B-Cells and T-Cells

These specialized cells are a critical part of the bodies humoral immune system. They recognize foreign antigens or invaders and mount a quick response. B-cells act quickly by developing antibodies to the antigen epitopes. T-cells react based on what serological class they are in. If it is a CD8 T-cell, its cytotoxic and can quickly fight and phagocytize the antigen, if it is a CD4 T-cell, it works in conjunction with B-cells and other T-cell subclasses to defend the host. This article will dive into B-cells, and every subclass of T-cells and how they work together to form the humoral branch of the immune system.


B-cells also known as B lymphocytes are a type of lymphocyte that functions as part of the humoral component of the adaptive immune system. It’s role is to secrete antibodies, but it also functions as an antigen-presenting cell (APC) that secretes cytokines. It possesses a B-cell receptor (BCR) on its surface that allows it to bind to a specific target antigen and initiate an immune response. B-cells develop from hematopoietic stem cells (HSCs) that originate within the bone marrow. They then develop into multipotent progenitor cells (MPP), which further differentiates into the common lymphoid progenitor (CLP). Development further progresses through several stages through various gene expression patterns and arrangements. Before maturation occurs, positive selection takes place to make sure that the pre-BCR and BCR can recognize and bind to specific ligands through antigen-independent signaling. If the cells are unable to bind, these B-cells cease to develop. Negative selection occurs through binding of self-antigen with the BCR. If the BCR is able to bind self-antigen it undergoes four fates; clonal deletion, receptor editing, anergy, or ignorance. Clonal deletion is the destruction of the B-cell through programmed cell death, in other words known as apoptosis. This is only for those B-cells that have expressed receptors for self-antigens. Receptor editing is exactly what the name suggests; editing of the BCR during the maturation process in an attempt to change the specificity the receptor to not recognize self-antigens. Anergy is used to describe lack of reaction by the bodies immune system. Its a way of saying that the B-cells that express BCRs for self-antigen will simply not be used. The last fate; ignorance means that the B-cell ignores the signal and continues through natural development. When negative selection is complete, the B-cells are now in a state of central tolerance. These mature B-cells do not bind with self antigens. From the bone marrow, B-cells migrate to the spleen as transitional B-cells. Within the spleen they become Follicular B-cells or Marginal zone B-cells depending on the signal received through the BCR. Once completely differentiated, they are now called naive B-cells.

B cell

B-Cell Activation

Activation usually occurs within the secondary lymphoid organs, such as the spleen and the lymph nodes. This is where naive B-cells are positioned once mature. When these naive immunocompetent B-cells encounter an antigen through its BCR, the antigen is internalized by receptor-mediated endocytosis, digested, and positioned on MHC II molecules on the B-cell surface. This allows the B-cell to act as an antigen-presenting cell to T-cells. T-cell dependent activation requires a T-cell helper, most commonly a follicular T-helper cell, to bind to the antigen-complexed MHC II molecule on the B-cell surface through its T-cell receptor (TCR) which drives T-cell activation. These T-cells express the surface protein CD40L and secrete cytokines IL-4, and IL-21 which bind to CD40 on the B-cell surface and act as co-stimulatory factors for B-cell activation. The co-stimulatory factors promote proliferation, immunoglobulin class switching, and somatic hypermutation. Activated T-cells then provide a secondary wave of activation that cause the B-cells to proliferate and form germinal centers. During the production of these germinal centers, activated B-cells may differentiate into plasma blasts, which can produce weak IgM antibodies. Within the germinal centers, B-cells differentiate into high affinity memory B-cells or long-lived plasma cells. The primary function of plasma cells is the secretion of clone-specific antibodies. There are very few antigens that can directly provide T-cell independent B-cell activation. Some components of bacterial cell walls (lipopolysaccharide), and bacterial flagellin are some to name a few. One other mechanism through which B-cell activation is enhanced is through the activity of CD21, CD19, and CD81; all three are surface proteins that form a complex. When the BCR binds to an antigen that is tagged with the complement protein C3, CD21 binds to C3, and downstream signaling lowers the activation threshold of the cell.

Memory B-cell Activation

Activation begins through detection and binding of the target antigen. When the antigen binds, it is taken up by the B-cell through receptor-mediated endocytosis, degraded, and presented onto the MHC II molecule within the B-cell surface. The memory B-cell then acts as an antigen-presenting cell that presents the antigen:MHC II complex to T-cells. Most commonly memory follicular T-helper cells that bind through their TCR. The memory B-cell is then activated and differentiates into either plasmablasts and plasma cells or generate germinal centers.


