Complete or partial deficiency

- "Complete insufficiency" of T cell function can result from hereditary conditions (also called primary conditions) such as severe combined immunodeficiency (SCID), Omenn syndrome, and cartilage–hair hypoplasia.

- "Partial insufficiencies" of T cell function include acquired immune deficiency syndrome (AIDS), and hereditary conditions such as DiGeorge syndrome (DGS), chromosomal breakage syndromes (CBSs), and B-cell and T-cell combined disorders such as ataxia-telangiectasia (AT) and Wiskott–Aldrich syndrome (WAS).

- "Primary (or hereditary) immunodeficiencies" of T cells include some that cause complete insufficiency of T cells, such as severe combined immunodeficiency (SCID), Omenn syndrome, and Cartilage–hair hypoplasia.

- "Secondary causes" are more common than primary ones. Secondary (or acquired) causes are mainly:

Presentations differ among causes, but T cell insufficiency generally manifests as unusually severe common viral infections (respiratory syncytial virus, rotavirus), diarrhea, and eczematous or erythrodermatous rashes. Failure to thrive and cachexia are later signs of a T-cell deficiency.

The symptoms are very similar to graft-versus-host disease (GVHD). This is because the patients have some T cells with limited levels of recombination with the mutant RAG genes. These T cells are abnormal and have a very specific affinity for self antigens found in the thymus and in the periphery. Therefore, these T cells are auto-reactive and cause the GVHD phenotype.

A characteristic symptom is chronic inflammation of the skin, which appears as a red rash (early onset erythroderma). Other symptoms include eosinophilia, failure to thrive, swollen lymph nodes, swollen spleen, diarrhea, enlarged liver, low immunoglobulin levels (except immunoglobulin E, which is elevated), low T cell levels, and no B cells.

Omenn syndrome is an autosomal recessive severe combined immunodeficiency associated with hypomorphic missense mutations in immunologically relevant genes of T-cells (and B-cells) such as recombination activating genes (RAG1 and RAG2), IL-7 Receptor α gene (IL7Rα), DCLRE1C-Artemis, RMRP-CHH, DNA-Ligase IV, common gamma chain, WHN-FOXN1, ZAP-70 and complete DiGeorge anomaly (DiGeorge Syndrome; CHARGE).

Leukocyte adhesion deficiency-1 (LAD1) is a rare and often fatal genetic disorder in humans.

PASLI disease is a rare genetic disorder of the immune system. PASLI stands for “p110 delta activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency.” The immunodeficiency manifests as recurrent infections usually starting in childhood. These include bacterial infections of the respiratory system and chronic viremia due to Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV). Individuals with PASLI disease also have an increased risk of EBV-associated lymphoma. Investigators Carrie Lucas, Michael Lenardo, and Gulbu Uzel at the National Institute of Allergy and Infectious Diseases at the U.S. National Institutes of Health and Sergey Nejentsev at the University of Cambridge, UK simultaneously described a mutation causing this condition which they called Activated PI3K Delta Syndrome (APDS).

Neutrophils (also known as neutrocytes) are the most abundant type of granulocytes and the most abundant (40% to 70%) type of white blood cells in most mammals. They form an essential part of the innate immune system. Their functions vary in different animals.

They are formed from stem cells in the bone marrow. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils.

The name "neutrophil" derives from staining characteristics on hematoxylin and eosin (H&E) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes.

Neutrophils are a type of phagocyte and are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation. They migrate through the blood vessels, then through tissue, following chemical signals such as Interleukin-8 (IL-8), C5a, fMLP, Leukotriene B4 and HO in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.

Neutrophils are recruited to the site of injury within minutes following trauma, and are the hallmark of acute inflammation; however, due to some pathogens being indigestible, they can be unable to resolve certain infections without the assistance of other types of immune cells.

Clinically, PASLI disease is characterized by recurrent sinopulmonary infections that can lead to progressive airway damage. Patients also suffer from lymphoproliferation (large lymph nodes and spleen), chronic viremia due to EBV or CMV, distinctive lymphoid nodules at mucosal surfaces, autoimmune cytopenias, and EBV-driven B cell lymphoma. Importantly, the clinical presentations and disease courses are variable with some individuals severely affected, whereas others show little manifestation of disease. This “variable expressivity,” even within the same family, can be striking and may be explained by differences in lifestyle, exposure to pathogens, treatment efficacy, or other genetic modifiers.

