BB LEC 3 ABO & Hh Blood Group Systems PDF

IMMUNOHEMATOLOGY - BLOOD BANKING RD ND LECTURE | 3 YEAR | 2 SEMESTER | PRELIMS | DEAN MILAN​ LESSON 3:THE ABO AND Hh BLOOD GROUP SYSTEMS LEARNING OUTCOMES -​ For ex: Th...

IMMUNOHEMATOLOGY - BLOOD BANKING RD ND LECTURE | 3 YEAR | 2 SEMESTER | PRELIMS | DEAN MILAN​ LESSON 3:THE ABO AND Hh BLOOD GROUP SYSTEMS LEARNING OUTCOMES -​ For ex: The mother looks like O and the father Why do we say and H? looks like O. -​ They are two diff blood group system. They are WHAT IS THE POSSIBLE BLOOD TYPES OF THE determined by the different set of genes, and these CHILDREN? O. genes are located in the chromosomes (?). -​ Suppose nagkaroon ng anak na type A yan, However, the H blood group system (BGS) possible kaya? Ibang father. influences expression of the ABO (actually wala -​ REMEMBER THE PRINCIPLE THAT ONLY THE namang O ags, noh? AB ags and so) sometimes BLOOD GRP AGS INHERITED FROM THE we will see them as ABH blood group system pero PARENTS CAN APPEAR IN THE CHILDREN. mali yun bcs they actually belong to the diff blood Why po? U will learn that here. In fact, grp systems. But the Hh is actually a diff BGS Medtechs can stand to be expert in courts by determined by a diff set of genes and they are proving exclusion of paternity in parentage (?) located in the diff chromosomes kaya dapat problem. EXCLUDING. So sasabihin mo na siya separate sila. ay likely na hindi tatay or di siya anak ng ganitong tao (so EXCLUSION). ​ Correlate why the ABO system is considered the major blood group in transfusion and ​ Given cases of blood typing reactions, identify the transplantation. phenotypes, both direct and reverse methods. TATANUNGIN NI DEAN SA ESSAY! -​ This one, u will have these experiences or testing Why do we consider it as the major blood grp in in ur lab. Try as much as possible to be able to transfusion & transplantation? perform. Hindi yung nanonood ka lang na ganyan. -​ Meaning to say that if px needs a blood type O. Magperform ka! U have u’re own px, u do ur (What blood are u going to give in transfusion? mixing of the reagent, u do the centrifugation, the Dapat type O din!) If a px who needed organ rocking of the slide dapat magawa niyo to. U transplantation who needed kidney transplant, should have the confidence to do it, hindi pwedeng dapat yung donor type O din. Why? We will only passive observer ka lang, gawin mo yung test. So be able to explain why when we finish the chapter. that when u will become interns later on, may quota yan ( like 50 blood typings, naspak ka kc u ​ Master the reciprocal ABO antigens and havent done anything yet, okay?) antibodies. -​ There should be no error. Hindi yung nag iisip ka ​ Explain the formation of Hh, A, B antigens on the pa. red cells from precursor substances as well as -​ For ex: What is the BGA in type A? A. Dapat ABH substances in secretor body fluids. ganon, automatic hindi yung mag iisip ka pa. -​ I keep telling my students, u will trace ur own -​ What are the specific antibodies in blood type HAB ags on ur own blood type. PART NG A? anti-B EXAM YAN (PRELIMS). Suppose i will tell u that Why is mastery important? iprove mo sa tracing na O lang ang -​ → Bcs all the BB works done in the lab, ABO mapproduce mo na ag (H lang). I WILL ASK BLOOD TYPING IS THE MOST COMMON YOU WHAT IS UR BLOOD TYPE, TRACE THE THING U R DOING IN THE BB LAB. So dapat FORMATION OF THE AG IN UR BLOOD TYPE. yung mastery mo parang alam mo na yung LAHAT KAYO IPPROVE NIYO YAN. 20 PTS. sagot na 1+1 = 2. Automatic yung sagot. We will develop mastery on the ABO blood grp ​ Describe the subgroups of ABO. system ags & abs so that in this regard -​ We have A1, A2.. Bombay subgroup ERASURES OF LETTERS ARE WRONG! CHANGING ANSWERS IN THE ABO TYPE IS ​ Correlate the importance of subgroups/ variants in WRONG. Why is that? Bcs in the lab, u blood transfusion. CANNOT SUPERIMPOSE LETTERS. Kung Type -​ This is the case where for ex ACQUIRED A A Yun tas isusuperimpose mo ng B, BAWAL phenomenon, can really create a problem in blood YUN. typing and even cross match. Legal Case that maam dean handled: ​ Predict the ABO phenotypes and genotypes of RA 5527, ano sinabi? UNANIMOUS DECISION diba offspring from various ABO genetic mating. for revocation of license? 3/3 pero outnumbered si -​ So we have to show MASTERY in the maam 2/3 ang decision. The case happened in landsteiner rule to be able to predict ABO DAVAO buti di namatay si px. phenotype and genotype of offspring fr previous ABO genetic mating. If a mother is ​ Given cases of atypical blood tying reactions, such a blood type and a father is such a blood resolve and identify the correct blood type. type, CAN WE PREDICT THE BLOOD TYPES -​ Atypical means not of the usual observation that u OF THE CHILDREN? YES, So that is what we see when u r doing blood typing. So dapat alam mean in genetic (making?). mo kung ano yung usual. Pag lumihis doon sa what is usual then that is atypical. -​ Like what maam said, BLOOD TYPING is other exist in B. If both agglutinins occur, they are ALMOST ALWAYS give 3+ or 4+ agglutination classified as C. Later on, itong C became type O (bcs reaction (that’s the usual) and it is QUICK TO type O has anti-A & anti-B). FORM AGGLUTINATION. But when it happens na “bat ka ito ang tagal mag agglutinate? Or bakit VON DECASTELLO AND STURLI kaya ang liliit ng mga agglutinate? Doon magtataka ka na. You are dealing w/ something ​ Discovered Type AB that is NOT TYPICAL. Maybe this is a variant (?). -​ Were actually students of Karl Landsteiner and So we also have that case like that again in they were able to identify the 4th blood type, AB. LUMED. BERNSTEIN (1924) ​ Identify or recognize the different causes of blood typing discrepancies. ​ described the first theory of inheritance of ABO, follows the simple Mendelian genetics. DISCOVERY OF THE ABO SYSTEM ​ Sabi niya, “ Blood types are determined by genes. And genes are obtained from parents. KARL LANDSTEINER (1901) So what the blood types of the parents are, ​ Father of Immunohematology (bcs he these will determine the blood type of the discovered the ABO blood grp system) children. For ex: Is it possible to have a parent ​ Transfusion started to happened or performed way who is type A and the other parent is type B, back 16th century. Can u imagine yung 300 yrs na and can they have an A (? di ko maintindihan) nagundertake sila ng transfusion even James child? Yes, if they are AO & BO. So w/ the Blundell , Jean Baptiste Denis (hit and miss sila sa parent whose type A & type B, they r both transfusion). Not until Karl Landsteiner discovered heterozygous. The 4 blood types are possible the B & O and meron yung isang guy sabi niya (A,B,O,AB). We will prove that in genetic dapat magkablood type. Doon palang nagstart mating. yung safer blood transdusion. Imagine 300 yrs ​ Gregor Mendel is the “father of genetics” bago nagkaroon ng understanding ng diff BGS. Bernstein just followed the law of genetics in the inheritance of ABO blood group system ​ discovered the first human blood group system → THOMPSON Types A, B, O (the method he used was actually a REVERSE BLOOD TYPING. Bcs at that time, ​ discovery of A1 and A2 subgroups. wala pang typing sera. So he got the spx fr one person and mixed it w/ the serum of another ABO PHENOTYPES AND GENOTYPES person. And then sabi niya, itong blood na ito was agglutinated by that serum but did not agglutinate the other red cells. So he just named it A, then B, then O (if he was not able to identify any ag on the red cell.) ​ How did he discover? He mixed plasma and RBCs from different individuals and came up with different reactions; some specimens on the test tube agglutinated