specific Immunity (adaptive) (18) 3 rd Line = Prophylaxis via Immunization! Topic 8 Specific Immunity (adaptive) (18) Topics - 3 rd Line of Defense - B cells - T cells - Specific Immunities 1 3 rd Line = Prophylaxis via Immunization! (a) A painting of Edward Jenner depicts a cow

More information

CHAPTER-VII IMMUNOLOGY R.KAVITHA, M.PHARM, LECTURER, DEPARTMENT OF PHARMACEUTICS, SRM COLLEGE OF PHARMACY, SRM UNIVERSITY, KATTANKULATHUR.

CHAPTER-VII IMMUNOLOGY R.KAVITHA, M.PHARM, LECTURER, DEPARTMENT OF PHARMACEUTICS, SRM COLLEGE OF PHARMACY, SRM UNIVERSITY, KATTANKULATHUR. CHAPTER-VII IMMUNOLOGY R.KAVITHA, M.PHARM, LECTURER, DEPARTMENT OF PHARMACEUTICS, SRM COLLEGE OF PHARMACY, SRM UNIVERSITY, KATTANKULATHUR. The Immune Response Immunity: Free from burden. Ability of an

More information

chapter 17: specific/adaptable defenses of the host: the immune response

chapter 17: specific/adaptable defenses of the host: the immune response chapter 17: specific/adaptable defenses of the host: the immune response defense against infection & illness body defenses innate/ non-specific adaptable/ specific epithelium, fever, inflammation, complement,

More information

Clinical Basis of the Immune Response and the Complement Cascade

Clinical Basis of the Immune Response and the Complement Cascade Clinical Basis of the Immune Response and the Complement Cascade Bryan L. Martin, DO, MMAS, FACAAI, FAAAAI, FACOI, FACP Emeritus Professor of Medicine and Pediatrics President, American College of Allergy,

More information

Chapter 24 The Immune System

Chapter 24 The Immune System Chapter 24 The Immune System The Immune System Layered defense system The skin and chemical barriers The innate and adaptive immune systems Immunity The body s ability to recognize and destroy specific

More information

Anti-infectious Immunity

Anti-infectious Immunity Anti-infectious Immunity innate immunity barrier structures Secretory molecules Phagocytes NK cells Anatomical barriers 1. Skin and mucosa barrier 2.hemo-Spinal Fluid barrier 3. placental barrier Phagocytic

More information

Chapter 23 Immunity Exam Study Questions

Chapter 23 Immunity Exam Study Questions Chapter 23 Immunity Exam Study Questions 1. Define 1) Immunity 2) Neutrophils 3) Macrophage 4) Epitopes 5) Interferon 6) Complement system 7) Histamine 8) Mast cells 9) Antigen 10) Antigens receptors 11)

More information

The Adaptive Immune Response. B-cells

The Adaptive Immune Response. B-cells The Adaptive Immune Response B-cells The innate immune system provides immediate protection. The adaptive response takes time to develop and is antigen specific. Activation of B and T lymphocytes Naive

More information

Principles of Adaptive Immunity

Principles of Adaptive Immunity Principles of Adaptive Immunity Chapter 3 Parham Hans de Haard 17 th of May 2010 Agenda Recognition molecules of adaptive immune system Features adaptive immune system Immunoglobulins and T-cell receptors

More information

Overview of the immune system

Overview of the immune system Overview of the immune system Immune system Innate (nonspecific) 1 st line of defense Adaptive (specific) 2 nd line of defense Cellular components Humoral components Cellular components Humoral components

More information

Immunity. Innate & Adaptive

Immunity. Innate & Adaptive Immunity Innate & Adaptive Immunity Innate: response to attack is always the same Mechanical mechanisms Chemical mediators Cellular response Inflammatory response Adaptive: response to attack improves

More information

Chapter 22: The Lymphatic System and Immunity

Chapter 22: The Lymphatic System and Immunity Bio40C schedule Lecture Immune system Lab Quiz 2 this week; bring a scantron! Study guide on my website (see lab assignments) Extra credit Critical thinking questions at end of chapters 5 pts/chapter Due

