why is sucrose test a screening test for PNH
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Here is a comprehensive explanation:
Sucrose Test as a Screening Test for PNH
The Principle
The sucrose (sugar water) hemolysis test works on the following principle:
When red blood cells (RBCs) are suspended in an isotonic sucrose solution (low ionic strength), complement is activated via the alternative pathway at a lower threshold than normal. In PNH, RBCs lack GPI-anchored complement regulatory proteins — specifically CD55 (DAF) and CD59 (MIRL) — which normally protect the cell membrane from complement-mediated lysis.
- CD55 (Decay Accelerating Factor) inactivates C3/C5 convertase complexes
- CD59 (Membrane Inhibitor of Reactive Lysis) blocks assembly of the membrane attack complex (C5b-9)
Without these, even the mild complement activation triggered by low ionic strength is enough to lyse PNH red cells. Normal red cells are not lysed under these same conditions.
Why It Is a Screening Test (Not Confirmatory)
| Feature | Sucrose Test | Ham's Test (Acidified Serum) |
|---|---|---|
| Sensitivity | High (sensitive) | High (sensitive) |
| Specificity | Lower (false positives) | Higher |
| Role | Screening | Confirmatory |
| Mechanism | Low ionic strength activates complement mildly | Acidified serum activates complement via alternative pathway |
| False positives | Megaloblastic anemia, autoimmune hemolytic anemia | Fewer |
The sucrose test is sensitive but not specific — it can be positive in conditions other than PNH (e.g., megaloblastic anemia). This is precisely why it serves as a screening tool: a positive result prompts further confirmatory testing with the Ham test or flow cytometry.
Notably, Harrison's states: "The sucrose hemolysis test is unreliable; in contrast, the acidified serum (Ham) test is highly reliable." — Harrison's Principles of Internal Medicine 22E
An Important Distinguishing Point
The sucrose test is negative in HEMPAS (CDA type II), even though the Ham test (acidified serum) is positive in both PNH and HEMPAS. This makes the sucrose test useful for differentiating the two:
- PNH → sucrose test positive
- HEMPAS → sucrose test negative — Quick Compendium of Clinical Pathology, 5th ed.
Current Status
Both the sucrose test and Ham test have been largely replaced by flow cytometry, which is now the gold standard. Flow cytometry directly detects the absence of GPI-anchored proteins (CD55, CD59, CD14, CD24) on RBCs, granulocytes, and monocytes — and using FLAER (fluorescein-labeled aerolysin), which binds selectively to the GPI anchor itself, offers even higher sensitivity for detecting minor PNH clones. — Henry's Clinical Diagnosis and Management by Laboratory Methods
Summary: The sucrose test is a screening test for PNH because it is sensitive (picks up most PNH cases) but not specific (can be falsely positive in other conditions). It uses low ionic strength to gently activate complement, exposing the complement-defenseless GPI-deficient PNH red cells to lysis. A positive result must always be confirmed by the Ham test or flow cytometry.
how sucrose activates compliment ?
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The textbooks don't go into the detailed mechanism of how sucrose activates complement — this is a fairly specialized biochemical point not elaborated in the available references. I'll explain it from established knowledge.
How Sucrose "Activates" Complement in the Sucrose Test
The short answer: sucrose doesn't directly activate complement. Instead, it creates a low ionic strength environment that lowers the threshold for the alternative complement pathway to deposit C3b on cell surfaces — and in PNH cells, there is no CD55/CD59 to stop what happens next.
Here's the mechanism step by step:
1. Low Ionic Strength from Sucrose Solution
The test uses an isotonic but low ionic strength sucrose solution (sucrose is electrically neutral — it has no ions). Normal isotonic saline contains Na⁺ and Cl⁻ ions; sucrose solution does not. So the osmolality is maintained (cells don't lyse from osmotic shock), but the ionic strength is very low.
2. Effect of Low Ionic Strength on Complement
In a low ionic strength environment:
- The electrostatic repulsion between complement proteins and the cell surface is reduced
- This allows complement proteins to bind more readily to cell membranes
- Specifically, it promotes C3 binding and deposition onto the RBC surface via the alternative pathway's "tick-over" mechanism — the slow, spontaneous hydrolysis of C3 into C3(H₂O) that happens continuously in plasma
Low ionic strength essentially amplifies the background alternative pathway activity that exists at all times, tipping C3b deposition toward the cell surface.
