HLA Complex 2026 — Transcript

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1. 0:00also
2. 0:03known as the major hystocompatibility
3. 0:06complex.
4. 0:08The major hisystocompatibility
5. 0:11complex
6. 0:12known as the human luccoite
7. 0:16antigen in humans. So we're going to
8. 0:19look at the fundamentals fundamental
9. 0:22definitions and the clinical
10. 0:25significance of this system.
11. 0:29It's relevant to hematology. Okay, we
12. 0:33won't go deep into the imunology of it.
13. 0:38So we'll just take um a brief
14. 0:40introduction on the immune system which
15. 0:42I will summarize orally briefly.
16. 0:46Then I also refer you to the blood
17. 0:49transfusion our blood transfusion in the
18. 0:52tropics that red book I also refer you
19. 0:55to that by professor Kof also refer you
20. 0:59to that booklet
21. 1:01with a section where uh we dealt we
22. 1:05discussed the major histompatibility
23. 1:08complex in that text. So we're going to
24. 1:11look at the definition of the MHC or the
25. 1:14HLA system as it being called in humans.
26. 1:19Then we look at the structure, the
27. 1:21classifications of this system, the
28. 1:24structure, the function,
29. 1:27the nomenclature, the genetics and also
30. 1:30look at the clinical significance, what
31. 1:32is the importance of this system to the
32. 1:37human body.
33. 1:39So in terms of HLA and transplantation,
34. 1:43HLA and transfusion therapy, HLA and
35. 1:47disease and also HLA typing.
36. 1:54So our objectives at the end of this
37. 1:57lecture, you should be able to
38. 1:59understand and explain
39. 2:03understand and explain what the HLA
40. 2:06system is. what the HLA system is
41. 2:12and what it means to be is compatible.
42. 2:21You should have a basic understanding of
43. 2:23organization and inheritance of the MHC.
44. 2:28You be able to describe the clinical
45. 2:30significance of the MHC complex. be able
46. 2:34to give an overview of pre-transfusion
47. 2:36test
48. 2:38screening and cross matching that has to
49. 2:41be done. Okay. Demonstrate an
50. 2:44understanding of the principles behind
51. 2:47molecular techniques used in HLA
52. 2:51typing.
53. 2:55So
54. 2:57um as a brief introduction before we go
55. 3:00into the definitions of this terminology
56. 3:04the HLA system
57. 3:07the HLA system
58. 3:10also known as the M jaw histo
59. 3:14compatibility complex. this system.
60. 3:19I know. Okay, let let me go back so that
61. 3:21you be able to um comprehend what I'm
62. 3:25trying to say precisely.
63. 3:28We did you did adaptive you know
64. 3:31adaptive immunity and you know about the
65. 3:35innate immunity very well. Okay. from
66. 3:38secondary school to primary school to
67. 3:40from primary to secondary school even in
68. 3:42your imunology class. You've know about
69. 3:46the innate immune system that fast
70. 3:50nonspecific
71. 3:52response by our macrofasages and
72. 3:56neutrofields that fights uh bacteria.
73. 4:01But you know that the innate immune
74. 4:03system does not have memory. See now we
75. 4:07have the adaptive immunity in the system
76. 4:10in our body that is highly specific and
77. 4:14specialized system
78. 4:16using the T- cells and the B cells.
79. 4:19Okay. And they can also create memory.
80. 4:23So these are the immune systems we also
81. 4:26used to you know very well about. Now
82. 4:29this HLA we are trying to discuss sits
83. 4:31in between them. So we say that the HLA
84. 4:35system serves as the primary molecular
85. 4:39bridge
86. 4:41between the innate nonspecific immune
87. 4:45response and that specific specialized
88. 4:47adaptive immune system. So the HLA
89. 4:50stands in between them. Okay. So
90. 4:54specifically HLA molecule they act as
91. 4:57cellular identity bridges for the body
92. 5:02to distinguish between self and nonself.
93. 5:07Okay. They are responsible for
94. 5:09presenting antigen
95. 5:12because
96. 5:13the
97. 5:15adaptive immune system that uses the
98. 5:18lymphocytes.
99. 5:21The lymphocytes on their own
100. 5:25cannot really
101. 5:27see the bacteras or the viruses that
102. 5:31invade our system.
103. 5:34They cannot really see it.
104. 5:38So it is our T- cell are completely
105. 5:41blind to floating pathogens. The tea
106. 5:45cells which constitute the adaptive
107. 5:48immune system they are completely blind
108. 5:51to floating okay bacteria or viruses in
109. 5:57our body. They can't see them.
110. 6:00So they can only access them if these
111. 6:05bacterials and viruses are processed
112. 6:09by like they are being broken down.
