Adaptive Immunity (MIC343) PDF

MIC343 ~Immunology~ The Adaptive Immunity CHAPTER 3_Part 2  LET’S RECAP-PREVIOUS CLASS Antibody and it’s basic structure Antibodies classes and subclasses Clonal selection and expansion Major histocompatibility complex (MHC) and Antigen Presenting Cell (APC) ❑ Exoge...

MIC343 ~Immunology~ The Adaptive Immunity CHAPTER 3_Part 2  LET’S RECAP-PREVIOUS CLASS Antibody and it’s basic structure Antibodies classes and subclasses Clonal selection and expansion Major histocompatibility complex (MHC) and Antigen Presenting Cell (APC) ❑ Exogenous antigen ❑ Endogenous antigen  SYLLABUS CONTENT Phases of Humoral/Antibody-mediated Immune Response Antibody Activation of Immune Cells Types of Humoral Response ❑ Primary Immune Response ❑ Secondary Immune Response  Course of the adaptive immune response  Humoral / antibody-mediated immune response Phases of humoral immunity (1) (2) Antigen Activation of B recognition lymphocytes (3) (4) Clonal Effector expansion & functions differentiation Phases of humoral immunity: antigen recognition i) Antigen recognition. Naïve B lymphocytes express two classes of membrane bound antibodies IgM and IgD which function as the receptors for antigens. Signalling requires cross-linking of at least two Ig receptors. Receptor cross-linking occurs when two or more antigen molecules in an aggregate or repeating epitopes of one antigen molecules bind to adjacent Ig molecules in the membrane of B cells. Phases of humoral immunity: antigen recognition Polysaccharides, lipids and other non protein antigens often contain multiple identical epitopes in each molecule and are therefore able to bind to numerous Ig receptors on a B cell at the same time. Signals initiated by antigen receptor cross-linking are transduced by Ig-associated proteins Ig and Ig. Phases of humoral immunity: activation of B lymphocyte ii) Activation of B lymphocyte. There are two routes from B cell activation to production of antibodies: - activation by Thymus dependent antigens (T-dependent antigens) - activation by Thymus independent antigens (T-independent antigens). Phases of humoral immunity: activation of B lymphocyte - Activation by Thymus dependent antigens (T-dependent antigens). Most antigens requires for T helper cells to induce antibody production. Binding of Ag to B-cell does not induce proliferation and differentiation to effector cells without additional interaction with T helper cells and the presence of appropriate cytokines. Phases of humoral immunity: activation of B lymphocyte The pathway: A. Antigen crosslinks two Ig receptors thus generate signal 1 - The B cell processed the antigen – the peptide are bound by MHC class II and presented on the membrane as peptide-MHC complex. B. TH cells recognize peptide-MHC class II on B-cell membrane – this activates TH cell. Phases of humoral immunity: activation of B lymphocyte C. TH cell begins to express CD40 ligand (CD40L) – interaction of CD40 and CD40L generate signal 2. D. B cell begins to express receptors for various cytokines - cytokines produced by TH cells bind to cytokines receptor on B cell and stimulate more B cell proliferation and antibody production. Phases of humoral immunity: activation of B lymphocyte Phases of humoral immunity: activation of B lymphocyte - Activation by Thymus independent antigens (T-independent antigens). Antigens can directly stimulate the B cells to produce antibody without the requirement for T cell help. Example of antigens are lipopolysaccharides & antigens with highly repetitious molecules. The humoral response to TI Ag is generally weak; no memory cells formed.  Phases of humoral immunity: clonal expansion & differentiation iii) Clonal expansion & differentiation. The transcription factors is activated – produce proteins that involved in B cell proliferation (clonal expansion) and differentiation – B cells differentiate into effector cells (plasma cells that secrete antibodies) and memory cells.  Phases of humoral immunity: clonal expansion & differentiation Once activated, B cell may generate up to 4,000 antibody –secreting cells which can produce up to 1012 antibody molecules per day. The secreted antibodies have the same specificity as the naïve B cell membrane receptors that recognized antigen to initiate the response. Repeated exposure to a protein antigen results in the production of antibodies with increasing affinity for the antigen- affinity maturation. This leads to the production of antibodies with improved capacity to bind and neutralize microbes and their toxins.  