while some did not ​ He is part of the one who tested or discovered the Rh system and some other blood grp system. -​ This is according to the law proposed by Bernstein; this table summarizes the percentage of individuals born with the particular blood types in various races -​ Most common to rarest blood type: O (O, A, B, AB) -​ Rare: AB -​ ABO blood types are genotypes (total genetic composition of an individual representing the maternally and paternally inherited genes) -​ Genotypes will now lead to the formation of phenotypes which are the observable characteristics of an individual NO NEED TO MEMORIZE THE NUMBERS BUT SIMPLY KNOW WHICH OF THIS IS THE MOST PREVALENT AMONG THE RACES. MOST PREVALENT - O ; LEAST - AB This is how Landsteiner came abt the blood A,B,O. B/N A & B SO CLOSE AMONG THE ASIANS (28 & Sabi niya there are 2 diff kinds of agglutinins. Reverse 26%) typing ang ginawa niya. One kind exists in A and the Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 2 IMPORTANT TO REMEMBER IS YUNG GENOTYPE According to Landsteiner’s rule: With the Rh type, sometimes when blood types are ▪​ Rule #1: Blood group antigens are found in being identified , u will see A+,O+. WHAT IS THE the surface of RBCs MEANING OF THE O POSITIVE THERE? Rh. ▪​ Rule #2: Antibodies opposite or reciprocal to the antigens present in the surface of the RBCs RULE ON AG AND ABS are found in the serum or plasma of whole blood ​ Blood group antigens found on the RBC ​ ABO blood group system is the only system membrane identifies the blood type. that follows the same rule -​ What is the antigen, that is ur blood type. Ex: -​ if u r type A on the red cell is A antigen. -​ If blood type B = B ag. RULE ON AG AND ABS -​ If AB ag = A & B ag -​ O = H ag (diba sabi ko nga ibang blood grp ang H.) DO NOT SAY NONE! WRONG! Kc meron; so u say No A ag & no B ag. -​ IN THE QUIZ OR EXAM, IF U SAY NONE, THEN WRONG! YOU HAVE TO SPECIFY NO A ANTIGEN , NO B ANTIGEN. MALIWANAG YAN HA! HOW DO U WRITE UR ANTIGEN? → please, capital letters! No cursive! (cursive na A o​ If the antibodies will match the antigens on the or cursive na small b is wrong) RBCs, what would happen? Antigen- antibody complex will form, the antibodies tend to react ​ Antibodies in plasma (serum) are reciprocal specifically with its specific antigen, and later (kabaliktad) to the antigens. cause the transfusion reactions; Ag-Ab complex -​ Ibig sabihin, if the ag on the red cells is A, what formation, it will entail always the formation of the should be the ab? anti-B (DO NOT SAY B immune response – that’s why the antibodies must ANTIBODY, WRONG! Bcs the prefix (dba na aral not match to the antigens present in the RBC and natin previous chap, we use the prefix anti-”name also what we are trying to avoid when performing of the ab”. So do not say B antibody, that’s wrong. cross-matching or blood transfusion You may be referring to antibody in blood type B which is anti-A. You say anti-B, anti- A (kabaliktad ni B). So if there are ag AB ags, there are no anti-A, anti-B in the plasma. DO NOT JUST SAY NONE! -​ The abs found in the type O are (take note tatlong klase! Pag binigay mo dalawa lang, wrong! Kc tatlo talaga ang ab groups that are found in type O which are: anti-A(coma),B, anti-A, anti-B (if 2 lang nilagay mo, mali!) -​ DID YOU KNOW? THAT IN BLOOD TYPE O THE anti-A,B is the ANTIBODY THAT CAUSES HDN (hemolytic disease of newborn) in O mothers. So significant ito, lalong lalo na if mataas titer niya. Kunwari lang yan, that’s not how ags look like. WAG This is an IgG in nature. NIYO TUTULARAN YUNG NONE! WRONG! -​ The anti-A and anti-B are IgM in nature while the Group O : No A antigen, no B antigen anti-A,B is IgG in nature which causes the HDN in Group AB: No anti-A, no anti-B the O mothers. (Ngayon palang piliin mo na sino papakasalan mo. Bago pa magpropose yung lalaki ** This is just to illustrate how the ags are found on the sayo, “Hi I am Peter, what’s ur blood type? “ If you red cell and what abs are found in the serum or do not know your blood type, I will not entertain plasma. Why do I say serum or plasma? you.” Serum - in-vitro in ur lab (kc eto prineprepare when -​ Sa chika ni maam: we r processing the spx) -​ Guy= Type B ; Girl= Type O (malakas anti-A ni Plasma - ON the blood of the px (IN- sa loob (ex: in girl) all their children had HDN. (Although it says the body fluid) ; ON - sa surface (on the red cells). naman ABO HDN is subclinical or not as serious WAG MALILITO!) as Rh HDN. Pwede siguro if the mother A+ (?) had *** DO NOT SAY SERUM WHEN U R REFERRING very high antibody titer. TO THE PLASMA OF THE PX INTRAVASCULAR. AGAIN! MASTERY CHECK ​ ANTIGEN identifies the blood type. What are the antigens in blood type O? ​ ANTIBODIES reciprocal to the antigen. -​ No A ag, No B ag What is the blood type if it has A ag? -​ Blood type A Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 3  characteristic ng IgM? They can activate What are the antibodies in type AB? complement, and complement once activated, it -​ No anti-A, no anti-B can lead to lysis of the red cells. What is the blood type if the patient has anti-A, -​ So the transfusion reaction that will happen anti-B, and anti-AB? with a mismatched blood in transfusion is a -​ Blood type O very serious fatal hemolytic transfusion What is the antibody in type B? reaction. Never dapat na mangyayari that u will -​ anti-A transfuse the wrong blood type! What are the antigens in type AB? -​ In transplantation ganon din, remember that we -​ A ag, B ag said A ag and the B ag, they are not only found on What is the antibody in type B? the red cells, they are also found on tissue cells -​ anti-A that is why we classified them as tissue Ags. What are the antigens in type O? Meaning to say, our cells that make up our organs -​ No A ag, no B ag like the kidney for example, surface cells of the What are the genotypes of type A? kidney merong A ag yan. So if u are type A, meron -​ AA/AO din silang A ag. Pag type B ka, meron din silang B The genotype is OO what is the blood type? ags. -​ Blood type O So anong mangyayari? What is the genotype of type B? -​ Si patient natin, type A manen, kailangan niya ng -​ BB/BO kidney transplant. Nakalimutan iblood type yung Give the Ags and Abs of type A donor, uy HLA compatible, pero nakalimutan -​ A Ag, anti-B idetermine yung ABO type. Yung ABO type pala Give the Ags and Abs of type B nung ay type B, heto nanaman tayo. Anti-B is very -​ B Ag, anti-A much present in the blood plasma of the patient and incoming tissue Ag of the kidney is type B, PROPERTIES/CHARACTERISTICS OF THE ABO what will happen to the anti-B? It will react to the B BLOOD GROUP SYSTEM Ag on the tissue, and Ag-Ab reaction → ​ The most important of all blood group systems in destruction of the transplanted organ. transfusion practice. -​ Main thing that we are trying to avoid is the ABO -​ Very easy yan once na connect na yung blood incompatibility which can lead to hemolytic vessel ng transplanted kidney tsaka yuung blood transfusion reactions vessel ng patient, pag nag connect na yan, blood -​ Later on u will know the reason why is this so. So will flow. Pag nag flow na yung blood dalala niya that is why we studied the antibodies in the plasma yung Abs sa plasma, madedetect na yun ni ab of the patient because of the presence of these yung specfif ag niya and will react to the specfific antibodies which are naturally occuring. Ibig ag and now here comes the complement, sabihin ng naturally occurring they are always pakialamerong compliment, nakita niya Oops there in the blood/plasma of the patient and they merong Ag-Ab complex makisali nga. Ayun, are expected to be there and