por TAREQ ALS'AIDI 3 dias atrás
19
Immunology
The immune system is an intricate network responsible for defending the body against various pathogens, including viruses, bacteria, and fungi. It is divided into two main responses:
por TAREQ ALS'AIDI 3 dias atrás
19
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patient who enters the hospital is considered to have hepatitis until proven otherwise
➢ As we know, 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.
➢ While 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
- Because the innate immune system defends nonspecifically against microorganisms, it doesn’t need many genes to be expressed, so with time, the ancestral gene didn’t have any major changes while it was changing to the modern gene, so, not that much of proteins will be needed for the innate immune system to do well.
- While in the case of adaptive immune system (the specialized branch), the ancestral gene went through many gene duplications and specializations, so that the modern genes of the adaptive immune system code for much diverse proteins that are needed for the adaptive immune system to do it’s job
- There are three phases that a B cell goes through when it reacts with an antigen:
1) The cognitive phase: which happens when the B cell recognizes an antigen and binds it.
2) The activation phase: this B cell will undergo proliferation, forming B cells with matching receptors.
3) Effector phase: eventually, the proliferating B cells will differentiate to plasma cells, which will secrete antibodies that will neutralize the antigen.
is an immune response that does not involve antibodies , Rather , cell-mediated immunity is the activation of phagocytes , antigen-specific cytotoxic T-lymphocytes and the release of various cytokines in response to an antigen
is mediated by antibody molecules that are secreted by plasma cells
in passive immunity the host receives antibodies that were produced from the immune system of
another host , like the passive rabies immunization.
The active immunity occurs when the host’s own immune system responds directly to an antigen and produce its antibodies against it, like when we give a vaccine to a person, his immune system will respond to the vaccine by producing antibodies
like using BCG vaccine that is used to vaccinate against tuberculosis in treating urinary bladder tumor
and a further understanding of why some organs have more success percentage (cornea for example) than other organs (like bone marrow for example).
by either taking the invading microbe and weaken him by heat or chemicals, or by taking the attachment proteins of this microbe and administer them to people.
But what if any process has failed in the immune system? This will lead to:
➢ Autoimmunity: When our immunity do not recognize self-cell from non-self-cell So it will destroy our tissue.
➢ Immunodeficiency: when there is no enough number of immune cells or malfunctioning immune cells.
➢ Allergies (Hypersensitivity): when there is excessive response from our immune system to a stimulus.
Also, we will understand how to make antibodies in the laboratory
If we understand the physiology of our immune system, then we will understand the process of transplantation successfully.
We give patient part of weakened bacteria as an example to remember them when this organism enters the body in the second time
➢ As we explained before, the adaptive immune system is the branch that deals with microorganisms specifically, has memory cells that recognize the pathogens that have invaded the body recently, and can recognize the self from non-self-cells.
➢ but this immune response, unlike the innate one, is slower in responding to invading microbes it takes week to ten days to make response.
➢ This branch of the immune system 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 is.
➢ it is also influenced by the number of somatic mutations that will result in much more diversity of immune receptors.
❖ The adaptive immune response includes:
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 as we took previously.
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 and deletion or inactivation of self-receptors.
➢ 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.
➢ T cell originate in bone marrow but go to thymus gland and develop to cytotoxic T cells and helper T cell (CD4+)
- Primary lymphoid organ = bone marrow
- Secondary lymphoid organs =spleen, lymph nodes, mucosa associated lymphoid organs
has memory cells, has the specificity to pathogens, and this is the branch that differentiates between self and non-self.
- This branch work by secretion of what is called antigen recognition molecules (B cell receptors/ antibodies) and T cell receptors.
- When antibody and T cell receptor (antigen recognition molecules) bind to protein on the surface of virus. So, virus will not bind to specific tissue.
- We called it neutralized and these molecules do what is called clonal selection.
➢ The innate (non-adaptive) immune system is -as explained beforethe branch of immune system that deals nonspecifically with the invading microbes in a quick manner.
➢ The innate immune system 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.
❖ The innate immune system is 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 and its components (mannan-binding lectin, for example).
5- Interferons divide to alpha, beta, gamma provide protection against virus ...
6- Inflammatory mediators.
This is the natural one that we are born with. In this branch, there are no memory cells and no specificity to one pathogen alone. This branch includes:
- The physical barriers to primary infection, like skin, mucus membranes, and so on.
- Phagocytosis.
- The complement system (general protection).
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
Mast cell
aid in release of histamine and other inflammatory mediators in type 1 hypersensitivity reaction
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.
