The Complement System Clears Immune Complexes from Circulation

The importance of the complement system in clearing immune complexes is seen in patients with the autoimmune disease systemic lupus erythematosus SLE . These individuals produce large quantities of immune complexes and suffer tissue damage as a result of complement-mediated lysis and the induction of type II or type III hypersensitivity see Chapter 16 . Although complement plays a significant role in the development of tissue damage in SLE, the paradoxical finding is that deficiencies in C1,...

Late Phase Reactions Induce Localized Inflammatory Reactions

Early And Late Asthmatic Reaction

As a type I hypersensitive reaction begins to subside, mediators released during the course of the reaction often induce localized inflammation called the late-phase reaction. Distinct from the late response seen in asthma, the late-phase reaction begins to develop 4-6 h after the initial type I reaction and persists for 1-2 days. The reaction is characterized by infiltration of neutrophils, eosinophils, macrophages, lymphocytes, and basophils. The localized late-phase response also may be...

Localized Inflammatory Response

Vascular Changes Acute Inflammation

The hallmarks of a localized acute inflammatory response, first described almost 2000 years ago, are swelling tumor , redness rubor , heat calor , pain dolor , and loss of function. Within minutes after tissue injury, there is an increase in vascular diameter vasodilation , resulting in an increase in the volume of blood in the area and a reduction in the flow of blood. The increased blood volume heats the tissue and causes it to redden. Vascular permeability also increases, leading to leakage...

Cellular Distribution of MHC Molecules

In general, the classical class I MHC molecules are expressed on most nucleated cells, but the level of expression differs among different cell types. The highest levels of class I molecules are expressed by lymphocytes, where they constitute approximately 1 of the total plasma-membrane proteins, or some 5 X 105 molecules per cell. In contrast, fibroblasts, muscle cells, liver hepatocytes, and neural cells express very low levels of class I MHC molecules. The low level on liver cells may...

Retrovirus HIV1 Is the Causative Agent of AIDS

Hiv Virions

Within a few years after recognition of AIDS as an infectious disease, the causative agent was discovered and characterized by efforts in the laboratories of Luc Montagnier in Paris and Robert Gallo in Bethesda Figure 19-8 . This immunodeficiency syndrome was novel at the time in that the type of virus causing it was a retrovirus. Retroviruses carry their genetic information in the form of RNA. When the virus enters a cell, the RNA is reverse transcribed to DNA by a virally encoded enzyme,...

Localized Anaphylaxis Atopy

In localized anaphylaxis, the reaction is limited to a specific target tissue or organ, often involving epithelial surfaces at the site of allergen entry. The tendency to manifest localized anaphylactic reactions is inherited and is called atopy. Atopic allergies, which afflict at least 20 of the population in developed countries, include a wide range of IgE-mediated disorders, including allergic rhinitis hay fever , asthma, atopic dermatitis eczema , and food allergies. ALLERGIC RHINITIS The...

Immune Response to Infectious Diseases

Earthworm Ureathral Pictures

If a pathogen is to establish an infection in a susceptible host, a series of coordinated events must circumvent both innate and adaptive immunity. One of the first and most important features of host innate immunity is the barrier provided by the epithelial surfaces of the skin and the lining of the gut. The difficulty of penetrating these epithelial barriers ensures that most pathogens never gain productive entry into the host. In addition to providing a physical barrier to infection, the...

The Classical Pathway Begins with Antigen Antibody Binding

Igm And Flagella

Complement activation by the classical pathway commonly begins with the formation of soluble antigen-antibody complexes immune complexes or with the binding of antibody to antigen on a suitable target, such as a bacterial cell. IgM and certain subclasses of IgG human IgG1, IgG2, and IgG3 can activate the classical complement pathway. The initial stage of activation involves C1, C2, C3, and C4, which are present in plasma in functionally inactive forms. Because the components were named in order...

In Agglutination Inhibition Absence of Agglutination Is Diagnostic of Antigen

Agglutination Inhibition Hcg Assay

A modification of the agglutination reaction, called agglutination inhibition, provides a highly sensitive assay for small quantities of an antigen. For example, one of the early types of home pregnancy test kits included latex particles coated with human chorionic gonadotropin HCG and antibody to HCG Figure 6-8 . The addition of urine from a pregnant woman, which contained HCG, inhibited agglutination of the latex particles when the anti-HCG antibody was added thus the absence of agglutination...