3. Why Normal Cells Are Unaffected
Normal RBCs have CD55 and CD59:
- CD55 degrades C3 convertase (C3bBb) — stopping the amplification loop
- CD59 blocks the membrane attack complex (MAC, C5b-9) from inserting into the membrane
Even with slightly enhanced C3 deposition in sucrose solution, normal cells survive because these regulators shut it down.
4. Why PNH Cells Lyse
PNH cells lack GPI-anchored CD55 and CD59 entirely. So:
- The modest C3b deposition triggered by low ionic strength goes unchecked
- The alternative pathway amplification loop runs freely
- MAC (C5b-9) assembles on the RBC membrane
- The cell lyses → hemolysis
Analogy
Think of the alternative pathway as a pilot light always burning at low level. Normally, CD55 and CD59 act as a fire extinguisher — any spark is immediately suppressed. Sucrose solution turns up the gas slightly (more C3b lands on the surface). For normal cells, the extinguisher handles it. For PNH cells, there is no extinguisher, so even the slightly bigger spark causes a fire.
Key Point for Exams
The sucrose test does not require exogenous complement or acidification — it simply exploits the fact that low ionic strength lowers the activation threshold of the naturally present complement in autologous serum. This is a gentler stimulus than the Ham test (which uses acid to directly activate complement), which is why the sucrose test is more sensitive but less specific — it can occasionally cause false-positive lysis in other conditions with complement-sensitive RBCs (e.g., megaloblastic anemia).
g6pd pathophyzuology
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G6PD Deficiency — Pathophysiology
The Normal Role of G6PD
In the pentose phosphate pathway (PPP), G6PD catalyzes the first and rate-limiting step:
Glucose-6-phosphate + NADP⁺ → 6-phosphogluconolactone + NADPH + H⁺
The NADPH produced is used by glutathione reductase to regenerate reduced glutathione (G-SH) from oxidized glutathione (G-S-S-G). G-SH is then used by glutathione peroxidase to neutralize hydrogen peroxide (H₂O₂) and other reactive oxygen species (ROS):
H₂O₂ + 2 G-SH → 2 H₂O + G-S-S-G
Why RBCs Are Uniquely Vulnerable
Two critical reasons:
- The PPP is the ONLY source of NADPH in RBCs. Other cells have alternative NADPH-generating pathways (e.g., malic enzyme). RBCs do not.
- RBCs have no nucleus or ribosomes — they cannot synthesize new G6PD enzyme. As the existing enzyme degrades (especially unstable mutant variants), protection against oxidative stress is irreversibly lost.
— Biochemistry, Lippincott Illustrated Reviews, 8th ed.
What Happens in G6PD Deficiency
When an oxidant stress hits (drug, infection, fava beans):
| Step | Event |
|---|---|
| 1 | Oxidant stress → H₂O₂ and free radicals generated inside RBC |
| 2 | G6PD is deficient → NADPH cannot be regenerated |
| 3 | Without NADPH → G-SH pool is depleted |
| 4 | H₂O₂ accumulates → oxidizes hemoglobin sulfhydryl groups |
| 5 | Oxidized Hb denatures → forms Heinz bodies (insoluble precipitates attached to RBC membrane) |
| 6 | Membrane proteins are also oxidized → membrane rigidity increases |
| 7 | Rigid, Heinz body-laden RBCs are trapped and destroyed by macrophages in the spleen → extravascular hemolysis |
| 8 | Severe cases → intravascular hemolysis as well |
Precipitating Factors
- Oxidant drugs — sulfonamides, dapsone, primaquine, nitrofurantoin, rasburicase
- Fava beans (favism) — contain vicine and convicine, which are oxidant compounds; particularly associated with the Mediterranean G6PD variant
- Infections — macrophages generate free radicals during the inflammatory response; these diffuse into RBCs causing oxidative damage
G6PD Variants and Severity
| Class | Residual Enzyme Activity | Clinical Features |
|---|---|---|
| I | <10% | Chronic non-spherocytic hemolytic anemia (CNSHA) |
| II* | <10% | Severe acute hemolytic anemia (e.g., Mediterranean variant) |
| III* | 10–60% | Moderate (e.g., G6PD A−, common in Africa) |
| IV | >60% | Asymptomatic |
Classes II and III are the most clinically common.
