Immunology PDF

Immunology Topic Learning Outcomes - After completing this topic, you should be able to: - 1. Identify and Explain terminology of the immune system. - 2. Identify and Explain the role of the immune system in health. - 3. Identify and Explain the components of the immune s...

Immunology Topic Learning Outcomes - After completing this topic, you should be able to: - 1. Identify and Explain terminology of the immune system. - 2. Identify and Explain the role of the immune system in health. - 3. Identify and Explain the components of the immune system What is immunology? - Immunology: the study of the immune system and its functions. - Importance of immunology in health and disease: o The immune system plays a crucial role in maintaining health by defending against pathogens and potentially harmful substances. o When the immune system malfunctions, it can lead to diseases such as allergies and autoimmune disorders. Key terms in immunology. Immune system: - Complex network of cells, tissues, and organs that work together. - To defend the body against harmful foreign substances, such as bacteria, viruses, and toxins. - Components: two main types o Innate immune system § Provides a rapid response to infections. o Adaptive immune system § Provides a longer-term response that is specifically tailored to the invading pathogen. § Potentially lifelong memory – where long term immunity come from. - Cells o Several types cells involved in the immune response. § Leukocytes (white blood cells) § Include neutrophils, macrophages, monocytes, dendritic cells, natural killer cells, lymphocytes (B cells, and T cells) - Tissues and organs: o lymph nodes, spleen, thymus, bone marrow. o mucosa-associated lymphoid tissue (MALT). o gut-associated (GALT). o bronchial associated (BALT) o Skin-associated (SALT) - Molecules o Antibodies o Cytokines o Complement o Major histocompatibility complex (MHC) molecules  - Antigens o Substances that stimulate an immune response, and can come from bacteria, viruses, and other foreign substances. - Antibodies o Proteins produced by B cells in response to an antigen. o They help neutralise or remove pathogens from the body. - Immune response: o A complex process that involves the activation of specific cells and the production of antibodies. à humeral response o Regulated by signalling molecules and cytokines. - Vaccination: o A way to prevent or reduce the severity of infectious diseases. o By triggering an immune response to specific antigens without causing the disease itself. - Immune system disorders: o The immune system can sometimes malfunction, leading to health conditions. § An overactive immune system can lead to allergies and autoimmune diseases. § An underactive immune system can result in immunodeficiency disorders. Innate immunity: components and mechanisms. - Innate immunity: o The body’s first line of defence against pathogens. o Non-specific and responds immediately to foreign substances. - Nonspecific cells o Phagocytes, natural killer (NK) cells (myeloid cells); no immunological memory. - Physical and chemical barriers: o Skin and mucus (pH), stomach acid ~pH2 o Antimicrobial secretions (lysozymes), lactoferrin, defensins, peroxidases) à directly block or lyse the bacteria. o Bronchial cilia à pushing foreign particles out of the body -> coughing. - Inflammation: stops spread of infection, promotes healing. o Four cardinal signs: redness, heat, swelling, pain. - Complement system: cascade of proteins. o Triggers inflammation. o Kills pathogens by cytolysis. o Tags cells for destruction. - Soluble recognition molecules o MBP (Mannose-binding lectin) o Acute phase proteins – from liver following infection. - Cell associated recognition. o PRR (Pattern recognition receptors) § regulate the innate immune response to infection. o PAMPs (pathogen-associated molecular patterns). o Cytokine receptor. Adaptive immunity: components and mechanisms - Adaptive immunity: o This is specific immune response that occurs after exposure to an antigen. o It is slower than innate immunity but has the advantage of memory. o Leads to a faster response upon re-exposure to the same antigen. o Highly specific cells: immunological memory, needs priming. o Clonal expansion: cells replicate. o Clonal deletion: cells die o] after immune response, some survive as memory cells. - Passive immunity o This involves the transfer of antibodies from one individual to another. o such as from mother to child during breastfeeding Adaptive immunity: antibody structure, function, and role. - IgG, IgM, IgA, IgD, IgE o ~12 domains, 2 heavy (H) and 2 light (L) chains. o Linked cysteine residues by disulphide bonds. o Flexible Y shape. o Has incredible specificity. o N-terminal domains (variable V) o C- terminal domains (constant C) o 