In the classical sense, acute graft-versus-host-disease is characterized by selective damage to the liver, skin (rash), mucosa, and the gastrointestinal tract. Newer research indicates that other graft-versus-host-disease target organs include the immune system (the hematopoietic system, e.g., the bone marrow and the thymus) itself, and the lungs in the form of immune-mediated pneumonitis. Biomarkers can be used to identify specific causes of GvHD, such as elafin in the skin. Chronic graft-versus-host-disease also attacks the above organs, but over its long-term course can also cause damage to the connective tissue and exocrine glands.

Acute GvHD of the GI tract can result in severe intestinal inflammation, sloughing of the mucosal membrane, severe diarrhea, abdominal pain, nausea, and vomiting. This is typically diagnosed via intestinal biopsy. Liver GvHD is measured by the bilirubin level in acute patients. Skin GvHD results in a diffuse red maculopapular rash, sometimes in a lacy pattern.

Mucosal damage to the vagina can result in severe pain and scarring, and appears in both acute and chronic GvHD. This can result in an inability to have sexual intercourse.

Acute GvHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of 1 to a high of 4. Patients with grade IV GvHD usually have a poor prognosis. If the GvHD is severe and requires intense immunosuppression involving steroids and additional agents to get under control, the patient may develop severe infections as a result of the immunosuppression and may die of infection.

In the oral cavity, chronic graft-versus-host-disease manifests as lichen planus with a higher risk of malignant transformation to oral squamous cell carcinoma in comparison to the classical oral lichen planus. Graft-versus-host-disease-associated oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-hematopoietic stem cell transplantation patients.

In the clinical setting, graft-versus-host-disease is divided into acute and chronic forms, and scored or graded on the basis of the tissue affected and the severity of the reaction.

- The "acute" or "fulminant" form of the disease (aGvHD) is normally observed within the first 100 days post-transplant, and is a major challenge to transplants owing to associated morbidity and mortality.

- The "chronic" form of graft-versus-host-disease (cGvHD) normally occurs after 100 days. The appearance of moderate to severe cases of cGVHD adversely influences long-term survival.

Currently, there are no reliable molecular markers reflecting the onset or clinical course of aGVHD. However, it has been shown that genes responsible for cytokine signaling, inflammatory response, and regulation of cell cycle are differentially expressed in patients with fatal GvHD versus "indolent" GvHD.

Patients with TAMA present with variable combinations of a morbilliform skin eruption, chronic diarrhea, and abnormal liver enzymes. The histopathology of the skin, liver, or bowel mucosa resembles GVHD.

The primary symptoms of a cytokine storm are high fever, swelling, redness, extreme fatigue, and nausea. In some cases the immune reaction will be fatal.

A cytokine storm, also known as cytokine cascade and hypercytokinemia, is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and white blood cells, with highly elevated levels of various cytokines. The term arose in the field of pathophysiology in discussions around immune disorders in 1993, was extended to discussions of infectious disease and sepsis, and has been used to describe severe manifestations of cytokine release syndrome, an adverse effect of some drugs.

Eosinophilia and comparatively fewer cases of hypereosinophilia are associated with the following known diseases that are known or thought to have an allergic basis: allergic rhinitis, asthma, atopic dermatitis, eosinophilic esophagitis, chronic sinusitis, aspirin-induced asthma, allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, and Kimura's disease.

Certain types of food allergy disorders may also be associated with eosinophilia or, less commonly, hypereosinophilia. Allergic eosinophilic esophagitis and the Food protein-induced enterocolitis syndrome are commonly associated with increased blood eosinophil levels.

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.

Thymoma is a common neoplasm arising from the thymus, the primary lymphoid organ where T cells become educated to distinguish "self" from "non self". In the setting of thymoma, abnormal thymic education occurs as a result of subtle differences in antigen processing. In TAMA these differences result in autoreactive T cells escaping from the thymus. This results in a condition similar to graft-versus-host disease.

