Primary Immunodeficiency Transcript Part 1 PDF

So we have Wednesday off for Thanksgiving, but hypersensitivity. I'm also making it asynchronous So if you guys need to travel go home You can easily listen to it on part like from from wherever you go home so that you have time to actually have a week off To chill I do that on purpose. I'm pretty s...

So we have Wednesday off for Thanksgiving, but hypersensitivity. I'm also making it asynchronous So if you guys need to travel go home You can easily listen to it on part like from from wherever you go home so that you have time to actually have a week off To chill I do that on purpose. I'm pretty sure your Tuesday classes do too I'm also fairly certain the other Monday classes are fairly amenable to you know Going home to be with your family, especially if you have to travel far away So that's there and that's the rest of the semester overall and here are our learning objectives for today So there are a lot of slides today with scary-looking charts You do not have to memorize these scary-looking charts These are the specific disorder examples will be talking through I do need you to be able to read the charts though because you will See one question at least where I provide a chart for you And if you can follow yes or no and kind of you know go down the columns of the questions you can get to the right answer and so that is my Solution for not having to teach you every single possible primary immunodeficiency disorder if you can solve one with given Like a given chart and table you will get that one, right? So we'll go through what I mean because again, you're gonna see it you're gonna freak out But it is how we diagnose it's the charting It's the charts that we use in order to diagnose immunodeficiency disorders, especially if it's not that common We have categories that we used to sort So obviously the failure of the immune system this leads to a reduced ability to resist infection immunodeficiencies Like they sound are defects in components of the immune system. It's a decreased immune response You have two main categories primary and secondary Primary is a disease in which there's a failure of Immunological function due to a defect in one or more genes and coding components of the immune system It is usually genetic but can't be the result of randomly occurring errors and developments of point sense mutations In utero during fetal development, so you didn't get the genes for it specifically, but it still occurred during development Most of these guys become apparent by about six months old if they're more common sometimes they're very odd and just rare and like the symptoms aren't really anything not obviously really pointing to anything and so a Lot of times they can get missed too But around six months is when we start to see most of them because that's when the maternal derived antibodies start to disappear And so if the child just suddenly keeps getting sick over and over and over again It keeps having recurrent bacterial infections over six months old some things going on that's making them more susceptible to this So it is it is so diverse the term inborn error of immunity is now being used to describe primary immunodeficiency disorder So if you see the word ie I used people thought that primary just sounded bad Because it sounds like it's the main grouping even though we have environmental ones which fall under secondary So we call these because again it's going to be during development whether it's the genes that you inherited specifically or some sort of point Mutation or malformation with cell division when you were developing in utero, so that's why they call that inborn error of immunity Secondary immune deficiencies are caused by the environment after you're born infection therapeutic treatments So you can even be immunocompromised because you are on immunosuppressants for an auto a primary autoimmune disorder and things like that And so you have various issues with that too cancer will also put you under an immunodeficiency And malnutrition if you don't have the right nutrients or vitamins needed to help you know your immune system function you're going to be immuno immuno deficient overall just because You don't have the right nutrients you need to function so there are multiple causes behind the scenes, too HIV also falls under secondary immuno because it's environment It's a virus you contract later in life These guys can occur at any time in life depending on when the exposure to the causative factor occurs It's like a new mass amounts of radiation caused it Obviously you need a triggering event of the mass amount of radiation in order to develop that immunodeficiency Both of them however if you're comparing and contrasting both of them are characterized by recurrent or chronic infections The inability to clear infectious agents typically after standard antibiotic therapy because antibiotics are there also to help You know control it enough for your immune system to step in and finish off the job So again if you have patients who are just constantly and again, we've tested for you know The antibiotic is supposed to work Bacteria or virus or the bacteria is susceptible to the antibiotic and we still provide it and it still doesn't work something else is going on Or the presence of unusual infectious agents So if you get a patient comes into primary care who has a bacterial infection You have never heard about that. We never talked about in micro Probably not that common and probably something you should investigate further and so those are Similarities between both primary and secondary, but the major differences are primary is birth like during birth and development And secondary our environment after birth Rare primary immunodeficiency diseases reveal how the immune system works We've actually learned more about the immune system based on how it doesn't work when people have certain malformations genetically with these primary Immunodeficiency disorders we have actually identified over 100 different primary immunodeficiency disorders overall which is why I'm not going to have you memorize all 100 of them There could even be a new one that's discovered in the time that you guys are working You could even discover when you never know And so as we see specific defective genes that we identify We're able to kind of you know Figure out what the causative agent is and learn a little bit more that like oh if they have a defect in this gene and it Affects, you know these cell behaviors that gene is linked to these cells in their function So we've learned a lot actually through them to Immunodeficiency these are actually less the rare than originally thought they thought it was like, you know One in three or four million now there are some that can be one in a hundred chances of you getting it So there could be people in this class who have a rare Immunodeficiency disorder they do depend and they vary in rarities We'll talk about some that are most common. These are the ones we'll talk about in class But there are some other ones too. We talked about the primary ones since they're inherited They can be caused by dominant recessive or even X linked gene defects They do kind of all differ so there can be some where only women can track it because they have 2x chromosomes Or only males experience it because they have a Y chromosome It can get complicated when you have like client filters and other like *** xxy xyy and things like that Which can also affect your ability to diagnose it If it's a little atypical in the presentation, too So here are the main groups and you guys are expected to know The group and the immunodeficiency with it because this is how So say you discover a new one we can at least figure out what group it's in based on how it presents So group one are immunodeficiencies affecting cellular and humoral immunity group two are combined Immunodeficiencies with associated or syndromic features and we'll talk about what that means But usually it's kind of multiple together causing just