Blood Physiology: Immunology Lecture Slides PDF

‫بسم الله الرحمن‬ ‫الرحيم‬ BLOOD PHYSIOLOGY L7,8,9: Introduction to Immunity Dr.ABDULRHMAN MUSTAFA MB,BS –MSc-MHPE, MHAE FAIMER FELLOWSHIP Crt  OBJECTIVES The student should be able to:  Discuss general overview of the immune system. ...

‫بسم الله الرحمن‬ ‫الرحيم‬ BLOOD PHYSIOLOGY L7,8,9: Introduction to Immunity Dr.ABDULRHMAN MUSTAFA MB,BS –MSc-MHPE, MHAE FAIMER FELLOWSHIP Crt  OBJECTIVES The student should be able to:  Discuss general overview of the immune system.  Differentiate between innate and adaptive immunity.  Identify the component of innate and adaptive immunity.  Define the term antigen, antibody and hapten.  Phases of immune response. 2  IMMUNITY Body’s ability to resist or eliminate potentially harmful foreign materials or abnormal cells. Immune system activities -Defends against invading pathogens. -Removes cells and tissue damaged by trauma. -Immune surveillance. Identifies and destroys abnormal or mutant cells that have originated in the body. Mounts inappropriate immune responses that lead either to allergies or to autoimmune diseases.  IMMUNITY Immunity Innate Adaptive Active Passive Cellular Humoral 4  INNATE IMMUNITY Innate/Non-specific/Natural Immunity: Nonspecific Responses work immediately when body is exposed to threatening agent Non-selective defend against foreign invaders First line of defense Rapid but limited responses Innate immunity Include: 1. Barriers Physical Chemical 2. Defensive cells WBCs Macrophages Natural killer cells (NK) 3. Chemical defenses Complement system 5  INNATE IMMUNITY Interferon: Are named after their ability to "interfere" with viral replication. α, β, and γ interferon. Released by virus infected cells. Function by blocking viral reproduction 6  INNATE IMMUNITY Complement system: Helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. Series of ~ 20 proteins. Activated by microorganisms -Coat the microorganisms -Adherence reactions -Biological active fragments Activate mast cells 7  ADAPTIVE IMMUNITY Adaptive or Acquired immunity Specifically targets foreign material to which body has already been exposed Body has taken time to prepare to attack Ultimate weapon against most pathogens Responses are mediated by B and T lymphocytes Formation of memory cells allows system to react more swiftly against specific invaders in the future Two types: 1. Active immunity 2. Passive immunity  ADAPTIVE IMMUNITY Two types: 1. Active immunity – direct encounter with the antigen. 2. Passive immunity – without encounter with the antigen  Antibodies transferred from mother to the fetus.  Immunization by injecting antibodies 9  ADAPTIVE IMMUNITY B AND T LYMPHOCYTES Mainly produced from lymphoid colonies in lymphoid tissues Lymphoid tissues Tissues that produce, store, or process lymphocytes Include Bone marrow Lymph nodes Spleen Thymus Tonsils Adenoids Appendix Peyer’s patches (GIT)  ADAPTIVE IMMUNITY Antigen – “any substance when introduced into the body stimulates the production of an antibody” Bacteria, fungus, parasite Viral particles Other foreign material Pathogen – an Antigen which causes disease. Hapten – is not antigenic by itself. When combines with protein it become an antigen 11  ADAPTIVE IMMUNITY Antibody – “a Y-shaped protein, found on the surface of B-Cells or free in the blood, that neutralize antigen by binding specifically to it” Also known as an Immunoglobulin Antige n 12 IMMUNITY  IMMUNE RESPONSE INNATE IMMUNITY ACQUIRED IMMUNITY Rapid responses to a Slower responses to broad range of microbes specific microbes External defenses Internal defenses Skin Phagocytic cells Humoral response Mucous membranes Antimicrobial proteins (antibodies) Secretions Inflammatory response Invading microbes Natural killer cells Cell-mediated response (pathogens) Complement (cytotoxic lymphocytes)  Inflammation and innate immunity Roles of Inflammation in innate immunity Initiation of phagocytosis – killing of pathogen Limiting the spread of infection Stimulate adaptive immune response Initiate tissue repair PHASES OF IMMUNE MECHANISM Initial phase/ antigen recognition phase Entry of antigen and its contact with the specific receptor on lymphocytic membrane. Central phase/ activation phase Cooperation among different subset of lymphocytes that proliferate and differentiate to form T & B lymphocyte + memory cells Effector phase/ elimination phase Inactivation of antigen by sensitized T & B lymphocytes Declining phase After eradication of the microorganism, the activated cells died and small proportion remain as memory cells 16  References Human physiology by Lauralee Sherwood, 9th edition Text Book Of Physiology by Guyton & Hall, 12th edition Review of Medical Physiology by Ganong, 24th edition  ‫بسم الله الرحمن‬ ‫الرحيم‬ BLOOD