A T-cell is another lymphocyte, which is a subset of white blood cells. They are called T-cells because they mature in the thymus from thymocytes. There are several subsets of T-cells, each with a specific role in the immune system. These T-cells, just like B-cells originate from hematopoietic stem cells in the bone marrow. These lymphoid progenitor cells populate the thymus and expand by cell division to immature thymocytes. The earliest thymocytes do not express either CD4+ or CD8+ and are classified as double negative cells. Through progression they become double positive and then eventually differentiate into single positive cells, either becoming CD8+, or CD4+. Its interesting to note that there is a small population of double positive T-cells within the peripheral circulation, although their function is unknown. About 98% of thymocytes undergo apoptosis during the development process by failing either positive selection or negative selection. The 2% that survive leave the thymus and become mature immunocompetent T-cells. Lets review positive and negative selection again. Positive selection selects for T-cells that are capable of interacting with MHC molecules. During positive selection signals by double positive precursors express either MHC class I or II receptors. A thymocytes fate is determined during positive selection. Double positive CD4+/CD8+ cells that interact with MHC class II molecules eventually become CD4+ cells, and on the contrary thymocytes that interact well with MHC class I molecules mature into CD8+ cells. Negative selection removes thymocytes that are capable of strongly binding with self MHC peptides.


T-Helper Cells

T-helper cells do just what their name suggests, they help other cells in immunological processes. This is evident in the activation of B-cells talked about previously. These cells are also most well known as CD4+ T-cells because the highly express CD4 glycoprotein on their surfaces. These T-cells become activated when they are presented with peptide antigens or epitopes by MHC class II molecules, usually present on antigen-presenting cells. Once activated, these cells proliferate rapidly and secrete multiple cytokines. T-helper cells differentiate into several subtypes; TH1, TH2, TH3, TH17, TH9, and THF, each secreting different cytokines to facilitate different pathways of the immune response. This is an article for another time.


Cytotoxic T-Cells

These killer T-cells destroy virus-infected cells and tumor cells. These cells are known as CD8+ T-cells since they express the CD8 glycoprotein on their surface. These cells recognize targets by binding to antigen epitopes that are associated with MHC class I molecules. Cytotoxic T-cells are highly regulated by Regulatory T-cells through IL-10, adenosine, and other molecules. They can be inactivated to an anergic state, which prevents autoimmune diseases.

T-cell CD8

Memory T-Cells

These memory T-cells are long-lived and when presented with an antigen that is recognized they can quickly expand and differentiate into large numbers of effector T-cells. These memory T-cells can either be CD4+ or CD8+ T-cells. There are four subtypes of memory T-cells that will be discussed below.

Central memory T-cells express CD45RO, C-C chemokine receptor type 7 (CCR7) and L-selectin which are all surface protein markers. They have high expression of CD44, and is commonly found within the lymph nodes.

Effector memory T-cells express CD45RO, but lack expression of CCR7 and L-selectin. These T-cells also have high expression of CD44, but are not found in the lymph nodes. These T-cells are found in the peripheral circulation and tissues.

Tissue resident memory T-cells occupy tissues without recirculating. The one specific surface marker that is associated with these cells is integral aeB7.

Virtual memory T-cells differ from all other memory subsets in that they do not originate from a clonal expansion event. These cells reside at low frequencies.

Natural Killer T-cells (NK)

First off, it should be mentioned that these cells should not be confused with natural killer cells of the innate immune system. Unlike conventional T-cells that recognize antigen epitopes presented on MHC I/II molecules, NKT cells recognize glycolipid antigens presented by a molecule called CD1d. When these cells are activated, these cells perform functions from both T-helper cells and cytotoxic T-cells. These cells specialize in recognizing tumor cells and cells infected with herpes viruses.



Enzyme-Linked Immunosorbent Assays (ELISA)

The first step in any ELISA assay is the immobilization of the antigen within the sample to the wall of the wells within a microtiter plate. These microtiter plates are usually 96-wells. This is by direct adsorption to the plates surface or by using a capture antibody. The capture antibody has to be specific to the  target antigen. After immobilization, another antibody is added called the detection antibody. This detection antibody binds to the adsorbed antigen which forms an antigen:antibody complex. This detection antibody is either directly conjugated to an enzyme, such as horseradish peroxidase (HRP), or provides an antibody-binding site for a secondary labeled antibody. There are four different types of ELISAs which will all be discussed below. ELISAs take advantage of an enzymatic label to produce a signal that can be quantified and correlated to the binding of an antibody to an antigen. The final assay signal is measured using spectophotometry.

