1、Specific Immune Response,Reading: Rang et al, Chapter 12, Local Hormones, Inflammation & Allergy The key cells involved in the specific immunological response are LYMPHOCYTES, falling into 3 main groups: 1.B Cellsresponsible for antibody (Ab) production 2.T Cellsimportant in the Induction Phase and

2、responsible for cell-mediated response 3.NK CellsNatural Killer Cells, specialised non-T, non-B cells that are activated in the “innate response” In the specific immune response there are 2 main phases: 1.Induction Phase 2.Effector phase This is further subdivided into: 2a.Humoral Component (Antibod

3、y-mediated) 2b.Cell-mediated Component,Specific Immune Response,Specific Immune Response,Induction Phase This involves the activation of T cells and B cells when a foreign antigen (Ag) is presented to a nave Helper T Cell by an Antigen Presenting Cell (APC). Remember: Antigen any foreign compound th

4、at initiates an immune response usually a protein or polysaccharide often found on the surface of microorganisms, transplanted tissues/organs, foods etc. Antibody specifically produced to neutralise ONE type of Antigen. Produced by B cells blueprint is kept by Memory T cells,Specific Immune Response

5、,Induction Phase Antigens reach the local lymph nodes via the lymphatics. The antigen is presented to lymphocytes by Antigen Presenting Cells. The APCs ingest and process the Ag and present it to an uncommitted or nave CD4-positive Helper T cell in conjunction with the MHC. These nave Helper T Cells

6、 begin to produce Interleukin-2-receptors as well as generating Interleukin-2. Interleukin-2 is a cytokine that has an autocrine function, that is, it causes the proliferation of activated Helper T Cells which are now called Th0 cells. Th0 cells then produce either Th1 or Th2 cells Th2 cell producti

7、on is stimulated by IL-4 (Interleukin-4) from Th0 cells. Th1 cell production is stimulated by IK-12 (Interleukin-12) secreted from the APCs after binding to Helper T cells.,Specific Immune Response,Figure 20-10 Vander et al, 8th Ed.,Specific Immune Response,These nave Helper T Cells begin to produce

8、 Interleukin-2-receptors as well as generating Interleukin-2.,Interleukin-2 is a cytokine that has an autocrine function, that is, it causes the proliferation of activated Helper T Cells which are now called Th0 cells.,Th0 cells then produce either Th1 or Th2 cells,Th1 cell production is stimulated

9、by IK-12 (Interleukin-12) secreted from the APCs after binding to Helper T cells.,Th2 cell production is stimulated by IL-4 (Interleukin-4) from Th0 cells.,Specific Immune Response,Th2 cells under the influence of IL-4 will promote the proliferation of B Cells which are responsible for our Antibody

10、mediated immune responses. Some B Cells become: Plasma Cells and release Ab into blood. Memory B Cells that retain the blueprint of the Ag for future Ab production should the same Ag enter the body later.,Induction Phase,Specific Immune Response,Induction Phase,Th1 cells produce several cytokines bu

11、t mf activating cytokines and Interferon g are most important initially. Interferon g is responsible for stimulating CD8 T Cells to become Cytotoxic T Cells This is the beginning of the cell-mediated pathway of the immune response.,Specific Immune Response,Figure 12.3 Rang et al.,Specific Immune Res

12、ponse,Specific Immune Response,Induction Phase Summary The 2 subsets of T Cells are important because they are responsible for providing the balance in response by the immune system. Also any dysfunction at this level will lead to deficiencies in both Ab-mediated and/or cell-mediated immunity. Th1 C

13、ells and Cell-Mediated Immunity Th1Cells produce the cytokines (IL-2, TNF-b and IFN g) that: activate macrophages stimulate CD8+ lymphocytes to release IL-2 yielding cytotoxic T cells inhibit Th2 cells by INFg action. Th2 Cells and Ab-Mediated Immunity Produce cytokines (IL-4, TGF-b, IL-10) that: St

14、imulate B Cell proliferation (CD4+ Cells) Stimulate differentiation of eosinophils Inhibit Th1 Cell function.,Specific Immune Response,Effector Phase Antibody-Mediated (Humoral) Response Abs are immunoglobulins (Igs) that have 2 functions: 1.Recognize and interact specifically with foreign Ags. 2.Ac

15、tivate one of more host defence mechanisms. Structure of Antibodies Y - shaped proteins containing: Fab portion that has the recognition site for Ag Fc portion that activates host defences.,Specific Immune Response,Effector Phase Among B cells there are clones that express individual Abs to recogniz

16、e specific Ags. Remember 5 classes of Igs: IgA, IgD, IgE, IgG and IgM Abs improve the hosts ability to recover from an invading Ag associated with a virus or a bacterial toxin. Abs interact with elements of the innate immune system as follows: Activate Complement Stimulate Ingestion of Bacteria Assi

17、st Cytotoxic Cell Function Stimulate Allergic Reactions,Specific Immune Response,Ab and Complement Ab binds to Ag forming an Ag-Ab Complex. This exposes the Fc portion of the Ab which is a binding site for Complement. Complement-Fc Complex results in activation of the complement sequence, particular

18、ly the Classical Pathway. Ie. C3aanaphylatoxin C5achemotaxic factor C3bopsonin Leading to lysis of the invading cell. Ab and Ingestion of Bacteria Ag-Ab Complex, exposes Fc portion Attracts phagocytic cells (neutrophils and macrophages) Begins ingestion process.,Specific Immune Response,Effector Pha

19、se Ab and Cellular Toxicity Ag-Ab Complex allows cross-links between a parasite and eosinophils. Eosinophils kill the microorganism. Useful for large pathogens such as protozoa and worms. Ab and Allergic Reactions Mast Cells and Basophils have receptors for IgE which can become attached to the cell

20、membrane. When Ag reacts with this cell-fixed Ab it yields an enormous response with the release of many inflammatory mediators.,Specific Immune Response,Effector Phase Cell-Mediated Response Lymphocytes involved are both: CD8+ (Cytotoxic T Cells) and Inflammatory, cytokine releasing Th1 Cells (CD4+

21、) Cytotoxic T Cells Attack virus-infected tissue cells in 2 steps: 1.Recognition and signalling that the cell is infected. Expression on the cell surface of peptides derived from the pathogen in association with MHC protein. 2.Protein-MHC complex is recognized by CD8+ T Cells which destroy virus-infected tissue cell.,Specific Immune Response,Effe