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)
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.
is the reaction of the immune system when it contacts an antigen for the second and subsequent times
is the reaction of the immune system when it contacts an antigen for the first time
➢ This theory is the accepted explanation nowadays. It assumes that there are certain cells dedicated to making antibodies, each cell makes a single kind of antibodies with its own unique antigen specificity and displays a copy of the antibody it makes on its cell surface, and that this is where antibody diversity is generated, stored and expressed.
➢ The antibodies each cell makes is determined randomly, completely independent of the antigenic universe, and any cell that makes antibody that is reactive with selfcells is eliminated or silenced. B cell already present our body but when meet antigen become activated (receptors prior exposure to antigens).
➢ They think when we are exposed to antigen, B cell will produce antibodies, also known as immunoglobulins (Ig)= anti bodies , B cell receptors, which are proteins used by the immune system to identify and neutralize foreign objects
➢ Which postulated that antigens play a central role in determining antibody specificity? This theory states that antigens encounter antibody templates. When they do, these antibody templates would wrap around the antigen, forming a complementary molecule which would neutralize similar antigen molecules in the future.
➢ Later, scientists discovered that this theory isn’t true because although it explained diversity and specificity, it didn’t explain how the body recognizes self from non-self, as a blank template would be blind.
In 1950, Bruce Glick was the first to discover two important immune cells, which are the B cells that were first seen in chickens in an organ called bursa of Fabricius, which is the site of hematopoiesis in chickens, and T cells that were first seen in the thymus gland. (He also discovered a disease called Brucella)
➢ In 20 century, Karl Landsteiner, an Austrian immunologist, was the first to discover the blood groups by taking blood samples from people and separating the blood 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 and based on that he discovered the ABO blood group system and was known as the father of blood transfusion
➢ In 1830, Eli Metchnikoff, a Russian zoologist, noticed while he was looking in a blood film a cell that engulfs another bacterial cell, and he named this process of engulfment as phagocytosis , and it was thought since that discovery that these phagocytic cells are the only cells that protect us against invading pathogens before the discovery of immunoglobulins, antibodies, or any other components of the immune
system.
In 1881, Louis Pasteur, a French chemist, was working on a disease called fowl cholera that causes diarrhea in chicken.
He found when he took the 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. And in 1885, Louis Pasteur contributed to the science of immunology by making the first rabies vaccine and tested it on Joseph Meister for the first time successfully
In addition to his discovery of anthrax vaccine by the same way he did for fowl cholera, but on sheep not chicken
In 1798, Edward Jenner, an English doctor, noticed that people who work in dairy and milk cows are used to get a disease called cowpox, which is a 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.
So, 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 (from the Latin word Vacca, which means cow). Because of such a discovery, Edward Jenner is known to be the father of immunology
➢ in the 15th century, when Chinese and Turks noticed that anyone who was infected and recovered from smallpox won’t get smallpox again by getting crusts of the lesions caused by smallpox and take them then giving it to those people.
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.
✓ This note came from their try to expose people who were infected with plague before to people that are dying because of plague for a very short time
➢ These cells are produced by the immune system to kill or eliminate the invading pathogens by producing antibodies or engulf invading pathogens to kill them
➢ This property allows the immune system to know which cells belong to the host’s body (self) and which cells do not belong to it (non-self).
➢ This property could be affected in some diseases when immune cells turn to destroy our (self) tissues, resulting in what we call an autoimmune disease.
➢ Our immune system does have a memory that helps it to remember and recognize pathogens that invaded the body previously and neutralize them in an easier and faster way when they invade the body for a second time
And you will later discuss how our immune system remember these pathogens whether through vaccines or by previous infection and so on
➢ This property is related to division of our immune system, which is the adaptive immune system.
➢ This division recognizes and deals with one specificity of pathogens at a time and kills or neutralizes it completely.
➢ The immune system protects the body against a broad spectrum of pathogens (viruses, bacteria, fungi, etc.).
➢ This potential of the immune system is related to the genes that the human inherits from his parents, the more genes the human inherits, the stronger his immune system is, and you will study this deeply in the immunology course.
➢ For example, the difference in the immunity between individuals who their parents are not related to each other (they will be more immunocompetent) and the individuals who their parents related to each other.
The word (immunology) is derived from the Latin word (Immunis) which means exempt or describes a state of protection or defense.
For a pathogen to cause a disease, it must enter the body in a certain dose that is called the infectious dose, which is influenced by what the pathogen that cause the disease, and the host factors which are represented by his immune system.
➢ So, if the host’s body has a good immune system that can defend it from the invading pathogens, then the host is immunocompetent.
➢ On the other hand, if the immune system is weakened so it cannot defend the host’s body from the invading pathogens (microorganism as corona virus), then the host is immunocompromised
