ALSHAWABKEH INTRO L10 PDF - Introduction to Immunology

Introduction to medicine {L10} ‫م‬ SHAWABKEH ‫ب‬ ‫ل‬‫ا‬...

Introduction to medicine {L10} ‫م‬ SHAWABKEH ‫ب‬ ‫ل‬‫ا‬ ‫مد شوا كة‬‫ح‬ Introduction to Immunology ❖ Introduction - Immunology: the study of immune system & defense mechanisms of the body. - Infectious diseases: ➔ Diseases that are caused by pathogenic microorganisms (microbes) ➔ The probability to acquire an infectious disease can be anticipated by the formula: Infectious Dose (MO) x Virulence (V) / Host defenses Infectious dose: number of MOs that enter the host body. Virulence: the ability of MO to cause a disease. Host defenses: the immune system. - Immunocompetent: The host has a good immune system that can defend it from the invading pathogens. - Immunocompromised: The host is weakened so it cannot defend the host’s body from the invading pathogens. ❖ Properties of the immune system 1 Diversity The immune system protects the body against a broad spectrum of pathogens. This is related to the genes that we inherit from his parents, the more diverse the genes, the stronger the immune system. Non-relative marriage → stronger immune system in the offspring. 2 Specificity Related to the Adaptive immune system. Ability to recognizes and deals with one pathogen specifically at a time. 3 Memory Related to the Adaptive immune system. It to remember and recognize pathogens that invaded the body previously and neutralize them in an easier and faster way. Vaccines is example of memory. 4 Recognize self from non-self The immune system to know which cells belong to the host’s body (self) and which cells do not belong to it (non-self). When immune cells turn to destroy our (self) tissues, resulting in what we call an autoimmune disease. 5 Production of effector cells Cells are produced by the immune system to kill or eliminate the invading pathogens by producing antibodies or engulf invading pathogens to kill them History of Immunology In 430 BC, Thucydides a Greek scientist - Noticed that when somebody is infected with plague and get recovered, he/she doesn’t get it again for the second time usually. in the 15th century, when Chinese and - Noticed that anyone who was infected and recovered from smallpox won’t get smallpox again. Turks In 1798, Edward Jenner, an English - Noticed that people who work in dairy and milk cows are used to get a disease called cowpox, which is a doctor mild disease that doesn’t kill usually, but the interesting thing he found is that these people who get the cowpox virus do not get the smallpox virus. - Which is more severe than the cowpox virus. - He started thinking about getting the cowpox virus from the vesicles it does on cows then inject it in healthy people, so they do not get the more severe smallpox virus. - This process of injecting activated or weakened viruses into humans was the beginning of the modern process of what is called vaccination. - Edward Jenner is known to be the father of immunology. vaccination from the Latin word Vacca, which means cow In 1881, Louis Pasteur, a French - Was working on a disease called fowl cholera that causes diarrhea in chicken. He found when he took the chemist causative organism from the infected chicken and heat it up then re- introduce it to a healthy chicken that the healthy chicken won’t get fowl cholera disease. - In 1885, Louis Pasteur made the first rabies vaccine and tested it on Joseph Meister for the first time successfully. - Discovery of anthrax vaccine on sheep. In 1830, Eli Metchnikoff, a Russian - Noticed while he was looking in a blood film a cell that engulfs another bacterial cell, and he named this zoologist process of engulfment as phagocytosis. In 20 century, Karl Landsteiner, an - Was the first to discover the blood groups by taking blood samples from people and separating the blood Austrian immunologist cells from the plasma and mixing each blood cell sample with plasma from a different sample. - He noticed that some of the mixing processes caused agglutination (clumping of particles) of the red blood cells while some didn’t. - Based on that he discovered the ABO blood group system. - Known as the father of blood transfusion. In 1950, Bruce Glick - Was the first to discover two important immune cells. - B cells that were first seen in chickens in an organ called bursa of Fabricius, which is the site of hematopoiesis in chickens. - T cells that were first seen in the thymus gland. (He also discovered a disease called Brucella). In 20 century The main two theories discussing the mechanism of development of the immune system: The clonal selection theory: The instructional theory: Each type of B and T cells has a unique antigen receptor, and it has to meet its postulated that antigens play a central role in antigenic counterpart to be activated. determining antibody specificity Once the lymphocyte encounters its antigenic counterpart, it is selected to It states that antigens encounter antibody proliferate and give “Clones” templates. then antibody templates would wrap This proliferation is called clonal expansion around the antigen, forming a complementary molecule. Scientists discovered that this theory isn’t true because it didn’t explain how the body recognizes self from non-self.  ❖ Primary & Secondary immune response: Primary immune response: Secondary immune response: - Is the reaction of the immune system when it contacts an antigen for the - Is the reaction of the immune system when it contacts an antigen for the first time. second and subsequent times. - The response is slow (7-10 days) & low because no memory cells are - The response is stronger & faster, because we have memory cells. there. - After the end of this response, there will be memory cells & antibodies - No memory cells and no specificity to one pathogen alone. - The physical barriers to primary infection, like skin, Innate mucus membranes, and so on. system - Phagocytosis. - The complement system (general protection). ❖ Branches of immune system - has memory cells, has the specificity to pathogens Adaptive - Includes T & B lymphocytes (including Ab) system - It works by antigen recognition molecules “B cell receptors (antibodies)” & “T cell receptors”. Immunology achievements process has failed in the immune system Development of vaccines by taking the invading microbe and weaken Autoimmunity do not recognize self-cell from non-self-cell him by heat or chemicals OR by taking the attachment proteins of this So it will destroy our tissue. microbe and administer them to people. Immunity to microbes Immunodeficiency no enough number of immune cells or malfunctioning. Organ transplantation Allergies excessive response from our immune system to a stimulus toward innocent antigen (Hypersensitivity) Treat hereditary defects in the immune system, treat allergies, treat autoimmune diseases Making antibodies in the lab (monoclonal antibodies) Treatment of cancer ❖ Case about hapatitis - Any patient who enters the hospital is considered to have hepatitis until proven otherwise - It’s recommended for medical students to take vaccinations for hepatitis virus before they enter clinical years. ❖ Transmission of infections (i.e. Viruses) by small droplets Prevented by continuous handwashing, and the use of face masks and tissues to prevent the spread of the air droplets. ❖ Organ transplant i.e. Kidney transplant - This is patient who has kidney failure - The patient must frequently do what is called hemodialysis to filter his blood from wastes - Kidney transplantation can help him  hygienically poor water source, since this water is contaminated with microbes that can infect infants and may lead to death. "Anything that does not kill you make you stronger." Note: Advancement in the field of immunology (i.e. Vaccines) results in huge reduction of infection deaths. Note: Most common killer protozoa worldwide are plasmodium (malaria). The innate immune system(non adaptive ) o The branch of immune system that deals nonspecifically with the invading microbes in a fast manner. o Is interconnected with the adaptive immune system in a way that the innate immune system sends signals to the adaptive immune system to be activated when an infection happens. o composed of: 1- Skin and mucus membranes (physical barriers). 2- Phagocytic white blood cells, like neutrophils and macrophages. 3- NK (natural killer) cells. 4- Complement system 5- mannan-binding lectin 6- Interferons divide to alpha, beta, gamma provide protection against virus 7- Inflammatory mediators. o oxidative burst reactions : phagocytic cells (green) that have granules within it, and these granules contain enzymes or substances , that kill any microorganism engulfed by these phagocytic cells. o Neutropenia : abnormally low in number of neutrophils →causes immunocompromised. o Neutrophilia : increasing the number of neutrophils. o phagocytic cell (red and pink) and bacteria cells (yellow) attached to the phagocytic cell’s surface. o Notice that for the phagocytic cell to engulf a bacteria cell, it must first bind to the surface of the phagocytic cell, then it will be engulfed by the phagocytic cell for further digestion and destruction of this invading microorganism. o Some phagocytic cells, like neutrophils, may die during this process and turn into what is called pus cells, while other phagocytic cells like monocytes and macrophages do not die during this process. The adaptive immune system (acquired immune) o The branch that deals with microorganisms specifically, has memory that recognize the self from non-self-cells. o But, unlike the innate one, is slower in responding to invading microbes it takes 7 to 10 days to make response. o Is influenced by the genetic diversity a person inherits from his parents, the more diverse genes a person inherits, the stronger his adaptive immune system. o It’s also influenced by the number of somatic mutations that will result in much more diversity of immune receptors. o composed of: 1- T and B lymphocytes. 