Symptoms in eosinophilc myocarditis are highly variable. They tend to reflect the many underlying disorders causing eosinophil dysfunction as well as the widely differing progression rates of cardiac damage. Before cardiac symptoms are detected, some 66% of cases have symptoms of a common cold and 33% have symptoms of asthma, rhinitis, urticarial, or other allergic disorder. Cardiac manifestations of eosinophilic myocarditis range from none to life-threatening conditions such as cardiogenic shock or sudden death due to abnormal heart rhythms. More commonly the presenting cardiac symptoms of the disorder are the same as those seen in other forms of heart disease: chest pain, shortness of breath, fatigue, chest palpitations, light headedness, and syncope. In its most extreme form, however, eosinophilic myocarditis can present as acute necrotizing eosinophilic myocarditis, i.e. with symptoms of chaotic and potentially lethal heart failure and heart arrhythmias. This rarest form of the disorder reflects a rapidly progressive and extensive eosinophilic infiltration of the heart that is accompanied by massive myocardial cell necrosis.

Hypereosinophilia (i.e. blood eosinophil counts at or above 1,500 per microliter) or, less commonly, eosinophilia (counts above 500 but below 1,500 per microliter) are found in the vast majority of cases of eosinophilic myocarditis and are valuable clues that point to this rather than other types of myocarditis or myocardial injuries. However, elevated blood eosinophil counts may not occur during the early phase of the disorder. Other, less specific laboratory findings implicate a cardiac disorder but not necessarily eosinophilic myocarditis. These include elevations in blood markers for systemic inflammation (e.g. C reactive protein, erythrocyte sedimentation rate), elevations in blood markers for cardiac injury (e.g. creatine kinase, troponins); and abnormal electrocardiograms ( mostly ST segment-T wave abnormalities).

Eosinophilic coronary periarteritis is a heart disorder caused by extensive eosinophilic infiltration of the adventitia and periadventitia, i.e. the soft tissues, surrounding the coronary arteries. The intima, tunica media, and tunica intima layers of these arteries remain intact and are generally unaffected. Thus, this disorder is characterized by episodes of angina, particularly Prinzmetal's angina, and sudden death due to heart dysfunction. The disorder is considered distinct from eosinophilic myocarditis.

Prodromal symptoms are flu-like ones, such as fever, cough, myalgia, headache, lethargy, and shortness of breath, which rapidly deteriorates into acute respiratory failure. It is characterized by the sudden onset of shortness of breath with rapidly evolving pulmonary edema; it is often fatal despite mechanical ventilation and intervention with potent diuretics. It has a fatality rate of 36%.

The symptoms of an infection depend on the type of disease. Some signs of infection affect the whole body generally, such as fatigue, loss of appetite, weight loss, fevers, night sweats, chills, aches and pains. Others are specific to individual body parts, such as skin rashes, coughing, or a runny nose.

In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host. In the latter case, the disease may only be defined as a "disease" (which by definition means an illness) in hosts who secondarily become ill after contact with an asymptomatic carrier. An infection is not synonymous with an infectious disease, as some infections do not cause illness in a host.

An example of a tuberculosis (TB) infection that comes under control: "M. tuberculosis" cells are engulfed by macrophages after being identified as foreign, but due to an immuno-escape mechanism peculiar to mycobacteria, TB bacteria are able to block the fusion of their enclosing phagosome with lysosomes which would destroy the bacteria. Thereby TB can continue to replicate within macrophages. After several weeks, the immune system somehow [mechanism as yet unexplained] ramps up and, on stimulation with IFN-gamma, the macrophages become capable of killing "M. tuberculosis" by forming phagolysosomes and nitric oxide radicals. The hyper-activated macrophages secrete TNF-α which recruits multiple monocytes to the site of infection. These cells differentiate into epithelioid cells which wall off the infected cells, but results in significant inflammation and local damage.