113. 6:12Okay, they are being broken down by our
114. 6:16macrofasages, specialized cells. They
115. 6:19are being broken down and then presented
116. 6:23on a platter, let's say, on a platter
117. 6:26before they adaptive immune system can
118. 6:31respond
119. 6:33or can mount an immune response. And
120. 6:35this platter where these bacterias are
121. 6:38or viruses are being presented
122. 6:42are what we refer to as the HA
123. 6:46complex.
124. 6:47So our innate immune system the
125. 6:51specialized cells
126. 6:53antigen presenting cells like our
127. 6:55macrofasages
128. 6:57that also participate in the innate
129. 6:59immune system. Okay.
130. 7:02takes up these bacterials and breaks
131. 7:05them down, chops them up, breaks them
132. 7:08down and then presents them on a
133. 7:11structure on a platter which we call the
134. 7:14HLA molecule. Okay, for the T lymphocy
135. 7:18for the adaptive immune system to now
136. 7:21begin its response of mounting immune
137. 7:25system. So the HLS molecule serves as
138. 7:29that platter to present a presenting
139. 7:33antigen to the T cells. So we say that
140. 7:37the human gluccoside antigen the HLA are
141. 7:41highly polymorphic cell surface
142. 7:43glyoproteins.
143. 7:46Okay. They are genes in the major
144. 7:49hystocompatibility complex that encode
145. 7:53proteins that help differentiate self
146. 7:56from nonself.
147. 8:00They present peptide antigens to tly
148. 8:03lymphocytes
149. 8:04and play a central role in immune
150. 8:08recognition, histompatibility,
151. 8:11transplantation and regulation of immune
152. 8:15response.
153. 8:20The term luccoite antigen originated
154. 8:24because these antigens were initially
155. 8:28identified through imunological reaction
156. 8:30that were involving white cells
157. 8:34although HLA molecules are not
158. 8:36restricted to luccoytes.
159. 8:39Okay. So is because they were identified
160. 8:42initially in luccoytes that was why they
161. 8:44were called the human luccoytes antigens
162. 8:47but they can be also be present in other
163. 8:50cells of the body. So as a recap
164. 8:56for those that are joining us now, we
165. 8:58said that we are familiar with our
166. 9:01innate and adaptive immune system and we
167. 9:05say that the HLA system sits in between
168. 9:08the two because the adaptive immune
169. 9:11systems which involves the tea cells are
170. 9:15completely blind to bacteria and viruses
171. 9:19that are floating in our body. They
172. 9:21can't see them. They can only mount
173. 9:24immune response to these bacteras and
174. 9:28viruses if these are processed broken
175. 9:33down by the macrofasages or special
176. 9:36presenting cells. antigen presenting
177. 9:38cells and then presented to them on a
178. 9:41platter and that platter we say that
179. 9:43platter is the HLA molecule the human
180. 9:47luccoite antigen that presents antigens
181. 9:50to the T cells. I hope that explanation
182. 9:54is clear for us to understand what the
183. 9:58HLA system where it stands in the immune
184. 10:01system of our body.
185. 10:04If that is clear, I want to see your
186. 10:07thumbs up so that I know that
187. 10:09explanation is clear. You need to know
188. 10:12what the human luccoite antigen is. All
189. 10:16right? So it sits in between the innate
190. 10:19and adaptive immune system. So if you
191. 10:22forgot what that means, you can go back
192. 10:24and check. The innate immune system
193. 10:26responds quickly, okay? But it's
194. 10:29nonspecific and it does not produce
195. 10:32antibodies, cannot produce memory for
196. 10:34subsequent attacks. But our adaptive
197. 10:37immune system cannot see the viruses or
198. 10:41the bacteras that affect our body except
199. 10:45if they are what processed and presented
200. 10:48to them on a platter and that we say
201. 10:51that platter is the HA before they can
202. 10:54be able to recognize it. So that is what
203. 10:57the HA is all about. All right. So let's
204. 11:02now go into the classification
205. 11:07and then the structure and then the
206. 11:09function of these molecules. So we say
207. 11:13that based on the structure and function
208. 11:16alone the structure and function alone
209. 11:19we have two major classes of the HLA
210. 11:22molecule. We have the class one and we
211. 11:25have the class two. You can see the
212. 11:28structure. This is the class one
213. 11:30molecule.
214. 11:44Okay. You can see this is the
215. 11:47um class one molecule. This is the class
216. 11:512 HLA molecule. This is class one. This
217. 11:54class two. Okay.