2- Cytokines (chemical substances that mediate signals between lymphoid cells, to share signals). 3- Antigens (substances that can induce an immune response). 4- Antigen recognition molecules, like T cell receptors, and immunoglobulins (aka antibodies or B cell receptors) which are clonally selected 5- Antigenic determinants (epitopes) which is the most specific part of an antigen that has a receptor either on B or T cells. 6- B & T cell receptors. B cell make antibody come from bone marrow 7- Major histocompatibility (MHC) antigens. 8- Modification of self-antigen 9- Deletion or inactivation of self-receptors. o Some of the viruses are so evasive, like influenza virus, which has a huge protein diversity that allows him to change the attachment proteins (called agglutinins) on its surface continuously. o T cell originate in bone marrow but go to thymus gland and develop to cytotoxic T cells and helper T cell (CD4+) - Lymphoid organs are categorized: Primary lymphoid organs: i.e.bone marrow, thymus gland Secondary lymphoid organs: i.e. spleen, lymph nodes , mucosa associated lymphoid tissues (MALT) ❖ Humoral vs Cell-mediated immunity : - humoral immune response: is mediated by antibody molecules that are secreted by plasma cells. - Cell-mediated immunity: is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. The innate immune system, which is considered the first line of defense, includes the physical barriers, the antigen presenting cells (APCs) like macrophages, and the complement system. The adaptive immune system, which is considered the second line of defense and the specific one, includes B lymphocytes that secrete specific immunoglobulins, and T lymphocytes that are specialized in the cell-mediated immunity. - We cannot get interferons of animal and use them on humans.  ❖ Genetic difference between innate and adaptive immune systems: - Innate system genes are fewer. - Innate system receptors are not specific, and are called pattern recognition molecules. - Adaptive systems genes are many. - Adaptive system receptors are specific, and are called Antigen recognition molecules (i.e. TCR, BCR, MHC). ❖ Phases of Adaptive immune response cognitive phase activation phase Effector phase ❖ Types of immune response ❖ Active immunity Vs Passive Immunity: Active immunity: our immune system makes an active response Can be: natural (i.e. due to infection), or artificial (i.e. vaccine). Passive immunity: the body received already formed Ab Can be: natural (i.e. through placenta, or milk), or artificial (i.e. monoclonal Ab).  ❖ The cells of the innate immune system 1- Neutrophils: cells of segmented nuclei (usually three segments), a cytoplasm filled with granules that digest bacteria within it and have short half-life 24 hours. 2- Eosinophils: appear in worm infections or hypersensitivity reactions, effective in killing parasites, also contain granules that stain pink in H&E staining, and a segmented nucleus (most with two segments). 3- Macrophages: effective in antigen presentation for B cells to activate them. It aids in phagocytosis and bactericidal mechanisms (cidal =kill). When macrophages are activated, they are called giant cells. 4- Mast cells: aid in release of histamine and other inflammatory mediators in type 1 hypersensitivity reaction. 5- Natural killer cells: it looks like a lymphocyte, but it isn’t. It isn’t a phagocytic cell, but it rather kills the viral-infected cells and tumor cells. ❖ antigen presenting cells: - which are the dendritic cells, macrophages, and B cells. ❖ Difference between B cells and T cells in the way of antigen recognition. - T cells (development in thumus)can’t recognize antigen unless it’s presented on Antigen presenting cell (APC) bound to MHC. MCH 1 → CD8+ MCH 2 → CD4+ - B cell (development in bone marrow) can directly recognize the Antigen. ❖ Antibody type : (MAGED): Ig Function IgM primary response, (strongest) IgA Mucosal immunity Has secretory piece Abundant in saliva and breast milk PRIMARY IMMUNE RESPONSE →IgM IgG Binds strongly to mast cells and most prevalent antibody molecule in appear first serum SECONDARY IMMUNE RESPONSE→IgG IgE evolved to protect against parasitic infections appear first IgD On surface of B-cell antigen receptor (BCR) ❖ The morphology of the adaptive immune system cells under the microscope - B cells, CD4+ T cells CD8+ T cells, have the same appearance under the microscope when they are inactivated, but their morphology changes after activation. ❖ The effect of multiple doses in hepatitis B vaccination - First dose : Primary immune response is slow and low - Second dose : Secondary immune response is faster and higher number of antibodies will be produced, and eventually, more memory cells will develop. - Third dose : a very high number of antibodies will be produced that will reach to the protective level of antibodies against hepatitis B virus. - why don't we give a 4th and 5th dose? The answer is there will be desensitization due to excessive antigen. - desensitization is used to treat allergies.