Adaptive Immune Response PDF

13 Adaptive immune response ILOs By the end of this lecture, students will be able to 1-Differentiate between active adaptive and passive adaptive immunity 2- Explain the sequence of events in the adaptive immune response, its outcome and downregulation after elimination of the offending an...

13 Adaptive immune response ILOs By the end of this lecture, students will be able to 1-Differentiate between active adaptive and passive adaptive immunity 2- Explain the sequence of events in the adaptive immune response, its outcome and downregulation after elimination of the offending antigen 3-Correlate the primary and secondary immune responses with the concept of vaccination. 4-Analyse the differences and interactions between the innate and adaptive immune response. ADAPTIVE IMMUNE RESPONSE Adaptive (Acquired) immunity is highly specific, has immunologic memory, and can respond rapidly and vigorously to a second antigen exposure. Forms of adaptive immunity I. Active adaptive immunity In the active immunity, the host cells learn to respond to foreign material, and the host actively produces the Abs, so they last longer than the readymade Abs given for immediate protection. Its major disadvantage is its slow onset especially the primary response. a) Active Natural Immunity It is the state of resistance built up in an individual following effective contact with foreign Ags (microorganisms or their products). The contact can be the result of clinical or subclinical infection. b) Active Artificial Immunity Through injection of killed or attenuated organisms i.e., immunization by vaccines. II. Passive adaptive Immunity Immunity is temporary, and it gives immediate protection as a result of receiving preformed Abs. a) Passive natural immunity IgG antibodies against some common infections pass trans placentally from mother to the foetus. IgA Abs are also present in the colostrum and can be transmitted to the new-born via breastfeeding. The natural immunity protects the baby for 4-6 months only. b) Passive artificial immunity The administration of preformed Abs, it is of greatest use when the illness is attributable to exotoxins. In such cases the antibodies are called antitoxins (e.g., botulism) Likewise, preformed antibodies to hepatitis B viruses (hepatitis B immunoglobulins) can be injected to neutralize the virus and thereby control viral replication. Cells involved in the specific immune response: 1. Macrophages - They are phagocytic cells which are mainly concerned with processing and presentation of protein Ags to the lymphocytes and so they are called the antigen presenting cells. Page 1 of 6 2. T lymphocytes or T- cells - They originate from a stem cell in the bone marrow, mature in the microenvironment of the thymus where they acquire cluster of differentiation (CD) molecules, differentiate into committed cells expressing specific T cell receptors (TCRs). - T lymphocytes are important in defence against intracellular microbes. - Several different subsets of T cells have been described, each with a distinct function. These include: a. CD4 effector cells - Th1 cells, Th2 cells, Th17 cells. - T regulatory cells: CD4 T cells can become T (T regs) when they are exposed to TGF-β alone. T reg cells function by suppressing T-cell responses. A b. CD8 positive T- cells - Which become differentiated into effector cytotoxic cells: cytotoxic T lymphocytes (CTLs), - They kill infected host cells as virus-infected cells and tumor cells by the delivery of toxic granule content (perforin, granzymes and granulysin) 3. B-lymphocytes or B-cells - Mature in the bone marrow and do not pass by the thymus. - They are responsible for the humoral immunity. - B cells carry IgM immunoglobulin on their surface. These immunoglobulins serve as receptors (B- cell receptors [BCRs]) for a specific antigen so that each B cell can respond to only one antigen or a closely related group of antigens. - Mature human B-lymphocytes perform many functions including antibody secretion (after changing into plasma cells), Ag processing and presentation and cytokine secretion Adaptive immune response involves antibody-mediated and cell-mediated immune responses Ø humoral or antibody-mediated immunity, is directed at extracellular pathogens & depends on B cells. Ø cell-mediated (or cellular) immunity, depends on T cells to eliminate intracellular pathogens. Adaptive immune responses develop in steps, consisting of: - Ag processing and presentation. - Activation, proliferation and differentiation of T-helper cell - Activation of T-cytotoxic cells. - Activation and differentiation of B-cells. - Formation of memory cells. - Elimination of the offending antigen. - Down-regulation of the immune response Page 2 of 6 The major events taking place in the specific immune response are: - Antigen processing and presentation: Proteins from exogenous antigens, such as bacteria, are internalized by the antigen presenting cells (APCs) and undergo denaturation or partial proteolysis then the peptide fragments eventually become expressed on the surface of the APC (as peptide–MHC complex) to be recognized by the receptor on the surface of the specific T-helper cell. -Antigen presenting cells such as macrophages, Langerhans cells of the skin, dendritic cells, and B- lymphocytes. - Activation of the T-helper cell: Figure 1: T-helper cell activation. Three kinds of signals are involved in activation of T cells by APC: 1-The first signal comes from the T cell receptor (TCR) on the T cell interacting with an MHC -peptide complex presented on the APC. 2- The second signal (co-stimulation): is derived from the interaction of B7 protein (CD80/CD86) costimulatory molecules on the APC with CD28 on