Adaptive Immunity - Chapter 3, Part 1 PDF

MIC 343 ~Immunology~ Adaptive immunity - specific body defense system CHAPTER 3_Part 1  Syllabus content Components of the adaptive immunity Development of lymphocyte populations Course of the adaptive immune response Immunolo...

MIC 343 ~Immunology~ Adaptive immunity - specific body defense system CHAPTER 3_Part 1  Syllabus content Components of the adaptive immunity Development of lymphocyte populations Course of the adaptive immune response Immunological memory Overall innate and adaptive immune response  Immune response Immune response: Definition: the reaction to and interaction with substances interpreted by the body as non-self. Also called as immune reaction. The immune response depends on a functioning thymus and the conversion of stem cells to B cells and T cells. These cells contribute to antibody production, cellular immunity and immunologic memory.  Components of adaptive immunity Components of adaptive immunity NK cells action  Lymphocyte Smallest leukocytes. Circulate in the blood and lymph and are able to migrate into the tissue spaces and lymphoid organs. Provide immune defense against targets for which they are specifically programmed. Types of lymphocytes: a) B cells b) T cells c) NK (natural killer) cells.  Lymphocyte B cell is first discovered in bursa of Fabricius (primary lymphoid organ) in birds. They matures in bone marrow. They produce antibodies, circulate in the blood and are responsible for antibody-mediated @ humoral immunity.  Lymphocyte T cells matures in thymus. Two subpopulation of T cells: i) T helper cell (TH cell). ii) T cytotoxic/killer cell (TC cell). T cells directly destroy their specific target cells by releasing chemicals that punch holes on the target cell, a process called cell-mediated immunity. B cell & T cell  B cell & T cell Mature lymphocytes that have not encountered their antigen are known as naïve lymphocytes. Activated lymphocytes that have differentiated are called effector lymphocytes. Some activated B cells and T cells differentiate into memory cells. Some activated B cells differentiate into plasma cells, which secrete antibody and present antigen to T cells.  B cell & T cell Activated T cells come in three main classes: Activated T cells Function i) Cytotoxic T cells kill infected cells ii) Helper T cells help activate B cells and other types of immune cell iii) Regulatory T cells suppress the immune response once the antigen is reduced or gone  B cell & T cell Each B and T cell has receptors on its surface for binding with particular type of antigens. B cell receptor T cell receptor  B-cell receptor (BCR) BCR is a transmembrane protein complex composed of membrane immunoglobulin (usually IgM and IgD) and disulfide- linked heterodimers called Igα/Igβ. The cytoplasmic tails of membrane immunoglobulin is too short to transduce signals, thus Igα/Igβ molecules are required for signal transduction. BCR has two identical antigen recognition sites – can recognize free antigens.  T-cell receptor (TCR) TCR is the receptor that recognized the peptide-MHC complexes on antigen presenting cells (APC). The TCR complex contains: i) the TCR for recognition ii) the accessory molecules (CD3 & zeta chain) for conveying signals. TCR has only one antigen-binding site.  T-cell receptor (TCR) Different types of T cell can be differentiated from each other by proteins expressed on their surface: i) CD4 is found on helper T cells and regulatory T cells. ii) CD8 is found on cytotoxic T cells. Functional Roles of CD4 & CD8: i) Early signal transduction. ii) Promote adhesion of T cells & APCs.  Components of the adaptive immunity Two arms of adaptive immunity: Antibody-mediated / Humoral Immunity Cell-mediated Immunity  1) Antibody-mediated/Humoral immunity The immunity involves the production of antibody molecules in response to an antigen. These antibody molecules circulate in the blood and body fluids (humor) and enter the tissue via inflammation. Ig on naïve B cells binds to Ag, this induces the B cells to proliferate into lymphoblasts which then differentiate into plasma cells and memory cells. Plasma cells then secrete antibodies specific to the antigen.  Antibody-mediated/Humoral immunity Humoral immunity is most effective against : extracellular pathogens such as bacteria bacterial toxins viruses (only before entry into hosts) The antibodies produced during humoral immunity ultimately defend the body by detecting and binding to antigens or opsonized antigens forming immune complexes.  2) Cell-mediated immunity Cell mediated immunity involves production of activated T cells which plays role to detect and eliminate cells that harbor intracellular microbes or tumor cells. It also plays a major role in transplant rejection.  