DIP Episode 14 - Comprehensive Immuno Pharmacology and The Monoclonal Alphabet

Welcome. My name is Divine. I am a fourth-year medical student. In today's episode of the Divine intervention podcasts, we're going to be talking about immunofarmacology. And in addition to talking about immunofarmacology, we are going to spend some time discussing the monoclonal antibodies that are classically tested on the board exams. We'll begin first by talking about some interleukins and some immunophysiology, and then we'll go from there. So, without further ado, let's get started. So, if we sort of want to have a basis for how many of these or I guess the functions of many of the interleukins that are classically tested, I think a good starting point is with the pluripotence-tempsil. That ultimately becomes a source of all our blood cell lines. So, if you have a pluripotence-tempsil, you expose it to interleukin 7. You can go down the lymphoid lineage. An easy way to remember that is the L in lymphoid if you flip that over becomes a 7. And, under the lymphoid lineage, remember we have BMT cells. And the B cells, the Express CD19, 2021. The terminal B cell line, you should hopefully remember that it's the plasma cell. Remember that plasma cells do not express CD20. That's actually very high yield to know for what exams. Now, your T cells on the other hand, they are generally CD3 positive. And, under that, we have the CD4 positive cells and the CD8 positive T cells. For the CD4 positive T cells, those are the helper T cells. They all start as T helper 0 cells.

But, we can either go down the T helper 1 route, which is more involved in cell mediated immunity, or the T helper 2 route, which is more involved in antibody mediated immunity. If you want to go down the T helper 1 route, you go from T helper 0 with interleukin 12. If you want to go down the IO 4 route, okay? I mean, sorry, if you want to go down the T helper 2 route from T helper 0, you go down that pathway with interleukin 4. Remember that 2 squared is 4. So, interleukin 4, T helper 2, those numbers that are go together. Now, you should also remember that interleukin 2 is a T cells stimulating factor. So, by giving interleukin 2, you can actually increase the rate of progression of a T cell from the G phase to the S phase. Now, try to remember this nomonic. It's something you'll hear about pretty commonly as you study for step 1, okay? On the different functions of certain high-yield interleukins, it's the hot T bone steak nomonic, okay? So, hot T bone, being bone, and then EAK in steak, okay? So, interleukin 1 is a pyrogen, okay? That's the hot interleukin 2 is a T cell stimulator. That's the T and T bone, okay? Interleukin 3 is a bone marrow stimulator, okay? So, kind of like GMCSF, if you may. That's the bean bone, okay? Interleukin 4 helps you class switch to IgG and IgE, okay? And it also helps you go down the T helper 2 line each, okay? So, that's the E in steak. Interleukin 5 helps you class switch to IgA, okay? And it also helps you proliferate your synophilus.

So, that's the A in steak. And then the K in steak is for interleukin 6, it's an acute, right? So, instead of a C, you think of a K, it's an acute phase reactant, okay? It's a pyrogen. And the EOT helper one cells, they actually release interferengamer, right? Which we know is like the stimulator factor for macrophages. Okay, and then just like we have CD4 positive cells that are more for antibody-mediated immunity, we have CD8 positive cells that are for cell-mediated or cytotoxic immunity. Although the CD4 positive cells, the T helper one subset, are also primarily involved in spursing up cell-mediated immunity. So, we also have the natural killer cells, remember they are kind of lymphocyte, but they're more than the pervue of the need immune system as against the adaptive immune system. And it's very high to know that the CD16 and 56 positive, okay? CD56 is actually the receptor for IgG, okay? I believe I mentioned alluded to this at a previous podcast where I was not sure. So, now I'm sure, okay? CD56 is in fact a receptor for IgG, okay? It's known as the FC gamma receptor. Basically, the constant region of IgG can dock to this receptor, okay?

And when the constant region of IgG dock to this receptor, the natural killer cell, if the antibody that docked, let's say the IgG that docked is bound to like a bug or some cell or something, the natural killer cell can release pervue to poke holes in the walls of the attached cell or bug, and then Granzyne B can go in and activate the apoptosis cascade, okay? So, you can get cell killing. This process is known as antibody-dependent cellular cytotoxicity, which is actually kind of high to know for step one, okay? And remember that ADCC may sound a lot like optimization, but they're actually different processes, okay? In optimization, yes, IgG can do that just like IgM, okay? Sorry, IgG can do optimization, IgM cannot do optimization. The only function that is shared by IgG and IgM is that they can both activate the classic complement cascade. But IgG, if it coats an organism, and then macrophage comes and swallows up the IgG and the organism, holers one in the process of phagocytosis, that will be optimization, okay? But if a natural killer cell, for example, binds to the concentration of IgG that's bound to some bug or some cell, and then releases factors that cause the death or destruction of that bug or that cell, that will be antibody-dependent cellular cytotoxicity. So that's it for the lymphoid lineage, okay? The myeloid lineage in general, if you expose your bone marrow to GCSF, right?