218. 11:58So the human luccoside antigen class
219. 12:00one. The cell surface glyoprotein
220. 12:03antigens of it contains the HLA that is
221. 12:07the classes of the class one. HLA are
222. 12:11made up of HLA1, HLA A, HLA B and HLA C
223. 12:16series. They are called the HLA class
224. 12:19one antigens and we say that they are
225. 12:23expressed on the surface of most
226. 12:25nucleated cells of the body. They are
227. 12:30expressed on all nucleated cells of the
228. 12:33body. That means any cell that's in our
229. 12:37body that does not have nucleus is not
230. 12:40nucleated
231. 12:41not be able to express the class one HLA
232. 12:45antigen. So and the classical example is
233. 12:49our mature red cells which does not is
234. 12:52not nucleated. Okay. So they cannot
235. 12:55express the HLA class one molecule.
236. 13:00So when you talk about in terms of uh um
237. 13:04they are found in soluble form in plasma
238. 13:07and are absorbed on the surface of
239. 13:10platelets.
240. 13:12They are found in soluble form in plasma
241. 13:16and are absorbed on the surface of
242. 13:20platelets.
243. 13:22Studies indicate that HLA B which is the
244. 13:25most polymorphic is the most significant
245. 13:28class of class one lucose followed by
246. 13:31HLA A and HLA C. So in terms of
247. 13:36reactions and clinical significance the
248. 13:39HAB is the most uh being the post most
249. 13:44polymorphic having different forms is
250. 13:48the most significant
251. 13:50um lucus.
252. 13:53Yeah.
253. 13:55Right.
254. 13:58So the class one antigen they have a
255. 14:00molecular weight of 59,000 datons and
256. 14:05consist of two chains. You can see the
257. 14:08chains here. You can see the chain these
258. 14:11three. I hope you are seeing my cursor
259. 14:14are the alpha chain. When you see the
260. 14:16class one molecules you have one alpha
261. 14:19chains which are combined together. You
262. 14:22can see it from this groove down and it
263. 14:25goes down to the cell membrane. consists
264. 14:28of two chain the alpha chain and a beta
265. 14:31micro globaline molecule which is 12
266. 14:34doton and is encoded by another
267. 14:37chromosome 15. Okay. So the mic the beta
268. 14:422 microline is not attached to the cell
269. 14:45membrane as you can see in this
270. 14:47structure. This is the cell membrane.
271. 14:49This uh beta microglobine does not go
272. 14:52down to the cell membrane. is only the
273. 14:55alpha chain that goes down that is
274. 14:57attached to the cell membrane. Okay, it
275. 15:01is associated with heavy chain but it's
276. 15:04not coalently
277. 15:06bound to it. Out of the three alpha
278. 15:09domains, the alpha 1 and alpha 2 domains
279. 15:13contains the polymorphic region carrying
280. 15:16the HLA antigen specificity. And this is
281. 15:20where their antigens are being presented
282. 15:23for the TE-C cells to recognize.
283. 15:31Okay.
284. 15:33So we are not going into deep
285. 15:36into the uh structures. We are just
286. 15:39mentioning the major
287. 15:41components of the structure that have to
288. 15:44do with what we are going to be
289. 15:45discussing.
290. 15:47Okay.
291. 15:49So the human luccoite class 2 antigen
292. 15:53can see the structure is quite different
293. 15:55from the structure of the class one
294. 15:59molecules. they still have um it has the
295. 16:03cell surface glyoprotein antigens are
296. 16:07the classes
297. 16:11the classes for are the HLA DR HLA DQ H
298. 16:17DP these are the ones that make up the
299. 16:20HLA class 2 antigens they have a
300. 16:24molecular weight of approximately
301. 16:28they have a molecular weights still
302. 16:31admitting those that are just entering
303. 16:33now. Okay. They have a molecular weight
304. 16:37of approximately 63 dons and consist of
305. 16:42structurally
306. 16:44similar alpha and beta glyoprotein chain
307. 16:51both of which are transmembrane that is
308. 16:54they pass through the membrane of the
309. 16:58cell. You can see that in the diagram.
310. 17:00Each chain has two amino acid domains of
311. 17:05which the outermost domain contains the
312. 17:08variable region of class 2 als this is
313. 17:11the place it chain has the outer this is
314. 17:14the place for the antigen presentation
315. 17:17of peptides. Okay that's the variable
316. 17:21region. Okay.
317. 17:27Okay. So that is the difference between
318. 17:30the HLA molecule class one and class 2.
319. 17:34You look at the
320. 17:36uh the domains the alpha domains alpha 1
321. 17:40alpha 2 which make up the variable
322. 17:43regions and then the beta 2 beta beta 1
323. 17:47beta 2 glyoprotein chains. While in that
324. 17:51of a class one molecule, we talked about
325. 17:54alpha the alpha chain and the beta micro
326. 17:58globaline
327. 18:04on this late commas.