Phases of humoral immunity: effector functions of antibodies iv) Effector functions of antibodies. Antibodies do not kill or eliminate antigens. Their roles are to bind to antigens and mediate effector functions. The binding of antibody to antigen can result in several mechanism.  Phases of humoral immunity: effector functions of Antibodies 1) Agglutination of Microorganisms. - Antibodies with multiple antigen binding sites cause agglutination of microbes thus reducing the chances of spread throughout the body. - Agglutination cause more effective phagocytosis. Phases of humoral immunity: effector functions of Antibodies 2) Complement activation. - Formation of immune complex can trigger complement cascade reaction which can lead to formation of pores and cell lysis. Phases of humoral immunity: effector functions of Antibodies 3) Opsonization & promotion of phagocytosis. - Antibodies coat microbes and promote their ingestion by phagocytosis. Phases of humoral immunity: effector functions of Antibodies 4) Neutralization of microbes and microbial toxins. - Antibody bind to and block/neutralize the infectivity of microbes and the interactions of microbial toxins with host cells. Phases of humoral immunity: effector functions of Antibodies 5) Antibody-Dependent cell-mediated cytotoxicity. - the linking of antibody bound with target cells with the FC receptors can induce/direct the cell cytotoxic activity of the effector cells against the target cells (lysis of the target cell). - A special type of ADCC mediated by eosinophils plays a role in defense against helminthic infections. Phases of humoral immunity: effector functions of Antibodies 6) Immobilization of Bacteria and Protozoans. - antibodies attach to cilia and flagella, thus the structure will be less active – easier for phagocytes to engulf.  Test Yourself! 1. Outline the antigen recognition phase in humoral immune response. (5 marks) 2. Most antigen require a thymus to induce antibody production. Outline the process that occurs after cross-linking of antigen with B cell receptors. (5 marks)  Antibody activation of immune cells Antibody response to the first exposure to an antigen is called primary immune responses and that to the subsequent exposures are called secondary immune responses.  Types of humoral response Primary immune response: Immediately after the first exposure to an antigen there is a duration called the lag period during which naïve B cells undergo clonal selection and expansion and differentiation into plasma cells and memory cells. The lag period is followed by a logarithmic increase in serum antibody level which reaches a peak, plateaus for a variable time and the declines.  Types of humoral response The duration of the lag time varies with the nature of the antigen. The antibody isotype in primary immune response is mainly IgM. Memory B cells formed during primary immune response stop dividing and enter the G0 phase of the cell cycle - these cells have variable life span.  Types of humoral response Secondary immune response: The response results from activation of memory cells. They differ both qualitatively and quantitatively. The amount of antibody produced after the first encounter with an antigen are smaller than amounts of antibody in secondary immune response.  Types of humoral response Secondary responses also showed increase antibody affinity. The lag period is shorter than in primary immune response. The antibody isotype in secondary immune response is IgG and under certain situations IgE and IgA. Types of humoral response  SYLLABUS CONTENT Phase of Cell-Mediated Immune Response Humoral Vs. Cell-Mediated Immune Response Immunological memory  Cell-mediated immune response  (1) Recognition of cell- associated microbes by T cells Phases of (2) (4) cell- Activation of Effector functions mediated T lymphocytes immunity (3) Clonal Expansion & differentiation  Phases of cell-mediated immunity i) Recognition of cell-associated microbes by T cells. Both TH and TC cells can recognize antigen ONLY when it has been processed and presented on the cell membrane of an Antigen Presenting Cell (APC) or Target Cell, respectively in association with self MHC. Antigen presenting cells : the cells which present antigen to CD4 TH cells. Target cells: The cells which present antigen to CD8 TC cells. MHC is also known as human leukocyte antigen. This process is called “Antigen processing and presenting”.  