Neutrophilia is an increase in the absolute neutrophil count in the peripheral circulation. Normal blood values vary by age. Neutrophilia can be caused by a direct problem with blood cells (primary disease). It can also occur as a consequence of an underlying disease (secondary). Most cases of neutrophilia are secondary to inflammation.

Primary causes

- Conditions with normally functioning neutrophils – hereditary neutrophilia, chronic idiopathic neutrophilia

- Pelger–Huet anomaly

- Down syndrome

- Leukocyte adhesion deficiency

- Familial cold urticaria

- Leukemia (chronic myelogenous (CML)) and other myeloproliferative disorders

- Surgical removal of spleen

Secondary causes

- Infection

- Chronic inflammation – especially juvenile rheumatoid arthritis, rheumatoid arthritis, Still's disease, Crohn's disease, ulcerative colitis, granulomatous infections (for example, tuberculosis), and chronic hepatitis

- Cigarette smoking – occurs in 25–50% of chronic smokers and can last up to 5 years after quitting

- Stress – exercise, surgery, general stress

- Medication induced – corticosteroids (for example, prednisone, β-agonists, lithium)

- Cancer – either by growth factors secreted by the tumor or invasion of bone marrow by the cancer

- Increased destruction of cells in peripheral circulation can stimulate bone marrow. This can occur in hemolytic anemia and idiopathic thrombocytopenic purpura

In some cancers, such as melanoma and colorectal cancer, lymphocytes can migrate into and attack the tumor. This can sometimes lead to regression of the primary tumor.

An increase in eosinophils, i.e., the presence of more than 500 eosinophils/microlitre of blood is called an eosinophilia, and is typically seen in people with a parasitic infestation of the intestines; autoimmune and collagen vascular disease (such as rheumatoid arthritis) and Systemic lupus erythematosus; malignant diseases such as eosinophilic leukemia, clonal hypereosinophilia, and Hodgkin's disease; lymphocyte-variant hypereosinophilia; extensive skin diseases (such as exfoliative dermatitis); Addison's disease and other causes of low corticosteroid production (corticosteroids suppress blood eosinophil levels); reflux esophagitis (in which eosinophils will be found in the squamous epithelium of the esophagus) and eosinophilic esophagitis; and with the use of certain drugs such as penicillin. But, perhaps the most common cause for eosinophilia is an allergic condition such as asthma. In 1989, contaminated L-tryptophan supplements caused a deadly form of eosinophilia known as eosinophilia-myalgia syndrome, which was reminiscent of the Toxic Oil Syndrome in Spain in 1981.

Eosinophils play an important role in asthma as the number of accumulated eosinophils corresponds to the severity of asthmatic reaction. Eosinophilia in mice models are shown to be associated with high interleukin-5 levels. Furthermore, mucosal bronchial biopsies conducted on patients with diseases such as asthma have been found to have higher levels of interleukin-5 leading to higher levels of eosinophils. The infiltration of eosinophils at these high concentrations causes an inflammatory reaction. This ultimately leads to airway remodelling and difficulty of breathing.

Eosinophils can also cause tissue damage in the lungs of asthmatic patients. High concentrations of eosinophil major basic protein and eosinophil-derived neurotoxin that approach cytotoxic levels are observed at degranulation sites in the lungs as well as in the asthmatic sputum.

Neutropenia can be acquired or intrinsic. A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood. The following list of causes is not complete.

- Medications - chemotherapy, sulfas or other antibiotics, phenothiazenes, benzodiazepines, antithyroids, anticonvulsants, quinine, quinidine, indomethacin, procainamide, thiazides

- Radiation

- Toxins - alcohol, benzenes

- Intrinsic disorders - Fanconi's, Kostmann's, cyclic neutropenia, Chédiak–Higashi

- Immune dysfunction - disorders of collagen, AIDS, rheumatoid arthritis

- Blood cell dysfunction - megaloblastic anemia, myelodysplasia, marrow failure, marrow replacement, acute leukemia

- Any major infection

- Miscellaneous - starvation, hypersplenism

Symptoms of neutropenia are associated with the underlying cause of the decrease in neutrophils. For example, the most common cause of acquired neutropenia is drug-induced, so an individual may have symptoms of medication overdose or toxicity.

Treatment is also aimed at the underlying cause of the neutropenia. One severe consequence of neutropenia is that it can increase the risk of infection.

