Hypersensitivity Type II (Cytotoxic reaction) - causes, pathophysiology, complement system

hypersensitivity reactions are exaggerated or inappropriate immune response to benign antigen it is the immune response and not the antigen that is actually harmful an external antigen such as a drug pollen or food can elicit an inappropriate immune response however an inappropriate immune response to a internal antigen such as your own skin or neuron would be called an autoimmune reaction hypersensitivity reactions can be the mechanism of diseases in some autoimmune reactions hypersensitivity reactions are antigen-specific it's antigen-specific because the immune system is educated and primed toward the antigen after the first exposure in this quick example first exposure or first contact to an external antigen such as a drug pollen or food causes the immune system to sensitize itself towards the particular antigen in other words it Prime's the immune system against that antigen so when the next time the antigen comes along the primed immune system including the t-cells antibodies and neutrophils they can mount an exaggerated and an inappropriate immune response aka a hypersensitivity reaction but the immune system can cause hypersensitivity reactions in different ways and that is why hypersensitivity reactions can be subdivided into four main types type 1 type 2 and 3 hypersensitivity reactions are antibody mediated whereas type 4 is a cell mediated hypersensitivity reaction now let's talk about hypersensitivity type 2 reactions also known as sera toxic reactions in where antibody is produced they bind directly onto antigens on the surface of plasma membranes and then activate the complement response to complement proteins complement proteins essentially are circulating proteins that when activated lead to an inflammatory response against a particular target hypersensitivity type 2 is an antibody mediated response against an antigen on the surface of cell membranes now this antigen can be for example a particular drug such as penicillin hydrochlorothiazide and Quinns which in rare cases can be found on the surface of red blood cells and platelets another example of an antigen could be part of a bacteria another antigen could be the rhesus antigen where a rhesus negative person will mount an antibody response against a rhesus positive red blood cell all of the antibodies produced against these antigens will then activate complement systems please note that all these antigens will be found on the surface of a particular cell membrane or plasma membrane in order to form antibodies in the first place there must be first contact of the antigen with the immune system here the antigen presenting cell will pick up the antigen and it can be any one of those we mentioned earlier the antigen presenting cell will process and present the antigen then on its surface the antigen presenting cell will travel to nearby lymph nodes where they will interact with naive T helper cells some naive T helper cells will be able to bind on to the antigen presented by the antigen presenting cell when this happens the antigen presenting cell will be able to activate the T cell the activated T helper cell will inactivate specific new cells the activated b-cell will become plasma cells and during the whole process they will undergo class switching where they change the class of their antibodies so for example here from a immunoglobulin deep IgG antibody it will become an IgG or IgM secreting plasma cell plasma cells are the cells which produce antibodies and the antibodies will only target a specific antigen IgG is a single monomer that circulates in the bloodstream and IgM is a pentamer five antibodies bound together and is usually the first antibody produced against an antigen both IgG and IgM immunoglobulins can activate the complement system the basic structure of an antibody involves inner heavy chains and outer light chains the areas here are the fab region which is the antigen binding fragment region that binds to antigens and the bottom part here is the FC region also known as the fragment crystallizable region now this region actually are able to bind to certain receptors and the FC region is the region that is responsible for activating the component proteins and we will soon see how again the fab region binds to specific antigens examples of hypersensitivity type 2 reactions involve for example an IgG antibody produced against the antibiotic penicillin now penicillins are able to bind sometimes onto the surface of red blood cells on the rare chance AGG penicillin antibodies bind to the penicillins via the fab region on the cell surface once bound the IgG antibodies activates complement via its FC region complement activation leads to four main things number one it increases inflammatory mediators and thus inflammatory response number two it causes opsonization on membrane surface leading to phagocytosis number three complement proteins form the membrane attack complex which causes essentially the cell to lyse and finally number four complement proteins can activate natural killer cells which will cause the natural killer cell to kill that particular cell thus in this scenario complement activation leads to the red blood cell death or hemolysis resulting in anemia complement activation is a bit more complicated and involves a number of steps in hypersensitivity the classical pathway of complement activation occurs in the classical pathway using the same scenario of the red blood cell what happens again is IgG or IgM antibodies recognize an antigen on the membrane surface of a cell via its fab region the FC region of the antibody acts as a bridge for the classical complement activation pathway now normally complement proteins are inactive as they circulate in the body but when cleaved the complement proteins are activated in the classical pathway the first important product form by the activation of some complement proteins is c3 convertase which is an enzyme c3 convertase is formed and bound to the membrane surface and its function is to cleave and activate c3 complement 3 to become c3a and c3b c3a and c3b are active forms of complement 3 and they do separate things c3 a is inflammatory mediator promoting the inflammatory response c3 be opsin eise's membrane surface so it attaches to the membrane surface of the cell for example the red blood cell in this case the opsin eyes red blood cell is recognized by phagocytes such as neutrophils and macrophages via complement receptors and thus it causes phagocytosis and destruction of the red blood cell c3b interestingly can also bind to c3 convertase to form c5 convertase another ends enzyme and if you haven't guessed it c5 convertase Cleaves and activates complement 5 c5 to become c5 a and c 5b c 5a and c 5b have different functions c 5a is an inflammatory mediator so C 3 a and C 5 a essentially increases vascular permeability allowing complement proteins to enter the inflamed area as well as allowing phagocytes to enter the area and help engulf opsin eyes cells as we have talked about c5b initiates formation of the membrane attack complex known as Mack for short c5-b binds with c6 c7 and c8 complement proteins which allow formation of a channel via complement 9 proteins this whole structure is the membrane attack complex and what it does is that it causes fluids it allows fluids to rush inside the cell causing the cell to lyse so the membrane attack complex causes lysis of the cell the complement proteins also mentioned before activates natural killer cells another example of hypersensitivity type 2 is where IgG or IgM antibodies against Quinn's queenan's are attached unto the platelet surface platelets are molecules important in forming plugs to stop bleeding normally now antibodies against Quinns bind to the Queenan on the surface of platelets bound IgG or IgM antibodies activate complement via the FC region of the antibodies as we've discussed when this happens you get opsonization and macrophages attacking the platelets and then you also get lysis of the platelets via the membrane attack complex all of this will lead to thrombocytopenia which is essentially low number of platelets in the blood now IgM antibodies against mycoplasma pneumoniae may also form in an acute setting a hypersensitivity type to reaction interestingly in cold temperatures these antibodies can cross react with the person's own red blood cells leading to complement activation and hemolysis causing anemia another example of hypersensitive type 2 or antibodies produced during pregnancy here is a research positive fetus a fetus with recess antigen on the red blood cell and in this scenario this is the second pregnancy of a rhesus positive fetus in a rhesus negative mother because this is the second pregnancy the mother may have already created a IgG antibodies against the rhesus antigen from the first pregnancy which means that the recess antibodies produced by the mother can cross the placenta and into the fetuses circulation attaching on to the red blood cells of the fetus and causing hemolysis in the fetus finally antibodies formed against the M protein of streptococcus pyogenes also known as Group A streptococcus can actually cross react with cardiac tissues cross reaction of the antibodies activates the complement system leading to a serious complication of strep pyogenes infection called rheumatic heart disease and this is another example of a hypersensitivity type to reaction you

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Keywords: Hypersensitivity reaction types, different types of hypersensitivity reactions, hypersensitivity reaction type one, hypersensitivity type II reaction, hypersensitivity type 1 vs type 2 reactions, Cytotoxic hypersensitivity reaction, types off drug reactions

Id: Em0Wi07dj4E

Length: 14min 44sec (884 seconds)

Published: Tue Dec 03 2019