#cell-mediated immunity

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What is Cell-Mediated Immunity and How Does it Work?

Cell-mediated immunity is a form of immunity that occurs when the immune cells that are found in the blood and lymph system function to fight off infection.

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Signaling through the T cell receptor (TCR) complex and the costimulatory receptor CD28

Signaling through the T cell receptor (TCR) complex and the costimulatory receptor CD28

Signaling through the T cell receptor (TCR) complex and the costimulatory receptor CD28

Curator: Larry H. Bernstein, MD, FCAP

LPBI

  New connections: T cell actin dynamics

Nancy R. Gough Sci. Signal.  19 Apr 2016; 9(424): ec95   http://dx.doi.org:/10.1126/scisignal.aaf8940

When T cells receive the appropriate signals through the T cell receptor (TCR) complex and the costimulatory receptor…

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A 29-Year-Old Immunocompetent Man With Meningitis and a Large Pulmonary Mass: Clinical Course Continued

Diagnosis: Pulmonary cryptococcosis with CNS dissemination in an immunocompetent host

Clinical Course Continued

Antifungal treatment with oral fluconazole was continued; however, repeat CT scan following 7 months of treatment showed no change in the size of the cryptococcoma. Serum cryptococcal antigen levels remained low (negative) throughout the course, and CNS symptoms did not recur. Since the patient was otherwise in good physical condition and continued to be symptomatic with intermittent hemoptysis, we decided to perform a right lower lobectomy to excise the mass. Intraoperatively, the mass was firm and palpable within the lower lobe. Grossly, it was a tan-yellow, well-circumscribed mass that measured 7.5 X 5.5 X 5 cm with a rubbery consistency and focal central necrosis. The surrounding lung parenchyma was normal and free of invasion by the mass.

Touch preparation slides showed numerous fungal organisms measuring 3 to 10 ^m with a thick capsule set in a background of abundant acute and chronic inflammatory cells as well as necrotic debris. Numerous histiocytes were identified. Features diagnostic of malignancy were not identified. Permanent hematoxylin-eosin-stained slides showed numerous fungal organisms measuring 3 to 10 ^m with thick capsules located in the alveolar spaces and inter-stitium (Fig 3). The adjacent lung parenchyma showed areas of organizing pneumonia. Special stains for mucicarmine highlighted the mucoid capsule of the organism (arrow, Fig 4). These gross, cytologic, and histopathologic findings are diagnostic of Cryptococcus. The patient recovered well from the surgery and continues to be treated medically for disseminated cryptococcal infection. The medicaments are supplied by Canadian Health&Care Mall that has a wide range of antibiotics for treating meningitis http://healthcaremall4you.com/meningitis-and-antibiotics-sold-by-canadian-health-and-care-mall.html

Discussion

Cryptococcus neoformans is an encapsulated yeast found in pigeon and other bird droppings and can be inhaled by humans. The yeast grows within the alveoli, sometimes resulting in an encapsulated mass that is then resistant to neutrophil phagocytosis. Since cell-mediated immunity plays an important role in fighting the infection, most clinically apparent cases are diagnosed in immunosuppressed patients with HIV, transplant patients, or those receiving corticosteroids. Despite the lung being the portal of entry, cryptococcal infection usually affects the CNS and symptomatic pulmonary infection is uncommon. Diagnosis is made by identifying the antigen in fluid or by tissue identification because normal subjects can grow the organism in sputum samples. For this reason, flexible bronchoscopy with transbronchial biopsy, transthoracic needle aspiration, or open-lung biopsy is often necessary to definitively make the diagnosis. Dissemination can then be assessed by analyzing spinal fluid, urine, and blood samples. Sites of hematogenous dissemination include the cerebrospinal fluid, skin, bones, joints, kidneys, spleen, and prostate, and is more commonly seen in immunosuppressed patients. Dissemination is likely if serum cryptococcal antigen is positive.

Pulmonary cryptococcal disease can cause vague symptoms such as fever, malaise, weight loss, dyspnea, or cough, or can be asymptomatic and only discovered incidentally on radiologic imaging. The disease is unusual in immunocompetent patients and is generally quite benign, although rapidly progressive fulminant infection has been described. Most reports of pulmonary cryptococcal disease are international, and only a limited number of cases have been reported in the United States. The pulmonary lesions in the majority of these cases resolved with antifungal treatment. In immunocompetent individuals, chest radiograph findings are variable but typically show single or multiple peripheral nodules with or without cavitation. A large, solitary cryptococcoma replacing the majority of a lobe, as seen in our case, is highly unusual.

Some authors believe that medical treatment is not even necessary when symptoms are minimal and dissemination is not apparent. For instance, pulmonary cryptococcus was reported in seven immunocompetent patients in one study, only one of whom had evidence of disseminated disease and was treated with antifungal medication. In the 7-year follow-up, none of the untreated patients had disseminated infection or progressive pulmonary infection. It is important to note that most of these reports were from the era before less toxic azole antifungal medications were available, and the focus was on trying to avoid the toxicity of amphotericin B. Although currently there are no set guidelines based on prospective data, treatment with azoles seems to be the preference even for localized disease; otherwise, close follow-up is warranted. When there is evidence of disseminated infection, however, all reports agree that antifungal treatment should be initiated, even in immunocompetent individuals. This involves fluconazole for 3 to 6 months, or itraconazole for 6 to 12 months as an alternative. For patients with more severe disease, amphotericin B may be necessary for 6 to 10 weeks.

