Lecture 7 Immunology

Transcription

1 Slide 1 Lecture 7 Immunology Structure Components Leukocytes Lymphoid tissue Recognition of self Innate Immunity Physical and chemical barriers Phagocytosis Inflammation Adaptive immunity Humoral responses (B cells) Cell mediated responses (T cells) Immune Disorders Autoimmune diseases AIDS Learning Outcomes 1. List the principal lymphoid tissues and outline their roles 2. List the differences between innate and adaptive immunity 3. Outline some key processes of innate immunity 4. Explain some key features of adaptive immunity 5. Explain the pathophysiology of some immune disorders. Dr Alan Tuffery Physiology Medical Science 7 1 Slide 2 Role of the Immune System (IS) A network of cells and tissues that: 1. Defends the body against invading pathogens 2. Removes worn-out cells 3. Destroys abnormal/mutant cells within the body (e.g. control of cancer) Immune System can also have harmful effects: 1. Allergies / autoimmune diseases 2. Tissue rejection. Dr Alan Tuffery Physiology Medical Science 7 2 1

2 Slide 3 Infection-causing organisms (Pathogens) FUNGUS Epidermophyton floccosum (athlete s foot) BACTERIA Staphylococcus aureus (causes sepsis) VIRUS PARASITE Tapeworm Dr Alan Tuffery Physiology Polio Medical Science 7 3 Slide 4 Components White Blood Cells Lymphocyte Monocyte/macrophage B cells - secrete antibodies T cells - directly destroy foreign cells Natural Killer cells - fight Phagocytosis Secrete cytokines (signalling molecules other than antibodies). viruses Dr Alan Tuffery Physiology Medical Science 7 4 2

3 Slide 5 Components Lymphoid Tissues CENTRAL LYMPHATIC TISSUES Bone marrow - site of B cell development (and pre- T cell) Thymus site of T cell development PERIPHERAL LYMPHATIC TISSUES Spleen Lymph nodes Gut-associated lymphatic tissue (GALT) [Peyer s Patches] Adenoids Appendix Tonsils. Dr Alan Tuffery Physiology Medical Science 7 5 Slide 6 Components self-recognition Major Histocompatibilty Complex MHC on every (nucleated) cell Also known as human leukocyte associated antigens (HLA) Normally the body s immune system does not attack cells that carry this self marker i.e. MHC No two individuals, except identical twins, will ever share identical MHC. Transplant rejection Organ transplants and skin grafts may be rejected due to presence of MHC To minimise rejection, the MHC of donor and recipient are matched as closely as possible i.e. tissue typing Siblings usually provide the closest match MHC do not play a role in transfusion reactions because red blood cells do not have MHC. Dr Alan Tuffery Physiology Medical Science 7 6 3

4 Slide 7 Organisation of the Immune System IMMUNE SYSTEM INNATE IMMUNITY (non-specific; natural) ADAPTIVE IMMUNITY (specific; acquired) Skin & mucous membranes Phagocytosis Inflammation HUMORAL-MEDIATED (antibody mediated) B cells CELL-MEDIATED T cells Dr Alan Tuffery Physiology Medical Science 7 7 Slide 8 Innate vs Adaptive Immunity Innate (Phagocytosis, Inflammation) Nonspecific Defends against any pathogen upon first exposure Responds to infectious agents, chemical irritants, tissue injury, burns Adaptive (Lymphocytes) Specific Responds to specific pathogens on 2nd or later exposure Comes into play after nonspecific responses have begun. Dr Alan Tuffery Physiology Medical Science 7 8 4

5 Slide 9 Innate Immunity Initial & immediate response against invasion by a variety of pathogens The response is rapid and non-specific Main mechanisms 1. Interferon, NK cells and complement system 2. Phagocytosis (by neutrophils & macrophages) 3. Inflammation. Dr Alan Tuffery Physiology Medical Science 7 9 Slide 10 Innate 1. Interferon, Natural Killer Cells Interferon Released by virusattacked cells Protects other cells from any virus Anti-cancer effects Slows cell division Enhances action of NK cells and cytotoxic T cells (qv) Natural Killer cells Attack virusinfected cells Cause lysis NB Both IF and NK cells are non-specific any virus. Dr Alan Tuffery Physiology Medical Science

6 Slide 11 Innate 1. Complement System Many very complex actions Innate response is recognition of microorganisms Lysis of invading micro-organisms Also reinforces other inflammatory responses [hence name!]. Dr Alan Tuffery Physiology Slide 12 Medical Science 7 11 Innate 2. Phagocytosis SEM macrophage engulfing bacteria Stages of Phagocytosis 1. Attachment 2. Internalisation (0.1 s) 3. Degradation 4. Exocytosis. S&G Dr Alan Tuffery Physiology Medical Science