there is no reason activated na ssiya and then that leads to rejection that these antibodies will not be there except in of the transplanted organ, this is called type AB. HYPERACUTE REJECTION -​ Bcs of the natural existence of these Abs in the -​ So the patient here can die immediately. plasma of diff blood types, this makes the reason Hyperacute rejection, breakdown agad ng why u should be able to use group specific blood cardiovascular system, mamatay yung patient. or use the same blood type of the patient and the -​ So that is how our blood group ABO system donor. For example, if ur patient is type A, what becomes very important not only in transfusion but should be the blood that u will have to give in even in transplantation, because of the ever transfusion? It should be blood type A. Suppose presence ng naturally occurring anti-A and anti-B that our patient is type A and there was a mistake in the plasma of the patient. in the identification of blood type and u transfused a type B blood, where do u think the problem will ​ The only system where antibodies are predictably come from? Ur patient is type A, anong antibody (expected) found in plasma/serum and reciprocal ang present sa kaniyang plasma? anti-B. to antigens on RBCs. Nabigyan mo siya ng type B blood mistakenly in ​ Taking advantage this characteristic in determining the accurate or the correct blood type of the transfusion, meron siyang anti-B, yung red cells B patient Ag. What will happen? The anti-B will react to the -​ Ito yung sinasabi na natin, u can almost predict incoming B red cells and that’s going to be a very kung ano yung ab that is found in the plasma. serious hemolytic transfusion reaction. Why? Its because they are IgM abs, at ano ang Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 4 ​ Transfusion due to incompatible antibodies can quick to occur and almost always 3-4+ ang result to immediate lysis of red cells → serious agglutination. If it becomes a mixed field or 2+ fatal transfusion reaction mixed field or the agglutination occurs very slowly ​ Most of the ABO antibodies are of IgM in nature – then you are dealing with an atypical specimen. only class of Ab that can activate the complement system When u are in ur blood typing all these thing u are -​ So often than not, this transfusion reaction is fatal. observing. Hindi yung sige sige type O yan. With The presence of 50mL incompatible blood that regards with the ABO testing, u have to be very entered into the patient can kill within 20 mins. focused and ur eyes is trained to be attentive to -​ Magkamali ka sa glucose testing by a few details. Attention to details, yan ang buhay sa numbers, mamatay kaya yung pag diagnose sa blood banking. patient? Hindi. Pero sa blood typing, nagkamali ka -​ Direct typing – this is the application of the first ng blood typing dahil sa malaking “K”, trinansfuse rule of Landsteiner’s in which we are trying to yung blood, nagkaroon ng HTR, 20 mins detect the RBCs’ antigens mamamatay yung patient. That is why it is a -​ Reverse/Indirect typing – it follows the second practice in blood transfusion that the patient is rule of Landsteiner in which we are trying to detect monitored/watched/babantayan in the first 15-20 the antibodies present on the patient’s mins para if ever a transfusion reaction would plasma/serum occur, madaling idisconnect yung blood. Yung -​ Correct match of these two methods are medtech sa lab, humanda ka patay ang lisensya. necessary to obtain an accurate blood type of a -​ Ang hirap ipasa ng lintek na blood banking, patient pumasa sa boards exam tas magkakamali sa -​ According AABB, both direct and indirect typing blood typing, patay ka, yang lisensya mo revoked. must be performed in order to accurately -​ This is the same reason immediate lysis of red determine the patient’s blood type; reverse typing cells, serious transfusion reaction. In the case serves as a confirmatory test for the ABO direct of transplantation, hyperacute rejection and typing that can also be fatal to the patient. Therefore, it -​ If it didn’t match, there’s a problem in the reagents becomes the ABO typing, ABO incompatibility or the patient has an ABO discrepancy testing or compatibility testing become the basis of pretransfusion testing. ​ ABO antigens are found on tissue cells → important in tissue/organ transplant ​ Testing to detect ABO incompatibility between ​ ABO and H antigens are secreted into body fluids donor and recipient is the foundation on which by secretors (produced by epithelial cells) all other pretransfusion testing is based. -​ Other than their presence on the red cells, the -​ Blood typing of the ABO, crossmatch of a ABO and H antigens are also secreted into the compatible blood, they are the basis of body fluids by secretor individuals. 80% of the compatibility or crossmatch testing. human population are secretors, only 20%(?) are nonsecretors. Ibig sabihin if u are type O, u don’t ​ Blood types can be determined by both direct/ forward and reverse typing. have A and B ags on the red cells but u have the H -​ In fact it is now the standard practice in blood bank ag on ur red cells and your saliva will also have the that blood types should be identified using the two H ag. If u r type A, ur red cells have A ag and ur methods. So u have to do the forward/direct body fluids (saliva, tears) also have A substance. typing, confirmed by the reverse typing. Dapat nag Correctly we do not say A ags, we say coconfirm yan kasi there r situations, lalong lalo na substance bcs the ags in the body fluids are sa acquired B phenomenon, akala mo type AB soluble substances. yung patient kasi both anti-A and anti-B may -​ Some epithelial cells are indirect contact with the reaction, pero nung nirecheck sa reverse typing, bodily fluids like saliva in which we have the secretors – are able to functionally raise antigens wala palang reaction or meron palang reaction. So doon mo lang makikita, that is where u will see na mali or misinterpreted yung result ng direct typing. U can only identify the correct blood type of the patient pag merong reverse. -​ ALWAYS BE ABLE TO DO UR TYPING WITH FORWARD AND REVERSE. The reverse should be able to confirm that the direct blood type is correct. -​ Also, u should be able to observe the quality of the agglutination reaction, ABO Antigen testing is very Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 5 PROPERTIES/CHARACTERISTICS​ OF THE ABO -​ So these genes are located at chromosome #9. BLOOD GROUP SYSTEM Yung H gene is located at chromosome #19. So magkaiba silang blood group system bcs they are determined by diff genes and the genes are located in diff chromosomes. ​ A and B genes = autosomal codominant What is the meaning of autosomal? -​ Meaning that the genes are located in autosomes. There are 2 types of chromosomes: The SOMATIC CHROMOSOME OR THE AUTOSOME and SEX CHROMOSOME. So they are 22 pairs ng autosome and meron isang pair ng isang sex chromosome. So yung sex chromosomes are the x TERMS: and the y. So the ladies have XX, and gentlemen have XY. Kaya ang mga gentlemen, there is ​ Dominant allele – only one allele must be inherited for it to be expressed always a lady part in them. And as I said earlier, ​ Recessive allele – in need to be expressed the O gene existing ‘yan kaya lang wala siyang homozygously in order for a certain characteristic product, so it is called an “amorph”. So it is called to be expressed (e.g., BB – dominant, Bb – black; an amorph. An amorph is a gene that does not blonde will be expressed since it is dominant over have a detectable prime. There is a reason for black; the recessive gene must be homozygously that. O