1. The Cell-Mediated Immune Response

Transcription

1 Chapter 17B: Adaptive Immunity Part II 1. Cell-Mediated Immune Response 2. Humoral Immune Response 3. Antibodies 1. The Cell-Mediated Immune Response 1 Basic Steps of Cell-Mediated IR 2a CD4 + MHC cl. I 2b 3 CD ) APC processes intracellular pathogen 2) peptides are presented on MHC class I & MHC class II 3) APC activates specific T H cell to become T H1 4) T H1 releases cytokines to activate specific CD8+ CTL to divide, differentiate into active CTLs, memory cells 1

2 Primary Cell-Mediated IR The initial activation of cytotoxic T cells due to an intracellular pathogen occurs as follows: 1) a dendritic cell or macrophage ingests or is infected by an intracellular pathogen 2) peptides fr. pathogen presented on MHC class II and MHC class I molecules 3) specific T H cells activated to become T H1 cells 4) T H1 cells activate specific CTLs to: undergo mitosis to produce more of that T cell clone differentiate into active CTLs OR memory T cells CTL-mediated Killing of Infected Cells Activated CTLs will cause the death of any cells that present the foreign peptide on MHC class I by: inducing programmed cell death (apoptosis) OR inducing cell lysis by releasing the protein perforin **Dendritic cell APCs are spared this fate!** Programmed Cell Death (Apoptosis) Programmed cell death (aka apoptosis) is a built in program present in every cell which which results in cell suicide : activated CTLs express a protein called Fas-ligand when they encounter a cell presenting an MHC class I-peptide complex that binds their T cell receptor Fas-ligand sets off a series of events that result in the destruction of the infected cell s DNA and its proteins (i.e., cell death!) 2

3 Summary of Cell-Mediated Immunity this takes several days to complete T Cell Memory Like B cells, T cells (whether T H or CTL) also produce extremely long-lived memory cells: activated directly upon subsequent exposure no need for activation signals from other T cells or APCs secondary responses are much more rapid and much more intense than primary responses this is the basis for immunizations the enhanced secondary response is so much more effective that the individual is largely protected from re-infection with the same pathogen 2. The Humoral Immune Response 3

4 Basic Steps of Primary Humoral IR For the sake of simplicity, we will consider humoral immunity in which a B cell serves as the APC: 1) specific B cell binds native antigen with its membranebound antibody (BCR) antigen is internalized and broken down into peptides peptides (processed antigen) are loaded onto MHC class II molecules 2) MHC class II molecules bearing peptides from the internalized pathogen are presented on the B cell surface various T H cells will now be able to sample peptides from the ingested pathogen any T H cells expressing a T cell receptor (TCR) that binds to peptides (processed antigen) from the ingested pathogen can now be activated 3) T H cells that recognize peptides from the pathogen are activated by the B cell, and in turn activate the B cell A B A) special proteins on the B cell surface will activate any T H cells that bind to the presented peptide antigens to become T H2 cells B) activated T H2 cells then release cytokines that in turn activate the B cell 4

5 4) the activated B cell clone divides multiple times and then these cells differentiate into plasma cells or memory B cells plasma cells are B cells that have become specialized to continually produce and secrete soluble antibody for a few days and then die initially plasma cells produce IgM class antibodies, however they can be induced to switch classes other B cell progeny instead become memory B cells **T H2 cells also divide and produce memory T cells** Summary of Primary Humoral IR The initial exposure of a B cell to its specific antigen results in its activation as follows: 1) dendritic cell, macrophage or B cell ingests extracellular antigen by phagocytosis 2) peptides fr. antigen presented on MHC class II 3) specific T H cells activated to become T H2 cells 4) T H2 cells in turn activate specific B cells to: undergo mitosis to produce more of that B cell clone differentiate into antibody secreting plasma cells OR memory B cells Summary of Humoral IR Primary immune response 1 BCR 2 antigen (T H2 cell help) 3 proliferation (mitosis) plasma cells 4 antigen memory B cells the entire process takes several days to complete Secondary immune response plasma cells memory B cells 5