The following symptoms (signs) are consistent with complement deficiency in general:

LAD was first recognized as a distinct clinical entity in the 1970s. The classic descriptions of LAD included recurrent bacterial infections, defects in neutrophil adhesion, and a delay in umbilical cord sloughing. The adhesion defects result in poor leukocyte chemotaxis, particularly neutrophil, inability to form pus and neutrophilia.

Individuals with LAD suffer from bacterial infections beginning in the neonatal period. Infections such as omphalitis, pneumonia, gingivitis, and peritonitis are common and often life-threatening due to the infant's inability to properly destroy the invading pathogens. These individuals do not form abscesses because granulocytes cannot migrate to the sites of infection.

The main sign of the disease is life-threatening, recurrent bacterial or fungal soft tissue infections. These infections are often apparent at birth and may spread throughout the body. Omphalitis (infection of the umbilical cord stump) is common shortly after birth. Other signs include delayed separation of the umbilical cord, periodontal disease, elevated neutrophils, and impaired wound healing, but not increased vulnerability to viral infections or cancer. Such patients have fever as the manifestation of infection, inflammatory responses are indolent.

A wide range of drugs are known to cause hypereosinophilia or eosinophilia accompanied by an array of allergic symptoms. Rarely, these reactions are severe causing, for example, the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. While virtually any drug should be considered as a possible cause of these signs and symptoms, the following drugs and drug classes are some of the most frequently reported causes: penicillins, cephalosporins, dapsone, sulfonamides, carbamazepine, phenytoin, lamotrigine, valproic acid, nevirapine, efavirenz, and ibuprofen. These drugs may cause severely toxic reactions such as the DRESS syndrome. Other drugs and drug classes often reported to cause increased blood eosinophil levels accompanied by less severe (e.g. non-DRESS syndrome) symptoms include tetracyclins, doxycycline, linezolid, nitrofurantoin, metronidazole, carbamazepine, phenobarbital, lamotrigine, valproate, desipramine, amitriptyline, fluoxetine, piroxicam, diclofenac, ACE inhibitors, abacavir, nevirapine, ranitidine, cyclosporin, and hydrochlorothiazide.

The toxic oil syndrome is associated with hypereosinophilia/eosinophilia and systemic symptoms due to one or more contaminants in rapeseed oil and the Eosinophilia–myalgia syndrome, also associated with hypereosinophilia, appears due to trace contaminants in certain commercial batches of the amino acid, L-tryptophan.

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.

LRBA deficiency presents as a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. Predominant clinical problems include idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), and an autoimmune enteropathy. Before the discovery of these gene mutations, patients were diagnosed with common variable immune deficiency (CVID), which is characterized by low antibody levels and recurrent infections. Infections mostly affect the respiratory tract, as many patients suffer from chronic lung disease, pneumonias, and bronchiectasis. Lymphocytic interstitial lung disease (ILD) is also observed, which complicates breathing and leads to impairment of lung function and mortality. Infections can also occur at other sites, such as the eyes, skin and gastrointestinal tract. Many patients suffer from chronic diarrhea and inflammatory bowel disease. Other clinical features can include hepatosplenomegaly, reoccurring warts, growth retardation, allergic dermatitis, and arthritis. Notably, LRBA deficiency has also been associated with type 1 diabetes mellitus. There is significant clinical phenotypic overlap with disease caused by CTLA4 haploinsufficiency. Since LRBA loss results in a loss of CTLA4 protein, the immune dysregulation syndrome of LRBA deficient patients can be attributed to the secondary loss of CTLA4. Because the predominant features of the disease include autoantibody-mediated disease (AIHA, ITP), Treg defects (resembling those found in CTLA4 haploinsufficient patients), autoimmune infiltration (of non-lymphoid organs, also resembling that found in CTLA4 haploinsufficient patients), and enteropathy, the disease has been termed LATAIE for LRBA deficiency with autoantibodies, Treg defects, autoimmune infiltration, and enteropathy.

Leukocyte adhesion deficiency (LAD), is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also known as LAD-1/variant. In LAD3, the immune defects are supplemented by a Glanzmann thrombasthenia-like bleeding tendency.

Vaccinations for encapsulated organisms (e.g., "Neisseria meningitidis" and "Streptococcus pneumoniae") is crucial for preventing infections in complement deficiencies. Among the possible complications are the following:

- Deficiencies of the terminal complement components increases susceptibility to infections by Neisseria.