The G6PD A− variant (common in African populations) affects mainly older RBCs (which have lower enzyme activity normally due to enzyme decay), so young RBCs survive — hemolysis is self-limiting. The Mediterranean variant has more severely reduced activity affecting all RBCs, causing more prolonged hemolysis.
Inheritance
X-linked recessive → predominantly affects males. Females can be mildly affected if heterozygous (mosaic expression due to X-inactivation) or homozygous.
Evolutionary Note
G6PD deficiency persists at high frequency in malaria-endemic regions because Plasmodium falciparum infection induces oxidant stress inside parasitized RBCs — in G6PD-deficient cells, the parasite's own oxidative load destroys the host cell before the parasite can complete its life cycle, conferring partial protection against malaria. — Biochemistry, Lippincott Illustrated Reviews, 8th ed.
The enzyme deficiency test is usually not done during an active state, but it is done after resolution of an active phase, or it may be performed weeks after the hemolytic episode results. That's because during an active state, all the G6PD deficiency enzymes are hemestep and it doesn't show properly or what is the reason, I forgot.
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You remembered the concept correctly. Here is the precise explanation:
Why G6PD Testing Is Unreliable During an Acute Hemolytic Episode
The Core Reason: Selective Destruction of the Most Deficient Cells
G6PD enzyme activity normally declines as RBCs age. In G6PD deficiency, this decline is accelerated — older RBCs have the lowest (or zero) G6PD activity and are the most vulnerable to oxidant stress.
During an acute hemolytic episode:
- The oldest, most G6PD-deficient RBCs are selectively destroyed first (they have the least enzyme activity and cannot withstand the oxidant load)
- The bone marrow responds by releasing a surge of reticulocytes and young RBCs into the circulation
- Young RBCs naturally have higher G6PD activity — even in G6PD-deficient individuals, young cells haven't yet run down their enzyme supply
The Result: A False-Normal Test
When you measure G6PD activity at this point, the sample is enriched with young cells with relatively higher enzyme levels. The assay reads as falsely normal (or borderline), masking the true deficiency.
"During an acute hemolytic episode, the assay would measure the enzyme activity present in reticulocytes where there are usually normal levels, resulting in a falsely normal assay." — Creasy & Resnik's Maternal-Fetal Medicine
"The oldest, most G6PD-deficient red cells have been selectively destroyed, and young red cells, having higher G6PD activity, are being released into the circulation. Under these conditions, only a quantitative test can give a definitive result." — Harrison's Principles of Internal Medicine, 22nd ed.
When to Test
- Wait 2–3 months after the hemolytic episode, when the RBC population has normalized and older cells (with low G6PD) are again present in adequate numbers
- If you must test urgently, use a quantitative assay (not a screening/spot test), which is more sensitive and may still detect deficiency even in a reticulocyte-rich sample
- DNA-based testing is not affected by the RBC age distribution and can diagnose at any time
Summary in One Sentence
During hemolysis, the deficient old cells are gone and young cells (with relatively normal G6PD) flood the blood — so the enzyme looks normal when it isn't. Testing must wait until the RBC population returns to its steady state.
to write in mz note one line above concept '
Here it is as a one-liner for your notes:
G6PD enzyme assay is done after resolution of acute hemolysis (not during) because selective destruction of oldest/most-deficient RBCs + reticulocytosis causes falsely normal enzyme levels.
Why parvovirus B19 infects progenitor erythroid cells or red cells and causes a temporary halt of erythropoiesis, usually leading to significant anemia in a setting of a pre-existing marrow stress, maybe like sickle cell anemia or something like that? Can you explain it a bit, why it's unaffected only progenitor red cells and why not progenitor white blood cells or platelet cells?
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Excellent sources. Here is the full explanation:
Why Parvovirus B19 Selectively Targets Erythroid Progenitors
The Receptor is the Key: P Antigen (Globoside)
Parvovirus B19 can only infect cells that display its specific receptor on their surface — globoside (blood group P antigen). This is the entire reason for its selective tropism.