So granulocyte, colonis-timulating factor, that helps you make a ton of granulocyte, right? And the easy way to remember your granulocyte is with the mnemonic band, I don't know if any of the podcast listeners has the name band, but that stands for Bizofils, Eocenophils and Neutrophils, okay? Remember, Neutrophils are the most common myeloid cell that you should find in the blood. Very decent mnemonic for that is never let monkeys eat bananas, right? So never is neutrophils, okay? Let that's lymphocytes, monkeys that's monocytes, eat that's Eocenophils, bananas that's Bizofils, okay? So that tells you from, we should be in the highest concentration amongst your myeloid cells that you find in the blood that we should be in the lowest concentration. Lowest concentration, Bizofils, highest concentration neutrophils, which are also known as Polybophonucleolucocytes. So if your bone marrow is exposed to GMCSF as against GCSF, right? So GMCSF is granulocyte monocytes colonis-timulating factor, that helps you make either granulocyte or E-granulocyte, right? So your granulocyte, I like your band, okay? And then your E-granulocyte includes your macrophages, okay? Now for a mega-carrier site, remember that mega-carrier sites are the precursors to platelets, okay? In general, if you want to induce a mega-carrier site to go down the platelet pathway, you want to expose your bone marrow to interlooking 11 or a thrombopoietin, okay?

So thrombopoietin interlooking 11, these all promote proliferation of platelets. Now, we know that EPO, right? If you expose your bone marrow to EPO, it helps, it makes your bone marrow turn out more red blood cells, because you're basically talking to your rethroid precursors, and you're telling them to make more and more red cells. So analogs like a rethropoietin and doublepoietin, okay? These are EPO analogs. You can actually use them to treat like anemia of chronic disease, or anemia if a person has renal disease, you can give them those analogs to spurs of your bone marrow to begin to make more red blood cells. Now, you should also not forget, as an aside, that there are certain cancers that express EPO as a perineoplastic phenomena, okay? So don't forget your renal cell carcinoma, okay? Remember that has AFP of a phytoprotin as a tumor marker, and then don't forget your brain tumor, the hemangioblastoma, the hemangioblastoma. So, let's begin to go into a couple of drugs, now that we've sort of lived the groundwork for how the immune system works, ish. The first drug I'll talk about is oprovekin. Oprovekin is an interleukin-11 analog, okay? Remember I just said that IL-11 or thrombo-poietin helps you proliferate platelets. So, if a person has a thrombocytopenia, for example, if they have ITP, immune thrombocytopenic paper, where you make autoantibodies against GP2 B3 A, remember that would scrub the aggregation step of primary hemostasis.

If you have ITP, you can actually give oprovekin as a medication for that, although classically ITP is treated with corticosteroids or IVIG, or if it's super severe, you'll get a spinectomy. So, remember in ITP in general, you don't give platelets, right? Because the antibodies are still around, so whatever platelets you're given, you just have them destroyed a periphery, so it's not worth it. But oprovekin, which is an IL-11 or normal, can be given for ITP. And as a general principle, if something ends in like luchen or vikin, those are usually interleukin analogs. That's why they have those terminal soft access in their names. Now, the next drug will go to is a L-thrombopag. Okay, a thrombopag is a thrombopoetin receptor agonist. Okay, so again, it helps you periphery platelets. You can also use this in the treatment of ITP. Next drug will be Romyplostim. Romyplostim is a thrombopoetin analog. Okay, you can also use it with Tridi-TP, right? So, one way to think about platelet proliferation is ask yourself, I can either give the interleukin analog or provikin, why can give the thrombopoetin analog, Romyplostim, why can give the thrombopoetin receptor agonist, which is a thrombopag. Okay, and you can use all these things to treat ITP. Now, if a person has chemoinduced neutropenia, right, so let's say they've taken very hardcore chemotherapy, and their bone marrow have been severely suppressed, and they have neutropenia, you're worried about life-threatening infections.