gene is an amorph, so the blood type O present to be expressed) ​ Homozygously dominant – blonde (because it’s can only be expressed if there are homozygous already dominant kahit isa lang ang lumabas sa OO Gene. whereas, A and B genes are genetic composition ng isang tao, ‘yon at ‘yon pa codominant. rin ang lalabas What is the meaning of codominant? ​ Codominance – black allele and black allele are -​ If they exist either with a recessive or another expressed as both capital and small letter B, dominant gene, they are always expressed. That is kapag naexpress yung dalawa, both of the why in type AB, they are codominant. characteristics that may be traced on this genotype will be expressed on a certain offspring (kapag If A gene is present and B gene is present, then black and blond mixture = black and blonde) what becomes expressed? ​ No allele or gene is dominant over the other -​ Both A ag and B ag. Thus, the px is type AB. ​ Recessive gene present in ABO blood group Now if the A gene and the B gene are in system: O gene – what would be the phenotype combination with the O gene, talo si O kasi or blood type? A, since O is recessive over A recessive siya so what becomes expressed as the ​ The presence of two homozygous gene will now blood type of the px will be A kasi more dominant lead to the expression of O phenotype ​ Example: your mother’s phenotype is siya, kaysa sa O. If B is in partnership with the O homozygous, and father’s phenotype is gene, ganon din. What is expressed as the ag is B. heterozygous -> 50% AO, 50% AB (basta nasa Because O is a recessive gene. notes ko siya, make a Punnett square na lang) ​ O gene = amorph, recessive, as compared to A INHERITANCE​ and B genes ​ 1924 – Bernstein- first described the theory of inheritance of ABO which follows Mendelian ​ Amorph means it will not cause any changes in the principle. patient’s or offspring’s phenotype ​ The ABO inheritance is controlled by the A, B, O genes. ​ Other genes that interact with ABO genes locus at -​ There are three genes that rules or controls the chromosome #9: H (19), Se (19), Le (19), I (6) and inheritance of the ABO blood type, these are the A P(22). -​ There are other genes that interact with the ABO gene, B gene, O gene. So merong existing na O genes which are located in chromosome 9. For ex. gene pero u will know later on bakit walang I told you earlier that the H gene is located at product. chromosome 19. The Se is located also at chromosome 19. And Le (Lewis) gene is also ​ An individual inherits one ABO gene from each parent = to comprise genotype → determines located at chromosome 19. Itong tatlong ‘to, phenotype → antigens develop on the red cells. they are closely linked w/ 1 another. So there is ​ According to Mendel, at least one gene is present a theory in genetics that is called ‘Closely-Linked from each parents Gene’, ibig sabihin yung locus nila or where they ​ ABO genes - at chromosome #9 are located in that particular area in the chromosome are very near each other. So closely Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 6  linked. Kaya the affect the H gene, Se gene, and was formed by the Gene O is not an active the Le gene have an interaction among the 3 of enzyme kasi may kulang doon sa base pairs. So, them to be able to express the Le ag. therefore, the enzyme that is formed by the Gene -​ And moreover, the H gene and the Se gene also O is not active. It is an inactive enzyme and can affects the ABO gene expression ang tawag sa not act on the H ag to produce its own kanila, MODIFYING GENE. The H gene and the immunodominant ag kaya walang na fo-form na ag Se gene have an effect on the expression of the yung type O. Ang nag re-remain sa kanyang ABO gene, they are called modifying genes. So structure is the H ag. You will learn later why the A they have an effect on the expression of the A, B, ag derives from the H, the B ag derives from the H. O genes. Ang chromosome for the big I ag, is Pero si O, hindi niya ma act yung H ag kasi hindi found at chromosome 6 and the P gene of the P active yung kanyang enzyme, kaya walang blood group system is found at chromosome nangyayari sa H ag. The reason why sa type O 22. Itong I is closely related also to the ag structure ang meron siyang ag sa RC is H ag kasi hindi niya of the ABO ags and also the. Pero they are na act yung H ag. ​ derived in diff. Chromosome number. So they are not the same. ​ H gene – present in more than 99.99% of random population. Genotype HH or Hh can produce H ​ The ABO genes do not code directly for the antigen from precursor substance → H antigen antigens, but instead, they code for the production (precursor of ABO antigen) of enzymes GLYCOSYLTRANSFERASES, which As we said earlier, H gene is independent of the ABO are involved in the formation of respective gene. Diba independent siya, meaning to say it has a antigenic determinants (epitopes of antigens) separate entity. Remember that H genes are located at ​ ABO only control the enzyme chromosome 19. Ang ABO gene located sa ‘glycosyltransferases’ chromosome 9. So they are not the same. Magkaiba sila. Now, for most human population, 99% are h gene ​ Gene O – amorph → NOT able to bring out the positive, meaning to say lahat tayo meron tayong H production of active enzyme. The inactive enzyme gene. That is why we are able to form an A ag or a B can NOT act on the H antigen to produce immunodominant sugar, thus, the H antigen ag, kasi meron tayong H gene. There is just the remains the same and abundant on the O red genotype of our H gene, our homozygous HH or cells. heterozygous Hh, yung small h represents the What is the reason why gene O does not have a recessive form of the Big H ag. And there are just but a product? very few individuals who do not have the H gene and -​ The genes of the ABO system code for a particular their genotype are small hh, and that give rise to the enzyme so yung amino acids that are produced by bombay phenotype or yung Oh the a gene, the b gene, and the O gene forms a ​ “h” gene is rare, thus hh genotype is extremely particular enzyme and these are called the rare → (Oh Bombay phenotype) glycosyltransferase enzyme. But there are very few of them, why Bombay? Ano ang role ng glycosyltransferase enzyme? Because the 1st person identified to have that kind of -​ They catalyze the formation of the specific ag variant phenotype was a resident of bombay india and determinant or epitope of the ag that characterizes so far today, literature says that there are just about the blood group ag. So itong enzyme na ito 200 or a little more than 200 identified na bombay sa actually adds, it catalyzes the addition of a population ng world. ​ particular sugar of a chain. On the chain of sugars, ​ particular end sugar which is called the Generally, humans in the general population, you must immunodominant sugar or the epitope of the have the big H gene and we are able to produce the particular ag. So that is the purpose of the product big H ag. ​ of the ABO gene, to create an enzyme that will ​ make possible the addition of a particular So very rare yung homozygous hh genotype and they immunodominant sugar on the sugar chain of the give rise to the Oh bombay phenotype. Dapat itong h ABO ag. na ito, naka subscript ito. Hindi siya OH! Bombay!