Some other clinical examples:

- Temporal arteritis

- Leprosy

- Coeliac disease

- Graft-versus-host disease

- Chronic transplant rejection

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

The onset of the disease results in proliferation of EBV-infected malignant B-cells and a cytotoxic T-cell response which in turn leads to organ infiltration and dysfunction of the affected organs. The disease typically always relapse after successful treatment due to inability of the immune system and current viral drugs to eliminate an EBV-infection. If the onset of the disease can be linked to use of immunosuppressive drugs then discontinuation of these drugs may hinder a relapse. Organs usually affected are the skin, lungs, central nervous system while liver and kidney are affected to lesser extent. The pulmonary complications are usually what leads to death, however, CNS involvement that affects up to one third of the patients can be very severe with mental status changes, ataxia, hemiparesis, seizures, unconsciousness and death, typically followed in that order.

The disease has been seen to transform to diffuse large B-cell lymphoma and while LYG is graded I-III based on the number of large EBV-positive B-cells, grade II and III can be considered as a variant of T-cell rich diffuse large B-cell lymphoma.

While the presence of lesions is the denominator among patients with PNP, the characteristics of the lesions differ. The five clinical presentations of lesions associated with PNP include:

- "Pemphigus-like": Flaccid blister (discrete), crusts over the raw exuding skin lesions

- "Pemphigoid-like": Tense blister(s) on brick red erythema

- "Erythema multiforme-like": Severe polymorphic skin and/or mucous membrane lesions

- "Graft-vs.-host disease-like": Widespread lichenoid eruption with severe mucous membrane involvement

- "Lichen planus-like": Small red flat-topped scaly papules

It is most common that mucous membrane lesions of the oral cavity are presented first. They can involve the oropharynx, nasopharynx, tongue, and vermilion (red portion) of the lips. They are also known to develop in the conjunctiva of the eye, anogenital (perineum) region, and esophagus. Cutaneous lesions tend to follow the onset of mucosal lesions. The blisters often erupt in waves, usually affecting the upper trunk, head, neck, and proximal extremities. Pemphigoid-like lesions are seen more often on the extremities. Lichenoid lesions are more common among children, presenting on the trunk and limbs, ranging from small red scaly papules to extensive violet to brown papules extending to the face and neck. Within the spectrum of lichenoid presentations are wounds that have features of erythema multiforme and graft-vs.-host disease. Scaly lesions on the palms of the hand and soles of the feet have been noted to coincide with the lichenoid lesions. Lesions of varying morphology may present simultaneously and transform from one type to another as the disease progresses.

Infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host tissues to the infectious agents and the toxins they produce. Infectious disease, also known as transmissible disease or communicable disease, is illness resulting from an infection.

Infections are caused by infectious agents including viruses, viroids, prions, bacteria, nematodes such as parasitic roundworms and pinworms, arthropods such as ticks, mites, fleas, and lice, fungi such as ringworm, and other macroparasites such as tapeworms and other helminths.

Hosts can fight infections using their immune system. Mammalian hosts react to infections with an innate response, often involving inflammation, followed by an adaptive response.

Specific medications used to treat infections include antibiotics, antivirals, antifungals, antiprotozoals, and antihelminthics. Infectious diseases resulted in 9.2 million deaths in 2013 (about 17% of all deaths). The branch of medicine that focuses on infections is referred to as infectious disease.

Type 4 hypersensitivity is often called delayed type hypersensitivity as the reaction takes several days to develop. Unlike the other types, it is not antibody-mediated but rather is a type of cell-mediated response.

CD4+ T1 helper T cells recognize antigen in a complex with the MHC class II major histocompatibility complex on the surface of antigen-presenting cells. These can be macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ T1 cells. CD4+ T cells secrete IL-2 and interferon gamma, inducing the further release of other T1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

The disease is believed to be induced by a combination of Epstein Barr virus infection and immunosuppression through; immunosuppressive drugs (with case reports of methotrexate and azathioprine), infections such as HIV or chronic viral hepatitis or endogenous T-cell defects.

