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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 Cells responsible for antibody (Ab) production
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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 Cells responsible for antibody (Ab) production 2. T Cells important in the Induction Phase and responsible for cell-mediated response 3. NK Cells Natural 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 (Antibody-mediated) 2b. Cell-mediated Component
Specific Immune Response • Induction Phase • This involves the activation of T cells and B cells when a foreign antigen (Ag) • is presented to a naïve Helper T Cell by an Antigen Presenting Cell (APC). • Remember: • Antigen • any foreign compound that 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 Induction Phase Antigens reach the local lymph nodes via the lymphatics. The antigen is presented to lymphocytes by Antigen Presenting Cells. The APC’s ingest and process the Ag and present it to an uncommitted or naïve CD4-positive Helper T cell in conjunction with the MHC. These naïve Helper T Cells 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 production is stimulated by IL-4 (Interleukin-4) from Th0 cells. Th1 cell production is stimulated by IK-12 (Interleukin-12) secreted from the APC’s after binding to Helper T cells.
Specific Immune Response Figure 20-10 Vander et al, 8th Ed.
Specific Immune Response These naïve Helper T Cells 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 Th1 cell production is stimulated by IK-12 (Interleukin-12) secreted from the APC’s after binding to Helper T cells. Th2 cell production is stimulated by IL-4 (Interleukin-4) from Th0 cells.
Specific Immune Response Induction Phase Th2 cells under the influence of IL-4 will promote the proliferation of B Cells which are responsible for our Antibody 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.
Specific Immune Response Induction Phase Th1 cells produce several cytokines but 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 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 Cells 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: • Stimulate 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 (Ig’s) that have 2 functions: 1. Recognize and interact specifically with foreign Ag’s. 2. Activate 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 Ab’s to recognize • specific Ag’s. • Remember 5 classes of Ig’s: IgA, IgD, IgE, IgG and IgM • Ab’s improve the host’s ability to recover from an invading Ag associated with • a virus or a bacterial toxin. • Ab’s interact with elements of the innate immune system as follows: • Activate Complement • Stimulate Ingestion of Bacteria • Assist 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, particularly the Classical Pathway. Ie. C3a anaphylatoxin C5a chemotaxic factor C3b opsonin 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 Phase 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 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+) • 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 Effector Phase Cytokine-Releasing Th1 Cells (CD4) Their main role is to activate macrophages. Some pathogens have evolved a survival mechanism of multiplying inside macrophages after being ingested. E.g. Mycobacteria and Listeria An infected Macrophage produces an Ag-MHC complex on its own surface which is recognized by cytokine-releasing Th1 cells. The cytokines released by the Th1 cells help the macrophage to kill the pathogen inside it. In all other cases, Th1 cells activate macrophages to engulf, ingest and digest the invading pathogen. In the process an Ag is bound to MHC to present Ag to the T Cells. What happens next depends on whether Th1 or Th2 cells are stimulated.
