# Adaptive Immune Function Immunobiology background primer From Brett Weinstein We can dichotomize system in different ways: 1 way -> we have innate immunity -> ability to recognize pathogens / disease causing patterns without having to have exposure Acquired immunity -> getting sick, fighting it off -> now you have the ability to recognize that pathogen (immune system has learned th eelectro-magnetic signature on the surface of the pathogen or the cells that have been infected) - good at finding and destroying Last creates a set of memory cells so that it is quicker to recognize future invasion by pathogen -> we don't normally get the same illness twice # Acquired immunity Carried in 2 kidns of cells -> - B cells -> make antibodies -> Y shaped protein floats freely and sticks to things based on the signature (electromagnetic charge). These attach to bacteria, virally infected cells -> consequences - T cells -> function like B cells, except instead of creating free-floating antibody - similar bodies are on surface of cell and function as receptors. T cells move around, and the B cells become triggered to be active if the right pathogen is present T cell can immediately destroy infected cell -> recognize antigen Other T cells can also provide help to the B cell -> build memory. Without T cell, the B cell has no memory (2 types of T cells) -> cytotoxic T cell and memory T cell ## Way in which acquired immunity is originally created Fascinating evolutionary process More or less in this way: You have an array of cells that produce antibodies which have an ability (general) to react to any large organic molecule -> any configuration of charges that an antigen might have. Multiple cells will react to it somewhat. Billions of this? Wide range of patterns of antigen that they can react to You have these things before you are born (in utero) React in principles to any sizable organic molecule, but not your own. This is beacuse, during critical period of development, your system eliminates any of these cells which would react to your own molecules. System wakes up to all of the members of class of cells that you produce in utero, and eliminates them. This the system is sure to only react to cells that are not from you -> tolerance to your own cells. failure to do this would be an autoimmune disorder Understsand this: the system in its initial state reacts to anything that isn't you. What isn't you might be a pathogen, or might not -> pollen? Just an organic molecule that you could react to, even if it's not dangerous -> allergy When invaded by bacetria, however, you are suddenly creating molecules that your system has never seen - > system reacts - > at first, very weakly because you don't have a specific program for recognizing the invader -> just a general reaction BUT The cells that react a little bit to the new pathogenc pattern create a bunch of offspring cells that rae not identical to each other Those cells (offspring) which react even more strongly to the pathogen are griggered to produce more offspring cells This uses evolution to generate a recognition of this new pathogen which your body had never sen before, which ou are now learning to recognize. The system becomes very good at it. At this point, it can recognize any place in the body which is making these new antigens and becomes capable of fending off teh pathogen. Cytotoxic T cells are the ones that kill. Imagine: you got sick, breathe in a virus, it invades cells, those cells make viral particles - > get recognized by adaptive immune system - > system becomes good at finding these and targeting these -> and then, you clear the infection because your system is good at recognizing it -> neow produces memory cells which remember the formula -> if triggered, these can create a large army of cells to attack pathogen Helper T-Cells are involved in helping to trigger B-Cell immunity in adaptive immune system, having discovered formula for the pathogen `This process is T-Helper cell dependent.` In context fo Covid, people have jheard discussion about whether or not infection of virus or vaccination triggers a robust B-Cell response. Can we detect an antibody titer? How well / how much affinity do antibodies have for antigen in question -> varies -> variant that the immune system was Second question ->Whether or not the system that crates antiboddies (short term immunity) has converted over to a system of memory for long-term immunity. Much harder to test to this second case. Testing whether or not you have long-term immunity based on cells having correct memory. B cells also do have memory, however -> you need memory in the B cells to be able to recall the antibodies upon exposure to the pathogen. B cell memory and T cell memory So, we should understand that some of these vaccines require two doses: - vaccine enters your cells - mRNA encodes spike protein - is introduced and taken up by cells. Why is it taken up by cells? Lipid nanoparticles will enhance the uptake of the if you would have it by itself, it becomes too soluble. In a lipid nanoparticle, it has ahigher affinity for cell membrane, instead of being attracted arbitrarily everywhere. Enhances uptake of mRNA because of structure and chemical nature, and size. Should be promoted and enhanced entry. You have an aqeous environment -> wet environment -> primiarly water -> cells surrounded by fat (not water soluble) -> by putting the mRNA in a lipid nanoparticle -> the affinity for the cell is higher -> drive them itno cell and then the mRNA is transcribed. Summary -> we talked about adaptive immunity system -> evolves through clono selection -> evolves to target and eliminate infection once acquired But this is not the full basis of immunity to pathogens We also have innate immunity -> does not require exposure in order to develop ## Innate Immunity Antibody part and cellular part of immunity (limiting focus to these) Antibodies are part of the acquired immunity -> they specifically recognize an antigen and they can also use memory Equivalent of this in Innate immunity -> natural antibodies -> produced by what we call an innate light-Cell -> preprogrammed B cell present at birth These natural antibodies, in contrast to antibodies by B cells in acquired - > have no antigen specificity -> they can recognize multiple antigens They are not recalled upon reexposure Humeral part of the innate system Cellular part: In contrast to T cells, not able to recognize a specific antigen that is presented oin a mutated cell Cells of innate ysstem -> natural killer cells ->they recognize in the non-specific way a kind of array of motifs on surface of infected or pathologically altered cell. This is not very specific for an antigen, but if a virus for example invads that cell -> all sorts of glycens on the surface fo cell -. pattern is formed, and becomes recognized by natural killer cells Pre-programmed-> act immediately -> first line of defense when a pathogen gets in You have a system which reacts to more or less the symptoms of a pathology. The ecells behave molecularly in an unsual way -. natural killer cells can recognize this and react, but they aren't specifically reacting to a one antigen ## Hazard of our current vaccine regime *According to Geert van den Bossche* Claims that the current vaccine vcampaign is so dangerous that ti should be halted. Brett believes GVDB's Possibility of our making our viral susceptibility to covid worse is present -> we are manufacturing the hazard that we might find ourselves in a year or two from now by our actions now What in a nutshell is the argument? ## Geert's Argument First of all, this vaccines are would be perfec tto be used outside of a pandemic. Because if you use them before you get exposed to the virus, you can build a full fledged immunity -> this takes time -> 2 doses -> colonal expansion -> in meantime you acquired memory and higher affinity This is a process sbefore you acquire full fledged immunity if you have full fledged immunity an then fin dpathgoen you either have everything uou need to fight it off OR ` Hypothetically speaking, the viurus emerges in Wuhan, world limits its spread, it is kept to Eurasia. Rest of the world has not faced the virus. Theyn, if we take the mRNA vaccine and vaccinate the population so that 80 - 90% is vaccinated before encountering the pathogen. Hazar is low, even if it is true that.` Just to be clear, here we are talking about original viruses -> wild virus If you diminish viral load without killing it Vaccine, from point of view from the patient -> patient gets a shot Tha tlooks the same to people, regardless of when they get vaccinated. Getting a vaccine is like showing up -> imagine that your nation is being invaded -> how useful is your rifle when it can't even be ee