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PDF | 10+ minutes read | On Jan 1, , Neil Blumberg and others published Manual of Clinical Immunology. Laboratory methods in genitourinary medicine. Techniques used in clinical immunology. A G Bird. Introduction. A wide variety of techniques are used in clinical. Clinical Immunology publishes original research on the molecular and cellular bases of .. The system converts your article files to a single PDF file used in.

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autoimmune diseases through clinical immunology are of great interest Immunology begins with the basic concepts and then details the immuno-. Immunology. Clinical. Immunology. The Spectrum of Clinical Immunology. Basic. Immunology. Inflammation. Immune Response. Loss of Tolerance. Deficiency. PDF | On Jan 1, , J David M Edgar and others published Clinical Immunology.

The principal function of B cells is the production of antibodies against foreign antigens [ 2 , 3 ]. When activated by foreign antigens, B cells undergo proliferation and differentiate into antibody-secreting plasma cells or memory B cells see Figure 2. These cells can be called upon to respond quickly and eliminate an antigen upon re-exposure. Plasma cells, on the other hand, do not express antigen-binding receptors. These are short-lived cells that undergo apoptosis when the inciting agent that induced the immune response is eliminated. Given their function in antibody production, B cells play a major role in the humoral or antibody-mediated immune response as opposed to the cell-mediated immune response, which is governed primarily by T cells [ 2 , 3 ].

Passive vs. It can occur naturally by transplacental transfer of maternal antibodies to the developing fetus, or it can be induced artificially by injecting a recipient with exogenous antibodies targeted to a specific pathogen or toxin.

The latter is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of chronic or immunosuppressive diseases. Active immunization refers to the production of antibodies against a specific agent after exposure to the antigen.

Immunology pdf clinical

It can be acquired through either natural infection with a microbe or through administration of a vaccine that can consist of attenuated weakened pathogens or inactivated organisms, Immunopathology As mentioned earlier, defects or malfunctions in either the innate or adaptive immune response can provoke illness or disease.

Such disorders are generally caused by an overactive immune response known as hypersensitivity reactions , an inappropriate reaction to self known as autoimmunity or ineffective immune responses known as immunodeficiency. Hypersensitivity reactions Hypersensitivity reactions refer to undesirable responses produced by the normal immune system. There are four types of hypersensitivity reactions [ 6 , 7 ]: Type I: immediate hypersensitivity Type II: cytotoxic or antibody-dependent hypersensitivity Type III: immune complex disease Type IV: delayed-type hypersensitivity Type I hypersensitivity is the most common type of hypersensitivity reaction.

It is an allergic reaction provoked by re-exposure to a specific type of antigen, referred to as an allergen. Unlike the normal immune response, the type I hypersensitivity response is characterized by the secretion of IgE by plasma cells.

JIACI · Journal of Investigational Allergology and Clinical Immunology

Later exposure to the same allergen, cross-links the bound IgE on sensitized cells resulting in degranulation and the secretion of active mediators such as histamine, leukotriene, and prostaglandin that cause vasodilation and smooth-muscle contraction of the surrounding tissue. Common environmental allergens inducing IgE-mediated allergies include cat-, dog- and horse epithelium, pollen, house dust mites and molds. Food allergens are also a common cause of type I hypersensitivity reactions, however, these types of reactions are more frequently seen in children than adults.

Treatment of type I reactions generally involves trigger avoidance, and in the case of inhaled allergens, pharmacological intervention with bronchodilators, antihistamines and anti-inflammatory agents. More severe cases may be treated with immunotherapy. Type II hypersensitivity reactions are rare and take anywhere from 2 to 24 hours to develop.

Type III hypersensitivity reactions occur when IgG and IgM antibodies bind to soluble proteins rather than cell surface molecules as in type II hypersensitivity reactions forming immune complexes that can deposit in tissues, leading to complement activation, inflammation, neutrophil influx and mast cell degranulation.

This type of reaction can take hours, days, or even weeks to develop and treatment generally involves anti-inflammatory agents and corticosteroids. Examples of type III hypersensitivity reactions include systemic lupus erythematosus SLE , serum sickness and reactive arthritis. Unlike the other types of hypersensitivity reactions, type IV reactions are cell-mediated and antibody-independent. They are the second most common type of hypersensitivity reaction and usually take 2 or more days to develop.

Their functions include cell activation, cytokine release, capture and rolling of leucocytes along the endothelial cells lining of blood vessels and extravasation. There are 3 main families: selection, integrin and ICAM. Neutrophils have the capacity to ingest more than one bacterium or fungus at once. When large numbers of phagocytes are involved in an infective process, an abscess filled with pus dead or dying neutrophils may form.