5 H classes: M, G, A, E, D o V region has 6 hypervariable regions (3 per chain) o => antigen-binding site. o MW ~160,000, can form dimers, or pentamers. - Adaptive immunity: Humoral and Cell-mediated response - IgM initially responds while IgG concentrations develops later. - Antibody response is altered in the second exposure. o IgG increase to 2-10 times higher and develops much earlier. o Presence of memory lymphocytes following initial exposure. - Adaptive immunity: Cytokines - Immune cell communication to: o Divide o Di]erentiate o Secrete antibody etc. - Proteins, at least 30 knowns. - IFNg– imp macrophage activator - TNFa – imp in inflammation - Act via cytokine receptor binding. Adaptive immunity: Cytokines - Key chains - - Immune cascade: - A series of reactions that occur in the body in response to a foreign substance. - Involves the activation, recruitment, and action of various immune cells and molecules. o Cells like macrophages, T cells and B cells. o Signalling molecules like cytokines and chemokines. - Importance in health and disease. o Crucial for eliminating pathogens. o But can also contribute to inflammation and tissue damage if not properly regulated. Cells of the immune system: Leukocytes - Leukocytes (white blood cells) o Formed by haematopoiesis in bone marrow. § Starts with multipotent haemopoietic stem cells (SC) § Cells develop into myeloid/lymphoid progenitor cells. - Myeloid cells: contribute to innate response. o Neutrophils § phagocytes, granulocytes, polymorphonuclear cells (nucleus segmented into 3- 5 lobes). § stain light pink/reddish-purple. § most numerous leukocyte Cells of the immune system: Leukocytes - Myeloid cells: contribute to innate response: o Eosinophils § Phagocytes, granulocytes, polymorphonuclear cells (nucleus usually bilobed). § Stain pink with eosin. § Larger cells fight parasites. o Basophils § Nonphagocytic, granulocytes, polymorphonuclear cells (nucleus bilobed/segmented) § granules contain histamine, heparin. § Involved in inflammatory response o least numerous leukocytes. o Mast cells § Non-phagocytes, granulocytes. § Involved in inflammatory response, releases inflammatory mediators when damaged, or IgE antibody binging. § Inflammation increase vascular permeability, allows complement and WBC to enter tissues from blood. o Monocytes § Phagocytes, antigen presenting cells. § Release cytokines to recruit other cells. § Only circulate in blood. § Di]erentiate into macrophages/dendritic cells. o Dendritic cells § phagocytes, antigen presenting cells. § release cytokines to recruit other cells. § circulate in lymph, blood, tissue. § consumes large proteins in interstitial fluid. § break bloodborne pathogens into small amino acid chains --> move to lymph node --> present antigens to T cells. o Macrophages § phagocytes, antigen presenting cells. § release cytokines to recruit other cells. § stay in connective tissue, lymphoid organs. § not in blood Cells of the immune system: Leukocytes - Lymphoid cells: contribute to the adaptive response (except NK cells) o NK cells § contribute to innate response. § complete development in bone marrow. § large, contain granules. § primarily target infected, cancer cells. § kill target cells with cytotoxic granules (punch holes in target cell membranes by binding to phospholipids --> enter cell, trigger apoptosis, programmed cell death) o B cells § complete development in bone marrow. § bind to specific antigens (antigen presentation not needed). § capable of phagocytosis, antigen presentation. § Load antigens on major histocompatibility complex (MHC) II, display to T cells. § T-cell activation--> B cells mature into plasma cells; secrete lots of antibodies/ immunoglobulins (B cell receptors in secreted-form, mark pathogens for destruction --> "humoral immunity") o T cells § complete development in thymus. § responsible for cell-mediated immunity. § bind to specific antigens (antigen presentation needed). § naïve T cells primed by antigen presenting cells (usually dendritic cells). § Generally categorized into CD4+, CD8+ T cells o CD4+ (helper) T cells secrete cytokines to coordinate immune response, only see antigens on MHC II. § CD8+ (cytotoxic) T cells kill target cells, cells with antigens on MHC I Immune cascade: activation, recruitment, action Immune cascade: activation, recruitment, action - Phagocytes o Reach around pathogens with cytoplasm, swallowing whole (phagosome o Destroy some pathogens with cytoplasmic granules (phagosomes fuse with granules à phagolysosomes; pH in vesicles drops killing pathogens) o Continue to swallow pathogens before oxidative burst ----> produces highly reactive oxygen (e.g. H2O2; destroys proteins, nucleic acids, killing pathogens, phagocyte). - Immune system disorders Role of immune system in diseases: - An