More information

Chapter 21: Innate and Adaptive Body Defenses

Chapter 21: Innate and Adaptive Body Defenses Chapter 21: Innate and Adaptive Body Defenses I. 2 main types of body defenses A. Innate (nonspecific) defense: not to a specific microorganism or substance B. Adaptive (specific) defense: immunity to

More information

ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT

ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS. Choompone Sakonwasun, MD (Hons), FRCPT ACTIVATION AND EFFECTOR FUNCTIONS OF CELL-MEDIATED IMMUNITY AND NK CELLS Choompone Sakonwasun, MD (Hons), FRCPT Types of Adaptive Immunity Types of T Cell-mediated Immune Reactions CTLs = cytotoxic T lymphocytes

More information

Immunity. Chapter 38

Immunity. Chapter 38 Immunity Chapter 38 Impacts, Issues Frankie s Last Wish Infection with a common, sexually transmitted virus (HPV) causes most cervical cancers including the one that killed Frankie McCullogh 38.1 Integrated

More information

Immunology for the Rheumatologist

Immunology for the Rheumatologist Immunology for the Rheumatologist Rheumatologists frequently deal with the immune system gone awry, rarely studying normal immunology. This program is an overview and discussion of the function of the

More information

immunity produced by an encounter with an antigen; provides immunologic memory. active immunity clumping of (foreign) cells; induced by crosslinking

immunity produced by an encounter with an antigen; provides immunologic memory. active immunity clumping of (foreign) cells; induced by crosslinking active immunity agglutination allografts immunity produced by an encounter with an antigen; provides immunologic memory. clumping of (foreign) cells; induced by crosslinking of antigenantibody complexes.

More information

3/28/2012. Immune System. Activation of Innate Immunity. Innate (non-specific) Immunity

3/28/2012. Immune System. Activation of Innate Immunity. Innate (non-specific) Immunity Chapter 5 Outline Defense Mechansims Functions of B Lymphocytes Functions of T Lymphocytes Active and Passive Immunity Tumor Immunology Diseases Caused By Immune System Immune System Anatomy - Lymphoid

More information

White Blood Cells (WBCs)

White Blood Cells (WBCs) YOUR ACTIVE IMMUNE DEFENSES 1 ADAPTIVE IMMUNE RESPONSE 2! Innate Immunity - invariant (generalized) - early, limited specificity - the first line of defense 1. Barriers - skin, tears 2. Phagocytes - neutrophils,

More information

Campbell's Biology: Concepts and Connections, 7e (Reece et al.) Chapter 24 The Immune System Multiple-Choice Questions

Campbell's Biology: Concepts and Connections, 7e (Reece et al.) Chapter 24 The Immune System Multiple-Choice Questions Campbell's Biology: Concepts and Connections, 7e (Reece et al.) Chapter 24 The Immune System 24.1 Multiple-Choice Questions 1) The body's innate defenses against infection include A) several nonspecific

More information

Immune System AP SBI4UP

Immune System AP SBI4UP Immune System AP SBI4UP TYPES OF IMMUNITY INNATE IMMUNITY ACQUIRED IMMUNITY EXTERNAL DEFENCES INTERNAL DEFENCES HUMORAL RESPONSE Skin Phagocytic Cells CELL- MEDIATED RESPONSE Mucus layer Antimicrobial

More information

Lymphatic System. Where s your immunity idol?