One thing you can do is to give a G-C-S-F analog, like Phil-Grastim, or a G-M-C-S-F analog, like S-A-G-Mostim. These drugs both spur off the bone marrow to increase your white count, especially your neutrophil count. Now, next drug I'll talk about is retoximap. Retoximap is a monoclonal antibody against CD-20. One higher mechanism of action you sort of want to keep in mind for your exam is that one of its mechanisms of killing is by promoting ADCC, because it's a natural antibody. So it has a constant region that combines to certain receptors on the surfaces of macrophages, or natural killer cells, and ultimately cause cell death. And because this is a monoclonal against CD-20, you can begin to opine that this does not affect plasma cells, right, because plasma cells remember they do not have CD-20. And as an aside, what's the receptor that's used by EBV to get into B cells? That's CD-21, okay, something how you to remember for step one. Okay, now, next drug I'll talk about is orders looking, right, so if it has looking in the name, that tells you that it's an inter-looking analog. Okay, this is an inter-looking to analog. By being an inter-looking to analog, it can stimulate T cells. Okay, in fact you can actually use this drug or just look into Traderinousel-Crasinoma, okay, because by giving something that stimulates T cells, you can spursal-cure immune system to fight the cancer. And somewhat similar concept is how bladder cancer can be treated.

Bladder cancer can actually be treated by intraversically, given the BCG vaccine, because when you give the BCG vaccine to the bladder, okay, you basically bring the immune system to comment, do like their damage duty on the bladder, and that can actually take you off the cancer as well. Now, next drug I'll talk about is interferon gamma, okay, remember interferon gamma is a microfiche stimulator. So if you have any disease where your microfuges are not working right, you could potentially give interferon gamma for that, right, so a classic, two classic examples. One will be CGD, chronic granulomata's disease, okay, remember that will have an NEDPH oxidase, deficiency, right, so you cannot deal with catalyst positive bugs. You can give interferon gamma stripping for CGD. Another thing you could also give interferon gamma for is osteoporosis, right, so that's more of an endocrine disease. It's called a brittle bone disease where your osteoclasts do not work right, so you just lay down bone in an aberrant fashion. And by laying down the bone in the aberrant fashion, one the person can have pathological fractures, and they could also have pancidopenia, because the bone marrow is not organized right. So one way you can actually treat osteoporosis, which hopefully remember, arises secondary to a carbonych and hydrates two deficiency, right, so your osteoclasts cannot form that raw food border and dump in acid to a reserve bone, okay.

One way you can actually treat osteoporosis is to give interferon gamma for that, okay, so interferon gamma can be used for microfage diseases like CGD, okay, remember, microfage is a powerful phagocytes and they're involved in the respiratory bursts. And remember, your osteoclasts are kind of macrophage, okay, they are basically the bone macrophages. Okay, now, the next drug I'm going to talk about is basically a decoy receptor against the TNF alpha, okay, it's a TNF alpha decoy receptor. I will sort of draw your attention as well to the NOSU map, the NOSU map is also an endocrine drug, it's a decoy receptor against the rank ligand, okay, against rank ligand, so just a somewhat similar concept, although it's a different pharmacology. Okay, now, so let's go ahead and jump to the monoclonal alphabet, okay, basically in this review I'm just going to talk about all the monoclonals that tested on step one, okay. So the first one I'll start out to start with, right, so start with the A, okay, up 60 map, okay, up 60 map and I'm going to go through this rapid fire up 60 map, okay, some monoclonal antibody against GP2 B3 A, okay. Remember, by taking this drug you're basically replicating a similar pathophysiology to immune thrombusidopenia, okay, remember, that's where you form autoantibodies against GP2 B3 A. And just as an aside, don't forget your other GP2 B3 A antagonists, right, so like tyrophibin and epithybotite.

Now, next drug in an armamentarium is adalimumap, okay, adalimumap, use it primarily to treat autoimmune diseases like Crohn's, okay, it's a monoclonal antibody against TNF alpha. Next drug in an arsumol is alirocumap, okay, alirocumap is a PCSK9 inhibitor, right, so let's talk about what PCSK9 does. PCSK9 basically causes endocytosis and destruction of your LDR receptors, okay. The thing is, if a person has high cholesterol, you want those people's LDR receptors to persist on the surface of hepatocytes, right, because if it persists, you'll clear more LDL from the serum. So one way you could potentially treat a person having very high levels of cholesterol, for example, in a familial hypercholesterolinea, if you may, is to inhibit the destructor of LDR receptors, which is PCSK9. So you can give a PCSK9 inhibitor, okay, like alirocumap, okay, like alirocumap. Now, next monoclonal is alim-tuzumap, okay, alim-tuzumap is a monoclonal antibody against CD52. It's actually used to treat chronic lymphocytic leukemia, okay, CLL. Remember, CLL on exams, right, doesn't show up in young people, it's an old person, a hematologic malignancy. So, classically, it shows up in like ladies or guys that are like in their 80s. They have like multiple infections, because yes, they have a very high white count, usually it's like 80 to 100,000, but those white cells don't work very well. Okay, remember that on histology in CLL, you'll see smudge cells, okay.