​ How about Gene O? ​ -​ Gene O is an amorph that is not able to bring This slide is important to remember, there are the about the production of an active enzyme. In other genes on the 1st column, 2nd column yung enzyme words, merong kulang sa kaniyang structure of A and the 3rd column ano yung ag na immunodominant gene. So there is a deletion that happens in the for the blood type ag and then on the last column, the structure of this gene. There is such a thing as ag that is developed on the RC. So yung H gene ang gene deletion kaya hindi na kumpleto yung product niya ay fucosyl transferase, ang sugar na structure ng base pairs. Kaya yung protein that ia-attach niya sa chan of sugars ay fucose. So H ag is formed from the action of the H gene. Sa A gene, the Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 7 enzyme is N-acetyl galactosaminyl transferase, the Anong meron Antibody sa Type A? ANTI-B immunodominant sugar or antigenic determinant or Binigyan ng AB blood, yung anti-B nag react sa B specificity sugar is N-acetyl galactosamine, for the A redcells ng type AB, nagkaroon ng Hemolytic ag. For the B gene, the enzyme is Galactosyl Transfusion reaction yung patient. Transferase, the immunodominant sugar or the Sana nag Reverse typing si medtech. specificity sugar is galactose. And the ag formed is B. Kailangan i memorize Acquired B phenomenon Happens, very commonly ngayon because they have high prevalance of colon INHERITANCE cancer. Nangyayari ito sa colon cancer, intestinal obstrucxtion, stomach cancer. INHERITANCE-4 GENE THEORY (BERNSTEIN) ​ o​ Glycosyltransferases are able to add those sugars to the precursor substances which now leads to the formation of complete INHERITANCE-6 GENE THEORY (THOMPSON) ABO antigens ​ ○​ INHERITANCE-4 GENE THEORY (BERNSTEIN)​ ​ ○​ INHERITANCE-6 GENE THEORY (THOMPSON ​ Glycosyltransferases are able to add those sugars to the precursor substances which now leads to the formation of complete ABO antigens ​ ​ A1 is more dominant than A2 (the antigen will be present in the RBCs is A1) Naalala niyo yung sinasabi ko na acquired P ​ A and B are codominant phenomenon? Where the A becomes like a P. So if ​ O is recessive you will see the structure of the A Antigen. n-acetyl galactosamine ang then the P antigen only as a Anong meron Antibody sa Type A? ANTI-B Galactose. So there are bacterial enzymes like E.coli Binigyan ng AB blood, yung anti-B nag react sa B that infects the human althought we know that e.coli is redcells ng type AB, nagkaroon ng Hemolytic a normal bacteria but there are times that E.coli Transfusion reaction yung patient. becomes pathogenic and yung enzyme na na Sana nag Reverse typing si medtech. creacreate ng E.coli has the tendency to cut off the n-acetyl component ng structure ng sugar na yon. Pag Acquired B phenomenon Happens, very commonly yung enyzme na yon naalis niya yung n-acetly, ang ngayon because they have high prevalance of colon nag reremain is galatosamine na very close sa cancer. Nangyayari ito sa colon cancer, intestinal structure ng galactose. So it's like the red cell A will obstrucxtion, stomach cancer. look like B red cells. So if you will blood type that patients red blood cell, Instead na mag nenegative If the patient has a phenotype A1, there are three siya sa Anti-B, Mag popositive siya sa Anti-B. Kaya genotypes. A1A1 homozygous, Heterozygous A1O, ang wrongly interpretation is Type AB kase yung and A1A2. galactosamine nawala yung N-acetyl group niya kaya nag rereact yung red cell sa Anti-B. Tho weaker Their is a Highers percentage of A1 subgroup among positive sa Anti-B, so yung interpretation ng medtech Type A2. Type AB ito. Hindi siya nag reverse Typing. in A2 there are only 2 genotype, A2A2 Homozygous, and A2O Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 8 Another thing we want to know is the antigens in the All you have to do is to know the genotypic red cells, in A1 dalawa. A1 antigen and normal A combination for example: In A2, only A antigen. WALANG A2 Both Parents are A, One parent homozygous the other is hetero, or both of them is hetero. So you do So when we go to the variance subgroup you will know your criss-cross combination. That's how you derive more qualitative and quantitative differences between your offspring A1 and A. tandaan niyo ito, yung genotype A1 and A2, give rise In the case of AO father and AO mother, possible to to phenotype A1 the antigen A1 is only found in A1 have a Type A baby and Type O baby, 50% 50%.​ subgroup and A1B. Lumabas sa board exam! If ever, in a genetic mating, you are not given the genotype of the parents, you’ll have to try all of the And it is a cause of discrepancies sa blood typing possible combinations. Halimbawa sinabi ko lang na Type A and B yung parents, tatanungin niyo ba ako GENOTYPE MATING “Ma’am Homozygous ba or Heterozygous?” So there is no way to test the genotype of the parents. You can only infer the genotype of the parents based on the offspring, kung ano yung blood type ng offspring. So if you were given a case to solve, hindi given yung genotype, you’ll have to try all possible combinations. And that is not only that when we have learned about the other blood group system, halimbawa sabihin natin, Father is A D+, Mother is O D-. Type N yung tatay, Type N yung mother, yung tatlong ’yon gagawin mo yung genetic mating separately.​ ​ So kahit na binigyan kayo ng 4 na blood type, ​ ABO- 1 crisscross, RH- 1 crisscross, M- 1 criscross. Hindi yung pagsasabay-sabayin niyo sa isang ganito, you will die. ABH ANTIGEN DEVELOPMENT GENES AND ENZYMES The H system is a separate blood group found on chromosome 19. Different from the ABO blood group found on chromosome 9. So that goes to show that they are really separate from one another. However it is such that the H gene affects the expression/ the development of the A and the B antigen on the red cells and the substances in the body fluids So in the category or in the language of heredity, we call this the modifying gene. The H gene is a modifying gene bcuz it affects the expression of other genes which may belong to other blood group systems. So important to remember as said from the previous discussion: the enzyme that are coded for, in the ​ *don’t memorize, magpunnett square ka na lang proteins, develop/made/described (?) by the H gene, daw the enzyme is fucosyl transferase. It transfers fucose. Fucose is the sugar and the enzyme is Whatever the phenotype of the father in combination called fucosyl transferase. with the phenotype of the mother, you create the genotype So the fucose there which is added to the chain of sugars, we call these precursor substances. Yung NOTHING TO MEMORIES ABOUT THIS!! terminal sugar provides the specificity of the H antigen. Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 9  When the H antigen is acted upon by the A gene, So if tinanong ni dean: which can exist as homozygous AA or heterozygous What is the immunodominant sugar or antigen that AO, this leads to the development of the A antigen. ​ describes/identifies the specificity of the H What does the A gene ulit have? antigen, this is: FUCOSE N-acetylgalactosyl transferase The same with A gene, N-ACETYL -​ Magaadd sya ng sugar na GALACTOSAMINYL TRANSFERASE. The sugar is n-acetylgalactosamine sa terminal sugar ng H N–acetyl galactosaMINE. So pagginawa mong antigen. descriptive ung term, galactosaMINYL…transferase. N-acetyl galactosamine is the antigenic determinant for The same way with the B genes, existing as the A antigen. homozygous or heterozygous. The H antigen will be converted into the B antigen. So ano ulit ung B gene? And then for the B gene is GALACTOSYL TRANSFERASE will add GALACTOSYLTRANSFERASE and the GALACTOSE to the terminal galactose of the H immunodominant sugar is GALACTOSE and that antigen. ​ specifies the B antigen. Tandaan nyo daw to ⚠ ​ Now we have the O antigen, sabi natin na the O gene does not produce any active enzymes. It is an AMORPH -​ So wala syang enzyme na active, it is not able to act on the H antigen, it is not able to modify