The virus's VP2 capsid protein binds to globoside → enters the cell → delivers its single-stranded DNA to the nucleus → hijacks host DNA and RNA polymerases to replicate → assembles new virions in the nucleus → lyses the cell upon release.
Cells that express globoside/P antigen include:
- Erythroid progenitors and erythroblasts — highest expression → primary target
- Megakaryocytes — express globoside too (more on this below)
- Endothelial cells
- Fetal myocardial cells
Cells that do not meaningfully express P antigen:
- Myeloid progenitors (neutrophil/monocyte lineage)
- Lymphoid progenitors
This is why the virus almost exclusively wipes out the erythroid lineage — it physically cannot enter cells lacking P antigen. Individuals who are naturally P antigen-negative (rare blood group phenotypes p or P1k) are actually resistant to B19 infection entirely.
— Sherris & Ryan's Medical Microbiology, 8th ed.; Creasy & Resnik's Maternal-Fetal Medicine
Why Does It Halt Erythropoiesis?
The virus specifically targets mitotically active immature erythroid progenitors in the bone marrow (CFU-E, pro-erythroblasts). Once infected:
- The cell ceases to proliferate and is lysed
- Erythroid output from the marrow drops to near zero
- Reticulocytes disappear from the peripheral blood within days
- This is called pure red cell aplasia (PRCA) — only the red cell lineage is affected
In a healthy person, RBCs live ~120 days. A 7–10 day shutdown of erythropoiesis causes only a trivial ~1% drop in hemoglobin — barely noticeable. The bone marrow recovers once the immune system clears the virus.
Why It Becomes Catastrophic in Underlying Hemolytic Conditions
In diseases like sickle cell anemia, hereditary spherocytosis, thalassemia, or G6PD deficiency:
- RBCs are being destroyed much faster than normal (lifespan reduced from 120 days to sometimes 10–20 days)
- The bone marrow is already running at maximum compensatory overdrive — producing red cells 6–8× the normal rate just to maintain baseline hemoglobin
- There is no reserve capacity
When B19 now shuts down erythroid production for even 7–10 days:
The hemoglobin crashes rapidly and severely → Transient Aplastic Crisis (TAC)
This can be life-threatening, requiring emergency transfusion. The anemia develops faster than the immune system can clear the virus.
— Harrison's Principles of Internal Medicine, 22nd ed.; Sherris & Ryan's Medical Microbiology
What About Platelets and White Cells?
| Lineage | P Antigen Expression | Effect of B19 |
|---|---|---|
| Erythroid progenitors | High | Directly lysed → aplasia |
| Megakaryocytes (platelet precursors) | Present | Can be infected, but less efficiently |
| Myeloid progenitors (WBC) | Absent/minimal | Not infected |
| Lymphoid progenitors | Absent | Not infected |
Megakaryocytes do express some globoside, which is why mild thrombocytopenia is occasionally seen in B19 infection. However, this is not the dominant effect because the expression level is lower and megakaryocytes are less critical in the same way. The WBC lineage (granulocyte/monocyte/lymphocyte progenitors) is essentially spared because they simply don't have the receptor.
The rare cases of autoimmune neutropenia and thrombocytopenia seen with B19 are immune-mediated (molecular mimicry, cross-reactive antibodies) — not from direct viral cytotoxicity.
One-Line Summary for Notes
B19 targets only erythroid progenitors because they uniquely express its receptor (P antigen/globoside) in high density; in normal persons the 7–10 day RBC production halt is trivial, but in compensated hemolytic anemia (where the marrow runs at maximum rate), even brief shutdown causes precipitous hemoglobin drop → transient aplastic crisis.
MONOSPOT OR heterophile agglutation test explainn why heterophile ? Inf mononucleosis
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Here is the full explanation:
Monospot / Heterophile Agglutination Test in Infectious Mononucleosis
What Does "Heterophile" Mean?
The word heterophile (Greek: hetero = different, phile = loving) refers to antibodies that cross-react with antigens from a completely different, unrelated species.