6 T-independent B Cell Activation Some antigens such as certain bacterial polysaccharides can activate B cells to secrete antibody without the help of T cells: results in a much more rapid antibody response however memory B cells are NOT produced thus there will NOT be any kind of enhanced response upon subsequent exposure Antibody Class Switching Following the first exposure to its specific antigen, an activated B cell will generate IgM producing plasma cells. Various cytokines produced by T H and other cells in the vicinity can induce plasma cells to switch the antibody class to IgG, IgA or IgE: usually switch to IgG and later to IgA or IgE involves DNA recombination in the gene encoding the antibody B Cell Memory Memory B cells remaining after the initial activation of a B cell have the following characteristics: they are extremely long-lived (years!) their BCRs are of the IgG, IgA or IgE class activated directly upon subsequent exposure no need for T cell help generate more plasma cells & memory cells such secondary responses are much more rapid and much more intense than primary responses generate more plasma cells & memory cells 6

7 artificial immunity results from the injection of antigen (active) or antibodies (passive) natural immunity results from natural expos. to antigen or transfer of antibodies fr. mother to child 3. Antibodies Every antibody have this same basic structure: 2 identical Heavy Chain polypeptides 2 identical Light Chain polypeptides Antibody Structure Each heavy & light chain has a Variable & a Constant region Heavy & Light chains are all held together by disulfide bonds the variable regions together bind Ag & are unique for each antibody due to heavy & light chain gene recombination 7

8 The Different Classes of Antibody All antibodies fall into 5 general classes based on their constant regions (which are the same for all antibodies in a given class) and other features: IgM (Immunoglobulin type M ) a pentameric structure consisting of 5 antibodies connected by disulfide bonds and a J chain polypeptide IgD only used as B cell receptor, never secreted IgM the first class of antibody produced by a B cell after its initial exposure to antigen that binds its B cell receptor most effective at agglutination, activating complement IgG a monomeric class comprising ~80% of serum antibodies and also found throughout the lymph good for opsonization, activating complement only class of antibody to cross the placenta to fetus IgA a dimeric structure consisting of 2 Ab s, a J chain & a secretory component present in saliva, mucus, breast milk & other secretions, is especially tough, and is the most abundant of all Ab s IgE a monomeric class that binds to IgE receptors on mast cells & basophils and triggers allergic reactions 8

9 The Roles of Antibodies Antibodies do no more than bind to antigens, however there are 5 general consequences of the binding of antibody to antigen: 1) neutralization prevents antigen (e.g., virus, toxin) from functioning 2) agglutination the cross-linking of antigens into a large complex 3) opsonization enhancing the process of phagocytosis 4) antibody-dependent cell-mediated cytotoxicity facilitating destruction of eukaryotic pathogens 5) activation of complement Neutralization of Antigens Agglutination Occurs since each antibody has 2 Ag binding sites: results in elaborate antigen-antibody complexes that localize pathogens, make them easier to dispose of 9

10 Opsonization Phagocytes such as macrophages have receptors for the constant region (F C ) of antibodies: F C receptors allow phagocytes to grab onto antigen-antibody complexes much more easily makes it much easier to engulf and destroy pathogens by phagocytosis Facilitating Cytotoxic Responses Eosinophils and NK cells also have F C receptors: in this way antibodies can tether these cells to parasites & facilitate chemical destruction of these pathogens Complement Activation Antibody bound to the surface of bacteria and other cellular pathogens can trigger complement cascade: this is the classical pathway of complement activation results in cell lysis or opsonization (C3b), influx of phagocytes 10

11 Key Terms for Chapter 17B plasma cell, memory B and T cells class switching apoptosis, Fas-ligand, perforin antibody: heavy & light chains, variable, constant agglutination natural vs artificial immunity active vs passive immunity Relevant Chapter Questions rvw: 1, 7, MC: 1-4, 8 11