So, maturbian T cells, they actually expressed CD52. So, you make a monoclonal antibody against this, and through antibody-dependent cellular cytotoxicity or other mechanisms of destruction, you can sort of bring down the proliferation of these aberrant lymphoid cells in CLL. So, alim-tuzumap, CD52 inhibitor, okay, used to treat CLL. Now, we're done with the A's list, jump to the B's, okay, the first B we'll talk about is bevacizumap. Bevacizumap is a monoclonal antibody against the VGF, okay. I remember that in macular degeneration, you have, especially the wet kind, you have an aberrant proliferation of blood vessels, which can opacify the eye, and then begin to cause problems, right, remember in macular degeneration, you lose central vision first, before you lose peripheral vision. You could potentially treat this condition with bevacizumap, which is a VGF inhibitor by inhibiting VGF, you'll make less and less of the blood vessels that are clouded, basically like a clouding out the eye. Now, the next thing I'll talk about is baseleximap. Baseleximap is a chimeric monoclonal antibody against a part of the interlooking two receptor, okay. To make things simple, let's just call it part of the interlooking two receptor. Let's just call it a monoclonal against the IO Tore receptor, okay. The IO Tore receptor, the subunit that's specifically inhibited by baseleximap is actually known as CD25, okay. So, remember that IO Tore is a T-cell stimulator, okay.

So by blocking the IO Tore receptor, you're blocking the stimulation of T-cells. So you can use this to basically deplete your T-cell population. And as an aside, one thing I'll just see with the interlooking two receptor. If you actually have a deficiency of this receptor, especially the gamma subunit, you actually have an increased risk of skid, okay. So a severe combined immunodeficiency. And also remember, another common cause of skid is an adenosine deaminase deficiency, right. So that's one common cause of a autosomal recessive skid. I talked about the pathophysiology of skid from adenosine deaminase deficiency in episode 13 of our podcast. So now we're done with the bees, okay. Now the seeds, okay. So the lusumap is the first seed. It's a TNF alpha inhibitor, nothing big there. Next seed is a cytoxymap. So the toxymap is a monoclonal antibody against the epidermal growth factor receptor, EGFR, okay. More specifically, the herb B1 receptor, herb B1. So please don't confuse herb B1 with herb B2, which is overexpressed in breast cancers, or can blocked by drugs like a trastuzumap, okay. But herb B1 is a tyrosine kinase receptor, okay. That's actually overexpressed in lots and lots and lots of colororectal cancers. So if you block to this epidermal growth factor receptor, you will potentially prevent the proliferation of colororectal cancer cells, okay. So that's how the toxymap works.

Now, one very high-yield thing that you could test on step one in relation to the epidermal growth factor receptor and the toxymap is how a person does not respond to the toxymap treatment. The thing is, the epidermal growth factor receptor uses Keras as one of its second messengers, okay. So if you have an activity nutrition in Keras, even if you're blocking the EGFR receptor, herb B1, you will not respond to that drug because it's like, oh, regardless, downstream of the receptor, you already have an over-activating mutation. And I'm really hoping that with this extra information I just mentioned, you can sort of tie another concept in here, which is the adenoma-carsenoma sequence in colororectal cancer, right. So remember, you'll classically start with an APC gene mutation, okay. And then you'll progress to a Keras mutation, and then you'll progress to a P53 mutation. Classic nomonic people use for this is an AK53, okay. So APC gene mutation, Keras mutation, P53 mutation, and then you progress from having an adenoma to having a full-blown colororectal carcinoma, okay. So that's one very nice way to tie that knowledge here. You're like, oh, wait, this person has a Keras mutation, so they're not responding to the toxymap, okay. The reason they're not responding to the toxymap is that even if you're blocking a B1, which is the epidermal growth factor receptor, you're not... The second messenger is already overactive, so you're basically screwed in that regard.

Okay, so we're done with the C's. Let's jump to the D's. I've already talked about one of these D's, okay. The nomosymap. It's a monoclonal antibody against a rank ligand, okay. So you can use it to treat a very nasty hypercalcemia, because remember that rank ligand is expressed by osteoblasts. It binds to the rank receptor that's found on osteoclasts, which activates the rank receptors, and then that causes your osteoclasts to be resorbable. So if you bound up rank ligand with a dummy receptor, like a denosymap, okay. It's a monoclonal antibody, you bound it, bound up the rank ligand, then you do not activate osteoclasts, and you do not resort bone. Alternatively, as an aside, if you want to bring in some more stuff here, there is a reason why women don't have bone problems until the past menopause. The mechanism behind that is estrogen, which is a hormone that's found in women, right. Increases the synthesis of something known as osteoportagrin. Osteoportagrin is a binder. It's a dummy receptor for rank ligand, okay. So by binding up rank ligand again, you don't have that rank-likeant-rank receptor interaction, so you don't activate osteoclasts, so you do not resort bone. Okay. So that's another high-yoda time there. Now, the next D is a daclizumap. Daclizumap, it sort of works like baselexemap, if you may. It's a monoclonal antibody against the IO Tore receptor, okay. More specifically, CD25. Okay. Now, the next D is a Digibind.

