12/6/2012

Concepts & Components of the Immune System

Very important concept for the adaptive immune system is that they are initially prepared in anticipation for the immune system stimulation by the different pathogens , which means that the adaptive immune system ,T and B lymphocytes ,will start by the development of the B lymphocytes , each one of us will have large numbers of different lymphocytes each with specific antigen receptor which pre-exist the encounter with the antigen { God create us with immune system that is found in the fetus before even the encounter of any bacteria, that each lymphocyte recognize specific antigen (specific antigen receptor which is the Ig) }. Later in life after we are exposed to the foreign antigens which is none-self ,( look at figure bellow ) here this antigen which is in yellow will stimulate specific type lymphocyte so this cell will proliferate , so the lymphocyte with the matching receptor (the receptor which fitting that antigen) will divide and form many B cells with identical antigen receptors , this is the concept of clonal selection , that is characteristic for the adaptive immune response this works for T and B lymphocytes specifically in the adaptive immune response.

In other words , we are born with cells which have already receptors on it and the clone that is selected is going to be activated and proliferated .

The dr. talked about the theory of Evolution , as Charles Darwin said that the human is the most advanced creature which his origin is the monkeys . When the scientists studied the evolution of the immune system in the different organisms they found certain observation of genes for the innate immunity . For example : one of the substances which is excellent against bacteria is the Lysozyme , its a substance that kills the bacteria which discovered by Alexander fleming that , so humans have lysozymes , and also we can find it in trees and different plants and animals , its part of the innate immunity , we notice that genes for lysozymes are the same , there is no change in them (no evolution in it among the animal kingdom and plants). In contrast , in the adaptive immune system for example the Ig genes differ from one creature to the another . Ig types: IgG, IgM, IgA, IgE, IgD, these 5 types are found in human and they have also subclasses so they all will be 9 types of Ig in human . The first Ig we found was in all organism was in Sharks. The Shark had only one type of Ig which is IgM. (Here the dr talked about Organisms and how much Ig every one has ) So if you look to the animal kingdom the adaptive immune response there is a lot of gene duplication and gene specialization , as if there is evolution . The most complicated immune system is the human one, we have 9 types of Ig , the rats have the most similar Ig to humans ! To sum it up : The innate immunity is fixed in all the organisms with no change or evolution , meanwhile the specific proteins for the adaptive immune response there is huge evolution and a lot of modification in the different proteins and genes .

Another major concept , we said before that the innate immunity there is non-self differentiation and for any form of immunity to react it has to recognize the substance in front of it then will has the ability to attack it , also we said that during fetal life we produce millions of B & T lymphocytes and during embryological development these lymphocytes are exposed to the

self antigens , these cells we must get rid of it otherwise will cause autoimmune disease (which is characteristic of the adaptive immune response Not due to innate immunity) The major charactaristics for the adaptive immune response , is that it doesnt work immediately. For example: titers against hepatitis B virus after vaccination , which this virus is very dangerous for medical people so they must take this vaccination , we take the first dose then after one month the second dose and the third dose at the sixth month , if we measure the response we will notice that after the first dose the response is slow and low in titer ( takes long time to the antibody to appear) after the second dose the speed of the antibody is higher greater and stronger, after the third dose this will be even much stronger and much higher (as you see in the figure bellow) . This type of response is characteristic for the adaptive immune system that due to the immunological memory, that the response will be more higher and diverse (will release different types of Ig each time we expose to the antigens ) .

But in the innate immunity the response for all the doses will be the same! its right that it is fast with no specification but without any ability to develop itself , it always has the same response !

Components of the immune system :

1- Neutrophils : they are in the blood responsible for the phagocytosis and the bacteriocidal mechanisms, in adults its usual percentage is 50% - 67% of the peripheral white blood cells. 2- Eosinophils: 1% - 2% they are more responsible for killing parasites.
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3- Macrophages: one of blood cells is the monocytes in the blood then when they invade into the tissue they become macrophages, they are like neutrophils responsible for phagocytoces and the bacteriocidal mechanisms and they have an extra function which is antigen presentation. So Neutrophils & Macrophages are sometimes called phagocytes. 4- Tissue mast cells: they produce histamine responsible for allergic reaction and parasitic infection; we will talk about them later. 5- natural killer cells: form of lymphocytes, they are part of the lymphocytic group of development , these are the innate cells that mediate the innate immunity.