PHYSIOLOGY L8: B LYMPHOCYTES Antibody Mediated Immunity Dr.ABDULRHMAN MUSTAFA MB,BS –MSc-MHPE, MHAE FAIMER FELLOWSHIP Crt  OBJECTIVES The student should be able to:  Explain the concept of humoral(antibody mediated ) immunity. Describe mechanism of action of antibodies Emphasis the importance of memory cell ( primary and secondary response) 19  Immunity Innate Acquired Active Passive Cellular Humoral 20  Adaptive Immunity TWO classes of adaptive immunity Antibody-mediated or humoral immunity Involves production of antibodies by B lymphocyte derivatives known as plasma cells Cell-mediated immunity Involves production of activated T lymphocytes Directly attack unwanted cells  T-Dependent and T-independent Antigens T-independent antigens: after binding with polysaccharide antigen, B cells are activated without assistance from T- helper cells T-dependent antigens: polypeptide antigen cannot stimulate B cells without the help of T- helper cells The majority of antigens to which B cell respond are T-dependent  T-Dependent and T-independent Antigens On binding with processed and presented antigen Most B cells differentiate into active plasma cells Other B cells become dormant memory cells A mature plasma cell then produces antibodies rapidly (2000 antibodies/sec) All antibodies eventually enter blood where they are known as gamma globulins or immunoglobulins  T-Dependent and T-independent Antigens Antibody (Immunoglobulin) subclasses IgM Serves as the B cell surface receptor for antigen attachment Secreted in early stages of plasma cell response IgG Most abundant immunoglobulin in blood Produced in large amounts when body is exposed to same antigen IgE Helps protect against parasitic worms Antibody mediator for common allergic responses IgA Found in secretions of digestive, respiratory, and genitourinary systems; also in milk and tears IgD Present on surface of many B cells Function is uncertain  The Antibodies Y-shaped molecules Composed of 4 interlinked polypeptide chains Two long, heavy chains Two short, light chains Properties of tail portion determine functional properties of the antibody( what it will do after binding with antigen)  Mechanism of Action of Antibodies Can physically hinder antigens By neutralization, they prevent harmful chemicals from interacting with susceptible cells Can bind to foreign cells by agglutination Pregnancy diagnosis tests uses this principle to detect hCG hormone in urine after conception Enhance activity of other defense systems by Activating complement system Enhancing phagocytosis Stimulating natural killer (K) cells Mechanism of Action of Antibodies Mechanism of Action of Antibodies  Primary and Secondary Response Memory cells Small percentage of B lymphocytes become memory cells Remain dormant Upon re exposure to same antigen, they are more ready for immediate action than the original lymphocytes of the clone Secondary response is quicker, more potent, and longer-lasting Can be induced by disease or vaccination Formation of memory cell can occurs through the person either actually having disease or being vaccinated Primary and Secondary Response  Active and Passive Immunity Active immunity “self-generated” Results from exposure to an antigen Passive immunity “borrowed immunity” Results from transfer of preformed antibodies Can provide immediate protection Example of passive immunity is transfer of IgG antibodies from mother to fetus Tetanus toxins, anti snake venom, rabies virus IMMUNITY  References Human physiology by Lauralee Sherwood, 9th edition Text Book Of Physiology by Guyton & Hall, 12th edition Review of Medical Physiology by Ganong, 24th edition  ‫بسم الله الرحمن الرحيم‬ BLOOD PHYSIOLOGY L9: T LYMPHOCYTES Cell- Mediated Immunity Dr.ABDULRHMAN MUSTAFA MB,BS –MSc-MHPE, MHAE FAIMER FELLOWSHIP Crt  Immunity Innate Acquired Active Passive Cellular Humoral 35  T (thymic) Lymphocytes development &maturation Lymphocytes precursors migrate from bone marrow to the thymus for processing to form “T” lymphocytes Processing in the thymus : Cells divide rapidly - Each cell develops specific reactivity for one antigen  End result: thousands of T lymphocytes each with different specific reactivities for different antigens Insures that each T lymphocyte will not react with the body’s own antigens (self antigen) Then the processed cells leave thymus to lymphoid tissues Most processing of T lymphocytes occurs prior to birth and completed after birth  T Lymphocytes function Carry out cell-mediated immunity They kill infected cell/ cancer cell/ any foreign cell. Mature T-cells have T cell receptors which are specific to one antigen.  