Digibind is the trade name, so you probably will never see this on a board exam. But the name you'll probably see on a board exam are the anti-dage fab fragments, anti-dage fab fragment. So remember, you use this to rescue from the joxin toxicity. Now, with the D's, let's jump to the E's. The first E is aculizumap. Aculizumap is monoclonal antibody against C5. Okay. I use this to treat paroxysmal, nocturnal hemoglobinuria. Okay. Remember, this is where you have a big A gene mutation. So you don't make GPI anchors. So things that are supposed to protect your red cells from complemented medial damage, like CD55, which is also known as DK accelerating factor, or CD59. Okay. They can hang out on your red cells, so complement goes nuts and destroys your red cells. Okay. So you get a cum's negative hemolycanemia. Okay. So one way you can prevent this is by essentially preventing the membrane attack complex from forming. And you can do that by giving a monoclonal agency five, like aculizumap. And one nice way that your friends at the endemic and tying aculizumap with microbiology is to sort of help you, is to sort of put for the question that asks about what you could do for a person after they get aculizumap as chronic a therapy for PNH. One thing you can do is to actually give those people nice cereal vaccinations. Okay. So like vacines against my cereal meningitis.

Because remember that people that have a C5 through C9 deficiency have an increased risk of recurrent my cereal infections. Okay. So by giving aculizumap, you're from a collogically inducing C5 deficiency, if you may. Okay. So those people need to be placed on my cereal vaccines. Okay. So that's the first key. Next is a evolocumap. Evolocumap works like a lyrocumap. It's a PCS K9 inhibitor. So you can use that for hypercholestrolemia. The G, so there's no F, the G is Gullimiumap. Gullimiumap is a monoclonal antibody against the TNF receptor. Okay. Just like at a LI Miumap, even the next drug I'm going to talk about influximap. Right. So it's an I. And influximap is also monoclonal against the TNF alpha receptor. Now, the next I am going to talk about is I. Dyrocumap. I. Dyrocumap. So I. Dyrocumap is actually used to reverse that big atron. In fact, in the hospital, this is known as prox bind. A reverse is production. Produx is the treatment for for that big atron. Okay. So in general, the common thinking was, oh, you can only reverse hypercholestrolemia and well, that's not exactly trained anymore. You can actually reverse. You can actually reverse a double gattron, which is a direct thrombin inhibitor. It's a factor two inhibitor with a Dyrocumap. Are you missing? Hmm. Divine. This monoclonal sound to low yield. I would encourage you to control F through your first date for 2018 book and you may be surprised. Okay. So next I, the next I is epilimiumab.

Epilimiumab is basically used in immune therapy. It's a monoclonal antibody against CTLA4. Okay. I would advise you to sort of look up that PDL1 CTLA4 business. It's actually kind of high yield to know for step one. I'll probably talk about it in a different podcast, but epilimiumab works against CTLA4 and by working against CTLA4, it prevents your cancer cells from telling your immune system to keep quiet. So immune system makes a lot of noise and when your immune system makes noise, cancer is meant the way. Okay. So that's how epilimiumab works. It's a CTLA4 inhibitor. Now we're done with the ice. Now let's jump to N. Okay. I don't believe there is an M monoclonal. So jump to, at least that's necessary for step one. There's maple lesiumab, but maple lesiumab is not relevant to our discussion. So jump to N. Okay. So the N we'll talk about is another lesiumab. Now the lesiumab is used to treat the multiple sclerosis. Okay. It's actually a monoclonal antibody against alpha-4-integrin. Okay. So by forming a monoclonal against alpha-4-integrin, remember that integrins mediate the adhesion step of your initial response to infection. Okay. So you can sort of imagine like if you formed a monoclonal against that, your white cells that cause some of the damage. Immortable sclerosis do not cross the blood-brain barrier and cause a lot of trouble. Okay. As an aside, please don't forget your integrin deficiency in leukocyte adhesion deficiency, right?

So that's like a CD18 defect where you have a delayed, the classic example presentation is a delayed separation of the umbilical cord or present that has been treated. Okay. So just something to keep in mind with integrins. Now the next N I'll talk about is a nevolumab. Okay. Nevolumab is a monoclonal antibody against a PD1. Okay. It's a checkpoint inhibitor just like epilimumab if you may. Okay. Remember that PD1 you actually find it on the surface of T cells. So PD1 on the surface of T cells is bound by PD1. Okay. PD1 ligand is known as PD01. Whenever you have an interaction of PD01, which is classically expressed by cancer cells with PD1, which is found on the surfaces of T cells, it tells your immune system to shut up. Okay. To not do anything to the cancer. Okay. So if you made a monoclonal against PD1, okay. On the surface of T cells, even if a cancer cell is expressing PD1, it's not a problem. So it's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem.