A low normal to low absolute lymphocyte concentration is associated with increased rates of infection after surgery or trauma.

One basis for low T cell lymphocytes occurs when the human immunodeficiency virus (HIV) infects and destroys T cells (specifically, the CD4 subgroup of T lymphocytes). Without the key defense that these T cells provide, the body becomes susceptible to opportunistic infections that otherwise would not affect healthy people. The extent of HIV progression is typically determined by measuring the percentage of CD4 T cells in the patient's blood – HIV ultimately progresses to acquired immune deficiency syndrome (AIDS). The effects of other viruses or lymphocyte disorders can also often be estimated by counting the numbers of lymphocytes present in the blood.

Treatments used to combat autoimmune diseases and conditions caused by eosinophils include:

- corticosteroids – promote apoptosis. Numbers of eosinophils in blood are rapidly reduced

- monoclonal antibody therapy – e.g., mepolizumab or reslizumab against IL-5, prevents eosinophilopoiesis

- antagonists of leukotriene synthesis or receptors

- imatinib (STI571) – inhibits PDGF-BB in hypereosinophilic leukemia

Monoclonal antibodies such as dupilumab and lebrikizumab target IL-13 and its receptor, which reduces eosinophilic inflammation in pateints with asthma due to lowering the number of adhesion molecules present for eosinophils to bind to, thereby decreasing inflammation. Mepolizumab and benralizumab are other treatment options that target the alpha subunit of the IL-5 receptor, thereby inhibiting its function and reducing the number of developing eosinophils as well as the number of eosinophils leading to inflammation through antibody-dependent cell-mediated cytotoxicity and eosinophilic apoptosis.

A T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated immunity. T cells can be distinguished from other lymphocytes, such as B cells and natural killer cells, by the presence of a T-cell receptor on the cell surface. They are called "T cells" because they mature in the thymus from thymocytes (although some also mature in the tonsils). The several subsets of T cells each have a distinct function. The majority of human T cells rearrange their alpha and beta chains on the cell receptor and are termed alpha beta T cells (αβ T cells) and are part of the adaptive immune system. Specialized gamma delta T cells, (a small minority of T cells in the human body, more frequent in ruminants), have invariant T-cell receptors with limited diversity, that can effectively present antigens to other T cells and are considered to be part of the innate immune system.

Memory T cells are a subset of infection- and cancer-fighting T cells (also known as a T lymphocyte) that have previously encountered and responded to their cognate antigen; thus, the term antigen-experienced T cell is often applied. Such T cells can recognize foreign invaders, such as bacteria or viruses, as well as cancer cells. Memory T cells have become "experienced" by having encountered antigen during a prior infection, encounter with cancer, or previous vaccination. At a second encounter with the invader, memory T cells can reproduce to mount a faster and stronger immune response than the first time in the immune system responded to the pathogen which is entered into the body. This behaviour is utilized in T lymphocyte proliferation assays, which can reveal exposure to specific antigens.

Dendritic cells (DCs) are antigen-presenting cells (also known as "accessory cells") of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and the adaptive immune systems.

Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood. Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response. At certain development stages they grow branched projections, the "dendrites" that give the cell its name (δένδρον or déndron being Greek for "tree"). While similar in appearance, these are structures distinct from the dendrites of neurons. Immature dendritic cells are also called veiled cells, as they possess large cytoplasmic 'veils' rather than dendrites.

The category of effector T cell is a broad one that includes various T cell types that actively respond to a stimulus, such as co-stimulation. This includes helper, killer, regulatory, and potentially other T cell types.

Lymphocytopenia caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections is treated with Lymphocyte T-Cell Immune Modulator.

The most common cause of temporary lymphocytopenia is a recent infection, such as the common cold.

Lymphocytopenia, but not idiopathic CD4+ lymphocytopenia, is associated with corticosteroid use, infections with HIV and other viral, bacterial, and fungal agents, malnutrition, systemic lupus erythematosus, severe stress, intense or prolonged physical exercise (due to cortisol release), rheumatoid arthritis, sarcoidosis, and iatrogenic (caused by other medical treatments) conditions.

Lymphocytopenia is a frequent, temporary result from many types of chemotherapy, such as with cytotoxic agents or immunosuppressive drugs. Some malignancies that have spread to involve the bone marrow, such as leukemia or advanced Hodgkin's disease, also cause lymphocytopenia.