328. 18:07Okay, for tissue distribution we say
329. 18:10that the class one molecule
330. 18:13are distributed on all nucleated cells
331. 18:16in the body where they are found. For
332. 18:19the class one, we say that they are
333. 18:21found on all the inucleated cells in the
334. 18:25body. For class 2 tissue distribution,
335. 18:29the antigen is confined to immunompetent
336. 18:32cells
337. 18:34such as the belymphocytes,
338. 18:39macrofasages, endothelial cells and
339. 18:42activated T lymphocytes.
340. 18:47Okay. So we say that the
341. 18:50class distribution of class 2 antigens
342. 18:53of the HLA molecules is only on the
343. 18:56antigen presenting cells. Okay, the
344. 18:59antigen presenting cells like also the
345. 19:02dendritic cells the macrofasages the B
346. 19:06cells. So they are on the imunompetent
347. 19:09cells that is where they are found.
348. 19:13The class 2 HLA molecules are found on
349. 19:18confined to immunompetent
350. 19:21cells antigen presenting cells. Okay.
351. 19:26While the class one molecules are
352. 19:29distributed on all nucleated cells of
353. 19:32the body.
354. 19:35Okay.
355. 19:37Since class 2 antigens initiate a
356. 19:40general immune response, they are
357. 19:43present on imunological artery cells and
358. 19:46not on all tissues. We have said that
359. 19:50the peptide binding group in class one
360. 19:53and class 2 molecule is critical for
361. 19:56functional aspect of HLA molecules.
362. 20:00Okay. Also we will also see that when we
363. 20:04discuss the function of this HLA
364. 20:07molecules
365. 20:09okay
366. 20:12okay we've said it the expression
367. 20:15is just a table form trying to also say
368. 20:18it class one is found on all nucleated
369. 20:24cells the class 2 HLA molecule is found
370. 20:28on antigen presenting cells the
371. 20:31belymphocytes, the macrofasages, the
372. 20:34dendritic cells, the endotellia cells.
373. 20:39Okay. The function
374. 20:42the class one molecules,
375. 20:45okay, will be able to identify
376. 20:49cells probably
377. 20:53cells that have been infected, invaded
378. 20:56by bacteria. Take for example a virus.
379. 21:00Take for example in a patient with
380. 21:03immune
381. 21:05uh HIV. Okay. You know what the virus
382. 21:09does is to invade the cells of the body
383. 21:14and
384. 21:16take up the mechanism of the body. So
385. 21:19they invade the cells and take up the
386. 21:22the cell function take up the mechanism
387. 21:25of the cell. So
388. 21:28it is the class one HLA molecule that
389. 21:32can recognize the cells of the body that
390. 21:35have been invaded by bacteria. Okay, and
391. 21:39destroy it. It is the function of the
392. 21:42class one molecule to recognize cells of
393. 21:47the body that have been invaded
394. 21:50by
395. 21:51bacteria or viruses and then destroy the
396. 21:55cells. You can see the the the the the
397. 22:00CD8. Okay, CD8. So they identify these
398. 22:05cells that have been invaded by viruses
399. 22:09and then destroy the cells. So for the
400. 22:14uh class 2 molecules, okay, they
401. 22:18identify
402. 22:19invader floating around the cells, okay?
403. 22:24they they identify uh invader that
404. 22:27floating around outside of the cells
405. 22:30maybe a bacteria that have invaded the
406. 22:33system and these bacteria are being
407. 22:37processed by the macrofasages and
408. 22:39presented to them. So we said that class
409. 22:42one molecule identify have endo
410. 22:45endogenous pathway for identifying
411. 22:49bacteras while class two molecules have
412. 22:52exogenous pathway for identifying
413. 22:56invaders of the body. We'll still look
414. 22:58at that when we see the okay [snorts]
415. 23:00functions of the HLA molecule.
416. 23:04Function of the HA molecule. So we said
417. 23:07that peptide antigen that fit into the
418. 23:11uh uh into the groove peptide binding
419. 23:14groove of the ha the peptide binding gve
420. 23:17are those groove that are formed by here
421. 23:21as you can see by this invariable region
422. 23:24this is the peptide binding groove okay
423. 23:27so peptide antigen that fit into the
424. 23:31peptide binding group of ha molecules
425. 23:34are 8 to N amino acids in length. We are
426. 23:38talking about the class one molecule.
427. 23:40They are derived from protein. Which
428. 23:46they are derived from protein. Who is
429. 23:48raising the hands
430. 23:50here? Do you have any question? Unmute
431. 23:53yourself then ask your question.