It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. It's not a problem. In fact, in kids that have like cystic fibrosis or they have like some kind of immune deficiency problem. If you sort of want to protect them against like asthma as prophylaxis, you can actually place them on an homalysium app. Although homalysium app can also just be used to prophylaxis against asthma. Although it's a pretty expensive drug actually. Although it's a pretty expensive drug actually. Okay. Now, jump to the piece. Okay. Palavizio map. Palavizio map is a monoclonal antibody against the anti-boregins. The anti-boregins. The RISV. Okay. Remember that you can actually use a riba variant to treat RISV as well. But that's a very contentious. It's not very commonly done. Okay. But you can actually prophylax against or treat RISV by giving Palavizio map, which is a monoclonal against the virus. Now, the next one I'll talk about. We're jumping to the RIS. We have retoximap. It's a CD20 monoclonal antibody. I already talked about that. The next R is RISV. Okay. RISV. So it works like Bavizio map. It's just a super more expensive version.

It's a monoclonal antibody against VEGF. You can also use this to treat wet age relief and macular degeneration, which I already talked about. And then we jump to the T's. The T's trust to Zuma. Trust to Zuma is an herb B2. Or I guess you can call it her too new in Hibitor. Remember that her B2 is very highly expressed in many breast cancers. Okay. So if you give a monoclonal antibody against that receptor, you could potentially stop that breast cancer in its track. So although in general, the expression of her B2 is a bad prognostic indicator in the setting of breast cancer. So remember that this drug is a trust to Zuma. It is associated with a dilated cardiomyopathy. Although the dilated cardiomyopathy with trust to Zuma is usually reversible. When you stop the drug, the cardiomyopathy usually goes away. Okay. Contrast that with your anthrocycline, like Dono and Doxorobecin, that associated with an irreversible dilated cardiomyopathy, which arises because those drugs love to kill it iron. And through the fainting reaction, you can have destruction of your cardiac muscle. Okay. So you could potentially profilax against that if you're taking Doxorobecin with an iron killiter like a dixerozoxin. Okay. So think of dixerozoxin as a fainting reaction inhibitor if you may. Okay. Now, let's see. So let's jump to the use. Okay. The you all talk about is ostequinomab. Ostequinomab is a monoclonal antibody against interlooking 12 and interlooking 23.

It's actually used for the treatment of psoriasis. So thinking there is that people think that O psoriasis is thought to be due to like a semi-dieted immune response. Okay. Remember that IL-12 helps you go down the T-helper-1 pathway and T-helper-1 cells are involved in semi-dieted immunity. So by giving this drug, you could potentially stop the pathophysiology of psoriasis. And it also, ostequinomab also prevents T-helper-17 differentiation. So remember, T-helper-17 cells are involved in autoimmune disease and to go from T-helper-0 to T-helper-17, you actually use interlooking 23 to make that happen. So by giving a monoclonal antibody against IL-23, you stop that from happening. Okay. Now, the final drug we'll talk about is an S secokinomab. Secokinomab. It sort of works like ostequinomab, but I can see how they could potentially try to twist your brains with this on step one. Okay. So let's sort of break this down real quick. The thing is, if you want to go down the T-helper-17 route, remember those cells are involved in autoimmune disease like I mentioned, you need IL-23 to make that happen. Okay. Now, the thing is T-helper-17 cells for them to mediate all their badness, they actually release interlooking 17. Okay. So the thing is, you have two drug strategies for targeting interlooking 17. I mean, T-helper-17 cells, sorry. You can prevent the differentiation by giving a monoclonal against IL-23, that's the mechanism of action of ostequinomab.

Alternatively, you can also make a monoclonal antibody against the cellular product, IL-17 in this case, with secokinomab. Secokinomab is a monoclonal antibody against interlooking 17. Okay. Now, that we're done with the alphabet, let's just clear up by talking about the remaining immune system drugs. Okay. The remaining immune system drugs, right? So we already said that interlooking 2 is a powerful T-cell stimulator. Okay. And one of the things you need to make, to act, let me transcribe the interlooking 2 gene, is you need a transcription factor. Okay. You need a transcription factor. And the thing is, the transcription factor for the IL-2 gene is N-fat. Okay. N-F-18. Okay. It increases the rate of transcription of the IL-2 gene. Okay. When N-fat is de-phosphoryleafate, it is active. When N-fat is phosphorylated, it is inactive. Okay. Now, it so happens that calcium urine is an enzyme that de-phosphoryleafs N-fat. Okay. I remember that de-phosphorylated N-fat is active. Okay. And calcium urine is the phosphatase, if you may, that de-phosphoryleafs N-fat. Okay. So, if you inhibit that calcium urine, you will prevent the de-phosphorylation of N-fat. If you do not de-phosphorylate N-fat, you do not increase the transcription of interlooking. You do not increase, well, I guess you can see, you do decrease the transcription of interlooking too. Okay. So, there are two classes of calcium urine inhibitors.