The best opsonins are complementing component C3b, C-reactive protein and antibody i. Then the intracellular phagosome becomes fused to neutrophil granules which releases its contents. Recurrent bacterial and fungal infections occur in conditions associated with failure of neutrophil's action e. They are more abundant in tissues where they survive for several weeks.

Basic and Clinical Immunology.pdf

The eosinophil cationic proteins are: major basic protein MBP , eosinophil cationic protein ECP and eosinophil neurotoxin. They are a feature of infiltrate in tissues involved in allergic responses e. Other mediators released in those conditions include leucotriens and platelet activating factor PAF.

Pdf clinical immunology

They have histamine containing granules and high affinity receptors for IgE. The major granule products are histamine and leucotriens which have profound effects on blood vessels and bronchial smooth muscles. The effects of these granule release products depend on the site and the stimulus, ranging from localized wheel to anaphylactic shock. They are activated in allergic and inflammatory conditions by IgE.

Also, the anaphylatoxins C3a, C4a and C5a activate basophils and may activate mast cells. The term complement was proposed by Paul Ehrlich to describe the ability of these proteins to complete or augment the actions of immunoglobulins during bacterial destruction. The complement proteins are formed mainly in the liver. The majorities are soluble but some are membrane bound. The soluble proteins circulate in an inactive state and each must be activated sequentially for the reaction to proceed.

Precursor molecules: - Capital C followed by the number for the classic and common pathway e. C1, C2, C3. Fragments "which are derived from enzymatic cleavage of the parent molecules": small letter suffix e.

C3a, Bb. Inactivated components: The letter I prefix e. The active state of isolated or integrated complement components: Bar over symbols e. C4b 2a.

The alternative pathway is relatively primitive and a part of the innate system while the classic pathway combines with antibody to initiate activation and therefore it is associated with acquired adaptive immunity. The classical pathway: o Activation of the classic pathway is usually initiated by antigenantibody complexes. Other activators include: aggregates of immunoglobulins e. Activated C1 causes cleavage of C4 to C4b which continues the reaction process and C4a which has other biological activities.

C2 is then cleaved by activated C1 into C2b and C2a which combines with C4b to form the classic pathway C3 convertase C4b 2a. The cleavage of C3 by C4b 2a forms two fragments C3a which has powerful biological properties and C3b which becomes bound to the membrane and to C3b 2a, leading to the formation of the classic pathway C5 convertase C4b 2a 3b, which cleaves C5 which is a component of the membrane attack pathway.

The alternative pathway. Activators of the alternative pathway include endotoxin found in gram negative bacterial cell walls, as well as fungal cell walls and insoluble polysaccharides. The main components of the alternative pathway are factor B, factor D and properdin factor P as well as C3b. Free C3b binds factor B and the C3b B complex is acted upon by a circulating enzyme factor D which cleaves factor B, removing Ba fragment and generating C2b Bb complex which is the alternative pathway C3 convertase which can cleave C3, when stabilized on bacterial surfaces especially in the presence of properdin.

C3b Bb then cleaves more C3 positive feedback loop and binds Ceb to form C3b Bb 3b which is the alternative pathway C5 convertase which initiate the membrane attack pathway.

The membrane attack pathway. This starts by cleavage of C5 by either the classic or the alternative pathway leading to the formation of the small fragment C5a which is biologically active and the larger fragment C5b which continues the reaction by binding C6 which then binds C7. Then the complex C5b67 becomes bound to the membranes.

The C3b fragment accounts for the most opsonic activity of the complement. It coats the bacterial wall and becomes bound to complement receptors on neutrophils leading to more efficient engulfment of the pathogen by neutrophils.

Cell activation: Anaphylatoxins as C3a, C5a and C4a can directly activate basophils and mast cells through specific receptors leading to their degranulation and release of inflammatory mediators as histamine. Removal of immune complexes: The binding of C3b to antibody in a complex inhibits lattice formation. This maintains the solubility of antigen antibody complexes.

The antibody coated C3b can attack to complement receptors found on many cells including R. It is also responsible for regulation of other plasma enzyme systems e. C1 esterase deficiency Heriditary angioneurotic oedema which is characterized by recurrent attacks of angioedema in the face, trunk and airway due to uncontrolled activation of complement and kinin system leading to tissue inflammation. Laryngeal oedema may be fatal.

Treatment of acute attack: Fresh frozen plasma.