Cell-mediated immunity Types of intracellular microbes combated by T cell-mediated immunity: i) Microbes that survived within phagolysosomes of phagocytes or those that manage to escape into the cytoplasm where they are not susceptible to the microbiocidal mechanism of the phagocytes such as: - Intracellular bacteria (Mycobacteria, Listeria monocytogenes, Legionella pneumophila). - Fungi ( Cryptococcus neoformans). - Protozoa (Leishmania, Trypanosoma cruzi).  Cell-mediated immunity ii) Microbes that infect non-phagocytic cells such as: - Viruses. - Protozoa ( Plasmodium falciparum, Cryptrosporidium parvum).  Antibody Antibody is a group of protein found in blood serum and other body fluids that are secreted by plasma cells in response to antigens and are capable of binding specifically to that antigens.  Antibody Characteristics of the arm regions of the Y determine the specificity of the antibody - paratope of antibodies binds to a specific antigenic determinants/epitopes of antigen (the valency of all antibodies is at least two or more). Properties of the tail portion of the antibody determine the functional properties of the antibody (what the antibody does once it binds with antigen). Basic structure of antibody  Basic structure of antibody Basic structure: Four peptide chains: - 2 identical light (L) chains. - 2 identical heavy (H) chains. Disulfide bonds: - inter-chain disulfide bonds (and noncovalent interactions) link the H and L chain, as well as two H chains. V=variable region; C=constant region - intra-chain disulfide bonds can be found in each polypeptide chains. Illustrate the basic structure of an antibody. (8 m)  Basic structure of antibody Variable and constant region on each chains with variability in the amino acid sequences: - L chain - VL (110 a.a.) and CL (110 a.a.). - H chain - VH (110 a.a.) and CH (330-440 a.a.). Hinge region is the region of antibodies that have some flexibility in the molecules – forms a Y. Antibodies are glycoprotein; carbohydrates attached to the C region.  Basic structure of antibody 3D images of antibody molecules showed that it is folded into globular regions each of which contains an intra-chain disulfide bond; these regions are called domains: - L chain domains: VL and CL. - H chain domains: VH and CH1 to CH3 (or CH4).  Antibodies types and subtypes The types are based on differences in the amino acid sequence in the C region of the L chain: i) ϰ light chains. ii) λ light chains. The subtypes are based on small difference in the amino acid sequence in the C region of the L chain: i) λ1 ii) λ2 iii) λ3 iv) λ4  Antibodies classes and subclasses The classes are based on difference in the amino acid sequences in the C region of the H chains. The subclasses are based on small difference in the amino acid sequences in the C region of the H chains. Antibodies classes and subclasses  Antibody classes and biological activities IgG structure: Contains four domains and a hinge region. All IgG's are monomers. The subclasses differ in the number of disulfide bonds and length of the hinge region.  Antibody classes and biological activities IgG functions: IgG is the most versatile because it is capable of carrying out all of the functions of immunoglobulin molecules. IgG is the major Ig in serum (75% of serum Ig) & extra vascular spaces. IgG is the main antibody produced during secondary immune response. IgG is the only class of Ig that crosses the placenta; IgG2 does not cross well. IgG can fixes complement; IgG4 does not fix complement. IgG is a good opsonin. Binding of IgG to Fc receptors on other types of cells results in the activation of other functions; IgG2 and IgG4 do not bind to Fc receptors.  Antibody classes and biological activities IgA structure: Contains four domains and a hinge region. Serum IgA is a monomer but IgA found in secretions is a dimer - a J chain join the Ig monomers together. It also has another protein associated with it called the secretory piece or T piece - helps IgA to be transported across mucosa and protects it from being hydrolyze/broken down by lytic enzymes.  Antibody classes and biological activities IgA functions: IgA is the 2nd most common serum Ig. IgA is the major class of Ig in secretions such as tears, saliva, colostrum, mucus – thus it is important in local (mucosal) immunity. Normally IgA does not fix complement, unless aggregated. IgA can bind to some cells - PMN's and some lymphocytes.  Antibody classes and biological activities IgM structure: Contains five domains but no hinge region. IgM normally exists as a pentamer but it can also exist as a monomer. In the pentameric form all heavy chains are identical and all light chains are identical. IgM has a J chain - functions in polymerization of the molecule into a pentamer.  