Direct ELISA

In the direct ELISA, the detection antibody is conjugated with either alkaline phosphatase (AP) or horseradish peroxidase (HRP). These substrates produce a colorimetric output that is then measured. The advantages of a direct ELISA is that it is a short protocol which saves time and reagent, and money. There is no cross-reactivity from a secondary antibody that can cause interference. The disadvantages are that there is no signal amplification, so the primary antibody must be conjugated for it to work.


Indirect ELISA

In the indirect ELISA, antibodies can be conjugated to biotin, which is then followed by a streptavidin-conjugated enzyme step. This is becoming more common place within the clinical laboratory. Alternatively, the detection antibody is typically a human IgG antibody that binds to the antigen within the wells. This primary antibody has multiple antibody-binding sites on it. A secondary rabbit anti-human IgG antibody conjugated with an enzymatic substrate is added. This secondary antibody binds to the first antibody and gives off a colorimetric signal which can be quantified by spectrophotometry. There are advantages over the direct ELISA, mainly that there is signal amplification by using several antibodies, allowing for high flexibility. This also creates a longer protocol, and increases the chances for cross-reactivity, which can be deemed disadvantages.


Sandwich ELISA

The sandwich ELISA is less common, but is highly efficient in antigen detection. It quantifies antigens using multiple polyclonal or monoclonal antibodies. Monoclonal antibodies recognize a single epitope, while a polyclonal antibody recognizes multiple antigen epitopes. The antigen that is to be measured must contain at least two antigenic epitopes capable of binding to an antibody for this reason. The first step is to coat the microtiter plate wells with the capture antibody within a carbonate/bicarbonate buffer (pH 9.6). Proceed to incubate the plate overnight at 4 degrees Celsius. Wash the plate twice using PBS. Incubate the plate again for at least 2 hours at room temperature. Wash the plate again using PBS. The next step is to add diluted unknown samples to each well. Its important to run unknown samples against those of a standard curve by running standards in duplicates or triplicates. Incubate for 90 minutes at 37 degrees Celsius. then remove the sample and wash with PBS again. Next, add diluted detection antibody to each well. Its important to make sure that the detection antibody recognizes a different epitope on the target antigen than the capture antibody. The prevents interference with antibody binding. To maximize specificity and efficiency, use a tested matched pair. Once the detection antibody has been added, incubate for 2 hours at room temperature. Wash once again with PBS. After washing, add conjugated secondary antibody to each well. Incubate once again at room temperature, then proceed to wash. Once again, horseradish peroxidase and alkaline phosphatase are used as enzymes conjugated to the secondary antibody. The substrates for HRP are called HRP chromogens. Cleavage of hydrogen peroxide is coupled to an oxidation reaction which changes color. Another common substrate used is ABTS. The end product is green.


The sandwich ELISA employs high specificity, even when using complex samples. Within the sandwich ELISA, both direct and indirect methods can be used. It can be challenging to find two different antibodies against the same target the recognize different epitopes.

Competitive ELISA

The competitive ELISA is exactly what its name suggests; it is a competitive binding process which is produced by the sample antigen, and an add-in known concentration of antigen. A primary unlabeled antibody is incubated with the unknown sample antigen. This creates antigen:antibody complexes, which are then conjugated to a microtiter plate which is pre-coated with the same antigen. Any free antibody binds to the same antigen on the well. Unbound antibody is removed by washing the microtiter plate. The more antigen within the unknown sample means that less antibody will be able to bind to the antigens within the wells, hence the assay gets its name. Its a competition. A secondary conjugated antibody that is specific for the primary antibody bound to the antigen on the pre-coated on the wells is added. When a substrate is added, the reaction elicits a chromogenic or fluorescent signal. The higher the sample antigen concentration, the weaker the eventual signal.