Lymphatic System. Where s your immunity idol? Lymphatic System Where s your immunity idol? Functions of the Lymphatic System Fluid Balance Drains excess fluid from tissues Lymph contains solutes from plasma Fat Absorption Lymphatic system absorbs

More information

COURSE: Medical Microbiology, MBIM 650/720 - Fall TOPIC: Antigen Processing, MHC Restriction, & Role of Thymus Lecture 12

COURSE: Medical Microbiology, MBIM 650/720 - Fall TOPIC: Antigen Processing, MHC Restriction, & Role of Thymus Lecture 12 COURSE: Medical Microbiology, MBIM 650/720 - Fall 2008 TOPIC: Antigen Processing, MHC Restriction, & Role of Thymus Lecture 12 FACULTY: Dr. Mayer Office: Bldg. #1, Rm B32 Phone: 733-3281 Email: MAYER@MED.SC.EDU

More information

2014 Pearson Education, Inc. Exposure to pathogens naturally activates the immune system. Takes days to be effective Pearson Education, Inc.

2014 Pearson Education, Inc. Exposure to pathogens naturally activates the immune system. Takes days to be effective Pearson Education, Inc. The innate immune interact with the adaptive immune system 1. Damage to skin causes bleeding = bradykinin activated, resulting in inflammation 2. Dendritic phagocytose pathogens Adaptive immunity 4. Dendritic

More information

Ch 12. Host Defenses I: Nonspecific Defenses

Ch 12. Host Defenses I: Nonspecific Defenses Ch 12 Host Defenses I: Nonspecific Defenses SLOs Differentiate between innate and adaptive immunity. Define and explain PRRs and PAMPs Differentiate physical from chemical factors, and list examples of

More information

NOTES: CH 43, part 1 The Immune System - Nonspecific & Specific Defenses ( )

NOTES: CH 43, part 1 The Immune System - Nonspecific & Specific Defenses ( ) NOTES: CH 43, part 1 The Immune System - Nonspecific & Specific Defenses (43.1-43.2) The lymphatic system is closely associated with the cardiovascular system. LYMPHATIC PATHWAYS Lymphatic capillaries

More information

Time course of immune response

Time course of immune response Time course of immune response Route of entry Route of entry (cont.) Steps in infection Barriers to infection Mf receptors Facilitate engulfment Glucan, mannose Scavenger CD11b/CD18 Allows immediate response

More information

Internal Defense Notes

Internal Defense Notes Internal environment of animals provides attractive area for growth of bacteria, viruses, fungi Harm via: 1. destruction of cells 2. production of toxic chemicals To protect against foreign invaders, humans

More information

Module 10 Innate Immunity

Module 10 Innate Immunity Module 10 Innate Immunity Chapter 16 Innate Immunity Lectures Lectures prepared prepared by by Christine HelmutL.Kae Case The Concept of Immunity Immunity: ability to protect against disease from microbes

More information

Adaptive Immunity. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R

Adaptive Immunity. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R 16 Adaptive Immunity The Body s Third Line of Defense Adaptive Immunity Adaptive immunity

More information

Chapter 16 Innate Immunity: Nonspecific Defenses of the Host

Chapter 16 Innate Immunity: Nonspecific Defenses of the Host Module 10 Chapter 16 Innate Immunity: Nonspecific Defenses of the Host The concept of immunity Immunity: ability to protect against from microbes and their o Aka, Susceptibility: vulnerability or lack

More information

4b. Innate (nonspecific) Immunity

4b. Innate (nonspecific) Immunity 4b. Innate (nonspecific) Immunity Chapter 16: Innate (nonspecific) Immunity! Some terms:! Susceptibility: Lack of immunity to a disease.! Immunity: Ability to ward off disease.! Innate immunity: Defenses

More information

all of the above the ability to impart long term memory adaptive immunity all of the above bone marrow none of the above

all of the above the ability to impart long term memory adaptive immunity all of the above bone marrow none of the above 1. (3 points) Immediately after a pathogen enters the body, it faces the cells and soluble proteins of the innate immune system. Which of the following are characteristics of innate immunity? a. inflammation

More information

The Immune System. Chapter 43. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for

The Immune System. Chapter 43. Biology Eighth Edition Neil Campbell and Jane Reece. PowerPoint Lecture Presentations for Chapter 43 The Immune System PowerPoint Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