Phases of cell-mediated immunity Processing= protein antigen is degraded into peptides. Presentation= association of peptide with MHC and transportation of MHC/peptide complex to the cell membrane. Cells which have been induced to function as APCs are as follows: i) macrophages ii) B lymphocytes iii) dendritic cells Identify the cells which can process the protein antigens before presenting them to T helper cells. (3 marks) (Dec 2018) T cytotoxic cell T helpercell  Phases of cell-mediated immunity ii) Activation of T lymphocytes. Antigen recognition by TCR triggers signals that are delivered to the interior of the cells. The signals are delivered by CD3 and  (zeta) proteins, as well as, the co-receptors (CD4 or CD8). Co-receptors recognize class II or class I MHC molecules respectively.  Phases of cell-mediated immunity In response to antigen, T lymphocytes especially CD4 TH cells, rapidly secrete several different cytokines that have diverse activities. The first cytokine to be produced within 1 to 2 hours after activation is interleukin 2 (IL-2) - main action is to stimulate the proliferation of T cells.  Phases of cell-mediated immunity iii) Clonal expansion and differentiation. Within 1 or 2 days after activation, T lymphocytes begin to proliferate resulting in expansion of antigen specific clones. Some differentiate into effector cells that function to eradicate infections.  Phases of cell-mediated immunity CD4 TH cells may differentiate into diverse effector cells that produce distinct sets of cytokines that perform different functions, such as: * produce interferon- which activate phagocytes, and stimulate the production of opsonizing & complement binding antibodies. * produce IL-2 which stimulate the production of IgE. * produce IL-5 which stimulates eosinophils which function mainly in defence against helminths. CD8 TC cells recognize peptides of intracellular protein antigens and may require help from CD4 TH cells to differentiate into effector CTLs.  Phases of cell-mediated immunity iv) Effector Functions. There are two types of cell-mediated immune reactions: i) CD4 TH cells activate macrophages : to kill ingested microbes that are able to survive in the vesicles of the phagocytes produce substances including reactive oxygen intermediates, nitric oxide and lysosomal enzymes that kill ingested microbes produce cytokines that induce inflammation.  Phases of cell-mediated immunity ii) Effector CTLs kill cells harbouring microbes in their cytoplasm. CTLs induce cell death via two mechanisms : a) the perforin/granzyme pathway. b) Fas/FasL pathway  Phases of cell-mediated immunity a) The perforin/granzyme pathway. The primary events in CTL-mediated death in the perforin/granzyme pathway are: i) Conjugate formation (binding of the CTL to the MHC-peptide). ii)CTL cytoplasmic rearrangement- golgi stacks and granules in CTL relocate toward the point of contact with target cells. iii) Granules contents are released by exocytosis. iv) Perforin contact with target cell membrane will form pores. v) Granzyme enters via pore, fragmentation of DNA occurs. vi) CTL dissociation and recycling. Phases of cell-mediated immunity  Phases of cell-mediated immunity b) Fas/FasL pathway. Fas is a transmembrane protein that can deliver a death signal when cross-linked by its natural ligand – Fas ligand which are found on the membrane of CTLs. Interaction of FasL with Fas on a target cell triggers apoptosis.  Humoral vs Cell-mediated immune response Overview of cell-mediated immunity Humoral vs cell-mediated immune response Distinguish humoral immunity and cell-mediated immunity  Immunological memory Immunization: The process of providing immunity artificially. A process that increases an organism's reaction to an antigen, thereby improving the organism's ability to resist or overcome infection. A technique used to : induce an immune response to a specific disease in humans by exposing the individual to an antigen in order to raise antibodies to that antigen.  Immunity Definition of immunity : All those mechanisms that provide the animal with the capacity to recognize materials as foreign to itself and to neutralize, eliminate or metabolize them with or without injury to its tissues  Active natural immunity i) Active natural immunity: The body are exposed to antigen by getting the disease. The body produces memory cells which make it immune to disease in the future. e.g.: Wild infection for example with hepatitis A virus (HAV) and subsequent recovery gives rise to a natural active immune response usually leading to lifelong protection.  Active artificial immunity ii) Active artificial immunity: The injection that cause the body to be exposed to the harmless antigen and produces antibodies and memory cells - long-lasting (possibly lifelong) protection.  