H antigen > so walang nangyayari sa H antigen kaya inagreremain sya na H antigen Now if the person has a homozygous hh >so ibig sabihin wala syang HH gene, but it has the recessive hh gene. Meaning to say it is not able to develop the big H antigen >> so the precursor substance is not PRECURSOR SUBSTANCE AND GENE ACTION → transformed. Nagreremain lang sya as same PS so it AG DEVELOPMENT isn't able to produce the H antigen. Therefore if there are no big H antigens that are formed >>> there will be no A, no B , no H antigens ​ -​ There are these groups of people – we cal the bombay phenotype peeps = they do not A,B or H antigens. HOWEVER, type O persons can still have H antigens (POINT OF DIFFERENCE!!) PRECURSOR SUBSTANCE This is how the precursor substance/sugars (PS) is acted upon by the H gene. The H gene can exist in the human population as homozygous (HH) or heterozygous Hh. Now in the presence of these genes–so remember meron ung fucosyl transferase. So this PS which consists of chain of sugars with the addition of fucose at the terminal galactose will produce the H ANTIGEN -​ Yang H antigen becomes the PRECURSOR or STARTING SUBSTANCE for the development of the a and b antigen Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 10  H ANTIGEN FORMATION ​ There should be a precursor substance in the RBC membrane in order for the immunodominant sugars to attach through their specific glycosyltransferase enzyme So sabi natin, if there is the H gene by the addition of ​ One of the requirements of the precursor FUCOSE at the TERMINAL END OF GALACTOSE substances is the addition of H antigen or fucose this now becomes the H antigen (kapag walang H antigen, walang magfoform na ABO antigen) Naadd ung fucose by the virtue of the enzyme: FUCOSYL TRANSFERASE Based on the image) These are the sugars that make H ANTIGEN DEVELOPMENT up ur precursor substance. So attach to the membrane of ur RBCS. through ceramide. ​ H antigen – the precursor for the A and B antigens. The First sugar is GLUCOSE >GALACTOSE > ​ Presence of HH or Hh genotype → Attachment of N-ACETYLGLUCOSAMINE > TERMINAL fucose to terminal galactose catalyzed by enzyme GALACTOSE fucosyl transferase → produce H antigen. Tatandaan nyo yan since Dean will ask the us to A ANTIGEN DEVELOPMENT develop and trace our antigen sa quiz or exam ​ A antigen development: ​ H antigen → presence of AA or AO genotype → TAKE NOTE!! There is a difference in the first sugar if attachment of N-acetylgalactosamine to the this is the soluble substance that is found in the body terminal galactose catalyzed by N- fluid— hindi GLUCOSE instead it is N-ACEYTYLGALACTOSAMINE. But on the red cells > acetylgalactosaminyl transferase → A antigen glucose. So again sugars (on red cells) are: Glucose > galactose > GLNAC > Galactose Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 11  ​ H antigen → presence of BB or BO genotype → attachment of galactose to the terminal galactose catalyzed by galactosyl transferase → B antigen ​ What about the B antigen? The B antigen there is another GALACTOSE that is added to the TERMINAL GALACTOSE. There is the fucose added to the terminal galactose, but because of the B gene which prescribes the GALACTOSYL TRANSFERASE, add another GALACTOSE to the TERMINAL GALACTOSE and that forms now the B ANTIGEN. What are the two sugars attached to the TERMINAL GALACTOSE? ○​ FUCOSE AND GALACTOSE ​ Now, what about if you are type AB? O GENE ​ O gene at the ABO locus does not elicit the production of catalytically active polypeptide. -​ The only thing that will be present is fucose, no other additions of other immunodominant sugars -​ fucose and precursor substances will necessarily remain the same because it is not ​ able to modify the precursor substance being So sabi natin the H antigen is the PRECURSOR for an amorph gene, not able to produce the A antigen. *tinuro ni maam ung fucose* So ung glycosylaminotransferase partna ung and the prior sequence = H antigen, Now because there is the A gene has the ​ What about the O gene? Yung O, hanggang H N-ACETYLGALACTOSAMINYL TRANSFERASE >> antigen formation lang siya, kasi the O gene is the sugar N-ACETYGALACTOSAMINE attaches to the an amorph, it does not produce an active enzyme terminal galactose and eto na ngaun ung A antigen and the H antigen is not modified or is not acted upon. So it remains to be simply the H antigen, with the FUCOSE sa TERMINAL GALACTOSE. So ano ung dalawang sugar added to the terminal ​ Remember I was telling you about LEWIS galactose? ANTIGEN, the lewis antigen very close ang action Fucose and N-acetylgalactosamine. niya with the H antigen. Yung LEWIS AG. B ANTIGEN DEVELOPMENT magaadd siya ng FUCOSE dun sa N-acetyl glucosamine. Pag wala yung FUCOSE sa Galactose, then mag-aadd siya dun sa subterminal N-acetyl glucosamine the it becomes the LEWIS antigen. ​ Now in the case of BOMBAY PHENOTYPE, the bombay phenotype does not produce the H antigen, so wala itong nafoform, therefore even if the bombay phenotype has the A GENE, remember separate ang H sa A, so yung bombay phenotype kahit na meron siyang A Gene pero wala siyang H antigen, will it be able to form the A antigen? NO, why not? Kasi precursor yung H antigen , so even if the bombay inherited the A gene or the B gene it will not be able to form an A antigen or B antigen kasi wala yung precursor. Wala yung H antigen na dapat its the starting point , the starting substance of the A ag. or the B ag. To be developed. That is why bombay person do not have Big H antigen, No A ag. And No B ag. Why? Because they do not have the H antigen, they only ​ B antigen development: Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 12  have the small h, they have not inherited the big H set of this pairing will spell a certain amino acid, so gene. there's a single base pair that is deleted in the ​ Yung AB, you have inherited both gene A and B, structure that is why yung protein base dapat na two antigens you are going to developed. So type mafoform was not form correctly. so the structure AB’s, they have both A ag. And B ag.on the red of the enzyme (take note: that enzymes are pure cells. Why? Because they have both genes, so protein). There is a single base pair that is deleted magdedevelop yung dalawang antigen, because A that made the protein not active. so it is an gene and B gene are CODOMINANT. So they will INACTIVE ENZYME. both express their products A ag. And B ag. ​ Being an inactive enzyme it is not able to catalyze ​ So yung nakakabit na sugar kila fucose and a reaction that will transform the H antigen into terminal galactose ay si N-acetyl galactosamine something else. The H antigen remains to be NOT and galactose? Yes, at first the H antigen should MODIFIED, remains to be an H antigen because developed first, there is the FUCOSE at the the enzyme that is supposed to be prescribed by TERMINAL GALACTOSE, dapat naform na yan the O gene is NOT ACTIVE. That's why it is called before na mag-aaction yung A gene, the an AMORPH because it DOES NOT HAVE A N-ACETYL GLUCOSAMINYLTRANSFERASE or DETECTABLE ACTIVE ENZYME PRODUCT. the B gene, GALACTOSYL TRANSFERASE. So ​ so in the development of our precursor substance dapat meron nayung H. the H antigen simply remains to be an H antigen ​ As mentioned a while ago, in the case of the TYPE cause it was not modified by the O gene. Thus if A, there are two sugars attached to the TERMINAL you compare the amount of H antigen with the GALACTOSE which are the FUCOSE and other blood group antigen, the O gene remains to N-ACETYL GALACTOSAMINE. In the case of B have the highest amount of the H antigen kasi kasi antigen, there is another GALACTOSE pero unreacted yung