7 Slide 13 Innate 3. Inflammatory Response 1. Bacteria enter tissue/damage 2. Release of histamine Increased blood flow Increased vascular permeability 3. Increased leucocytes at site Results Destroy or inactivate invaders - Remove débris - Prepare for healing & repair. Animation of allergic (atopic) response Atopic_Dermatitis Dr Alan Tuffery Physiology Medical Science 7 13 Slide 14 Adaptive Immunity 1. Specificity Lymphocytes (B and T cells) bind and respond to foreign molecules known as antigens via antigen receptors 1. Diversity The body possesses millions of lymphocytes that can recognise and respond to millions of antigens (one each) Memory 1 st exposure to an antigen generates lymphocytes & long-lived memory cells next exposure to the same antigen, memory cells react more quickly & stronger response Self-Tolerance Lymphocytes can distinguish self (our normal antigens) from non-self (antigens from foreign material). Dr Alan Tuffery Physiology Medical Science

8 Slide 15 Adaptive Immunity humoral (antibody-mediated) 1. B Cells Clonal Selection Antigen fits B cell s receptors Proliferation and differentiation into S&G 23.7 (see Sherwood 12-11) 1. Plasma cells Produce antibodies in blood (immunoglobulins I g G, I g M, I g E, I g A, I g D) Short-lived 2. Memory cells (clone) With same receptor Long-lived. Dr Alan Tuffery Physiology Medical Science 7 15 Slide 16 Adaptive Cell-mediated Immunity T cells must become activated before they can attack pathogens The antigen is presented to the T cell by an ANTIGEN PRESENTING CELL (e.g. an infected macrophage) via its MHC Dr Alan Tuffery Physiology Medical Science

9 Slide 17 Activated T cell enlarges & divides into: CYTOTOXIC T CELLS kill infected cells by lysis (direct action) HELPER T CELLS (~70% of T cells) secrete cytokines that enhance the activity of cytotoxic T cells; enhance phagocytosis stimulate development of B cells into plasma cells (indirect action) SUPPRESSOR T CELLS secrete cytokines that suppress the activity of B cells, helper T cells and cytotoxic T cells; inhibit phagocytosis. Dr Alan Tuffery Physiology Medical Science 7 17 Slide 18 Adaptive Immunity can be NATURAL or ARTIFICIAL Adaptive Immunity Natural Artificial ACTIVE Antibodies or lymphocytes are produced as a result of infection PASSIVE Antibodies are passed to foetus via placenta or colostrum ACTIVE Antibodies are produced as a result of immunisation with a vaccine PASSIVE Antibodies that have been produced by another animal or given artificially. Dr Alan Tuffery Physiology Medical Science

10 Slide 19 Immune Disorders Autoimmune Diseases If immune system does not recognise its self (e.g. MHC), it reacts against normal cells and tissues DISEASE Systemic lupus erythematosus (SLE) SYMPTOMS fever, arthritis, mouth ulcers, Rheumatoid arthritis (RA) Multiple sclerosis (MS) (p116) inflammation and damage to the cartilage and bone of joints T cells attack myelin: Blurred vision, Muscle weakness, Ataxia Dr Alan Tuffery Physiology Medical Science 7 19 Slide 20 Immune Disorders - AIDS AIDS is caused by Human Immunodeficiency Virus (HIV) HIV binds to the surface of helper T cells and its nucleic acids (RNA and DNA) enter the T cell Inside the cell, HIV uses the cell to make copies of itself HIV slowly destroys helper T cells in the body (Helper T cells = 70% of all T cells) When T cell function is impaired, immune responses weaken and other diseases develop. Dr Alan Tuffery Physiology Medical Science

11 Slide 21 Immune Disorders - AIDS SYMPTOMS HIV AIDS Fatigue, fever, swollen glands, headache Swollen lymph nodes, decreased T cell count; Susceptibility to pneumonia and Kaposi sarcoma; AIDS dementia TRANSMISSION Through blood, semen, vaginal secretions and breast milk. Dr Alan Tuffery Physiology Medical Science 7 21 Slide 22 Learning Outcomes 1. List the principal lymphoid tissues and outline their roles Thymus (T cell dev.); Gut B cells) 2. List the differences between innate and adaptive immunity Specificity, 1st exposure, cell-mediated, speed 3. Outline some key processes of innate immunity phagocytosis, inflammation, immune memory, self recognition) 4. Explain some key features of adaptive immunity 5. Explain the pathophysiology of some immune disorders. Dr Alan Tuffery Physiology Medical Science