More information

生命科学基础 (21)- 动物的免疫器官. The Immune System. KE, Yuehai 柯越海. Zhejiang University, School of Basic Medical Sciences (BMS-ZJU) 浙江大学基础医学院

生命科学基础 (21)- 动物的免疫器官. The Immune System. KE, Yuehai 柯越海. Zhejiang University, School of Basic Medical Sciences (BMS-ZJU) 浙江大学基础医学院 生命科学基础 (21)- 动物的免疫器官 The Immune System KE, Yuehai 柯越海 Zhejiang University, School of Basic Medical Sciences (BMS-ZJU) 浙江大学基础医学院 Outlines The Immune System 1. Innate immunity 2. Adaptive immunity 3. Immune

More information

Adaptive immune responses: T cell-mediated immunity

Adaptive immune responses: T cell-mediated immunity MICR2209 Adaptive immune responses: T cell-mediated immunity Dr Allison Imrie allison.imrie@uwa.edu.au 1 Synopsis: In this lecture we will discuss the T-cell mediated immune response, how it is activated,

More information

Topics in Parasitology BLY Vertebrate Immune System

Topics in Parasitology BLY Vertebrate Immune System Topics in Parasitology BLY 533-2008 Vertebrate Immune System V. Vertebrate Immune System A. Non-specific defenses against pathogens 1. Skin - physical barrier a. Tough armor protein KERATIN b. Surface

More information

Adaptive Immunity. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R

Adaptive Immunity. PowerPoint Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University C H A P T E R CSLO7. Describe functions of host defenses and the immune system in combating infectious diseases and explain how immunizations protect against specific diseases. PowerPoint Lecture Presentations prepared

More information

Resisting infection. Cellular Defenses: Leukocytes. Chapter 16: Innate host defenses Phagocytosis Lymph Inflammation Complement

Resisting infection. Cellular Defenses: Leukocytes. Chapter 16: Innate host defenses Phagocytosis Lymph Inflammation Complement Resisting infection Chapter 16: Innate host defenses Lymph Inflammation Complement Bio 139 Dr. Amy Rogers Innate defenses (ch. 16) Physical & chemical barriers; cellular defenses; inflammation, fever;

More information

April 01, Immune system.notebook

April 01, Immune system.notebook I. First Line of Defense: Skin and Mucus Membranes Non Specific A. Skin Surface 1. dry, dead, thick, secretions 2. sweat and sebaceous glands: antibiotics, lactic acid, RNase B. Mucus (moist and sometimes

More information

T cell-mediated immunity

T cell-mediated immunity T cell-mediated immunity Overview For microbes within phagosomes in phagocytes.cd4+ T lymphocytes (TH1) Activate phagocyte by cytokines studies on Listeria monocytogenes For microbes infecting and replicating

More information

General Biology. A summary of innate and acquired immunity. 11. The Immune System. Repetition. The Lymphatic System. Course No: BNG2003 Credits: 3.

General Biology. A summary of innate and acquired immunity. 11. The Immune System. Repetition. The Lymphatic System. Course No: BNG2003 Credits: 3. A summary of innate and acquired immunity General iology INNATE IMMUNITY Rapid responses to a broad range of microbes Course No: NG00 Credits:.00 External defenses Invading microbes (pathogens). The Immune

More information

INNATE IMMUNITY Non-Specific Immune Response. Physiology Unit 3

INNATE IMMUNITY Non-Specific Immune Response. Physiology Unit 3 INNATE IMMUNITY Non-Specific Immune Response Physiology Unit 3 Protection Against Infection The body has several defenses to protect itself from getting an infection Skin Mucus membranes Serous membranes

More information

Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell?

Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell? Abbas Chapter 2: Sarah Spriet February 8, 2015 Question 1. Kupffer cells, microglial cells and osteoclasts are all examples of what type of immune system cell? a. Dendritic cells b. Macrophages c. Monocytes

More information

MICROBIO320 EXAM 1-Spring 2011 Name True/False (1 point each) T 2. T cell receptors are composed of constant and variable regions.