Another cause is infection with Influenza A virus subtype H1N1 (and other subtypes of the Influenza A virus) and is then often associated with Monocytosis; H1N1 was responsible for the Spanish flu, the 2009 flu pandemic and in 2016 for the Influenza-epidemic in Brazil.

Large doses of radiation, such as those involved with nuclear accidents or medical whole body radiation, may cause lymphocytopenia.

Lymphocyte-variant hypereosinophila, also termed lymphocyte variant eosinophilia, is a rare disorder in which eosinophilia or hypereosinophilia (i.e. a large or extremely large increase in the number of eosinophils in the blood circulation) is caused by aberrant population of lymphocytes. These aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells termed colony forming unit-Eosinophils or CFU-Eos.

The overly stimulated CFU-Eos cells mature to apparently normal eosinophils, enter the circulation, and may accumulate in, and severely damage, various tissues. The disorder is usually indolent or slowly progressive but may proceed to a leukemic phase and at this phases is sometimes classified as acute eosinophilic leukemia. Hence, lymphocyte-variant hypereosinophilia can be regarded as a precancerous disease.

The order merits therapeutic intervention to avoid or reduce eosinophil-induced tissue injury and to treat its leukemic phase. The latter phase of the disease is aggressive and typically responds relatively poorly to anti-leukemia chemotherapeutic drug regimens.

Lymphocyte-variant hypereosinophilia usually takes a benign and indolent course. Long term treatment with corticosteroids lowers blood eosinophil levels as well as suppresses and prevents complications of the disease in >80% of cases. However, signs and symptoms of the disease recur in virtually all cases if corticosteroid dosages are tapered in order to reduce the many adverse side effects of corticosteroids. Alternate treatments used to treat corticosteroid resistant disease or for use as corticosteroid-sparing substitutes include interferon-α or its analog, Peginterferon alfa-2a, Mepolizumab (an antibody directed against IL-5), Ciclosporin (an Immunosuppressive drug), imatinib (an inhibitor of tyrosine kinases; numerous tyrosine kinase cell signaling proteins are responsible for the growth and proliferation of eosinophils {see clonal eosinophilia}), methotrexate and Hydroxycarbamide (both are chemotherapy and immunosuppressant drugs), and Alemtuzumab (a antibody that binds to the CD52 antigen on mature lymphocytes thereby marking them for destruction by the body). The few patients who have been treated with these alternate drugs have exhibited good responses in the majority of instances. Reslizumab, a newly developed antibody directed against interleukin 5 that has been successfully used to treat 4 patients with the hypereosinophilic syndrome, may also be of use for lymphocyte-variant eosinophilia. Patients suffering minimal or no disease complications have gone untreated.

In 10% to 25% of patients, mostly 3 to 10 years after initical diagnosis, the indolent course of lymphocyte-variant hypereosinophilia changes. Patients exhibit rapid increases in lymphadenopathy, spleen size, and blood cell numbers, some cells of which take on the appearance of immature and/or malignant cells. Their disease soon thereafter escalates to an angioimmunoblastic T-cell lymphoma, peripheral T cell lymphoma, Anaplastic large-cell lymphoma (which unlike most lymphomas of this type is Anaplastic lymphoma kinase-negative), or Cutaneous T cell lymphoma. The malignantly transformed disease is aggressive and has a poor prognosis. Recommended treatment includes chemotherapy with Fludarabine, Cladribine, or the CHOP combination of drugs followed by bone marrow transplantation.

Primary immunodeficiency diseases are inborn errors in the immune system due to defective genes. Certain of these disorders are sometimes or often associated with hypereosinophilia. The list of such diorders includes ZAP70 deficiency (defective "ZAP70" gene), CD3gamma chain deficiency (defective "CD3G" gene), MCHII deficiency (defective "RFXANK" gene), Wiskott–Aldrich syndrome (defective "WAS" gene), IPEX syndrome (defective "IPEX" gene), "CD40" gene defect, and autoimmune lymphoproliferative syndrome (defective "Fas receptor" gene). More than 30 other primary immunodeficiency diseases are sometimes associated with modest increases in eosinophil counts, i.e. eosinophilia. The hyperimmunoglobulin E syndrome is associated with hypereosionphilia or eosinophilia due to mutations in any one of the following genes: "STAT3, DOCK8, PGM3, SPINK5", and "TYK2" (see mutations in the hymperimmoglobulin E syndrome). Omenn syndrome is a severe combined immuodeficiency disease characterized by skin rash, slenomegaly, and lymphadenopathy due to a causative mutation in "RAG1, RAG2]]", or, more rarely, one of several other genes.