Erythropoietin (EPO)

The role of red blood cells is to carry oxygen. Just like anything in the body, this is tightly regulated by a mechanism that monitors whether or not there is adequate oxygen getting to tissues and other cells. Hypoxia is detected by the peritubular fibroblasts of the kidneys which causes erythropoietin (EPO) to be released. The EPO gene has a hypoxia-sensing region in its 3’ regulatory component which causes hypoxia inducible factor-1 (HIF-1) transcription factor to be assembled and it interacts with the 3’ enhancer of the gene causing increased EPO mRNA and production of more EPO.  EPO is a true hormone, being produced in the kidneys, and acting upon another distant location being the bone marrow. When EPO binds to its ligand (receptor) on red blood cell progenitors it initiates a cascade which is mediated through the JAK2 signal transducers which ultimately effects the gene expression. EPO has three main physiological effects on the body; it allows early release of reticulocytes from the bone marrow, prevents apoptosis, and reduces the time needed for cells to mature in the bone marrow before release into the periphery. 

There are two mechanism for which EPO stimulates early release of red cell precurors into the bone marrow. It induces changes in the adventitial cell layer of the marrow sinuses that increases the width of the spaces that the red cells squeeze out of. It also down regulates red blood cell surface receptors for adhesive molecules that are located on the bone marrow stroma. As a result the red cells are able to pass through without the receptor so that they won’t bind to the stroma and delay release.

Apoptosis is programmed cell death. EPO inhibits apoptosis by removing the induction signal. Under normal physiology the bone marrow produces more CFU-Es than needed that are stored in the bone marrow which have a “head start” in the maturation process. About a 10 day head start in maturation. The CFU-Es (Colony-forming unit-erythroid) are red blood cell progenitor cells that develop from BFU-Es (Burst-forming unit-erythroid). Both BFU-E and CFU-E are red blood cell progenitor cells that develop into the pronormoblast, which is the first morphologically identifiable red blood cell precursor. If healthy, those cells live out there life span and undergo apoptosis. If there is a deficiency of red blood cell mass, those cells undergo maturation to be released, while simultaneously the apoptosis induction signal is inhibited. The normal death signal consists of a death receptor being FAS, on the membrane of the earliest red blood cell precursors (CFU-Es/BFU-Es), and FASL ligand on the maturing red blood cells precursors. When EPO levels are low, because there is adequate oxygen delivery the older FASL bearing cells cross-link with earlier FAS precursors which stimulates apoptosis. EPO is able to subdue apoptosis by stimulating the more mature precursors to be released from the marrow, especially in times of hypoxia. At which point there will no FASL bearing cells to cross-link the early FAS bearing precursors. Its a two fold effect, the more mature cells are released to help increase red cell mass in times of need, and the early precursor are allowed to mature and be released without undergoing apoptosis. When EPO binds to its ligand on the red blood cell activates the JAK2-STAT pathway, which ends in and up-regulation of transcription for BCL-2, which is an anti-apoptotic protein. This anti-apoptotic protein rests on the cell membrane and prevents the release of cytochrome c, which initiates apoptosis. 


EPO has an effect on the bone marrow transit time of a red blood cell precursor in two different ways; increased rate of cellular processes, and decreased cell cycle times. What this means is that EPO stimulates synthesis of red cell RNA, such as the production of hemoglobin. It also stimulates the production of egress-promoting surface molecules within the bone marrow which allow the red blood cells to flow through the marrow easier. EPO stimulates cells to enter cell cycle arrest earlier than normal, and as a result, spend less time maturing and are able to be released. These cells may appear larger in size and have a bluish tinge to their cytoplasm because of this.

Donath-Landsteiner Antibodies

The history of the DL antibody goes back to the 1900’s. It was one of the first recognized forms of immune mediated hemolysis and responsible for inducing Paroxysmal Cold Hemoglobinuria (PCH). PCH is a transient condition, meaning that it comes on when immunoglobulins (Antibodies) are formed in response to a viral, bacterial, or spirochete infection. Its history will suggest that there is an association between PCH and syphilis. In over 90% of the cases of PCH in early history, the patient was co-diagnosed with syphilis. Throughout the 1900’s the condition began to evolve and is now seen most commonly in children following some sort of infection. Although it should be noted that PCH is not limited to those of adolescent age. So what really is the Donath-Landsteiner antibody and how does it contribute to PCH?