MICROBIO320 EXAM 1-Spring 2011 Name True/False (1 point each) T 2. T cell receptors are composed of constant and variable regions. True/False (1 point each) T 1. Mature T cells (lymphocytes) bind only to processed antigen. T 2. T cell receptors are composed of constant and variable regions. F 3. Natural Killer cells do not proliferate

More information

Immune System. Biol 105 Lecture 16 Chapter 13

Immune System. Biol 105 Lecture 16 Chapter 13 Immune System Biol 105 Lecture 16 Chapter 13 Outline Immune System I. Function of the Immune system II. Barrier Defenses III. Nonspecific Defenses A. Immune system cells B. Inflammatory response C. Complementary

More information

I. Defense Mechanisms Chapter 15

I. Defense Mechanisms Chapter 15 10/24/11 I. Defense Mechanisms Chapter 15 Immune System Lecture PowerPoint Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Defense Mechanisms Protect against

More information

TCR, MHC and coreceptors

TCR, MHC and coreceptors Cooperation In Immune Responses Antigen processing how peptides get into MHC Antigen processing involves the intracellular proteolytic generation of MHC binding proteins Protein antigens may be processed

More information

Chapter 38- Immune System

Chapter 38- Immune System Chapter 38- Immune System First Line of Defense: Barriers Nonspecific defenses, such as the skin and mucous membranes, are barriers to potential pathogens. In addition to being a physical barrier to pathogens,

More information

LYMPHOCYTES & IMMUNOGLOBULINS. Dr Mere Kende, Lecturer SMHS

LYMPHOCYTES & IMMUNOGLOBULINS. Dr Mere Kende, Lecturer SMHS LYMPHOCYTES & IMMUNOGLOBULINS Dr Mere Kende, Lecturer SMHS Immunity Immune- protection against dangers of non-self/invader eg organism 3 components of immune system 1 st line: skin/mucosa/cilia/hair/saliva/fatty

More information

Immune response. This overview figure summarizes simply how our body responds to foreign molecules that enter to it.

Immune response. This overview figure summarizes simply how our body responds to foreign molecules that enter to it. Immune response This overview figure summarizes simply how our body responds to foreign molecules that enter to it. It s highly recommended to watch Dr Najeeb s lecture that s titled T Helper cells and

More information

Unit 5 The Human Immune Response to Infection

Unit 5 The Human Immune Response to Infection Unit 5 The Human Immune Response to Infection Unit 5-page 1 FOM Chapter 21 Resistance and the Immune System: Innate Immunity Preview: In Chapter 21, we will learn about the branch of the immune system

More information

Innate Immunity. Bởi: OpenStaxCollege

Innate Immunity. Bởi: OpenStaxCollege Innate Immunity Bởi: OpenStaxCollege The vertebrate, including human, immune system is a complex multilayered system for defending against external and internal threats to the integrity of the body. The

More information

T Cell Effector Mechanisms I: B cell Help & DTH

T Cell Effector Mechanisms I: B cell Help & DTH T Cell Effector Mechanisms I: B cell Help & DTH Ned Braunstein, MD The Major T Cell Subsets p56 lck + T cells γ δ ε ζ ζ p56 lck CD8+ T cells γ δ ε ζ ζ Cα Cβ Vα Vβ CD3 CD8 Cα Cβ Vα Vβ CD3 MHC II peptide

More information

Introduction to Immunology Lectures 1-3 by Bellur S. Prabhakar. March 13-14, 2007

Introduction to Immunology Lectures 1-3 by Bellur S. Prabhakar. March 13-14, 2007 Introduction to Immunology Lectures 1-3 by Bellur S. Prabhakar. March 13-14, 2007 TheComponents Of The Immune System and Innate Immunity: Ref: Immunobiology-5 th edition. Janeway et al. Chapters-1 & 2.

More information

Chapter 17. The Lymphatic System and Immunity. Copyright 2010, John Wiley & Sons, Inc.