Antibody classes and biological activities IgM functions: IgM is the third most common serum Ig. IgM is the first Ig to be made by the fetus. IgM is the first Ig to be made by a virgin B cells when it is stimulated by antigen - IgM act as indicator to show whether an infection has occurred previously or for the first time. IgM is a good complement fixing Ig - efficient in leading to the lysis of microorganisms. IgM is a good agglutinating Ig - very good in clumping microorganisms for eventual elimination from the body. IgM binds to some cells via Fc receptors. Found on the surface of B cells as monomer - functions as a receptor.  Antibody classes and biological activities IgD structure: Contains four domains and a hinge region. Exists only as a monomer.  Antibody classes and biological activities IgD functions: IgD is found in low levels in serum; its role in serum is uncertain. IgD is primarily found on B cell surfaces - functions as a receptor for antigen – it has extra amino acids at C-terminal end for anchoring to the membrane. IgD does not bind complement  Antibody classes and biological activities IgE structure: Contains five domains but no hinge region. Exists as a monomer.  Antibody classes and biological activities IgE functions: IgE is the least common serum Ig since it binds very tightly to Fc receptors on basophils and mast cells even before interacting with antigen. IgE involved in allergic reactions - binding of the allergen to the IgE on the cells results in the release of various pharmacological mediators that result in allergic symptoms. Since serum IgE levels rise in parasitic diseases, measuring IgE levels is helpful in diagnosing parasitic infections. Eosinophils have Fc receptors for IgE - binding of eosinophils to IgE- coated helminths results in killing of the parasite. IgE does not fix complement. Development of lymphocyte populations  Clonal selection and expansion Clonal selection is the process by which some lymphocytes are destroyed and others are allowed to mature. Lymphocytes bearing receptors for self are lost through the process of clonal deletion before they become fully mature. When a mature naïve lymphocytes binds to its particular antigen, the lymphocytes proliferates and differentiates to form a clone of cells all specific for that particular antigen.  Clonal selection and expansion Clonal selection theory : An individual lymphocyte expresses membrane receptors that are specific for a distinct antigen. The specificity is determined before it is exposed to the antigen. Binding of antigen to its specific receptor activates the cell, causing it to proliferate into a clone of cells. The clone of cells have the same immunologic specificity as the parent cell. It produce memory cells (longer life span) and effector cells. Only these cells will be mobilized for an immune response. Clonal selection and expansion  Antigen Presentation : Major histocompatibility complex Major histocompatibility complex (MHC) is a set of cell surface proteins essential for the adaptive immune system to recognize foreign molecules - MHC help immune cells to discriminate “self” and “nonself”. A major role of the MHC is to bind small peptides and to present them to the cell surface where the antigen can be recognized by T cell receptors. MHC molecules display both ‘self’ peptides derived from their own proteins, and foreign peptides derived from invading pathogens. Antigen Presenting Cell Cells that display antigen complexed (APC) with MHC on their surface  Phases of cell-mediated immunity Antigen processing and presenting of an exogenous antigens:  Phases of cell-mediated immunity Antigen processing and presenting of an endogenous antigens:  Phases of cell-mediated immunity Criteria MHC I MHC II Responsive T cells TC cells TH cells Types of APCs/target All nucleated cells B cells, macrophages & cells dendritic cells Source of protein Endogenous – Exogenous – antigens synthesized in the cell internalized from extracellular environment Site of peptide loading Rough endoplasmic Lysosome of MHC reticulum  TEST YOURSELF! 1. Compare the function of all five (5) classes of immunoglobulin. (10 marks) 2. Differentiate B cell receptor and T cell receptor. (8 marks) 3. Describe five (5) characteristics of cytokines effect in human body. (10 marks)  Chapter 5 (group presentation) Type of immunoassay: Precipitation and agglutination Enzyme Immunoassays (EIA) Fluoroimmunoassays (FIA) Chemiluminescenceimmunoassay (CLIA) Principle, labels, classification, example of test