Active artificial immunity The person maybe injected with : Attenuated Killed or Toxoid microbes inactivated organisms, An Living, fragmented exotoxin treated harmless, m/organisms, so as to be non- non-virulent or antigens poisonous but strains of a produced by still microbe. recombinant immunogenic. DNA Eg: MMR Eg : Tetanus technology. vaccine toxoids (measles, components of mumps, and Eg: Influenza Lockjaw rubella). vaccines. vaccines.  Vaccination Vaccination: The procedure of injection of vaccine to produce immunity against a disease. A vaccine typically contains an agent that resembles a disease causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. Enable the immune system to respond – the body produce memory cells against a particular pathogen without the pathogen causing disease – means a person become immune without getting any symptoms.  Vaccination Booster shots: repeated vaccinations that maintain larger populations of memory cells – give rise to secondary immune response - ensure long-lasting immunity. Some vaccines contain many different antigens to protect against different strains of pathogens. The balance of risk and benefit of vaccination is crucial.  Vaccination Components: i) The antigen. - a piece of protein from a bacteria or virus, tells the immune system what to react to. ii) The adjuvant. -the component of a vaccine that increase/aid/stimulates the immune system to react against the pathogen represented by the vaccine's other components. The choice of adjuvant can make an enormous difference in how effectively a vaccine stimulates an immune response.  Vaccination Benefits and dangers of vaccination: Benefits Dangers Eradication of some Low percentage of vaccinations produce side diseases, e.g. small effects, including symptoms of disease, pox. sometimes serious or lethal. Reduced rate of Artificial immunity not as effective at producing infection; less illness immune response as in natural immunity. and death. Reduced long-term Excessive vaccination may reduce the ability of disability. the immune system to respond to new diseases.  Overall innate & adaptive immune response Innate immunity Adaptive immunity Non-specific immunity Specific immunity First and second line defense Third line defense Response is antigen independent Response is antigen-dependent Not an acquired immunity An acquired immunity Immediate maximal response Delay maximal response (presence of lag time) No immunological memory Produce immunological memory Point out the characteristic of innate and adaptive immunity. (10 marks)  How to strengthen your immune system Eliminate all sugar and allergens from your diet. -Small amount of sugar may damage WBC up to 50% for very short periods of time. -Eliminating your allergens will help our immune cells to strengthened in order to combat other invaders rather than the allergen. Eliminate or reduce exposure to dangerous toxins in your environment. -Air Pollution, smoking, cleaning products will stress your immune system with frequent exposure.  How to strengthen your immune system Regular, moderate exercise. -It helps to strengthen your immune system (extreme exercise may suppress immune system function). -e.g.: An increase in blood flow associated with moderate exercise helps to circulate antibodies along with white blood cells necessary to fight infection more quickly. -e.g.: The increase in body temperature as a result of physical activity may aid in inhibiting the growth of bacteria; thus allowing the body to fight infection more effectively.  How to strengthen your immune system Learn how to properly deal with stress. Acute (short term) stress will positively strengthen your immune system function. Chronic (long term) stress will suppress your immune system function. Sleep Helps Strengthen Your Immune System. A healthy, deep sleep allows our body to release a significant amount of growth hormone that boost the immune system and aids in the growth and repair of the body.  How to strengthen your immune system Drink plenty of water. Water keeps our immune system operating optimally while improving the way we feel, look and live. Eating A Nutritious Diet. Quality food keep our cells healthy, strengthen our immune system, and provides energy to the body. Wash Your Hands. Maintaining a high standard of personal hygiene care could avoid infection and keep your immune system strong.  Test Yourself! 1. Cell-mediated immune response consists of 4 phases. Explain the recognition process of cell-associated microbes by T cells. (5 marks) 2. By using a flow chart, illustrate how cytotoxic T lymphocyte mediates the killing of target cells by means of Fas/FasL pathway. (3 marks) 3. Illustrate the concentration of antibody produced in serum following the first and second time a person is exposed to the same antigen. (3 marks)