Certain malignancies cause a secondary eosinophilia or, less commonly, hypereosinophilia. These increases in blood eosinophils appear due to the release of stimulatory cytokines or invasion of the bone marrow and thereby irritation of resident eosinophils or their precursors. Malignancies associated with these effects include gastric, colorectal, lung, bladder, and thyroid cancers, as well as squamous cell cancers of the cervix, vagina, penis, skin, and nasopharyrnx. Some hematological malignancies are likewise associated with secondary rises in blood eosinophil counts; these include Hodgkin disease, certain T-cell lymphomas, acute myeloid leukemia , the myelodysplastic syndromes, many cases of systemic mastocytosis, chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic myelomonocytic leukemia, and certain cases of T-lymphoblastic leukemia/lymphoma-associated or myelodysplastic–myeloproliferative syndrome-associated eosinophilias.

Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the innate immune system. The role NK cells play is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to viral-infected cells, acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect major histocompatibility complex (MHC) presented on infected cell surfaces, triggering cytokine release, causing lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the initial notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

NK cells (belonging to the group of innate lymphoid cells) are defined as large granular lymphocytes (LGL) and constitute the third kind of cells differentiated from the common lymphoid progenitor-generating B and T lymphocytes. NK cells are known to differentiate and mature in the bone marrow, lymph nodes, spleen, tonsils, and thymus, where they then enter into the circulation. NK cells differ from natural killer T cells (NKTs) phenotypically, by origin and by respective effector functions; often, NKT cell activity promotes NK cell activity by secreting interferon gamma. In contrast to NKT cells, NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors, but they usually express the surface markers CD16 (FcγRIII) and CD56 in humans, NK1.1 or NK1.2 in C57BL/6 mice. The NKp46 cell surface marker constitutes, at the moment, another NK cell marker of preference being expressed in both humans, several strains of mice (including BALB/c mice) and in three common monkey species.

In addition to the knowledge that natural killer cells are effectors of innate immunity, recent research has uncovered information on both activating and inhibitory NK cell receptors which play important functional roles, including self tolerance and the sustaining of NK cell activity. NK cells also play a role in the adaptive immune response: numerous experiments have demonstrated their ability to readily adjust to the immediate environment and formulate antigen-specific immunological memory, fundamental for responding to secondary infections with the same antigen. The role of NK cells in both the innate and adaptive immune responses is becoming increasingly important in research using NK cell activity as a potential cancer therapy.

The morphology of dendritic cells results in a very large surface-to-volume ratio. That is, the dendritic cell has a very large surface area compared to the overall cell volume.

A cytotoxic T cell (also known as T, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected (particularly with viruses), or cells that are damaged in other ways.

Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigen. An antigen is a molecule capable of stimulating an immune response, and is often produced by cancer cells or viruses. Antigens inside a cell are bound to class I MHC molecules, and brought to the surface of the cell by the class I MHC molecule, where they can be recognized by the T cell. If the TCR is specific for that antigen, it binds to the complex of the class I MHC molecule and the antigen, and the T cell destroys the cell.

In order for the TCR to bind to the class I MHC molecule, the former must be accompanied by a glycoprotein called CD8, which binds to the constant portion of the class I MHC molecule. Therefore, these T cells are called CD8+ T cells.

The affinity between CD8 and the MHC molecule keeps the T cell and the target cell bound closely together during antigen-specific activation. CD8+ T cells are recognized as T cells once they become activated and are generally classified as having a pre-defined cytotoxic role within the immune system. However, CD8+ T cells also have the ability to make some cytokines.

Lymphocytosis is a feature of infection, particularly in children. In the elderly, lymphoproliferative disorders, including chronic lymphocytic leukaemia and lymphomas, often present with lymphadenopathy and a lymphocytosis.