Clinical Presentation

Paroxysmal Cold Hemoglobinuria (PCH) is an autoimmune hemolytic anemia (AIHA). Autoimmune meaning that they are antibodies that have cross-reacted to attack the individuals own cells. Hemoglobinuria means that there will be hemoglobin present in the blood, which suggests intravascular hemolysis. PCH is one of the more common intravascular hemolytic anemias. Typical patients present with fever, chills, abdominal and back pain, and pronounced hemoglobinuria. PCH typically presents in children following and upper respiratory infection or immunization. These patients often have a rapidly progressing anemia with hemoglobins that can fall as low as 2.5 g/dL. Peripheral blood smears show significant red blood cell agglutination and anisocytosis and poikilocytosis. Anisocytosis indicating variance in size of the red blood cells and poikilocytosis indicating variance in structure to the red blood cells. Schistocytes, spherocytes, and polychromasia are common findings. The spherocytes and polychromasia are indicative of the bone marrow trying to replenish the red cell population as best it can so it forces out immature erythrocytes into the peripheral blood. Its an effort to sustain the hemoglobin as best it can. One distinguishing peripheral blood smear finding in patients with PCH is erythrophagocytosis. Lets break this word down. Erythro- short for erythrocyte meaning red blood cells. Phagocytosis is mediated by neutrophils and monocytes as a way to kill foreign pathogens. In the case of erythrophagocytosis in PCH, neutrophils are characteristically seen engulfing red blood cells, which is diagnostic for AIHA.

The Donath-Landsteiner Antibody

The DL antibody, although being recognized as an cold autoantibody, is an IgG antibody that has developed P antigen specificity and it is a biphasic hemolysin. What that means is that when someone has the DL antibody and is exposed to cold temperatures, it will bind to the individuals red blood cells through the P antigen, but does not cause hemolysis until the coated red blood cells are heated to 37 degrees Celsius as they (RBC:antibody complex) travel from the peripheral fingertips and toes to the core of the human body.   At cold temperatures, the IgG molecule is able to recruit complement (C3), and at the higher temperatures, activates the membrane attack complex (C5-C9) and lyses the red blood cells. One very interesting piece of information regarding the difference between Cold Agglutinin Syndrome (CAS), another autoimmune hemolytic anemia caused by Anti-I, is that the hemolysis from PCH is stronger and more severe because of the DL antibodies ability to detach from lysed red blood cells and reattaching to other cells. 

Laboratory Diagnosis

There are a few different ways to pinpoint PCH in the blood bank. One is by use of a Direct Coombs test (DAT). This test provides information regarding the type of hemolysis, whether it be acquired or inherited. It also tests for antibodies that have are bound in vivo. The most common DAT result in PCH is red blood cells coated with C3d causing a positive reaction. This is sensitive in 94-99% of cases. The other way to diagnosis DLAIHA (Donath-Landsteiner Autoimmune Hemolytic Anemia) is by the indirect DL test. This process involves collection of a fresh serum specimen that is strictly maintained at 37 degrees Celsius from collection all the way through to testing. If the sample is allowed to cool or is refrigerated, there could potentially be autoadsorption of the DL anti-P antibodies onto the patients autologous red blood cells. This could cause a false negative result. Upon testing, the patients serum is mixed with P antigen positive, group O red blood cells, and fresh donor serum. The fresh donor serum is added because the complement level within the patients may be low due to consumption. The patient and donor serum mixture is incubated in a melting ice bath (O degrees Celsius) for 30 minutes, then warmed to 37 degrees Celsius for one hour. The specimen is then centrifuged and examined for hemolysis. If hemolysis is present then this constitutes a positive result for DL antibody.


Indirect DL test: As you can see in tubes 1 and 4, the presence of hemolysis indicates a positive test result for the DL antibody.


There is unfortunately no cure for PCH, and very little reliable treatment options for those with the DL antibody. It is recommended to avoid cold climates as much as possible and when inside to have the temperature at 30 degrees Celsius to keep the hemoglobinuria low. This doesn’t treat the PCH, but it will minimize the recurrence and induced anemia. Steroids have been through extensive trials for treatment of PCH and there are mixed results. Theory is that steroids are better at clearing red blood cells coated with IgG, and less effective at clearing red blood cells that are coated with complement. More aggressive treatment such as splenectomy and Rituximab, which is an monoclonal antibody that targets the transmembrane protein CD20 present on B cells has been found effective for those patients with refractory PCH.

Iron Deficiency and Microcytic Anemias

Iron is an essential element for oxygen transport within hemoglobin. Oddly enough it is the element that is missed the most in regards to adequate intake and proper nutrition. Over 1.62 billion people in the world are effected by anemia, which is most commonly caused by iron deficiency. Iron deficiency can be caused by chronic blood loss, and is most common in women and teenagers from loss of blood due to menses. Iron loss leads to increased fatigue and depression, pallor, and dry and splitting hair. It can also lead to confusion cognitive effects. Hemoglobin is made of four polypeptide chains, two of which are alpha, and two are beta that come together to form a tetramer heme group with iron located in the middle. Ferrous iron within each heme molecule reversibly binds to one oxygen molecule. With iron deficiency, there becomes a hemoglobin deficiency. A decreased hemoglobin lowers oxygen-carrying capacity leading to anemia. Anemia by definition is a reduced oxygen-carrying ability. Tissue hypoxia can wreak havoc on almost every cell of the body, and can shift the oxygen dissociation curve in an unfavorable direction. The structure of hemoglobin and its function and key elements can be reviewed here.

