Immunity

Immunity : 

Immunity Dr Prabal Dutta MBBS

The cellular immune response : 

The cellular immune response T cells regulate the activities of B cells, T cells, and other cells participating in immune responses. They provide help for antibody production by B cells, and they are also the effectors of antigen-specific cell-mediated immunity (CMI). CMI is important in the elimination of cells infected with pathogens that replicate intracellularly (eg, viruses, mycobacteria, and some bacteria) and cells exhibiting aberrant differentiation (eg, neoplasms).

PRINCIPAL T CELL LINEAGES : 

PRINCIPAL T CELL LINEAGES Prethymic phase — During the prethymic phase, pluripotent stem cells develop into lymphoid progenitor cells capable of becoming T cells, B cells, or natural killer cells. This process begins during ontogeny with hemopoiesis in the fetal liver and spleen, then in the bone marrow during infancy and thereafter. Progenitor cells reach the thymus via the blood, and enter the outer cortex of the thymus.

PRINCIPAL T CELL LINEAGES : 

PRINCIPAL T CELL LINEAGES Early thymic phase — A variety of highly specialized types of epithelial cells play critical roles in thymic T cell development. How many truly functionally distinct types of these cells exist is unknown. They are classified based upon location within the thymus, physical appearance, surface staining characteristics, and secreted products.

T cell co-receptors CD4 and CD8 : 

T cell co-receptors CD4 and CD8 The surface antigens CD4 and CD8 distinguish two major subsets of T cells. Normal mature cells express either one of these molecules, but not both. The CD8 antigen is required for T cell interaction with cells expressing MHC class I molecules, while CD4 is necessary for interaction with cells expressing MHC class II.

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Late thymic phase — Cells that fail to interact with self MHC die by apoptosis. Following positive selection (see below), the T cells become double-positive (DP) cells, ie, TCR-CD3hiCD4hiCD8hi. At this stage, alpha gene rearrangement ceases, and cells begin to express CD45. DP cells are the targets of the selective processes that establish the repertoire of TCR specificities. In the final phase of thymic T cell development, cells become single-positive, ie, they express only CD4 (MHC class II-restricted) or CD8 (MHC class I-restricted).

PRINCIPAL T CELL LINEAGES : 

PRINCIPAL T CELL LINEAGES

Major Histocompatibility Complex (MHC) or HLA (for Human Leukocyte Antigens) : 

Major Histocompatibility Complex (MHC) or HLA (for Human Leukocyte Antigens) The class I region contains the genes encoding the "classical" class I HLA antigens include HLA A, B, and C. They are expressed on almost all cells of the body, except erythrocytes and trophoblasts, at varying density The class II region contains the genes encoding the HLA class II molecules, HLA-DR, DQ, and DP. They are constitutively expressed on B cells, dendritic cells, and monocytes, and can be induced during inflammation on many other cell types that normally have little or no expression.

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Class III region The region in between class I and class II is known as the class III region. Although this region does not contain any of the HLA genes. It contain many genes of importance in the immune response like Several complement components (C2, C4, and factor B) Tumor necrosis factor Heat shock protein

T-cell activation : 

T-cell activation To elicit a T cell response, an antigen must be captured, processed, and recognized by the appropriate T cell(s). Knowledge of the cells, proteins, and mechanisms contributing to the potent T cell priming activity of professional antigen presenting cells (APCs) is critical in understanding normal immune responses as well as the pathogenesis underlying a host of disorder including - infections, autoimmune pathologies, allergic responses, tissue/organ transplant rejection, and the therapeutic immune response to tumors.

Representation of T-cell activation : 

Representation of T-cell activation

B cell development : 

B cell development Antigen-independent development — The precise combination of signals resulting in the differentiation of hemopoietic stem cells into lymphoid precursors, and subsequently into B cell progenitors, is not completely known. We may operationally define a developmental stage where the stem cell has committed itself to become a B cell, thereby losing the capacity to become any other type of cell.

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B CELL ACTIVATION BY ANTIGENS — With respect to the antibody response, antigens may be categorized as thymus-independent type 1, thymus-independent type 2, or thymus-dependent (TD) antigens. ACTIVATION SIGNALS — B cells require two signals to become activated and begin differentiating to memory or plasma cells.

B cell development in the germinal center : 

B cell development in the germinal center

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Germinal centers are organized into several "compartments," each devoted to particular processes in the generation of an antibody response. The dark zone contains many rapidly dividing B cells called centroblasts which do not express surface Ig. These cells continually give rise to centrocytes, non-dividing cells which have regained surface Ig which migrate into the basal light zone. If they contact their specific antigen, they enter the apical light zone, otherwise they die. The mechanisms determining whether cells will become memory cells or antibody-producing cells (plasma cells) may operate within the apical light zone.

The humoral immune response : 

The humoral immune response Passive humoral immunity is the acquisition of preformed antibodies from an external source, such as the administration of intramuscular or intravenous human immunoglobulin (Ig). Active immunity is the response generated during the encounter of the immune system with antigen. This may occur during the course of a natural infection, or after intentional antigen administration (vaccination).

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IMMUNOLOGIC MEMORY — The immune response in an animal that has never before encountered a given antigen is called a primary immune response. The response in an animal that has been primed by at least one prior exposure to the antigen is called a secondary immune response. Following antigen exposure, there occurs the lag period before antibody is detected. This period corresponds to the cellular events in the activation, proliferation, and differentiation of B cells to antibody-secreting cells. Primary and secondary responses differ with respect to the lag period, the magnitude and duration of the response, and the isotypes and affinity of antibodies produced.