432. 23:59Why are you raising up your hand?
433. 24:04Why are you raising up your hand? Can
434. 24:06you unmute yourself and speakh?
435. 24:16You're raising up your hand.
436. 24:19>> Okay.
437. 24:20>> Why are you raising up your hand?
438. 24:23You're not talking. I'll go ahead.
439. 24:26All right.
440. 24:28So, where did I stop? Okay. So we are
441. 24:31talking about the function of the uh
442. 24:34class one molecules
443. 24:37the HLA class one molecules. So we are
444. 24:41saying that they present an endogenous
445. 24:44proteins. These endogenous proteins I
446. 24:47said for example when a virus invades a
447. 24:51cell invades a cell of the body like in
448. 24:55HIV patients. I need to mute you people
449. 24:58so that can be clear.
450. 25:01when like when a HIV virus invades the
451. 25:04cell mechanism of the body and takes up
452. 25:07the mechanism of the body that to
453. 25:10destroy that HIV virus it is this um it
454. 25:14is the HLA class one molecules that are
455. 25:18being engaged okay
456. 25:23so the T- cells like the killer cells
457. 25:26the cytotoxic tea cells identify these
458. 25:29cells that have been invaded by these
459. 25:32viruses and present the
460. 25:36present the antigen of these viruses to
461. 25:39the class one at a molecule for
462. 25:42destruction by the T-C cells
463. 25:46the killer cells the cytotoxic T- cells
464. 25:50okay
465. 25:53class one molecule with peptides are
466. 25:55transported to cell surface where they
467. 25:58are available
468. 26:00to interact with CD8 positive T cells.
469. 26:05If the
470. 26:07if the T uh Tymphocy receptor of the
471. 26:12Tlymphocytes the cell receptor of the
472. 26:15Tlymphosy can bind antigenic peptide it
473. 26:18will now elicit an inflammatory response
474. 26:21cytotoxic effect.
475. 26:24Okay. So the HLA class one molecule
476. 26:28identify endogenous proteins and destroy
477. 26:32and present it to the Tlymphocytes the
478. 26:36cytotoxic Tlymphosytes the CD8 cells to
479. 26:40so that it can now mount an immune
480. 26:43response and destroy the invaded cell in
481. 26:47the body.
482. 26:54That is for the class one molecules. So
483. 26:57for the class two molecules you can see
484. 27:00that okay the class two molecules are
485. 27:03synthesized in the india cells but
486. 27:06peptides antigen are not inserted in the
487. 27:08peptide binding growth. They need to uh
488. 27:12they need to be transported to the
489. 27:16endoome where the invariant chain that
490. 27:18is covering that area is being removed.
491. 27:22Okay. So but class 2 antigenic peptide
492. 27:25is then inserted into the groove. Okay.
493. 27:28So the peptides are derived from
494. 27:30exogenous proteins. That's the diff the
495. 27:34main difference you will know in the
496. 27:36function of the class one and class 2
497. 27:39molecules. That class one molecule
498. 27:41presents endogenous
499. 27:44pathogen processes endogenous pathogen
500. 27:47and present it to the Tlymphosy
501. 27:51cytotoxic Tlymphosytes.
502. 27:53While the class 2 molecules was able to
503. 27:57identify exogenous proteins, okay, and
504. 28:01also maybe derived from bacteria,
505. 28:04process it, present it on it, antigen
506. 28:07presenting cells for the CD4 positive,
507. 28:11we call them T- helpper cells, I think,
508. 28:14call them T- helpper cells to recognize
509. 28:16them and mount an immune response. you
510. 28:19know t- helpper cells will always
511. 28:23uh lead to the production of antibodies
512. 28:26that will now go to destroy the
513. 28:29pathogen. Okay,
514. 28:34resulting in the production of
515. 28:36antibodies against the invading
516. 28:39bacteria. So that is the pathway for the
517. 28:42class 2 HLA molecules leads to the
518. 28:46production of antibodies. Why? For class
519. 28:49one is cytotoxic.