severe You know everything gets taken out with these guys here, too Group three predominantly affects antibodies and antibody deficiencies group four is diseases of immune dysregulation So the immune system is activated But then doesn't function the way that it's supposed to group five is congenital defects and phagocyte number function or both Uh group six is defects in intrinsic and innate immunity like say we're taking out your macrophages or your neutrophils that could affect that, too Which can also kind of loosely tie into group five. So I am very nice when I present stuff like that group seven is auto inflammatory Which can be kind of considered considered like autoimmune But it's basically where we attack self and lead to just massive inflammation in the body And group eight is all of your complement deficiencies Obviously, there are a lot of different genes involved You do not need to memorize these guys here But it is kind of cool that we figured out kind of where a lot of these guys found within these groups Are affected by overall So we talk about group one and i'm just trying to get to a point at the charts on the next slide. So It will be okay i'll walk you through them Also, you can't really read them because they're so tiny because I had to squeeze it onto a powerpoint slide I'll make them bigger for the exam. So, you know what's going on group one affects cellular and humoral immunity So this this is a diagnosis chart Proposed by aai on how to diagnose Different immunodeficiency disorders that fall just within group one And so kind of when they're going through here too, like if it's severe and combined They can go through these guys here and they look does this one have decreases in cd19 counts? So you guys could imagine it affects, you know b cells Then we'll go down these guys here and like are you also missing nk cells? Cool, then you go down these guys here. So there are additional like testing you can do but this gives you the red Are the terms and diseases found within this chart so if you can read a chart like I say, hey, you know It is a severe combined in group one And you have normal levels of cd19 cool Then you guys go here and you read down this column And so basically that's kind of how I set you up for it here like here It's you know has low levels of t cells. You have normal b cells, but you have Normal nk cells. Cool. Then you go down here and read this here And so it gives you kind of just it narrows down the focus when we're diagnosing the various disorders So I would give you a chart like this and actually be one of the charts from this powerpoint and give you the information Needed so as long as you can answer the questions and read down the chart It'll get you to the answer area Okay Is everyone comfortable with this process because this is what you're going to do if you go into this field of practice They don't expect you to memorize all I mean grants if you work in this field for a very long period of time You might memorize them if you're really good But it's not expected for you to memorize them But it is expected for you to be able to follow a flow chart Of the different tests that you've done to start narrowing down what a patient's diagnosis is And so that's why I use this as an exam question To get you comfortable with practicing going through this process here, too We will talk about some of these look cd40 ligand deficiency falls into this category here So some of the names you are familiar with some of them you aren't you guys might remember zap 70 But there are deficiencies that affect zap 70 overall here, too There are some that affect your ability to have mhc class one So some terms may sound familiar But again, we will talk about very very specific ones too as we go through here, too So when we're knocking out the lymphoid lineage with group one It results in defective function of both b and t cell numbers. Although from that previous chart You can have some normal b cells too Functions or both so it may not always be equal either You could have normal levels of b cells, but they may not be able to function So, you know various aspects of a group one is kind of one of the broader categories I think if you talk about so an example of severe combined immunodeficiency disorders This is a specific example to know or scid This one was originally believed to be one disease But now it's actually kind of a group of diseases overall Caused by different defects in individual genes that have similar functional consequences in that we Pretty much wipe out the functioning of your entire adaptive immune response here, too And so because of that you lose the ability to have cell mediated lysis delayed type 1 hyper sensitivity can get affected which we'll talk about later Obsonization can get affected Antibody production is decreased antibody dependence mediated cytotoxicity gets decreased, too You also have you know difficulty with massive degranulation because if it requires IGE Produced by b cells and you're affecting your b cells You're in trouble there, too. And so there's a lot of overlap here, too The classic example of defects in combined lymphocyte lineage is cid. So it's the primary one described often The cid related defects may occur in genes like rag 1 rag 2 So as you guys know that would affect recombination machinery and the ability to make your t cell receptors and your b cell receptors That's a significant knock out here, too And so obviously that affects the ability to produce the variable regions of your immunoglobulin molecules in your t cell receptors You can also knock out cytokine receptors, too So that cells can't respond or function like think about you knocked out aisle 7 you talked about that heavily with b cells There's a problem with that too or your even ability to you know, lead to t and b cells So a lot of it makes logical sense kind of if you think about it here, too It can also affect, you know cell-to-cell interaction where you have normal levels, but they can't talk to each other So they can't activate each other and they can't function. And so those are consequences as well, too And so an example of one within cid is ada which is a little bit more common It's called adenosine deaminase deficiency or ada it is in a metabolic immunodeficiency disorder That is one of the causes of cid. So cid is a group of disorders And so this is the one example within we do know the inheritance pattern here It is caused by mutations in the ada gene and it counts for about 10 to 15 percent of all cases of autosomal recessive Cid among a non inbred population With this one, it's showing that both parents were carriers of the disorder And so males are in squares and females are in circles here And so the functional copy is in green the defective copy is in red. And so obviously again It's a random one and fourth meat Well, actually one half mutation at that point when anytime you flip a coin the chance of your child inheriting it here, too But you need both defective copies in order for it to display So you can also have generations of a family where maybe they only have two kids and both kids ended up becoming just carriers And so a lot of times too going back and looking at family trees and genetics to kind of figure out what the disorder is Can kind of narrow down what some of them are But this one this is one of the few ones where we can go back and actually do genetic testing to look for issues with ada Genes to see if a patient has developed it That way so we will stop there since it is at time Do you have any questions about that? Is everyone comfortable with the idea of the charts because if you look ahead There are many charts But for each group each group has a chart But because I don't expect you to memorize all of these different things I will provide a chart for you So as long as you can follow and you know I'll give you the information needed to go down the different combos or columns You can figure out what it is based on that We'll do some practice questions too for your end of the week quizzes