Causes of absolute lymphocytosis include:

- acute viral infections, such as infectious mononucleosis (glandular fever), hepatitis and Cytomegalovirus infection

- other acute infections such as pertussis

- some protozoal infections, such as toxoplasmosis and American trypanosomiasis (Chagas disease)

- chronic intracellular bacterial infections such as tuberculosis or brucellosis

- chronic lymphocytic leukemia

- acute lymphoblastic leukemia

- lymphoma

- post-splenectomy state

- smoking

Causes of relative lymphocytosis include: age less than 2 years; acute viral infections; connective tissue diseases, thyrotoxicosis, Addison's disease, and splenomegaly with splenic sequestration of granulocytes.

Since NK cells recognize target cells when they express nonself HLA antigens (but not self), autologous (patients' own) NK cell infusions have not shown any antitumor effects. Instead, investigators are working on using allogeneic cells from peripheral blood, which requires that all T cells be removed before infusion into the patients to remove the risk of graft versus host disease, which can be fatal. This can be achieved using an immunomagnetic column (CliniMACS). In addition, because of the limited number of NK cells in blood (only 10% of lymphocytes are NK cells), their number needs to be expanded in culture. This can take a few weeks and the yield is donor-dependent. A simpler way to obtain high numbers of pure NK cells is to expand NK-92 cells whose cells continuously grow in culture and can be expanded to clinical grade numbers in bags or bioreactors. Clinical studies have shown it to be well tolerated and some antitumor responses have been seen in patients with lung cancer, melanoma, and lymphoma.

Infusions of T cells engineered to express a chimeric antigen receptor that recognizes an antigen molecule on leukemia cells could induce remissions in patients with advanced leukemia. Logistical challenges are present for expanding T cells and investigators are working on applying the same technology to peripheral blood NK cells and NK-92.

In a study at Boston Children's Hospital, in coordination with Dana-Farber Cancer Institute, whereby immunocompromised mice had contracted lymphomas from EBV infection, an NK-activating receptor called NKG2D was fused with a stimulatory Fc portion of the EBV antibody. The NKG2D-Fc fusion proved capable of reducing tumor growth and prolonging survival of the recipients. In a transplantation model of LMP1-fueled lymphomas, the NKG2D-Fc fusion proved capable of reducing tumor growth and prolonging survival of the recipients.

Hodgkin lymphoma (Hodgkin's disease) often elicits severe eosinophilia; however, non-Hodgkin lymphoma and leukemia produce less marked eosinophilia. Of solid tumor neoplasms, ovarian cancer is most likely to provoke eosinophilia, though any other cancer can cause the condition. Solid epithelial cell tumors have been shown to cause both tissue and blood eosinophilia, with some reports indicating that this may be mediated by interleukin production by tumor cells, especially IL-5 or IL-3. This has also been shown to occur in Hodgkin lymphoma, in the form of IL-5 secreted by Reed-Sternberg cells. In primary cutaneous T cell lymphoma, blood and dermal eosinophilia are often seen. Lymphoma cells have also been shown to produce IL-5 in these disorders. Other types of lymphoid malignancies have been associated with eosinophilia, as in lymphoblastic leukemia with a translocation between chromosomes 5 and 14 or alterations in the genes which encode platelet-derived growth factor receptors alpha or beta. Patients displaying eosinophilia overexpress a gene encoding an eosinophil hematopoietin. A translocation between chromosomes 5 and 14 in patients with acute B lymphocytic leukemia resulted in the juxtaposition of the IL-3 gene and the immunoglobulin heavy-chain gene, causing overproduction production of IL-3, leading to blood and tissue eosinophilia.

There is no information on birth ratios/rates, but "X-Linked SCID is the most common form of SCID and it has been estimated to account for 46% to 70% of all SCID cases."

X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells. In the absence of T cell help, B cells become defective. It is an x-linked recessive trait, stemming from a mutated (abnormal) version of the IL2-RG gene located at xq13.1 on the X-chromosome, which is shared between receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.

Allergic reactions to drugs are a common cause of eosinophilia, with manifestations ranging from diffuse maculopapular rash, to severe life-threatening drug reactions with eosinophilia and systemic symptoms (DRESS). Drugs that have been shown to cause DRESS are aromatic anticonvulsants and other antiepileptics, sulfonamides, allopurinol, nonsteroidal anti-inflammatory drugs (NSAIDs), some antipsychotics such as risperidone, and certain antibiotics. Phenibut, an analogue of the neurotransmitter GABA, has also been implicated in high doses. The reaction which has been shown to be T-cell mediated may also cause eosinophilia-myalgia syndrome.