520. 28:51They they recognize the cells that have
521. 28:54been invaded and destroy the cell
522. 28:57because the virus have already overtaken
523. 29:00the cells over can imagine HIV that I
524. 29:03used to give example the virus have
525. 29:06already invaded the cell taking up the
526. 29:08cell mechanism and detecting the
527. 29:10function of the cell. So the outright
528. 29:13correcting is to destroy the cell itself
529. 29:16unlike the class 2 that recognizes
530. 29:19exogenous pathogen probably a bacteria
531. 29:21that is floating within the cell within
532. 29:24the body and you know that these
533. 29:26bacteras the first innate immune
534. 29:28response is for the macrofasages to
535. 29:31capture these bacteras now process it
536. 29:35and present it on their structure that
537. 29:38their antigen presenting structure they
538. 29:40present it now on their HLA molecule
539. 29:43which is the class 2 HLA molecule where
540. 29:48the CD4 cells lymphocytes will be able
541. 29:51to recognize it and mount initiate an
542. 29:54immune response by producing an
543. 29:57antibbody producing antibbody that will
544. 30:00now go to attack the bacteria that
545. 30:03invaded the system. So that is the
546. 30:06distinct process pathway for handling
547. 30:10bacteria or invaders
548. 30:13mounting immune response for the class
549. 30:16one and class two. So you should be able
550. 30:18to differentiate the two classes in
551. 30:20terms of their structure. We have seen
552. 30:22their structure and in their function as
553. 30:25in regards to their antigen presenting
554. 30:28pathway. How do they present antigen to
555. 30:31the body? that is the main uh function
556. 30:35of it that we are considering in this
557. 30:38class.
558. 30:42So the human luccoite
559. 30:45antigen
560. 30:48genetics the genetics of the human
561. 30:51gluccoite antigens.
562. 30:55Okay. So we said that the HLA complex
563. 30:58contain about 35 to 40 genes group into
564. 31:03three regions located on the short arm
565. 31:07of chromosome 6. You can see the
566. 31:10chromosome 6 here. Here is the short arm
567. 31:13and this image enlarges the the the the
568. 31:17the genes that are the HLA or the major
569. 31:22histompatibility complex molecules. the
570. 31:24HLA molecules you can see class one
571. 31:27class 2 class 3 but we are not
572. 31:29considering class three here okay we are
573. 31:32measuring on the class one and class two
574. 31:36molecules so this is the location and
575. 31:38organization of the human luccoite
576. 31:40antigen on chromosome 6
577. 31:45late commas
578. 31:47disturbing us
579. 31:50supposed to stop by 6:30 Okay. So
580. 31:56as per genetics we say that the class
581. 31:58one this encodes for the alpha
582. 32:01polyeptide chain of two class one
583. 32:03molecules. The beta chain of the class
584. 32:06one molecule is encoded by a gene on
585. 32:10chromosome 15 that is the beta
586. 32:12microglobine gene. Okay, you can see
587. 32:15that class one gene encodes for the
588. 32:18classic transplantation molecules the
589. 32:22HLA A HLA B HLA C it also encodes for
590. 32:26additional non-classic genes HLA E F and
591. 32:30G okay so the class 2 genes code for the
592. 32:34alpha and beta polyeptide chain of the
593. 32:37class 2 molecules okay these are their
594. 32:40gene when you say this gene codes for
595. 32:43this you're just saying that this gene
596. 32:46the product of that gene is this. So the
597. 32:49class 3 gene code encodes many diverse
598. 32:53molecule including complement factors
599. 32:55but we're not considering them here. The
600. 32:58protein coded by DRA and DRB genes
601. 33:02results in this is for class 2 HLA DR1
602. 33:06through HA DR18.
603. 33:09the product of A and B gene express HLA
604. 33:13this and that. So when we say that this
605. 33:16gene en quotes or codes for this, we
606. 33:18saying that this gene the product of
607. 33:20that gene is that. So
608. 33:24that's all what this information is all
609. 33:26about. Okay, thank you. So the human
610. 33:30luccoyite antigen moment
611. 33:35see the HA as we begin to go into the uh
612. 33:40typing and then the clinical
613. 33:44significance
614. 33:46you'll be able to appreciate the fact
615. 33:48that the HLA antigen is a very complex
616. 33:52uh it's a very complex gene okay so how
617. 33:56they number it just like we have The IUP
618. 33:58pack in chemistry there are systems of n
619. 34:02there are systems of naming these are
620. 34:05just systems of naming the HLA molecules
621. 34:09okay that the this first this is at
622. 34:12least the HLA you're talking about the
623. 34:14HLA genes this signifies the HLA gene
624. 34:17you're talking about then the first
625. 34:19letter here goes to show the locus okay
626. 34:24then this depicts the protein chain
627. 34:28Okay. Then this depicts the AL family.
628. 34:31The first number here shows the AL
629. 34:34family and then this last digit we show
630. 34:37the ALA variant. So this is what is
631. 34:40similar to what we refer to up in
632. 34:43chemistry the nomature the naming system
633. 34:46for the HLA antigens and we can just
634. 34:49take it at this primary level.
635. 34:52So that's it.