Patients can develop two clinical phases: an acute septic phase and a chronic eruptive phase associated with skin lesions. In the acute phase (also known as Oroya fever or "fiebre de la Oroya"), "B. bacilliformis" infection is a sudden, potentially life-threatening infection associated with high fever and decreased levels of circulating red blood cells (i.e., hemolytic anemia)and transient immunosuppression. "B. bacilliformis" is considered the most deadly species to date, with a death rate of up to 90% during the acute phase, which typically lasts two to four weeks. Peripheral blood smears show anisomacrocytosis with many bacilli adherent to red blood cells. Thrombocytopenia is also seen and can be very severe. Neurologic manifestations (neurobartonellosis) are altered mental status, agitation, or even coma, ataxia, spinal meningitis, or paralysis. It is seen in 20% of patients with acute infection, in which the prognosis is very guarded with an about 50% mortality. The most feared complication is overwhelming infection mainly by Enterobacteriaceae, particularly "Salmonella" (both "S. typhi" and " S. "non-"typhi", as well as reactivation of toxoplasmosis and other opportunistic infections .

The chronic manifestation consists of a benign skin eruption with raised, reddish-purple nodules (angiomatous tumours). The bacterium can be seen microscopically, if a skin biopsy is silver stained (the Warthin–Starry method).

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.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a "primary" immunodeficiency, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 100 recognized PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of various organs. There are currently no cures for these conditions; treatment is palliative and consists of managing infections and boosting the immune system.

Paraneoplastic pemphigus is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes.

While patients with malignant and benign tumors are both at risk, malignancy is associated with high mortality rates (near 90%). Current treatment focuses on general wound healing and administering corticosteroids, which has not demonstrated a high success rate. Recent research developments aim to treat the underlying tumor in order to alleviate the symptoms of PNP.

A chronic condition is a human health condition or disease that is persistent or otherwise long-lasting in its effects or a disease that comes with time. The term "chronic" is often applied when the course of the disease lasts for more than three months. Common chronic diseases include arthritis, asthma, cancer, COPD, diabetes and some viral diseases such as hepatitis C and HIV/AIDS.

In medicine, the opposite of chronic is acute. A chronic course is further distinguished from a recurrent course; recurrent diseases relapse repeatedly, with periods of remission in between.

The non-communicable diseases are also usually lasting medical conditions but are separated by their non-infectious causes. In contrast, some chronic diseases, such as HIV/AIDS, are caused by transmissible infections.

In the United States 25% of adults have at least two chronic conditions. Chronic diseases constitute a major cause of mortality, with the World Health Organization (WHO) attributing 38 million deaths a year to non-communicable diseases.

Severe combined immunodeficiency, SCID, also known as alymphocytosis, Glanzmann–Riniker syndrome, severe mixed immunodeficiency syndrome, and thymic alymphoplasia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in heterogeneous clinical presentations. SCID involves defective antibody response due to either direct involvement with B lymphocytes or through improper B lymphocyte activation due to non-functional T-helper cells. Consequently, both "arms" (B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is the most severe form of primary immunodeficiencies, and there are now at least nine different known genes in which mutations lead to a form of SCID. It is also known as the bubble boy disease and bubble baby disease because its victims are extremely vulnerable to infectious diseases and some of them, such as David Vetter, have become famous for living in a sterile environment. SCID is the result of an immune system so highly compromised that it is considered almost absent.

SCID patients are usually affected by severe bacterial, viral, or fungal infections early in life and often present with interstitial lung disease, chronic diarrhoea, and failure to thrive. Ear infections, recurrent "Pneumocystis jirovecii" (previously carinii) pneumonia, and profuse oral candidiasis commonly occur. These babies, if untreated, usually die within one year due to severe, recurrent infections unless they have undergone successful hematopoietic stem cell transplantation.