In other words: the antibodies produced during EBV infection in a human patient happen to recognize and bind to antigens on sheep, horse, and ox red blood cells — which are phylogenetically unrelated. There is no logical evolutionary reason for this — it is a quirk of molecular mimicry where certain carbohydrate/surface antigens on animal RBCs structurally resemble something triggered during EBV infection.
Why Does EBV Cause Heterophile Antibodies?
EBV infects B lymphocytes (via CD21 receptor). This causes polyclonal B cell activation — meaning B cells are mass-stimulated to produce a wide variety of antibodies in a non-specific, chaotic fashion, not just antibodies targeted at EBV itself.
Among the flood of antibodies produced during this polyclonal B cell activation, some happen to be IgM antibodies that cross-react with a carbohydrate antigen shared between:
- Human EBV-infected cells
- Red blood cells of sheep, horses, and cattle
These are the heterophile antibodies (also called Paul-Bunnell antibodies).
Key point: heterophile antibodies are not directed against EBV — they are a byproduct of nonspecific B cell activation. They do not correlate with disease severity and are not protective. — Sherris & Ryan's Medical Microbiology, 8th ed.
How the Monospot Test Works
The Monospot is a rapid slide agglutination test:
- A drop of patient serum is placed on a card/slide
- It is first mixed with guinea pig kidney cells — these absorb away cross-reacting antibodies from serum sickness and other conditions (specificity step)
- Then horse RBCs (or sheep RBCs in older versions) are added
- If heterophile antibodies are present → they agglutinate the horse RBCs → positive result
The guinea pig kidney absorption step is the trick that makes it specific: serum sickness also produces heterophile-like antibodies, but those ARE absorbed by guinea pig kidney cells. EBV heterophile antibodies are not absorbed by guinea pig kidney → they remain and cause agglutination → positive monospot.
Why Called "Heterophile Agglutination"?
| Term | Meaning |
|---|---|
| Heterophile | Antibodies that react with antigen from a different species |
| Agglutination | Clumping/aggregation of RBCs by the antibody |
So the test = agglutination of animal (horse) RBCs by human antibodies that were cross-reactively produced during EBV infection = heterophile agglutination.
Performance of the Test
| Feature | Value |
|---|---|
| Sensitivity | ~75–85% (adults); only ~40% in children; <20% in children <4 yrs |
| Specificity | ~90% |
| Antibody type | IgM |
| Appears | Week 1–2 of illness |
| Peaks | Week 2–3 |
| Persists | Up to 3–6 months |
False positives: HIV, SLE, rubella, lymphoma, viral hepatitis
False negatives: early disease, young children (children mount a weaker heterophile response)
When monospot is negative but mononucleosis is strongly suspected → send EBV-specific serology (VCA-IgM, VCA-IgG, EA, EBNA).
— Quick Compendium of Clinical Pathology, 5th ed.; Harrison's, 22nd ed.
One-Line Summary for Notes
Heterophile = IgM antibodies produced by nonspecific polyclonal B cell activation during EBV infection that cross-react with antigens on unrelated species (horse/sheep RBCs); the Monospot detects these by agglutination after absorbing out non-specific antibodies with guinea pig kidney.
Cd34= means hematopoietic stem cells, Cd55 meand DAF CD19 and IL5 , CD21 iam so confudssed can you create a notes with all this imp markers amd what i shou;ld know to siolve usmle question immunolgy
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I now have enough from the textbooks to build a comprehensive, USMLE-focused CD marker reference. Let me compile this.
USMLE CD Marker Master Notes
HOW TO THINK ABOUT CD MARKERS
CD markers = proteins on cell surfaces. They tell you what the cell IS and what it DOES. On USMLE, questions give you a CD pattern → you identify the cell or disease.