636. 34:57And as the
637. 35:01research progresses and discovering more
638. 35:04the nomature keeps also changing. So
639. 35:08that's just what that is. So inheritance
640. 35:10of the human luccoite antigens
641. 35:15can see this is a segregation of human
642. 35:17luccoite antigen haploides in family. So
643. 35:22this represents the father and then the
644. 35:25mother and you can see their HLA makeup,
645. 35:29their genetic makeup. This is the father
646. 35:31and this is the mother
647. 35:34shown in different colors. So these are
648. 35:37now the children child one, child two,
649. 35:40child three and child four.
650. 35:44Okay. So we say that the
651. 35:48uh
652. 35:50the HLA system
653. 35:52they are dominant. Okay. So and each of
654. 35:59each of the a hlo type let me okay
655. 36:02explain to you what a hlo type is. A
656. 36:04hloype is a combination of alals
657. 36:08inherited together on the same
658. 36:11chromosomes. So when you see this child
659. 36:15the alals he inherited on the same
660. 36:19chromosome you can see this one is
661. 36:20coming this red one is coming from the
662. 36:22father while this blue one is coming
663. 36:25from the mother. So this als this
664. 36:30combination of alals that this child
665. 36:32inherited is what we call the hapluti.
666. 36:37Okay. So
667. 36:41and we say that the HLA molecule the
668. 36:43inheritance is co-ominant. So each of
669. 36:47the ali you inherit either from your
670. 36:50father you must must be expressed. You
671. 36:53can see this red being expressed this
672. 36:55blue from the mother is expressed. So
673. 36:57they are co-dominant they are being
674. 37:00expressed. So when the HLA antigen are
675. 37:03listed as they are detected by tissue
676. 37:06typing technique it is known as HLA
677. 37:09phenotype. Okay. Inheritance follows the
678. 37:12established rules of genetics. Okay.
679. 37:15Every person has two copies of
680. 37:17chromosome six and possesses two haploes
681. 37:22one from each parents.
682. 37:25Okay. HLA genes are autotosomal
683. 37:29dominant and co-dominant. The phenotype
684. 37:33represents the combination
685. 37:36the combined expression of both haplo
686. 37:39types. So what it means is that
687. 37:44in the hla genetics
688. 37:46an individual or a child will express
689. 37:51all the genetic makeup inherited from
690. 37:53both parents. There is nothing like it's
691. 37:57recessive. You are not being expressed.
692. 37:59It expression means um
693. 38:04how do I put it? Okay, let me probably
694. 38:06somebody inherited a gene for for brown
695. 38:10eyes. Okay. And you look at the person
696. 38:13the eyes is brown. It's expressing that
697. 38:17uh gene that he inherited. That's what
698. 38:19we mean by expression and co-ominant.
699. 38:23When you inherit something, you must
700. 38:25express it. It must show it must be
701. 38:27functional in the body. So whatever we
702. 38:31inherit from our mother in terms of the
703. 38:34HLA molecule and from the father must be
704. 38:37expressed by the child.
705. 38:44So there are some terminologies that we
706. 38:47need to understand when we are dealing
707. 38:49with the HLA molecule. So that when we
708. 38:52go into the clinical significance of the
709. 38:54HAL we'll understand why what is
710. 38:57happening it's happening. So
711. 38:59polymorphism
712. 39:01is when there is uh different forms of a
713. 39:05gene the different forms of a gene. So
714. 39:09we say polymorphism at the HLA locus is
715. 39:12extreme. So the HLA molecule is
716. 39:16extremely polymorphic. It has different
717. 39:19forms of the gene. Okay. It evolved to
718. 39:23counter all different peptides from
719. 39:26evading organism. This is a an immune
720. 39:30mechanism. Okay. This is also an immune
721. 39:32mechanism by the body to be able to
722. 39:35counter organisms from environment that
723. 39:38may want to um overpower the immunity of
724. 39:43immune response of the body. So the HA
725. 39:46system is such that it's very very
726. 39:48polymorphic. It can have different
727. 39:50forms. Okay.
728. 39:53So that it will be able to en counter
729. 39:55some immune response invading organisms.
730. 39:59Okay. Each HLA molecule differ from the
731. 40:01other in its amino acid sequence that is
732. 40:05different forms. Okay. The HLA system is
733. 40:08highly polymorphic
734. 40:10with the number of officially recognized
735. 40:13HLA alsi
736. 40:17over time. According to the IPD
737. 40:21database as at this time we can see
738. 40:25there are about 44,000 over HLA alil are
739. 40:29currently recognized.