You can use these drugs to clobber the immune system, right, so that you can prevent organ rejection, if you may. Okay. So, one drug is a cyclosporine. Okay. Cyclosporine. The way it works is, it marries cyclophiline. Together, they go ahead and inhibit that calcium urine. These drugs have a few high-yield things. They want you to know for the USML Step 1 exam. Okay. The big, big one you certainly want to know is Nefertoxicity. Okay. The thing is cyclosporine causes these construction of the affront and the effren materials in the nephron. Okay. So, that decreases your GFR. Okay. So, you can basically have over activation of your renein and your tensing out of the sterile system, right. And that reduces your blood pressure. So, actually hypertension is a very big side effect with cyclosporine. Okay. And that's the, explain the mechanism behind the nefertoxicity. There's also studies, or I guess some people that are saying that cyclosporine is like directly toxic to the nephron as well, like to your convoluted tubules. So, that could be another potential mechanism behind the nefertoxicity. But I'll say the big one you want to remember is causing visual construction of your effren and your affren materials. And the thing is cyclosporine is actually metabolized by your cytochrome P450 system. Okay. So, the thing is if you actually gave a CEPP450 inhibitor, you could actually give a lower dose of cyclosporine. Okay.

Classically, the drug you actually use for this purpose is deltaism. Remember deltaism is a non-dihydroperidine construction blocker. Right. So, it's a class-frontarant make. It so happens that delta is a CEPP450 inhibitor. So, you may see like define that super awkward. Why are you giving delta? I mean, there are many other drugs that reduce the activity of your, I guess, inhibitor, cytochrome P450 system. The reasoning behind that is yes, delta is a CEPP450 inhibitor. Right. So, it lowers the dose of cyclosporine. You need to give. But we just said that cyclosporine causes hypertension. Okay. Deltaism, I mean, it's sort of a weak effect, but it can also actually help you lower your blood pressure by opening up your urinal vasculature. Okay. So, just another high out time there. Now, another high out side effect of cyclosporine is gingival hyperpleasure. Okay. If you look up pictures of this online, it's actually a pretty disturbing. But it's just a side effect associated with cyclosporine. No one really knows why that's the case. Okay. But you definitely want to know that concept for step one. And you also want to actually know the other drugs that are associated with gingival hyperpleasure. Right. So, drugs like phenitone, remember, phenitone is a sodium channel blocker. That's an anti-segeome medication. Your calcium channel blockers actually both your dihydropyredine, like amlodipine, felodipine, lyphedipine, and your non-dihydropyredine drugs like verapamilandiotisem.

They are also associated with gingival hyperpleasure. Okay. And one bizarre thing, this will be a step one question that many people will miss. But hopefully you would not be one of them because you listen to those podcasts or pathoma if you may, is that acute monocytic or monoblastic leukemia is actually also associated with gingival hyperpleasure. Okay. So those are the high yield things with cyclosporine. Cyclosporine maries cyclophylline to inhibit calcium urine causes never toxicity. It's broken down by CEPP450 so you can give the otiasem to lower the dose of cyclosporine into administer. And it's also associated with the gingival hyperpleasure. Okay. Now the second class of calcium urine inhibitors includes atacroliomas. Tacroliomas is also known as FK506. Okay. It's a calcium urine inhibitor and the way the inhibits calcium urine is, it maries a different person this time. Instead of marinsyclophylline, like cyclosporine does, it actually maries FKBP, FKBB binding protein, okay. And together the inhibit calcium urine. Okay. And the big toxicity you want to know with, with, with, um, tacroliomas is that it's also never toxic, but it's not as never toxic as cyclosporine. Now the next drug I'll talk about is myromonab. Okay. Myromonab is also known as orthoplone T3 or OKT3. Okay. So it sounds like a robotic or I guess an alien name, but anyhow. Okay. So it's an inhibitor of CD3. Okay. Remember CD3, you find it on the surface of all your T cells. Okay.