Lectures in Clinical Immunology at the phil-nat. faculty

They are secreted by the liver under the effect of certain cytokines e. CRP is produced in the liver and binds phosphorylcholine moieties which constitute a major component of bacterial cell wall constitute a major component of bacterial cell wall teichoic acid. When CRP is bound, it can activate complement through the classical pathway independently of the antibody deposition of C3b on the surface of the microbe its opsonization.

Immunology pdf clinical

Its blood levels raise folds within hours of the starts of infective or inflammatory process. Since it has a relatively short half life, so its level in blood can be used to monitor infective or inflammatory process and particularly their response to treatment.

It cleaves bacterial cell wall at a precise point. Acquired Immunity The cardinal features of acquired immune response are specificity, memory and a variable response.

In general, the acquired and innate immune responses are not independent e. The molecular target of the acquired immune response is the antigen. Antigens, antigen recognition and antigen receptors A cardinal feature of the specificity of the immune response is its ability to recognize and respond to molecules that are foreign or non self and avoid making a response to those molecules that are self. Most biological materials serve as antigens which function as immunogens i.

Some antigens act as tolegens i. Large homopolymers are not immunogenic. In general they are multideterminant antigens. Glycoproteins are immunogenic. B Exposure to the antigen: - Each antigen has an optimum dose for immunogenicity.

C Nature of recipient: - Very young animals and elderly have less efficient immune system. Haptens: Haptens to grasp Low molecular weight antigens which are not capable of inducing an immune response by themselves i. The smallest portion of the antigen that binds specifically with the binding site of an antibody or a receptor on a lymphocyte is called antigenic determinant or "epitope".

Compounds may have one or more epitopes capable of reacting with immune components. The part of the antibody which contacts the antigen is called paratope. They cannot interact directly with soluble antigens i. The antigen must be degraded, held and presented to the T-cells by other glycoprotein molecules MHC molecules. The T-cell recognizes both MHC and the peptide antigen. The T-cell receptor recognizes a combination of the shapes formed by the peptide antigen and the wall of the groove in the MHC molecule.

The binding may involve electrostatic interactions, hydrogen bonds and Van der Waals forces. It is the functional affinity, e.

Antibodies Definition They are soluble glycoprotein molecules that exhibit antigen binding ability. They are termed immunoglobulins Ig because they belong to the -globulin class of proteins and have an immune function. The most important features are specificity and biologic activity. Each heavy chain is attached to a light chain by interchain disulphide bonds.

The variability is critical for generating the potential to bind to more than different antigen structures. The C regions are relatively constant in each molecule and hold the effector functions of the molecules e. These bonds bend segments back into themselves creating regions called domains, within the heavy and light chains. This domain structure is very distinctive. Similar structure was found in MHC molecules adhesion molecules, T-cell receptors, and cellular co-receptors.

So, these were given the term immunoglobulin supergene family. This increases the chances of binding two antigens at one time. C In Lab. Sciences: Antibodies are used in a vast range of diagnostic and research studies.

IgG is further divided into 4 subclasses IgG This antibody is confined mainly to the intravascular space. It is the major antibody formed in primary immune response i. Elevated levels indicate recent infection or recent immunization. It does not cross the placenta. Elevated levels of IgM in a newborn infant, indicates intrauterine infection. It has multiple functional domains; therefore it is the most potent Ig activator for complement. It has potential binding sites. So, it is on efficient agglutinating antibody!

IgM antibodies include "natural isohaemagglutinins" which are naturally occurring antibodies against red cell antigens of the ABO blood groups. They are responsible for transfusion reactions which arise as a result of ABO incompatibility in which the recipient haemagglutinins react with the donor's R.

It is present as a monomer and has a high antigen affinity. It is the major antibody in secondary immune response. This gives some specific protection on the new born during the period when its own immune system is immature. This placental transfer is responsible for the hemolytic disease of the newborn erythroblastosis foetalis.

This is caused by maternal antibodies to foetal red blood cells. The maternal IgG antibodies produced by Rh ve mother to Rh antigen, pass across the placenta and attack the foetal R. IgG1 and IgG3 are produced mainly in response to protein antigens such as tetanus toxin and many viruses. They are good opsonins, binding Fc receptors on neutrophils and activating complement. IgG2 and IgG4 are produced in response to polysaccharide antigens e. It can occur as monomer in serum and as a dimmer where two molecules are joined together by a short peptide J chain.

It is the major Ig secreted into external surfaces saliva, bronchial fluid, GIT secretions, tears, milk where it is secretory IgA.