The components for the adaptive immunity:

1- B lymphocytes: when they become active they produce immunoglobulins and they will change into plasma cells. 2- T lymphocytes: there are many types : T lymphocytes which are cytotocsic (CD8) and the healthier or activated T lymphocytes (CD4), we will talk about them later. These cytotoxic T cells or cell mediated immunity cytotoxic means the cells those kill the cell in front of them that they recognize and activate by releasing cytokines.

We have two major parts of the immune system Adaptive ( acquired, specific) immune response & the innate (natural, nonspecific) immune response. the cells of the innate immunity Neutrophils , Eosinophils, Macrophages, mast cells &natural killer cells so these are the cellular innate immunity But the complement and the other factors are innate humeral immunity. The adaptive immune responsible by lymphocytes there are cellular component which are the lymphocytes and the humeral components which rare due to the B lymphocytes by the immunoglobulin that they produce. So we have till now 4 arms of the immune system cellular and humeral, adaptive and innate.

Active and passive immunity :

clearer from the book: two further divisions of immunity exist. Active immunity is where the individual plays a direct role in responding to the antigen - for example, after an encounter with a virus (vaccination). this is contrast to Passive immunity wherein immunity is transformed from one individual to another by transferring immune cells or serum from an immunized individual to an unimmunized individual - for example when anti-rabies antibody is provided after a dog bite. the antibodies to rabies virus are developed in other individuals and administrated to confer protection more rapidly than can be achieved by the injured individuals making the necessary antibodies themselves. plz see box 4.1 page 20

Another concept that immunity can be natural in cell and can be artificial , Can be active or can be passive, thats means that some time we need to stimulate or give immunity in a passive form ,For example if somebody is bitten by a snake and we have huge problem with snake venom toxicity causing disease to the person, if this person faced the snake venom in the past they will be immunized and have antibodies against snake venom; these antibodies can be protective and can decreases the mortality and the death and the disease from that snake venom in the last time. so snake venom antitoxin, we have like hepatitis B immunoglobulin a form of passive artificial immunity , so once again we can have the immunity in natural way or artificial one .For example vaccination and anti-snake anti venom is artificial. you have to know that natural here doesn't mean the nonspecific immunity.

Phases of immune response :

Any form of immunity ether adaptive or innate ,humeral , cellular , passive , active ,any form of immunity has to pass throw three stages which are : cognitive phase Which means recognition of the antigen , so if the B , T lymphocytes ,monocytes, neutrophils ,complement or any other type of immune response should be initially a phase of recognition that something is foreign or something is dangers and this is called Cognitive phase .
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activation phase After the cognitive phase the component of the immune system pass throw the activation phase in this phase the immunity become activated , For example for B lymphocytes instead of single cell they will divide into millions and millions of cells with the same receptor against that antigen because its needed . usually this stage involve proliferation which means dividing and increasing the number (proliferation). effector phase Eventual elimination of the antigen ,which means killing the antigen and getting rid of it and the affect that the body need . for example for B lymphocytes this will be the production of that immunoglobulin that will get rid of the antigen , so the third stage of is differentiation this means that the cell will be more specialized and it will be different shape and function than the initial one. The last concept today for our lec. is that any arm of the immune system for any action occur has to pass three stages *cognitive phase(recognition), *activation phase and *effector phase (killing mechanisms). and for each arm of the immune system uses different cognitive phases mechanisms, different activation phases and different effector phases depending on what do we need. If we have four arms of the immune system there are innate cellular, innate humeral, adaptive cellular (T lymphocytes), adaptive humeral (B lymphocytes) each one of them will have the three phases for each one of them So we have 4X3 different steps and phases for each one of the immune system. Our book describing each one of these stages and phases, how B lymphocytes recognize the antigen? how T lymphocytes recognize the antigen? how the complements recognizes the antigen?how nutrophyls recognize the antigen? and things like this.

Quiz
1- in repeated exposures to have a stronger and earlier response to infections is seen in: -passive immunity -innate immunity -humeral immunity -cellular immunity -adaptive immunity P.S. dr. said that the Q has something wrong !! 2- anticipatory defense "something prepared in the body before pathogen present" present in : -Neutrophils (phagocyte bacteria)
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-Complements (fixing bacteria) -natural killer cells (killing cancer cells) -antibody production (against a virus) -lysozyme (enzyme killing a bacteria)

Good Luck