The Membrane Attack Complex Can Lyse a Broad Spectrum of Cells

Erythrocyte Membrane Blebbing

The membrane-attack complex formed by complement activation can lyse gram-negative bacteria, parasites, viruses, erythrocytes, and nucleated cells. Because the alternative and lectin pathways of activation generally occur without an initial antigen-antibody interaction, these pathways serve as important innate immune defenses against infectious microorganisms. The requirement for an initial antigen-antibody reaction in the classical pathway supplements these nonspecific innate defenses with a...

Chemically Or Physically Induced Tumor Antigens

Tsta Antigen

Methylcholanthrene and ultraviolet light are two carcinogens that have been used extensively to generate lines of tumor cells. When syngeneic animals are injected with killed cells from a carcinogen-induced tumor-cell line, the animals develop a specific immunologic response that can protect against later challenge by live cells of the same line but not other tumor-cell lines Table 22-2 . Even when the same chemical carcinogen induces two separate tumors at different sites in the same animal,...

Immune Surveillance Theory

The immune surveillance theory was first conceptualized in the early 1900s by Paul Ehrlich. He suggested that cancer cells frequently arise in the body but are recognized as foreign and eliminated by the immune system. Some 50 years later, Lewis Thomas suggested that the cell-mediated branch of the immune system had evolved to patrol the body and eliminate cancer cells. According to these concepts, tumors arise only if cancer cells are able to escape immune surveillance, either by reducing...

HIV1 Infection Leads to Opportunistic Infections

Seroconversion Images

Isolation of HIV-1 and its growth in culture has allowed purification of viral proteins and the development of tests for infection with the virus. The most commonly used test is for the presence of antibodies directed against proteins of HIV-1. These generally appear in the serum of infected individuals by three months after the infection has occurred. When the antibodies appear, the individual is said to have serocon-verted or to be seropositive for HIV-1. Although the precise course of HIV-1...

Cytokine Secretion by TH1 and Th2 Subsets

The immune response to a particular pathogen must induce an appropriate set of effector functions that can eliminate the disease agent or its toxic products from the host. For example, the neutralization of a soluble bacterial toxin requires antibodies, whereas the response to an intracellular virus or to a bacterial cell requires cell-mediated cytotoxicity or delayed-type hypersensitivity. A large body of evidence implicates differences in cytokine-secretion patterns among TH-cell subsets as...

Secondary Lymphoid Organs

Secondary Lymphoid Organs Malt

Various types of organized lymphoid tissues are located along the vessels of the lymphatic system. Some lymphoid tissue in the lung and lamina propria of the intestinal wall consists of diffuse collections of lymphocytes and macrophages. Other lymphoid tissue is organized into structures called lymphoid follicles, which consist of aggregates of lym-phoid and nonlymphoid cells surrounded by a network of draining lymphatic capillaries. Until it is activated by antigen, a lymphoid follicle called...

Passive Immunization Involves Transfer of Preformed Antibodies

Jenner and Pasteur are recognized as the pioneers of vaccination, or induction of active immunity, but similar recognition is due to Emil von Behring and Hidesaburo Kitasato for their contributions to passive immunity. These investigators were the first to show that immunity elicited in one animal can be transferred to another by injecting it with serum from the first see Clinical Focus, Chapter 4 . Passive immunization, in which preformed antibodies are transferred to a recipient, occurs...

Inappropriate Expression of Class Ii Mhc Molecules Can Sensitize Autoreactive T Cells

The pancreatic beta cells of individuals with insulin-dependent diabetes mellitus IDDM express high levels of both class I and class II MHC molecules, whereas healthy beta cells express lower levels of class I and do not express class II at all. Similarly, thyroid acinar cells from those with Graves' disease have been shown to express class II MHC molecules on their membranes. This inappropriate expression of class II MHC molecules, which are normally expressed only on antigen-presenting cells,...

Vaccine May Be the Only Way to Stop the Hivaids Epidemic

The AIDS epidemic continues to rage despite the advances in therapeutic approaches outlined above. The present expense of HAART (as much as 15,000 per year), the strict regimen TABLE 19-61 Why AIDS does not fit the paradigm for classic vaccine development Classic vaccines mimic natural immunity against reinfection generally seen in individuals recovered from infection there are no recovered AIDS patients. Most vaccines protect against disease, not against infection HIV infection may remain...