It is transported by a secretory component to the mucosal surface. It has an important function in protection against bacterial, viral and protozoal infections of the mucosae. Its protective effect is by preventing the invading organism from attachment to and penetration of epithelial surfaces. For IgA responses, localized antigen exposure gives rise to generalized mucosal immunity which is important in vaccination. This is because after encountering antigen, IgA precursor B cells in the mucosal lymphoid follicles journey to regional lymph nodes.

After clonal expansion, the cells return to the systemic circulation via the thoracic duct and circulate to settle in the MALT not just the area of antigen exposure. IgD is present on the surface of B lymphocytes and may have an immune regulatory role. It has been suggested to have a role in B lymphocyte activation. It is present in the serum of healthy individuals at extremely low levels. Most of IgE is membrane bound on high affinity receptors on mast cells and basophils.

Its levels in the serum rise in response to parasitic infestations especially nemtodes e.

Pdf clinical immunology

After the latent phase a time before the antibody is detected in serum which is about weeks, which includes the time taken for T and B cells to contact the antigen, proliferate and differentiate and the plasma cells secrete antibodies in sufficient amount to be detected. Then there is arise in concentration of antibodies which becomes steady and then decline.

The first class of the antibodies detected is the IgM sometimes the only class detected. Then IgG production occurs with rapid cessation of IgM production. There is a class shift where the IgG appears in large amounts than IgM, which may be greatly reduced or disappear altogether. So, the secondary response is therefore antigen specific and demonstrates acquisition of memory and higher in intensity.

This is called anamnestic memory response, which may last even years.

Monoclonal antibodies are produced by the hybridoma technique. Human monoclonal antibodies are produced by genetic engineering recombinant DNA technology. Each epitope may be targeted by more than a single antibody molecule. Thus, may clones of plasma cells and many antibody types are produced in a typical antibody response Polyclonal antibody.

These are present in vertebrate species. This polymorphism creates a difference in tissue compatibility between different subjects which is a barrier to organ transplantation.

Kupffer cells, follicular dendritic cells and activated T-lymphocytes. They comprise a pain , of two chain domains. They present exogenous peptides, plasma proteins, cell surface proteins and bacterial proteins to T-cell receptor of CD4 Tlymphocytes. T-cell receptor makes contact with the lips of the groove within the MHC molecules and the peptide antigen, only T-cells bearing CD4 surface glycoproteins can bind to class II presented peptides, while CD8 is required for interaction with those presented by class I.

B8 DR4. Cs but no agglutinins in serum. Cs but has both anti A and anti B in serum. Fate of antigens after penetration: The reticulo endothelial system RES or the mononuclear phagocyte system is designed to trap foreign antigens that have penetrated the body and to subject them to ingestion and degradation by the phagocytic cells of the system.

Also, there is constant movement of the lymphocytes throughout the body, this movement allows deposition of lymphocytes in strategic places along lymphatic channels. The system not only traps antigens but also provides sites the secondary lymphoid organs where antigens, macrophages, T-cells, and B cells interact within very small area to initiate an immune response.

Then the spleen releases the antibodies directly into the circulation. Lymphocytes also leave the spleen to the circulation. From these tissues, the antigen free or trapped by antigen presenting cells, is transported through the afferent lymphatic channels into the regional draining lymph nodes. Eventually, antigen specific T-cells and antibodies which have been synthesized in the lymph node enter the circulation and are transported to the various tissues.

Antigen specific T and B cells and antibodies also enter the circulation via the thoracic duct and are thereby redistributed to various tissues. There it will interact with macrophages and lymphocytes. Antibodies synthesized in these organs are deposited in the local tissue. In addition, lymphocytes entering the efferent lymphatic are carried through the thoracic duct to the circulation and are thereby redistributed in various tissues.

Definition: These are individual surface molecules which are assigned a cluster of differentiation CD numbers defined by a cluster of monoclonal antibodies reacting with that molecule. In other words: It is a surface molecule found on cells according to their lineage and differentiation and identifiable by one or more monoclonal antibodies. Its function is signal transduction, as a result of antigen recognition by T-cells.

Mononuclear phagocytes and specialized antigen presenting cells. They migrate to various tissues and undergo further differentiation into macrophages which are included in the previously called RES which is not termed mononuclear phagocyte system, which is widely distributed throughout the body.

Monocytes migrate either: Randomly, into sites of inflammation or in a tissue directed way to become specialized cells. These include: Kupffer cells in the liver, alveolar macrophages in the lung, splenic macrophages, peritoneal macrophages, microglial cells in CNS, mesangial cells in the kidney and osteoclast cells in bone.

Also, multinucleate giant cells in sites of chronic inflammation granulomas e.