LRBA deficiency is a rare genetic disorder of the immune system. This disorder is caused by a mutation in the gene "LRBA". LRBA stands for “Lipopolysaccharide (LPS)-responsive vesicle trafficking, beach- and anchor-containing” gene. This condition is characterized by autoimmunity, lymphoproliferation, and immune deficiency. It was first described by Gabriela Lopez-Herrera from University College London in 2012. Investigators in the laboratory of Dr. Michael Lenardo at National Institute of Allergy and Infectious Diseases, the National Institutes of Health and Dr. Michael Jordan at Cincinnati Children’s Hospital Medical Center later described this condition and therapy in 2015.

Cyclic neutropenia is a disorder that causes frequent infections and other health problems in affected individuals. People with this condition have recurrent episodes of neutropenia during which there is a shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. The episodes of neutropenia are apparent at birth or soon afterward. For most affected individuals, neutropenia recurs every 21 days and lasts about 3 to 5 days.

Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses, so people with cyclic neutropenia typically develop recurrent infections of the sinuses, respiratory tract, and skin. Additionally, people with this condition often develop open sores (ulcers) in the mouth and colon, inflammation of the throat (pharyngitis) and gums (gingivitis), recurrent fever, or abdominal pain. People with cyclic neutropenia have these health problems only during episodes of neutropenia. At times when their neutrophil levels are normal, they are not at an increased risk of infection and inflammation.

DIRA displays a constellation of serious symptoms which include respiratory distress, as well as the following:

Nuclear factor-kappa B Essential Modulator (NEMO) deficiency syndrome is a rare type of primary immunodeficiency disease that has a highly variable set of symptoms and prognoses. It mainly affects the skin and immune system but has the potential to affect all parts of the body, including the lungs, urinary tract and gastrointestinal tract. It is a monogenetic disease caused by mutation in the IKBKG gene (IKKγ, also known as the NF-κB essential modulator, or NEMO). NEMO is the modulator protein in the IKK inhibitor complex that, when activated, phosphorylates the inhibitor of the NF-κB transcription factors allowing for the translocation of transcription factors into the nucleus.

The link between IKBKG mutations and NEMO deficiency was identified in 1999. IKBKG is located on the X chromosome and is X-linked therefore this disease predominantly affects males, However females may be genetic carriers of certain types of mutations. Other forms of the syndrome involving NEMO-related pathways can be passed on from parent to child in an autosomal dominant manner – this means that a child only has to inherit the faulty gene from one parent to develop the condition. This autosomal dominant type of NEMO deficiency syndrome can affect both boys and girls.

Deficiency of the interleukin-1–receptor antagonist (DIRA) is a autosomal recessive, genetic autoinflammatory syndrome resulting from mutations in "IL1RN", the gene encoding the interleukin 1 receptor antagonist. The mutations result in an abnormal protein that is not secreted, exposing the cells to unopposed interleukin 1 activity. This results in sterile multifocal osteomyelitis, periostitis (inflammation of the membrane surrounding the bones), and pustulosis due to skin inflammation from birth.

Langerhans cell histiocytosis (LCH) is a rare disease involving clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes. Clinically, its manifestations range from isolated bone lesions to multisystem disease. LCH is part of a group of clinical syndromes called histiocytoses, which are characterized by an abnormal proliferation of histiocytes (an archaic term for activated dendritic cells and macrophages). These diseases are related to other forms of abnormal proliferation of white blood cells, such as leukemias and lymphomas.

The disease has gone by several names, including Hand–Schüller–Christian disease, Abt-Letterer-Siwe disease, Hashimoto-Pritzker disease(a very rare self-limiting variant seen at birth) and histiocytosis X, until it was renamed in 1985 by the Histiocyte Society.

Cyclic neutropenia (or cyclical neutropenia) is a form of neutropenia, a white blood cell deficiency, that tends to occur every three weeks and lasts three to six days at a time due to changing rates of cell production by the bone marrow.

Cyclic neutropenia is the result of autosomal dominantly inherited mutations in ELA2, the gene encoding neutrophil elastase,

and is estimated to occur in 1 in 1 million individuals worldwide. Treatment includes G-CSF and usually improves after puberty.

The disease spectrum results from clonal accumulation and proliferation of cells resembling the epidermal dendritic cells called Langerhans cells, sometimes called Dendritic Cell Histiocytosis. These cells in combination with lymphocytes, eosinophils, and normal histiocytes form typical LCH lesions that can be found in almost any organ. A similar set of diseases has been described in canine histiocytic diseases.

LCH is clinically divided into three groups: unifocal, multifocal unisystem, and multifocal multisystem.

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.