T Lymphocytes Types -Cytotoxic, or killer T cells Destroy host cells harboring antigen -Mostly helper T cells Modulate activities of other immune cells Secrete chemicals that amplify the activity of other immune cells Β-cell growth factor T-cell growth factor (interleukin 2) Macrophage-migration inhibition factor -Suppressor T Cells -Memory T Cells  Cytotoxic T Cells When exposed to infected/dysfunctional somatic cells, TC cells release the cytotoxins perforin, granzymes, and granulysin. Through the action of perforin, granzymes enter the cytoplasm of the target cell and eventually lead to apoptosis (programmed cell death)  Types of T Lymphocytes: Helper T cells Most numerous Secretes lymphokines (IL-2, 3, 4, 5, 6) Regulatory functions of lymphokines: Stimulation of B cell growth and differentiation Activation of the macrophage system Positive feedback effect on the helper cells They help in the functioning of Cytotoxic T – cells. HIV virus destroys these cells & hence both the types of immunity are lost.  Suppressor T Cells Capable of suppressing actions of cytotoxic and helper T cells Prevent excessive damage to the body tissue – Immune tolerance Known as regulatory T cells  Antigen Presentation T-Lymphocytes respond only to antigens presented to them by antigen-presenting cells Antigen-presenting cells: Macrophage, dendritic cell, Blymphocytes, somatic cells. Steps of antigen presentation antigen presenting cell engulfs and ingests microbe, it digests the microbe into antigenic peptides Antigenic peptides bind to a MHC molecule which transports the bound antigen to the cell surface where it is presented to lymphocytes Antigen-presenting cell secretes interleukins Enhances differentiation and proliferation of now-activated T-cell clone  Self-antigens ( major histocompatibility complex/MHC) Plasma membrane-bound glycoproteins called MHC molecules Synthesis is directed by group of genes called major histocompatibility complex (MHC) genes. Exact pattern of MHC molecules varies from one individual to another ( BIOCHEMIAL FINGER PRINTS/ “MOLECULAR IDENTIFICATION CARDS). FUNCTIONS: - Directing response of T-lymphocytes - Rejection of transplanted tissue  Immune System Tolerance of Self-Antigens Tolerance refers to preventing the immune system from attacking the person’s own tissues Mechanisms involved in tolerance Clonal deletion Clonal anergy: in which specific lymphocytes are present but functionally inactive Inhibition by regulatory T cells Immunological ignorance: lymphocytes could remain in resting status after exposure to the antigen. Immune privilege: Sites with immune privilege are anatomical regions that are naturally less subject to immune responses than most other areas of the body. Immune- privileged sites include the central nervous system, the eyes and the testes. Even foreign antigens accessing these tissues do not generally trigger immune responses.  Immune Diseases Due to abnormal functioning of the immune system 2 general ways Immunodeficiency diseases Too little immune response Examples severe combined immunodeficiency AIDS Inappropriate immune attacks Too much or mistargeted immune response Categories of inappropriate attacks Autoimmune responses Immune complex diseases Allergies  Autoimmune Diseases Arise from loss of tolerance to self-antigens e.g. multiple sclerosis, rheumatoid arthritis, myasthenia gravis Some Causes : Normal self-antigens may be modified by factors such as drugs, environmental chemicals, viruses, or genetic mutations so that they are no longer recognized and tolerated by the immune system. Exposure of the immune system to a foreign antigen structurally identical to a self-antigen  Hypersensitivity When an immune reaction results in considerable damage to the body its called hypersensitivity. Four types Type I hypersensitivity (Anaphylaxis) Type II hypersensitivity (antibody mediated cytotoxicity) Type III hypersensitivity (immune complex disorder) Type IV hypersensitivity (delayed type of hypersensitivity)  Type I hypersensitivity (Anaphylaxis) Mast cell degranulation Ig E response eg. Allergic rhinitis Eczema Acute urticaria Occurs within minutes Mediators Histamine Slow reacting substance of anaphylaxis (SRS-A) Its called Atopy  VACCINE Vaccine (vaccinus – pertaining to cows) By Edward Jenner for small pox. Act on the principle of “mock” infection Types of Vaccines Live, Attenuated Vaccines Inactivated Vaccines Subunit Vaccines Toxoid Vaccines Live, attenuated vaccines - Measles, mumps, rubella, polio Inactivated or killed vaccines- Cholera, flu, hepatitis A Toxoid vaccine - Diphtheria, tetanus Mump s measle s ‫النكا‬ ‫الحصب‬ ‫ف‬ ‫ة‬ Tuberculosis ‫مرض‬ ‫السل‬ Diphther Tetanus ia ‫الكزاز‬ ‫الخناق‬ Polio ‫شلل‬ ‫األطفال‬ Hepatitis ‫التهاب‬ ‫الكبد‬ IMMUNITY  References Human physiology by Lauralee Sherwood, 9th edition Text Book Of Physiology by Guyton & Hall, 12th edition Review of Medical Physiology by Ganong, 24th edition