740. 40:31You can equate that to
741. 40:34the red cell antigens. You know, we say
742. 40:37that because this HLA antigens were
743. 40:40initially recognized in white cells,
744. 40:42they were referred to that they were
745. 40:44referred to as the human luccoyte
746. 40:47antigens. Now, how many red cell
747. 40:50antigens are recognized up to date? Can
748. 40:54you think about that? Now we are saying
749. 40:56that for this HLA alles
750. 41:00uh 44,000 alles are currently
751. 41:03recognized. Okay.
752. 41:06Uh when you break it down HLAA you can
753. 41:09see their figures 7,000 11,000 9,000
754. 41:12respectively among the class 2 localai
755. 41:16can see the numbers also increasing.
756. 41:19However, polymorphism is also population
757. 41:22specific. When we discuss about the
758. 41:24clinical significance of this HLA
759. 41:27system, you will understand this better.
760. 41:29In India population, the common hloype
761. 41:33are as follows. Okay, they have a
762. 41:36database for that. So that is that this
763. 41:40polymorphism aspect of HLA. We
764. 41:42appreciate that better when we discuss
765. 41:44about the clinical significance of the
766. 41:47HLA molecule. This is also still showing
767. 41:50the the increase in the alex that's been
768. 41:54discovered up to date. Okay.
769. 42:00Okay.
770. 42:11There's also another phenomenon we call
771. 42:15linkage dise equilibrium. Those that are
772. 42:17coming now I won't ad meet you again.
773. 42:20Okay
774. 42:23linkage this equilibrium
775. 42:27the frequency of alals at one locus
776. 42:31should not affect the frequency of alil
777. 42:35at another locus.
778. 42:40Okay. However in HLA genetics this is
779. 42:43not true.
780. 42:45Okay. This is not true.
781. 42:49A classical example is all this. Okay.
782. 42:54Oh dear.
783. 42:55This late commas
784. 43:01late commas. Okay. So we say that the
785. 43:04HLA molecule that the frequency of
786. 43:07allayout at one locus should not affect
787. 43:11the frequency of alals at another locus
788. 43:20but in HLA it is not. So okay
789. 43:27let me admit these people so so that
790. 43:31can flow.
791. 43:34Okay.
792. 43:36So linkage dise equilibrium is the
793. 43:40non-random association.
794. 43:42See it nonrandom association of alals at
795. 43:47two or more genetic local within a
796. 43:52population.
797. 43:55Settle this
798. 43:58online classes.
799. 44:00Okay.
800. 44:03So,
801. 44:06so if two HLA alles are found together
802. 44:11on the same chromosome more frequently
803. 44:16than is expected by chance, they are
804. 44:19said to be in linkage dise equilibrium.
805. 44:24Okay, let's say that the frequency of
806. 44:27this HLA
807. 44:29antigen, let's say a that the frequency
808. 44:31is two and then the frequency of this
809. 44:34one is three. You expecting to see them
810. 44:37in a population like their frequency
811. 44:40together in a population to be something
812. 44:43like 2 * 3 that six. But when you can
813. 44:46when you now evaluate the population you
814. 44:49find out that their frequency maybe you
815. 44:51are observing them maybe 25 times
816. 44:54higher. Okay. So you will say that they
817. 44:57are in this equilibrium. I hope this
818. 45:00sentence will just help you to um
819. 45:03understand it. frequency of allay at one
820. 45:06locus should not affect
821. 45:09the frequency of alles at another locus.
822. 45:13However, in HLA genetics, this is not uh
823. 45:18true.
824. 45:25Okay. So
825. 45:28um it will still imply when we talk
826. 45:30about the the clinical implications of
827. 45:34this but
828. 45:38know that we are not talking about don't
829. 45:40uh think about linkage
830. 45:43don't think about linkage linkage
831. 45:48okay let me leave let me not go into
832. 45:50details that so that you won't get
833. 45:52confused so just know that in Um
834. 45:58in uh HLA
835. 46:01that is what we call linkage this
836. 46:04equilibrium.
837. 46:06Okay.
838. 46:09You know how to put it so that you
839. 46:10understand it all this terminology.
840. 46:12Okay. Let me see the next slide. Oh
841. 46:14dear. Oh la. I can't go into the method
842. 46:18now.
843. 46:20Okay. So let me take some questions from
844. 46:22you. Do you have any questions?
845. 46:25Let me take your question so that I know
846. 46:29um we will do the
847. 46:32HLA typing methods
848. 46:35need to understand what HLA is. Now next
849. 46:37time we now go into the HLA typing
850. 46:40methods cuz it's quite complex.
851. 46:44So let me take your questions. Let me
852. 46:47unmute you. Take your question. Okay.
853. 46:53Let me
854. 46:56go there.
855. 46:58If you have any questions,
856. 47:01let