To understand iron deficiency its important to recognize important aspects of iron metabolism and transportation in cells. Review the Iron Absorption and Metabolism article here for that information. There are also laboratory values that give a good picture of the iron status within the body that one should pay attention to. Transferrin; which is measured as the total iron binding capacity (TIBC) indicates how much or how little iron is being transported throughout the body. Serum iron is an important indicator of the tissue iron supply, and finally serum ferritin gives a picture of iron storage status within the bone marrow and cells.

Iron Deficiency Anemia

There are three stages within iron deficiency. Each comes with their own classic picture of laboratory results and worsen from stage to stage. In the first stage, there is storage iron depletion. This is mild and the patient may not even feel a difference physically. The patients hemoglobin is normal, normal serum iron, and TIBC. There is however decreased ferritin which indicates that there is decreased storage of iron. The second stage of iron deficiency is characterized by transport iron depletion. The hemoglobin may or may not be abnormal, but there is increased TIBC, and decreased serum iron. An increased TIBC, means that there are more substrate (iron) binding spots within the transferrin molecule. This implies that less iron is binding, which when coupled with a decreased serum iron makes sense. The patient may experience mild anemia which comes with increased fatigue and pallor. A peripheral blood smear will most often start to exhibit anisocytosis and poikilocytosis. These reference indicators represent abnormal sized red cells and abnormal shaped red blood cells respectively. A good indicator is an increased RDW, an increased RDW indicates some degree of anisocytosis. This is accurate because the red blood cell is realizing the loss of this oxygen-carrying capacity so its trying to release red blood cells as fast it can from the bone marrow to compensate for the loss, and as a result these red blood cells will appear smaller in diameter and hypochromic. Hypochromasia indicates that there is less hemoglobin within the cell and there is more of a central pallor. The thought is that even though there is less hemoglobin within each cell, if the bone marrow can produce more of these red blood cells than normal then that equals out. This leads to a microcytic anemia, micro meaning small. Stage three of iron deficiency is often referred to as functional iron deficiency. Within this stage there is an unmistakable decrease in hemoglobin, serum iron, and ferritin. There is also a large increase in TIBC.

The overall effect of iron deficiency anemia on the body and on the bone marrow is ineffective erythropoiesis. The red cell production within the bone marrow is compromised. As a result, the bone marrow becomes hypercellular with red cell precursors reducing the M:E (Myeloid:Erythroid) ratio.


This picture depicts how a peripheral blood smear would illustrate iron deficiency anemia. The red cells are smaller and there is more of a central pallor to them, indicating a loss of hemoglobin. This is also called hypochromia.


This picture depicts a normal peripheral blood smear. The red blood cells are larger in size and they have more color to them.

Anemia of Chronic Disease

Anemia of chronic disease is another form of microcytic anemia similar to iron deficiency anemia. It usually arises from a chronic infection or from chronic inflammation, but its also associated with some malignancies. A buildup in inflammatory cytokines alters iron metabolism. IL-6, which is an inflammatory cytokine inhibits erythrocyte production. It also increases hepcidin production. Hepcidin blocks iron release from the macrophages and the hepatocytes by down-regulating ferroportin. Without ferroportin there is no transportation of iron throughout the body and no production of hemoglobin or red blood cells. Laboratory findings will usually demonstrate low serum iron, low TIBC, low transferrin, and an increased to normal ferritin. The reticulocyte count is also normal, and sometimes increased. Reticulocytes are released from the bone marrow in times of red cell shortages to compensate.

This is just a brief overview of iron deficiency anemia and other microcytic anemias. This is just the beginning, follow and look forward to more in-depth reviews of each microcytic anemia. Key differences to look for is the TIBC value. In iron deficiency anemia the TIBC is increased and in anemia of chronic disease the TIBC is decreased. Ferritin is increased in anemia of chronic disease because the stored iron can’t be released from cells and the bone marrow due to the increased hepcidin production. Also the degree of anemia is mild compared to the more severe iron deficiency anemia.