antigen don. And the 2nd highest nandun na si fucose. is the A2, 3rd is B and in decreasing order ​ You can transform the A antigen red blood cell or A2B—A1—A1B making the A1B the least to have the B antigen red blood cell into a simple a H antigen and the most amount is O red cells. FUCOSE. How? Just detached the galactose an ​ so when you are describing antigens present on enzyme, sisirain mo lang ito, itong link na ito , the the A, AB and O antigen you do not say for an O linkage between the galactose and the terminal na no antigen because merong H however simply galactose, you can detached this galactose and say no A and no B antigen. the substance simply remains an O. The same ​ But if I tell you that “give the possible ABH antigen way with type A, simply detached the N-acetyl in different blood groups” then you can say “has H galactosamine, and you can retain the H antigen. antigen but no A and B antigen”. For type AB tatlo, A antigen, B antigen and H antigen pero ​ O gene has been identified to have a single DNA pinakakonti siya ng H antigen. base pair deletion (at position 258 near the N- SUMMARY terminus when compared to the A gene). ​ This deletion creates a premature codon, resulting to an O-transferase that is inactive, thus incapable of modifying the H antigen. ​ Thus, the H substance remain unmodified. ​ Thus, the O blood group has the highest amount of H antigens on the red cells. ​ O>A2>B>A2B>A1>A1B (H antigen in decreasing amount) ​ Decreasing in population: O>A>B>AB ABH ANTIGEN DEVELOPMENT ​ Why is gene O an amorph? because there's a ​ ABH antigens begin to develop in the 5th-6th problem of deletion somewhere at its structure at week of fetal life. position 258 compared to the structure of A gene. ​ Antigens are not well developed at birth. So, there is a base pair that is deleted. So the ​ Weak agglutination observed in fetal cells. structure of the O gene was not completed and ​ Adult levels are reached until 3 years of age. remains inactive. ​ Yung protein na prescribe by the gene remember your GCAT/ATGC yung ganon na pairing diba the Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 13  Adult RBC​ Infant RBC ABH SUBSTANCES IN SECRETIONS A antigen sites:1,170,000​ 250,000- 370,000 ​ The presence of H substance in body secretions B antigen sites: 610,000 – 830,000​ 200,000 is controlled by the Se gene. A1B (A ag): ​ 460,000- 850,000​ 220,000 ​ Individuals who have Secretor genes (SeSe or (B ag): ​310,000- 560,000 Sese) are called secretors (80% of the ​ The ABH antigens begins to develop very early in population). life even in the fetal life magstart ng magproduce -​ Secretors are individuals who are able to form yung antigen about 5TH-6TH WEEK OF FETAL ABO antigens in the body fluid LIFE ​ sese genotypes → nonsecretors ​ When the baby is born even the development ​ Precursor substance (type 1 chain): N- starts very early, when the baby is born this acetylgalactosamine—galactose–​ N- antigens are NOT YET WELL DEVELOPED acetylglucosamine (1,3 linkage to) – terminal So what is the meaning of NOT WELL galactose. DEVELOPED? ​ ABH substances in secretions in body fluids, this ​ it means in terms of ANTIGENIC SITES meaning if happens because of inherited genes that is called you compare it with the antigen site on an infant the Se gene that is refer to as secretor gene. RBC that will be around 250k-370k as compared ​ Secretor gene is another gene or separate gene to an adult A antigen 1,170,000 million. yun ang inherited other than the ABO. ABO again I keep ibig sabihin ng NOT WELL DEVELOPED, it is in telling you chromosome 9, sila chromosome 19 terms of ANTIGENIC SITES kung ilang antigenic magkakatabi yan sila H antigen which is also site ang nandoon sa napakaliit na RBC 1.1 million called the CLOSELY-LINKED GENE THEORY ng napakaliit na RBC dat is y agglutination TAKE blood group system because they are located NOTE of this agglutination of A antigen and B closely with one another. So that if you inherit 1 antigen on the red cells will always give you a very you might as well inherit the other 1 something like strong reaction. 4+, 3+ kaya mong iproduce yan sa that. A and B antigen. So what is the reason for that? ​ Also there is what we call the secretor gene 80% because of the NUMBER OF ANTIGENIC SITES of the human population inherit the SeSe or on the red cells, there are so many of these Sese (homozygous or heterozygous). antigens that will be reacted upon by the specific ​ The non-secretor genotype is composed of sese, antibodies so the reaction/agglutination becomes they are non-secretors roughly around 20% of the very very strong. that's why Dean keep telling us human population. You can either be homozygous na if the agglutination is 1+, 2+ lang MAGDUDA ka or heterozygous (SeSe/Sese gene). This secretor because it is NOT THE TYPICAL ABO TYPING gene is responsible for the development of the you will have to doubt that maybe you are dealing soluble substance in the body fluid so meron din with Lupus patient that nakadevelop na ng sila precursor substance no, by the way if the ABH anti-lupus antibodies or anticoagulant substance and secretions is base on the (nakinekwento ni Dean) na siya na pala yung development of the Type 1 chain, sa red cells type nagcacause ng agglutination hindi yung antibody. 2 chain, sa body fluids Type 1 chain yung kanilang ​ With the B antigen, there are much lesser than the precursor substance so the first sugar is A antigen sites 600k-800k traces only whereas in N-ACETYLGALACTOSAMINE followed by the infant it's around 200k GALACTOSE followed by ​ The A1B the A antigen is higher still than the B L-ACETYLGLUCOSAMINE followed by terminal antigen. no need to memorize the numbers gusto GALACTOSE. So san nagkakaiba with the red cell niya lang na iREMEMBER natin na A antigen precursor? sa base nila yung sa red cell ang una being 1.1 or 1.2 M antigenic sites so that they are GLUCOSE while sa secretor ang una is very very much more as compared to the infants N-ACETYLGALACTSAMINE. the linking is also na 200k-300k ang antigenic sites. So expect an different in the secretor 1,3 linkage sa type 2 is 1,4 agglutination reaction when you are dealing with between the N-acetylglucosamine and the terminal newborn baby, the reaction is WEAKER. Don't galactose, the linkage which is 1,4 —first Carbon, expect a 4+ or 3+ with a baby kasi konting konti pa fourth Carbon. 1st Carbon, N-acetylglucosamine lang ang kanilang red cells. third Carbon of the galactose. sa 1,4 linkage is the ​ Although they develop very early in the life, fetal first and the fourth carbon of the galactose. You life pa lang nagdedevelop na yung antigen but have a difference between the Type 1 and Type 2 they do not get full develop until they have become chain in structure of the precursor substance on adults. Adult levels are reached UNTIL 3 YEARS the red cells and that of soluble substance. OF AGE. ​ take note: N-acetylgalactosamine ang first ito sa secretor. Ano ang first sugar sa red cells? Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 14  glucose. All the rest of the sugars are the same ​ H substance → attachment of fucose to terminal except lang for the LINKAGE galactose of precursor substance. What substance develops these ABH substances? ​ A substance → attachment of ​ EPITHELIAL CELLS. Sa blood group ag. It is N-acetylgalactosamine to terminal galactose of H developed on the RED CELLS. Sa substances substance. they are formed by the EPITHELIAL CeLLS. ​ B substance → attachment of galactose to terminal galactose of H substance. ABH SUBSTANCES IN SECRETIONS ​ Group O secretor = has H substance in secretions ​ Group A secretor = has A and H substance in secretions ​ Group B secretor = has B and H substance in secretions ​ Individuals who are homozygous sese (do not have the Se gene) are NONSECRETORS (20% of the population) ​ The precursor substance of ABH substances in secretions are Type 1 chain; ABO antigens present in the RBCs are Type 2 chain ABO ANTIBODIES ​ Starts to develop shortly after baby is born. ​ This illustrates only the structure of the precursor -​ So while the baby is still in the uterus not unless substance, meron siyang exposure through infection, there ​ TYPE O= N-ACETYLGALACTOSAMINE> are no ABO antibodies in the new born baby. GALACTOSE> TANDAAN NIYO YAN N-ACETYLGLUCOSAMINE>TERMINAL -​ Not unless nagkaroon siya ng intrauterine GALACTOSE>FUCOSE infection. Halimbawa nagkaroon ng intrauterine ​ TYPE A= N-ACETYLGALACTOSAMINE> infection ang E.coli, nagkaroon ng sepsis yung GALACTOSE> N-ACETYLGLUCOSAMINE> mother, pumasok sa baby, so it’s possible to TERMINAL produce IgM antibodies ang baby but while the GALACTOSE>N-ACETYLGALACTOSAMINE>FU baby develop normally, there are no ABO COSE antibodies in a newborn baby ​ TYPE B= N-ACETYLGALACTOSAMINE> -​ The baby starts to develop only when he/she is GALACTOSE> born, why is that? Bakit pag napanganak nalang N-ACETYLGLUCOSAMINE>TERMINAL siya, dun lang siya nadedevelop ng antibody? Bcs GALACTOSE >GALACTOSE>FUCOSE of the exposure to the environment, dun lang siya ​ Pareho ng sugars except form the first Sugar. makakahinga na galing sa environment, air in the environment which might be dealing with different types of antigen na we do not see that they are seen like mold, pollens whatever that are found in the environment. -​ So there is only when they are born that they develop ABO antibodies ​ Adult level is reached at age 8-10 years. -​ So antigen : 3 years old and antibody : 8-10 years old ​ Naturally-occurring (not immune type)- produced in response to blood group- similar antigens from the environment (food, bacteria, pollens, etc) Why are they called naturally occuring? -​ Bcs they are produced to substances that are similar to blood group antigens but not definitely known. May pagkakaiba yun ha? Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 15 -​ They are exposed to antigens whose antigenic ​ Activate the complement properties may be similar to A antigen or B antigen -​ By what pathway? Classical pathway but what are they exactly? We do not know, okay? -​ Now again, if you are type A what is your ABO ​ Anti-A, anti-B antibody? Anti-B -​ Are typically IgM however as an exception, the -​ So if you are type A you are not foreign to A Anti-A,B they are usually IgG Tandaan niyo to, antigen, you are foreign to B antigen. Na exposed they are the causative agent of HDN in type O ka sa B antigen substances kagaya ng barbeque, mothers. Why? why can they cause HDN? Bcs banana, bulalo and another banana, ano pa ba they can cross the placental, they are IgG ang B? Bangus. So that is why you develop Anti-B therefore they can cross the placental. because you are foreign to B substances, so that -​ In the exam i will let you differentiate the ABO explains why there is a reciprocal relationship of antibodies, the Anti-A, Anti-B vs Rh antibodies the antibodies to antigen because if you are pagcocompare mo sila. exposed to the foreign substances that are B and -​ The Rh essentially they are IgG okay? So they are you are foreign to that, then you develop B IgG, they are non-saline agglutinating, they would antibodies or Anti-B need the AHE high protein medium or LISS, warm -​ If you are type B, what are the antibodies that you temperature, cannot activate the complement but should have? Anti-A. Now since A antigens are they can cause extravascular hemolysis and can foreign to you then you develop Anti-A. Example of cause HDN. A are Apple, Arroz Caldo, Atis, Anglit, Angpep ( it -​ Always remember the characteristics, we call this should be substances not smell, anyamet the serological properties or the serologic agituyen). So that is how you develop Anti-A if you characterics of the ABO antibodies bcs in blood are type B typing, in cross matching, in antibody screening, -​ Now if you are type AB, you are not foreign to A, antibody identification, remains the same ang you are not foreign to B that’s why you do not kanilang characteristics. So if you are presented develop Anti-A and Anti-B. But in type O you are with a reaction that is positive with saline reaction foreign to A antigens and B antigens so pag ano ang iisipin mo? I think I'm dealing with an IgG. naexpose ka doyan idedevelop mo yung tatlong Pag nagkaroon ng hemolysis yung RBC, i think im groups ng antibody, Anti-A, Anti-B and Anti-A,B dealing with a very strong IgG okay po? That explains why they are called -​ So ang kalaban natin sa blood banking is naturally occurring antibodies. antibodies so dapat you should know the -​ Parang tinanong ko sa inyo ito sa quiz? What kind characteristics of the antibodies of B cells produce natural occurring antibodies? CD5+ B cells, they are type of B cells that can ​ Anti-A,B – usually IgG. Causes HDN in type O easily react to nature antigens however, walang mothers IgG production except siguro yung type ?? kung ​ ABO antibodies are antibodies that are naturally bakit siya IgG okay? occurring, that started to develop after birth. Naturally occurring meaning the formation of this ​ IgM, saline agglutinins, cold temperature- reactive particular antibodies are produced in response to -​ Tandaan niyo yan, they are able to agglutinate red different stimulants in the environment. cells that are suspended in saline medium, ​ Immune antibodies are formed with individuals strongly aggluninating antibodies sila and they are exposure to different sources of sensitization from called reactive, they are called agglutinins why? I a foreign antigen such as previous transfusions, asked this in the quiz why? What kind of bonding previous pregnancies and others. do they have? HYDROGEN BONDING, hydrogen ​ Most of ABO antibodies are IgM in nature, bonding reaction is exothermic, naggigive off ng remember! that IgM antibodies are cold reactive heat kaya dapat you cool it down that is why they antibodies, they are able to optimally react at are supposed to be incubated at room temperature temperatures below body temp. They are also or in the ??. However class there is a group of known as saline agglutinins meaning they can antibodies na IgM na reactive sila kahit na sa 30 agglutinate with the help of only NSS, they react deg and they become clinically significant in that best with NSS. sense kaya meron tayong cold autoantibodies like Anti-H ?? they are very very strongly hemolytic okay? So there is a need na you have to bring them down even at a refrigeration temperature okay? So they are called reactive another characteristic they can activate the complement. Green - Sir Sumaya | Maroon - dean ​ ALMODOVAR 🩸KUAN 🩸 ALCAIDE 🩸AQUINO 🩸BAYOTA 🩸 LAGARTEJA 🩸MERCADO 🩸 RAMIREZ 🩸STEVENS🩸TADIFA III-2 | 16 ​ WHAT MAKES YOUR abo antibodies very -​ This is a mouse monoclonal ab so you are using FATAL? Most of the antibodies belonging to the a monoclonal reagent. This means that the ABO blood group system are IgM and they are antibodies are produced in an animal na mouse. able to activate the complement. IgM are Very potent complement fixing antibodies it is able to What technology is used in the acquiring of these cause hemolytic transfusion reactions. IgM monoclonal bodies? antibodies: anti A and Anti B are antibodies that is HYBRIDOMA TECHNOLOGY invented by Milstein IgM in nature and Kohler. ​ IgG in nature: Anti AB is the causative antibodies of Autoimmune hemolytic anemia (AIHA