Ab production : 

Ab production

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Placental transfer of IgG provides the neonate with a serum level that is usually slightly higher than the mother's at the time of birth. These antibodies are decreased by at least 50 percent in two to three months after birth (red line). The rate of the infant's IgG production becomes greater than the rate of loss of the mother's IgG by about four to six months of age (blue line). Serum IgG levels increase gradually in the first three years, then plateau at about 60 percent of the adult concentration, while the rate of increase becomes very slow. Normal adult levels are reached in late childhood or early adolescence.

Immunity in children : 

Immunity in children

Types of immunoglobulins : 

Types of immunoglobulins IgG constitutes 75 percent of serum immunoglobulin in an adult human; the concentration is between 500 and 1,500 mg/dL (5 to 15 g/L). IgM occurs as a monomer when located in the B cell membrane. The serum concentration of IgM is about 50 to 400 mg/dL (0.5 to 4 g/L); its half-life in the circulation is five days. IgA concentration in serum is about 50 to 350 mg/dL (0.5 to 3.5 g/L), but it is the predominant antibody class in secretions. IgA has a serum half-life of about six days.

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IgD is present at low levels in serum, <10 mg/dL (<0.1 g/L) and has a serum half-life of three days. IgE has the lowest concentration in normal human serum. The concentration is usually expressed as international units (IU); one unit is equivalent to 2.4 ng. Approximately 100 IU/mL, or 250 µg/L, is the upper limit of normal. It plays a prominent role in immune responses to eukaryotic parasites, and in allergic reactions.

Ig as diagnostic tool : 

Ig as diagnostic tool Immunoglobulin (Ig) molecules are multifunctional tools used by cells to mediate interactions of antigen molecules with a variety of cellular and humoral effector mechanisms. The variable regions of the immunoglobulin heavy and light chains form the antibody combining site. The function of the variable region primarily involves antibody-antigen interactions, including precipitation, agglutination, and neutralization of antigen. These techniques have also been combined with histological methods, yielding the procedures known as immunohistochemistry

immunohistochemistry : 

immunohistochemistry Antibodies labeled with an enzyme (eg, horseradish peroxidase) produce pigment deposits when incubated with a substrate. Binding of radioactively-labeled antibodies may be detected when the specimen is coated with a photographic emulsion; the radioactive emissions create silver grain deposits. Antibodies labeled with fluorescent compounds may be visualized in a fluorescence microscope. Antibodies labeled with gold can be detected in electron micrographs. All of these methods are powerful tools for localizing particular molecules within cells and tissues.

Coombs' test : 

Coombs' test It is an indirect agglutination test. In this method, antibodies bound to erythrocytes are detected. A positive direct Coombs' test results when anti-human globulin (Coombs' reagent) binds antibodies coating the erythrocytes and causes agglutination. The indirect Coombs' test detects erythrocyte-reactive antibodies in serum. In this technique, erythrocytes are incubated with a patient's serum, washed, then exposed to anti-human globulin.

Active immunization : 

Active immunization The goal of active immunization of a vaccine or toxoid is to stimulate the host to produce a primary immune response (usually by inducing B-cell proliferation, antibody response, and T-cell sensitization). If an individual is subsequently exposed to the pathogen against which the vaccine is directed, the exposure results in a secondary response that includes increased proliferation of B-cells and formation of antibodies. The secondary response protects the individual from developing disease, ideally for life.

Vaccines : 

Vaccines Vaccines used for active immunization are derived from whole killed bacteria, live attenuated bacteria or viruses, or antigenic subunits of organisms. Vaccines recommended for healthy adults are the pneumococcal, influenza, hepatitis B, MMR, varicella, and hepatitis A vaccines. Some vaccines require boosters to sustain protection.

Toxoids : 

Toxoids Toxoids are bacterial toxins that are modified to render them nontoxic and used for active immunization. Toxoids induce the formation of antitoxin antibody. If the host is exposed to the bacterial toxin after immunization, the antitoxin antibody binds to the bacterial toxin, thereby preventing toxin-mediated disease. Toxoids recommended for healthy adults are tetanus and diphtheria toxoid.

Passive immunization : 

Passive immunization It involves administration of antibodies (as intramuscular immune globulin derived from pooled human serum or antitoxin derived from serum harvested from immunized animals). Passive immunization offers short-term protection to people who have already been or will be exposed to a specific pathogen.

Safety of immunization : 

Safety of immunization Most vaccines are safe to administer, causing only minor side effects. The more common problem with immunization is the missed opportunity to vaccinate based in part upon public misconceptions about the safety of immunization. Many vaccines and toxoids cause side effects such as fever, local reactions at the site of injection, or even serum sickness-like reactions. These adverse reactions can be caused by the immunogenic moiety in the vaccine or by trace amounts of antibiotics, preservatives, stabilizers, and residual animal proteins.

True contraindications to vaccine administration : 

True contraindications to vaccine administration Previous anaphylactic reaction to a specific vaccine Avoid revaccination with the specific vaccine because of risk of recurrence. History of anaphylaxis to eggs or egg-protein Avoid measles, mumps, influenza and yellow-fever vaccine because these vaccines are prepared in embryonated chicken eggs or cultures and vaccines may contain residual egg protein. Previous anaphylactic reaction to neomycin or streptomycin Avoid measles, mumps, rubella (MMR) vaccine because the MMR vaccine contains trace amounts of neomycin.

Contraindications to vaccine : 

Contraindications to vaccine History of severe systemic reactions to the cholera, typhoid or plague vaccine Avoid revaccination with the specific vaccine because of risk of recurrence. Adults who are immunocompromised as a result of disease or its treatment Avoid live virus vaccines because there is an increased risk of viral replication in immunocompromised individual. Pregnant women Avoid all live virus vaccines because of the potential risk to the fetus.