Chapter 17. The Lymphatic System and Immunity. Copyright 2010, John Wiley & Sons, Inc. Chapter 17 The Lymphatic System and Immunity Immunity Innate Immunity Fast, non-specific and no memory Barriers, ph extremes, Phagocytes & NK cells, fever, inflammation, complement, interferon Adaptive

More information

Helminth worm, Schistosomiasis Trypanosomes, sleeping sickness Pneumocystis carinii. Ringworm fungus HIV Influenza

Helminth worm, Schistosomiasis Trypanosomes, sleeping sickness Pneumocystis carinii. Ringworm fungus HIV Influenza Helminth worm, Schistosomiasis Trypanosomes, sleeping sickness Pneumocystis carinii Ringworm fungus HIV Influenza Candida Staph aureus Mycobacterium tuberculosis Listeria Salmonella Streptococcus Levels

More information

The Adaptive Immune Response: T lymphocytes and Their Functional Types *

The Adaptive Immune Response: T lymphocytes and Their Functional Types * OpenStax-CNX module: m46560 1 The Adaptive Immune Response: T lymphocytes and Their Functional Types * OpenStax This work is produced by OpenStax-CNX and licensed under the Creative Commons Attribution

More information

Chapter 13 Lymphatic and Immune Systems

Chapter 13 Lymphatic and Immune Systems The Chapter 13 Lymphatic and Immune Systems 1 The Lymphatic Vessels Lymphoid Organs Three functions contribute to homeostasis 1. Return excess tissue fluid to the bloodstream 2. Help defend the body against

More information

Innate Immunity: Nonspecific Defenses of the Host

Innate Immunity: Nonspecific Defenses of the Host PowerPoint Lecture Presentations prepared by Bradley W. Christian, McLennan Community College C H A P T E R 16 Innate Immunity: Nonspecific Defenses of the Host Host Response to Disease Resistance- ability

More information

I. Critical Vocabulary

I. Critical Vocabulary I. Critical Vocabulary A. Immune System: a set of glands, tissues, cells, and dissolved proteins that combine to defend against non-self entities B. Antigen: any non-self chemical that triggers an immune

More information

1. The scavenger receptor, CD36, functions as a coreceptor for which TLR? a. TLR ½ b. TLR 3 c. TLR 4 d. TLR 2/6

1. The scavenger receptor, CD36, functions as a coreceptor for which TLR? a. TLR ½ b. TLR 3 c. TLR 4 d. TLR 2/6 Allergy and Immunology Review Corner: Cellular and Molecular Immunology, 8th Edition By Abul K. Abbas, MBBS, Andrew H. H. Lichtman, MD, PhD and Shiv Pillai, MBBS, PhD. Chapter 4 (pages 62-74): Innate Immunity

More information

PATHOGENS AND DEFENCE AGAINST INFECTIOUS DISEASE. By: Stephanie, Emily, Cem, and Julie

PATHOGENS AND DEFENCE AGAINST INFECTIOUS DISEASE. By: Stephanie, Emily, Cem, and Julie PATHOGENS AND DEFENCE AGAINST INFECTIOUS DISEASE By: Stephanie, Emily, Cem, and Julie Pathogen Pathogen: an organism or virus that causes a disease. Examples: bacteria, fungi, protozoa, virus Disease Cause

More information

Chapter 24 The Immune System

Chapter 24 The Immune System Chapter 24 The Immune System PowerPoint Lectures for Biology: Concepts & Connections, Sixth Edition Campbell, Reece, Taylor, Simon, and Dickey Lecture by Edward J. Zalisko Introduction: The Kissing Disease?!?

More information

1. Overview of Adaptive Immunity

1. Overview of Adaptive Immunity Chapter 17A: Adaptive Immunity Part I 1. Overview of Adaptive Immunity 2. T and B Cell Production 3. Antigens & Antigen Presentation 4. Helper T cells 1. Overview of Adaptive Immunity The Nature of Adaptive

More information