T CELL MARKERS
| Marker | Cell | What to Know |
|---|---|---|
| CD3 | All T cells | Forms complex with TCR. Pan-T cell marker — if it's a T cell, it has CD3. Loss of CD3 = no T cell signaling |
| CD4 | Helper T cells | Binds MHC II. Also the receptor HIV gp120 binds (with CCR5/CXCR4 as co-receptor). CD4 count monitors HIV progression |
| CD8 | Cytotoxic T cells | Binds MHC I. Kills virus-infected and tumor cells |
| CD28 | All T cells (CD4 > CD8) | Costimulatory receptor on T cells. Binds B7 (CD80/86) on APCs → Signal 2 for T cell activation. Without it → T cell anergy |
| CD40L (CD154) | Activated CD4⁺ T cells | Binds CD40 on B cells → triggers B cell class switching. Hyper-IgM syndrome = CD40L deficiency → can't switch from IgM to IgG/IgA/IgE |
| CD25 | Activated T cells & Tregs | IL-2 receptor α-chain. Tregs = CD4⁺CD25⁺FoxP3⁺ |
| CD45RA | Naïve T cells | "RA = Raw/new" |
| CD45RO | Memory T cells | "RO = Old/memory" |
| CD1 | Developing T cells, Langerhans cells | Presents lipid antigens (like mycobacterial antigens) — MHC I-like |
| CD2 | T cells, NK cells | Adhesion molecule; marker of T cell activation |
| CD7 | T cells, stem cells | Marker for T-cell ALL and stem cell leukemia |
B CELL MARKERS
| Marker | Cell | What to Know |
|---|---|---|
| CD19 | All B cells (not plasma cells) | Pan-B cell marker. Part of B cell co-receptor complex (with CD21 + CD81). Target of rituximab in lymphoma treatment |
| CD20 | Pre-B → mature B cells (not plasma cells) | Rituximab target. Lost when B cell becomes plasma cell (that's why rituximab doesn't kill plasma cells) |
| CD21 | Mature B cells, follicular dendritic cells | CR2 = Complement receptor 2 — binds C3d. Also the EBV receptor (EBV binds CD21 to enter B cells → infectious mononucleosis) |
| CD40 | B cells, macrophages, dendritic cells | Receives signal from CD40L on T helper cells → class switching |
| CD10 | Pre-B cells, germinal center B cells | Marker for ALL (B cell) and follicular lymphoma |
| CD5 | T cells + some B cells (B-1 cells) | B cells expressing CD5 → seen in CLL and mantle cell lymphoma |
| CD23 | B cells, macrophages, eosinophils | Low-affinity IgE receptor (FcεRII). Elevated in CLL (CLL = CD5⁺ CD23⁺) |
| CD38 | Early B and T cells, plasma cells | Marker for plasma cells and multiple myeloma. Target of daratumumab |
| CD138 (Syndecan-1) | Plasma cells | Definitive plasma cell marker. Positive in multiple myeloma |
NK CELL MARKERS
| Marker | Cell | What to Know |
|---|---|---|
| CD16 | NK cells, macrophages | FcγRIII — binds IgG Fc → mediates ADCC (antibody-dependent cellular cytotoxicity) |
| CD56 | NK cells | Pan-NK marker. Also seen in NK/T cell lymphoma |
| CD57 | NK cells, some T cells | Mature NK cells |
MYELOID / MONOCYTE MARKERS
| Marker | Cell | What to Know |
|---|---|---|
| CD14 | Monocytes, macrophages | LPS (endotoxin) co-receptor. GPI-anchored — absent in PNH |
| CD15 | Granulocytes | Marker for Reed-Sternberg cells in Hodgkin lymphoma (CD15⁺ CD30⁺) |
| CD30 | Activated T/B cells | Reed-Sternberg cells in Hodgkin lymphoma (CD15⁺ CD30⁺). Target of brentuximab vedotin |
| CD64 | Monocytes, macrophages | High-affinity FcγRI |
| CD11b / CD18 | Neutrophils, macrophages | Integrin — mediates adhesion. Deficiency → LAD (Leukocyte Adhesion Deficiency) |
STEM CELL / PROGENITOR MARKERS
| Marker | Cell | What to Know |
|---|---|---|
| CD34 | Hematopoietic stem cells | The HSC marker. Used to identify and isolate stem cells for transplant. Stains HSC-derived tumors (e.g., some AML, GIST also CD34⁺) |
| TdT (Terminal deoxynucleotidyl transferase) | Pre-T, Pre-B cells | Enzyme in immature lymphocytes. Positive in ALL, negative in mature lymphomas |
COMPLEMENT REGULATORY PROTEINS (GPI-anchored — critical for PNH)
| Marker | Cell | What to Know |
|---|---|---|
| CD55 (DAF — Decay Accelerating Factor) | All blood cells | Degrades C3/C5 convertase → stops complement amplification. Absent in PNH → complement-mediated hemolysis |
| CD59 (MIRL — Membrane Inhibitor of Reactive Lysis) | All blood cells | Blocks MAC (C5b-9) assembly. Absent in PNH — most important protein protecting RBCs. GPI-anchored |
| CD35 (CR1) | RBCs, B cells, monocytes | Complement receptor 1 — binds C3b/C4b → phagocytosis |
PNH high-yield: PNH = loss of all GPI-anchored proteins (due to PIG-A mutation) → CD55 and CD59 absent → uncontrolled MAC → intravascular hemolysis. Flow cytometry showing absent CD55/CD59 = gold standard diagnosis.