The differential diagnosis of meningitis with a concomitant pulmonary lesion is fairly limited, and all these conditions are extremely rare in immunocompetent hosts (Table 1). Interestingly, cryptococ-cal meningitis in conjunction with a pulmonary cryptococcoma has been reported in several international reports, most commonly from China. Some authors advocate deferring surgery in the setting of recent meningitis, whereas other authors feel that excision of the cryptococcoma is actually useful to relieve the meningitis. However, most reported pulmonary cases, even large masses, have resolved with antifungal treatment, and surgery has not been necessary. The present case described is unique because such cases of large pulmonary cryptococcoma in immunocompetent patients are extremely rare in the American literature; additionally, this one did not respond to a prolonged course of antifungal therapy and ultimately required resection via a lobectomy.

Clinical Pearls

1. Although rare, pulmonary cryptococcal infection can occur in immunocompetent hosts and is typically asymptomatic but can cause pulmonary symptoms, such as hemoptysis.

2. The diagnosis is established by identifying the yeast on cytology or documenting positive serum antigens; sputum samples can be falsely positive.

3. In asymptomatic, immunocompetent hosts with disease limited to the lung, treatment with oral fluconazole seems to be sufficient, although no treatment with close follow-up can also be considered.

4. Surgical excision of a cryptococcoma may be required with bulky disease, as antifungal treatment may not be effective once the lesion is well encapsulated or when antifungal treatment is not tolerated.

Figure 3. Fungal organisms with thick capsules with the alveolar spaces and interstitium (hematoxylin-eosin, original X 400).

Figure 4. Staining highlights the mucoid capsule (arrow) of the organism (mucicarmine, original X 200).

Table 1—Differential Diagnosis of Combined CNS and Pulmonary Lesions

Malignancy Infectious Tuberculosis Pyogenic Nocardiosis Brucellosis Fungal Coccidiomycosis Histoplasmosis Blastomycosis Cryptococcosis Aspergillosis Paracoccidiomycosis Candidiasis Other Neurosarcoidosis Langerhan cell histiocytosis Neurosyphilis

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A 29-Year-Old Immunocompetent Man With Meningitis and a Large Pulmonary Mass

Cryptococcal meningitis was diagnosed in a 29-year-old, previously healthy Hispanic man at an outside hospital, and he recovered clinically after starting a course of fluconazole. All testing for immunosuppressive conditions returned negative (HIV negative; CD4 count, 502 cells/^L). He had no recent travel history or sick contacts and was not a smoker. Pulmonary tuberculosis was diagnosed following a purified protein derivative skin test, and a triple-drug regimen was started although sputum culture findings were negative for acid-fast bacilli. Chest radiography showed an area of rounded consolidation (Fig 1, white arrow) within the right lower lobe anteriorly and along the diaphragm that was thought to represent pneumonia or round atelectasis. When the patient was seen in our pulmonary clinic a few months later, he denied fever or weight loss but did continue to complain of cough with associated back pain and intermittent hemoptysis. On physical examination, he did not appear ill and seemed otherwise healthy. Vital signs were normal, heart sounds had regular rate and rhythm without murmur, and the chest was clear to auscultation bilaterally and the abdomen was soft, nontender, and nondistended, with no organomegaly. Laboratory values were as follows: WBC, 5,200/^L; hemoglobin, 13.4 g/dL; hematocrit, 38.1%; 75% neutrophils; 15% lymphocytes; 8% monocytes; and 2% eosinophils. Electrolytes and liver function test results were within normal limits. Follow-up chest radiography showed that the right lower lobe mass had increased in size and was now concerning for a mass or diaphragmatic hernia. A chest CT scan was performed, which showed a 4.6 X 7.9 X 6.7-cm heterogenous, enhancing mass within the medial aspect of the right lower lobe abutting the first branch of the right lower lobe bronchus, the esophagus, and the vertebral bodies. A few smaller satellite lesions and interstitial thickening were also noted, although there was no evidence of lymphadenopa-thy. The findings were suspicious for neoplasm or sequelae of infection (Fig 2). Flexible bronchoscopy showed complete occlusion secondary to an endobronchial mass at the right lower lobe bronchial opening. Cytology from bronchial washings did not show evidence of malignant cells or acid-fast bacilli, and biopsy of the mass demonstrated yeast-like organisms with thick capsules along with fibroblasts and neovascularization suggesting granulation tissue with necrosis. What is the diagnosis? Figure 1. Chest radiograph showing round consolidation (arrow) in the right lower lobe. Figure 2. CT scan showing the large right lower lobe mass.

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T cell-mediated immune responses & signaling pathways activated by TLRs

T cell-mediated immune responses & signaling pathways activated by TLRs

T cell-mediated immune responses & signaling pathways activated by TLRs

Larry H. Bernstein, MD, FCAP, Curator

Leaders in Pharmaceutical Innovation

Series E. 2; 6.10

Bruce A. Beutler, Jules A. Hoffmann, Ralph M. Steinman

Bruce Beutler, MD

Regental Professor; Raymond and Ellen Willie Distinguished Chair in Cancer Research, in Honor of Laverne and Raymond Willie, Sr.

Department Center for Genetics…

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Leprosy– Causes, Symptoms, Diagnosis, Treatment and Ongoing care

A chronic, granulomatous infection caused by Mycobacterium leprae, an acid-fast bacillus, preferentially affecting cooler regions of the body (e.g., skin, mucous membranes, peripheral nerves) Leprosy– Causes, Symptoms, Diagnosis, Treatment and Ongoing care

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HIV Infection and AIDS– Causes, Symptoms, Diagnosis, Treatment and Ongoing care

HIV is a retrovirus that integrates into CD4 T lymphocytes (a critical component of cell-mediated immunity), causing cell death and resulting in severe immunodeficiency, opportunistic infections (OI), and malignancies HIV Infection and AIDS– Causes, Symptoms, Diagnosis, Treatment and Ongoing care