overactive immune system can lead to allergies and autoimmune diseases. o Immune system mistakenly attacks the body’s own tissues and cells. - An underactive immune system can result in immunodeficiency disorders. o Immune system is unable to function properly, o Leading to increase susceptibility to infections. o Transplant rejection. o Immunosuppression. Overactive immune system (hypersensitivity): allergies and autoimmune diseases Types of hypersensitivity: - I - Acute (allergic; anaphylactic; immediate; reaginic) o mediated by IgE together with mast cells (e.g. allergic rhinitis) - II – Antibody mediated (cytotoxic) o mediated by IgG or IgM together with complement or phagocytic cells (e.g. blood transfusion reactions) - III – Antigen-antibody complex mediated. o inflammation involving complement, polymorphs etc (e.g. Arthus reaction, serum sickness) - IV – Cell-mediated (delayed; tuberculin-type) o T-cell dependent recruitment of macrophages, eosinophils etc (e.g. chronic asthma) Overactive immune system (hypersensitivity): allergies and autoimmune diseases, drug-induced Type I Acute (allergic; anaphylactic; immediate; reaginic) - Allergens: o Often small MW proteins (insect enzymes, bee stings, peanuts) o Or molecules that bind to host proteins (penicillins) o dendritic cells (APCs), Th2 inflammation (IL4, IL13, IL5), IgE producing B cells. o atopic (raised IgE levels). o Mast cells, Basophils. o histamine, leukotrienes, prostaglandins (Immediate symptoms). o Eosinophils, Neutrophils, Lymphocytes recruitment (Late-phase reaction) - Allergic rhinitis medications: o Mediator eWect blockers § Oral or nasal antihistamines. § Leukotriene receptor antagonists (LTRA) Montelukast. o Mast cell stabilizers (preventative) § local chromone (cromoglycate) § intranasal CS o Inhibit degranulation and mediator release. § intranasal anticholinergics (ipratropium) o Immunotherapy - Allergic conjunctivitis medications o Mediator eWect blockers § Topical antihistamines o Mast cell stabilizers (preventative) § local chromone (cromoglycate) (preventative) § topical CS/ NSAIDs Type I Acute (allergic; anaphylactic; immediate; reaginic) - Asthma medications: o anti-inflammatory agents (Preventers) ICS, LTRA Montelukast, targeted biologic agents. o Plus, bronchodilators (relievers) SABAs, LABAs, SAMA/LAMA muscarinic antagonists - Anaphylaxis medications: o Adrenaline § Bronchodilator § Reduces oedema. § Heart muscle contractor.. Type II Antibody mediated (cytotoxic) - Immune complex excess - If not rapidly phagocytosed, induce serious inflammatory changes (skin, small BVs) via complement activation and enzyme release by polymorphs. - Mediated by IgG or IgM - E.g. blood transfusion reactions, rheumatic fever, stimulation of thyroid TSH receptor in thyrotoxicosis, many autoimmune diseases. Type III Antigen-antibody complex mediated. - Immune complex excess - If not rapidly phagocytosed, induce serious inflammatory changes (skin, small BVs) via complement activation and enzyme release by polymorphs. - III – inflammation involving complement, polymorphs etc. - E.g. Arthus reaction (injection), serum sickness, SLE, chromic glomerulonephritis. Type IV delayed, Chronic and cell-mediated inflammation. - Contact sensitivity (plant or chemical molecule) react with proteins in the skin. - Stimulate TH and Tc cell response, eczema – like reaction. - E.g. dermatitis. o episodic vs chronic – atopic or contact. o Mediators associated with skin inflammation, primarily Th1 (topical CS). o Th2 cells with IgE associated to urticaria (oral antihistamine) - Can occur in absence of any specific immune response. - Increase vascular permeability, activation of complement, T-cell dependent recruitment influx of polymorphs, lymphocytes and monocytes, eosinophils etc. - E.g. chromic asthma, Crohn’s disease, ulcerative. Auto-immune disease - Failure of self-tolerance, breakdown or be induced to fail. - Generics or result of infection. - Autoantibodies. - Autoreactive T cells. Immunodeficiency: Transplant rejection. - Donor – Recipient incompatible - MHC polymorphism. - T cells detect non-self MHC antigens. - Organ or blood. - T and B cells, complement, macrophages, antibody, type II, III or IV hypersensitivity. - Takes a weak or more. - Graft-versus-host (GVH_ reactions, bone marrow grafting. - Immunosuppression: non-specific, specific, Treg, antilymphocyte antisera (ALS). Immunodeficiency: Immunosuppression - Management of organ transplantation, severe hypersensitivity and autoimmunity. - Non-specific immunosuppression. - Interfere with specific T and B cells, without causing damage to other viral functions. - Deplete T cells – antilymphocyte antisera (ALS) o But normal response to infection depleted as well. - Inhibit cell division. - Non-specific e]ector inflammatory pathways.