ADHESION / TRAFFICKING MARKERS
| Marker | Cell | What to Know |
|---|---|---|
| CD11a/CD18 (LFA-1) | Leukocytes | Binds ICAM-1. Required for leukocyte extravasation. Absent in LAD type I |
| CD31 (PECAM-1) | Endothelial cells, platelets | Mediates leukocyte migration through vessel walls |
| CD62L (L-selectin) | Naïve lymphocytes | Homing receptor for lymph nodes — naïve T cells use this to enter lymph nodes |
CYTOKINE RECEPTORS (USMLE-RELEVANT)
| Marker | Cytokine | Key Disease |
|---|---|---|
| CD25 | IL-2 receptor α | Tregs = CD4⁺ CD25⁺ FoxP3⁺ |
| CD122 | IL-2/IL-15 receptor β | NK and memory T cell survival |
| CD127 | IL-7 receptor | Critical for T cell development in thymus |
| CD132 | Common γ chain (γc) | Shared by IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 receptors. X-linked SCID = γc deficiency → no T, B (dysfunctional), NK cells |
IL-5 receptor: on eosinophils and basophils. IL-5 = the eosinophil growth/activation cytokine. IL-5 blockade (mepolizumab) treats severe eosinophilic asthma.
DISEASE-MARKER QUICK LOOKUP
| Disease / Scenario | Key Markers |
|---|---|
| T-ALL | TdT⁺, CD7⁺, CD3⁺, CD4⁺CD8⁺ (double positive) |
| B-ALL | TdT⁺, CD19⁺, CD10⁺ (CALLA), CD20⁺ |
| CLL | CD5⁺, CD19⁺, CD20(dim)⁺, CD23⁺, TdT⁻ |
| Mantle Cell Lymphoma | CD5⁺, CD19⁺, CD20⁺, CD23⁻, Cyclin D1⁺ |
| Follicular Lymphoma | CD10⁺, CD19⁺, CD20⁺, BCL-2⁺ |
| Multiple Myeloma | CD138⁺, CD38⁺, CD19⁻, CD20⁻ |
| Hodgkin Lymphoma (RS cells) | CD15⁺, CD30⁺, CD45⁻ |
| PNH | CD55⁻, CD59⁻ on RBCs/WBCs |
| LAD | CD11b/CD18⁻ (integrin absent) |
| X-linked SCID | CD132 (γc) deficiency |
| Hyper-IgM syndrome | CD40L (CD154) deficiency on T cells |
| HIV target cell | CD4⁺ T cell (gp120 binds CD4 + CCR5/CXCR4) |
| EBV entry into B cells | CD21 (EBV receptor) |
| Rituximab target | CD20 (B cells in lymphoma/RA) |
ONE-LINE MNEMONICS
- CD3 = TCR's partner (always together, always T cell)
- CD4 = "4 letters in HELP" → helper; also HIV's door
- CD8 = "8 = kill" → cytotoxic killer
- CD19/20 = B cell's ID card (lost when becoming plasma cell)
- CD21 = EBV + C3d receptor (2 jobs, 1 marker)
- CD34 = Stem cell marker (think: "34 = stem")
- CD55/59 = PNH's missing bodyguards
- CD40L = T cell's signal to B cell ("switch now!") → absent = Hyper-IgM
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