Intracellular Events Also Regulate Mast Cell Degranulation

Effects Camp

The cytoplasmic domains of the p and 7 chains of FceRI are associated with protein tyrosine kinases PTKs . Crosslink-age of the FceRI receptors activates the associated PTKs, resulting in the phosphorylation of tyrosines within the ITAMs of the 7 subunit as well as phosphorylation of residues on the p subunit and on phospholipase C. These phos-phorylation events induce the production of a number of second messengers that mediate the process of degranulation Figure 16-6 . Within 15 s after...

Primary Lymphoid Organs

Primary Lymphoid Organ

Immature lymphocytes generated in hematopoiesis mature and become committed to a particular antigenic specificity within the primary lymphoid organs. Only after a lympho- Scanning electron micrograph of follicular dendritic cells showing long, beaded dendrites. The beads are coated with antigen-antibody complexes. The dendrites emanate from the cell body. From A. K. Szakal et al, 1985, J. Immunol. 134 1353 1996 by American Association of Immunologists, reprinted with permission. Scanning...

Chemical and Enzymatic Methods Revealed Basic Antibody Structure

Igg Molecular Weight Light Chain

Our knowledge of basic antibody structure was derived from a variety of experimental observations. When the 7-globulin fraction of serum is separated into high- and low-molecular-weight fractions, antibodies of around 150,000-MW, designated as immunoglobulin G IgG are found in the low-molecular-weight fraction. In a key experiment, brief digestion of IgG with the enzyme papain produced three fragments, two of which were identical fragments and a third that was quite different Figure 4-3 . The...

Attenuated Viruses and Bacteria Cause Immunity Without Disease

In some cases, microorganisms can be attenuated so that they lose their ability to cause significant disease pathogenicity but retain their capacity for transient growth within an inoculated host. Attenuation often can be achieved by growing a pathogenic bacterium or virus for prolonged periods under abnormal culture conditions. This procedure selects mutants that are better suited to growth in the abnormal culture conditions and are therefore less capable of growth in the natural host. For...

Antigen Selection of Lymphocytes Causes Clonal Expansion

Clonal Expansion Proliferation

A mature immunocompetent animal contains a large number of antigen-reactive clones of T and B lymphocytes the antigenic specificity of each of these clones is determined by the specificity of the antigen-binding receptor on the mem- Processing and presentation of exogenous and endogenous antigens. a Exogenous antigen is ingested by endocytosis or phagocytosis and then enters the endocytic processing pathway. Here, within an acidic environment, the antigen is degraded into small peptides, which...

The Nature of the Immunogen Contributes to Immunogenicity

Cytochrome Tertiary Structure

Immunogenicity is determined, in part, by four properties of the immunogen its foreignness, molecular size, chemical composition and complexity, and ability to be processed and presented with an MHC molecule on the surface of an antigen-presenting cell or altered self-cell. In order to elicit an immune response, a molecule must be recognized as nonself by the biological system. The capacity to recognize nonself is accompanied by tolerance of self, a specific unresponsiveness to self antigens....

Inflammation Represents a Complex Sequence of Events That Stimulates Immune Responses

Vasoactive Hormones Blood Pressure

Tissue damage caused by a wound or by an invading pathogenic microorganism induces a complex sequence of events collectively known as the inflammatory response. As described above, a molecular component of a microbe, such as LPS, may trigger an inflammatory response via interaction with cell surface receptors. The end result of inflammation may be the marshalling of a specific immune response to the invasion or clearance of the invader by components of the innate immune system. Many of the...

Systemic Function of the Immune System

The many different cells, organs, and tissues of the immune system are dispersed throughout the body, yet the various components communicate and collaborate to produce an ef fective response to an infection. An infection that begins in one area of the body initiates processes that eventually involve cells, organs, and tissues distant from the site of pathogen invasion. Consider what happens when the skin is broken, allowing bacteria to enter the body and initiate infection. The tissue damage...

Recombinant Vector Vaccines

Genes that encode major antigens of especially virulent pathogens can be introduced into attenuated viruses or bacteria. The attenuated organism serves as a vector, replicating within the host and expressing the gene product of the pathogen. A number of organisms have been used for vector vaccines, including vaccinia virus, the canarypox virus, attenuated poliovirus, adenoviruses, attenuated strains of Salmonella, the BCG strain of Mycobacterium bovis, and certain strains of streptococcus that...