So this is a drug that basically depletes your T cell population. Okay. Remember your T cells could have CD4, CD8s. They also have like the T cell receptor, which has an offer and a bit of chain. So this drug by binding to CD3, it basically clubbers your T cell numbers. But one thing I will just draw your attention to is this drug usually, or I guess you can see occasionally. Okay. By initially binding to CD3, it actually causes an initial activation of CD3. Okay. So initially you can actually have T cell activation with myromonab. Okay. In fact, this side effect is called the first dose activation effect. Okay. So initially you actually activate your T cell population. You release a lot of cytokines and you can become like hypotensive. You can have like a flu-like reaction that could actually be pretty severe. Okay. But as time goes on, that inflammatory response decreases. Okay. And your T cell population is depleted. In fact, OK, T3, myromonab is classically used like in the immediate period after a transplant to prevent acute rejection because it's actually really, really good at bringing down your, bringing down your T cell population. Okay. Now the next drug I'll talk about is my cofenolate morphetil. I believe this is known as cell sept in the hospital. It's an I know sin monofosophyte dehydrogenase inhibitor. Okay. Remember if you're going from IMP to GMP, you need IMP dehydrogenase to make that happen. Okay.

So by inhibiting IMP dehydrogenase, you basically decrease the synthesis of purines because you're making less guanine nucleotides. Okay. So that's how this drug works as an amino suppressant. Remember that ribovaric, which we used to treat areas V and also have B and C also works by inhibiting IMP dehydrogenase. Now the next drug I'll talk about is serolimus. It's also known as rapamycin. Okay. Serolimus binds to the same protein that Tachorolimus binds to. Okay. So serolimus binds to FK binding protein. Okay. But it does not inhibit calcium urine. It inhibits MTOR. Okay. MTOR stands for mammalian target of rapamycin. Okay. So remember that MTOR is signaling molecule that is downstream of the interlooking to receptor. So you're basically making a T cell not respond to IL to signaling. So one way you can do that we already mentioned is you could block the IL to receptor. We drugs like that. Close your map and bust a lexemap. Alternatively, you can kill the IL to signaling cascade by inhibiting MTOR with a drug like serolimus. So, so you can use serolimus to prevent a rejection of transplants. Alternatively, if you're an interventional cardiologist or I guess if you're a metz student listening to this, you're future interventional cardiologist. You actually quote stents that you put in coronary arteries with these drugs because by preventing T cell proliferation, you do not form like scar tissue. Right. You don't make your immune system.

Think of the stent as a foreign molecule. Okay. So to prevent like stenosis of a stent. Okay. You can actually quote those stents with Iverolimus or serolimus. Right. So they are like similar drugs. They accomplish the same the same purpose. Now, the last drug I'll talk about is anti thymocyclobulin. Okay. Anti thymocyclobulin. Its mechanism of action is it basically binds to T cells. Okay. It's an immunoglobulin. The thing is the constant region of anti thymocyclobulin can be recognized by receptors on the surface of macrophages. Okay. So basically your macrophages when they bind to this constant region, they can basically swallow up your T cells that way. Okay. So this is sort of like an optimizing mechanism if you may and you basically deplete your T cell population by doing that. As an aside, please don't forget that IGG is the only antibody that can do optimization. Okay. C3 B is also complement protein that can do optimization. But remember that IGG and IGM can both do a compl... Classic complement cascade activation. Okay. And this anti thymocyclobulin is actually derived from animals. So you can actually get serum sickness with this drug. Okay. Remember serum sickness is a kind of type three hyper sensitivity reaction. So this brings us to the end of immunofarmacology. I believe if you know everything in this podcast, you know all the immunofarmacology needs to know for basically you USMLE exams, both step one and step two CK.

And you should also know all your monoclonal antibodies for the exams with the drugs we talked about in the monoclonal alphabet. So I wish you all the best happy Easter to those that celebrate Easter and I wish you all a wonderful week ahead. Have a great day and God bless you. I'll see you in the next podcast. Thank you.

They are calcineurin inhibitors, preventing NFAT translocation and T-cell activation.

It has a narrow therapeutic index, and plasma concentration variability dictates dosing to prevent toxicity or rejection.

Interleukin-2 (IL-2).

Cyclosporine and Tacrolimus.

Calcineurin inhibitors plus mTOR inhibitors (e.g., tacrolimus + sirolimus).

Calcineurin Inhibitors.

The dephosphorylation and nuclear translocation of NFAT (Nuclear Factor of Activated T-cells).

IL-2.

Therapeutic Drug Monitoring (TDM) of trough plasma levels.

Cyclosporine and Tacrolimus.

Calcineurin Inhibitors.

The dephosphorylation and nuclear translocation of NFAT (Nuclear Factor of Activated T-cells).

IL-2.

Therapeutic Drug Monitoring (TDM) of trough plasma levels.

Cyclosporine and Tacrolimus.