the T cell. 3-A third signal: cytokines delivered by the APC. During these events, these Th cells are able to proliferate and differentiate into effector T helper cells i.e., Th1 & Th2 cells and Th17 cells. They produce cytokines which act on other cells of the immune system as T-cytotoxic cells, B-cells, and macrophages causing their proliferation and activation. -Th1 cells are stimulated by intracellular pathogens (secrete cytokines mainly IFN-γ and IL-2): o IL2 which acts on CD8 positive cells to enhance their proliferation and differentiation. o IFN-Y amplifies Th1 response, activate macrophages. -Th2 cells is activated in response to large extracellular pathogens or allergens (produce cytokines e.g., IL4, IL5, IL13) which promote humoral immunity The cytokines released from T helper cells cause B lymphocytes to isotype switch to IgG, IgA and IgE. - Th17 cells: Th17 cells are of importance in the defence against fungal infection. -Activation of B-cells: humoral or antibody-mediated immune response There are two major pathways of B-cell activation: Page 3 of 6 1) T-cell dependent activation: the full response of B cells to protein antigens requires help from T cells. B-cells recognize their specific antigen by surface membrane Ig receptors. B cells also act as APCs—they ingest protein antigens, degrade them, and display peptides bound to class II MHC molecules for recognition by T helper cells. T helper cells secrete cytokines, to activate the B cells. Upon activation, B lymphocytes proliferate and then differentiate into antibody secreting plasma cells. Also, B cells start to class switch to induce the production of antibodies of different classes (IgG, IgA, IgE). Helper T cells also stimulate the production of long-lived plasma cells and memory B cells. Figure 2: T-cell dependent- antigen activated B lymphocytes 2) T- cell-independent activation. Polysaccharides, lipids and lipopolysaccharides are called T cell independent antigens because they induce antibody responses without T cell help. Most T independent antigens contain multiple identical epitopes that can cross link many Ig receptors on a B cell providing signals that stimulate B cell responses. The response to T independent antigens is generally weaker than other classes of antigens. It is dominated by IgM production, as class switching is dependent on cytokines released from T helper cells. The plasma cells generated are short lived and there is no generation of memory cells. ( Figure 3 ) Figure 3: B-cell activation by T independent antigens Page 4 of 6 - Activation of T-cytotoxic cells: T-cytotoxic cells become activated when they recognize their antigen on the surface of a target cell, complexed with MHC class I molecule, and also by the effect of cytokines (e.g., IL 2) produced by Th1 cells. They differentiate into effector cytotoxic cells (CTLs) which proceeds to kill the infected cell. They kill infected host cells as virus-infected cells and tumour cells by the delivery of toxic granule contents (perforin, granzymes). Figure 4 Figure 4: Cytotoxic T cell activation Some activated B and T-cells remain as Memory Cells which can respond to subsequent encounters with the same antigen, enabling a faster and more efficient response to re-infection with the same organism. The usual outcome of the immune response is the Elimination of the offending antigen. -After the offending antigen elimination, the response is down-regulated by regulatory T-cells to prevent unnecessary activation of lymphocytes and unregulated production of antibodies. (Figure 5) Activated T helper cell APC T helper cell Cytotoxic T cell (Tc) Antibodies Cell-mediated immunity Humoral immunity Memory Tc Effector Tc Lysis Figure 5: The specific or adaptive immune response. Page 5 of 6 Ø Antibody Responses A. The Primary Response When an individual encounters an antigen for the first time, the antibody produced in response to that antigen is detectable in the serum within days. The serum antibody concentration continues to rise for several weeks and then declines; the antibody level may drop to very low levels (Figure 6). The first antibodies produced are IgM. Then, IgG and IgA are made. IgM levels tend to decline sooner than IgG levels. B. The Secondary Response In the event of a second encounter with the same antigen months or years after the primary response, the second antibody response is more rapid and generates higher levels than during the primary response (Figure 6 ). This change in response is attributed to the persistence of antigen- sensitive memory cells that were generated during the primary immune response. In the secondary response, the amount of IgM produced is qualitatively similar to that produced after the first contact with the antigen; however, more IgG is produced, and the level of IgG tends to persist much longer than that produced in the primary response. N.B. This concept is medically important because the protection by the first administration of a vaccine is less than that afforded by a booster shot. Figure 6: Rate of antibody production following initial antigen administration and a second “booster” injection. Ø Interaction Between Innate and Adaptive Immune responses The innate and adaptive arms of the immune response do not operate independently of one another. *Phagocytic cells process and display antigen to facilitate stimulation of specific T-lymphocytes. *Macrophages secrete cytokines which help trigger the initiation of specific immune responses. *T lymphocytes produce cytokines (IFN-Y) which enhance the microbicidal activities of phagocytes. * Antibodies produced by plasma cells bind to pathogens and assist with phagocytosis and antibody dependent cell mediated cytotoxicity. Page 6 of 6