Proposed Mechanisms for Induction of Autoimmunity

A variety of mechanisms have been proposed to account for the T-cell-mediated generation of autoimmune diseases Figure 20-8 . Evidence exists for each of these mechanisms, Inappropriate MHC expression on non-APCs Inappropriate MHC expression on non-APCs TH cell B cell Plasma cell TH cell B cell Plasma cell Proposed mechanisms for inducing autoimmune responses. Normal thymic selection appears to generate some self-reactive TH cells abnormalities in this process may generate even more...

Lymphoid Cells and Organs Evolutionary Comparisons

Lymph Chains

While innate systems of immunity are seen in invertebrates and even in plants, the evolution of lymphoid cells and organs evolved only in the phylum Vertebrata. Consequently, adaptive immunity, which is mediated by antibodies and T cells, is only seen in this phylum. However, as shown in Figure 2-23, the kinds of lymphoid tissues seen in different orders of vertebrates differ. As one considers the spectrum from the earliest vertebrates, the jawless fishes Agnatha , to the birds and mammals,...

2. Fill In The Blanks In The Following Statements With The Most Appropriate Terms A. And All Function As Antigen

Kaisho. 2001. Toll-like receptors Critical proteins linking innate and acquired immunity. Nature Immunol. 2 675. Burnet, F. M. 1959. The Clonal Selection Theory of Acquired Immunity. Cambridge University Press, Cambridge. Cohen, S. G., and M. Samter. 1992. Excerpts from Classics in Allergy. Symposia Foundation, Carlsbad, California. Desour, L. 1922. Pasteur and His Work translated by A. F. and B. H. Wedd . T. Fisher Unwin Ltd., London. Fritig, B., T. Heitz, and M....

Immune Dysfunction and Its Consequences

The above overview of innate and adaptive immunity depicts a multicomponent interactive system that protects the host from infectious diseases and from cancer. This overview would not be complete without mentioning that the immune system can function improperly. Sometimes the immune system fails to protect the host adequately or misdirects its activities to cause discomfort, debilitating disease, or even death. There are several common manifestations of immune dysfunction Graft rejection and...

Evidence Implicating the CD4 T Cell MHC and TCR in Autoimmunity

The inappropriate response to self-antigens that characterizes all autoimmune diseases can involve either the humoral or cell-mediated branches of the immune system. Identifying the defects underlying human autoimmune diseases has been difficult more success has been achieved in characterizing the immune defects in the various animal models. Each of the animal models has implicated the CD4 T cell as the primary mediator of autoimmune disease. For example, the evidence is quite strong that, in...

Multivalent Subunit Vaccines

Experience has shown that not every vaccine candidate that was successful in laboratory and animal studies prevents disease in humans. Some potential vaccines cause unacceptable side effects, and some may even worsen the disease they were meant to prevent. Live virus vaccines pose a special threat to those with primary or acquired immunodeficiency (see Chapter 19). Stringent testing is an absolute necessity, because vaccines will be given to large numbers of well persons. Adverse...

Designing Vaccines for Active Immunization

Antibody Mediated Resonse Polio

Several factors must be kept in mind in developing a successful vaccine. First and foremost, the development of an immune response does not necessarily mean that a state of protective immunity has been achieved. What is often critical is which branch of the immune system is activated, and therefore vaccine designers must recognize the important differences between activation of the humoral and the cellmediated branches. A second factor is the development of immunologic memory. For example, a...

There Are Several Phases of the DTH Response

Macrophage Receptor Cryptococcus

The development of the DTH response begins with an initial sensitization phase of 1-2 weeks after primary contact with an antigen. During this period, TH cells are activated and clonally expanded by antigen presented together with the requisite class II MHC molecule on an appropriate antigen-presenting cell Figure 16-17a . A variety of antigen-presenting cells have been shown to be involved in the activation of a DTH response, including Langerhans cells and macrophages. Langerhans cells are...

General Organization and Inheritance of the MHC

Mouse Mhc Molecule

The concept that the rejection of foreign tissue is the result of an immune response to cell-surface molecules, now called histocompatibility antigens, originated from the work of Peter Gorer in the mid-1930s. Gorer was using inbred strains of mice to identify blood-group antigens. In the course of these studies, he identified four groups of genes, designated I through IV, that encoded blood-cell antigens. Work carried out in the 1940s and 1950s by Gorer and George Snell established that...