Primer- Secondary Immunodeficiencies Flashcards
(30 cards)
What is the most common cause of immunodeficiency?
Malnutrition-affects both innate and adaptive immunity
When are maternal IgG antibodies transferred to fetus?
after 32 weeks
What vitamin helps macrophage activity in treating M. TB
Vitamin D
What gene in Down Syndrome contributes to phagocyte dysfunction?
overexpression of Down Syndrome Critical Region 1 (DSCR1)
What immunodeficiency do Antiepileptics cause? and Bactrim?
hypogammaglobulinemia; leukopenia
Betamethasone is ___ X more potent than cortisol?
25
Which transcription factor due glucocorticoids activate?
NFkB, nuclear factor of activated T cells, and activator protein 1
How do glucocorticoids work?
The overall results are decreased cytokine production (IL-1, IL-6, and TNF-α) and impaired leukocyte chemotaxis, cell adhesion, phagocytosis, and lymphocyte anergy. Lymphopenia occurs as a result of the proapoptotic activity and inhibition of IL-2–mediated proliferative responses. When used at large doses, antibody responses and delayed-type hypersensitivity responses are reversibly suppressed
How do calcineurin inhibitors work?
bind cytoplasmic proteins from the immunophilin family and inhibit their interaction with calcineurin, which is essential for the activation of IL-2 transcription and T-cell function
What is the advantage of calcineurin inhibitors over corticosteroids and cytotoxic drugs?
The advantage of these drugs over corticosteroids and cytotoxic drugs is to spare macrophage and neutrophil functions, reducing the spectrum of susceptibilities to infections. However, these drugs cause respiratory tract and skin infections, usually of viral cause, to occur with increased frequency.
What are the most common adverse effects of calcineurin inhibitors?
hypertension and renal dysfunction; less common but more serious is the increased frequency of lymphoproliferative disorders and skin neoplasias.
What was the first drug developed in the calcineurin inhibitor category
The first drug in this category was cyclosporine, which has been extensively used to prevent organ transplant rejection, GvHD, and corticosteroid-resistant autoimmune disorders
What are other agents besides Cyclosporine with a similar mech of action and immune selectivity?
tacrolimus and pimecrolimus. The latter is the most recent member of this group, and it was developed for topical use in the treatment of severe atopic dermatitis. An agent with a similar name, sirolimus or rapamycin, also binds an immunophilin but does not inhibit calcineurin. Instead, sirolimus inhibits the IL-2–induced response by inhibiting the mammalian target of rapamycin, a protein essential for cell activation and proliferation.
What are examples of cytotoxic agents?
Effective in autoimmune and inflammatory disorders, including GvHD and the prevention of graft rejection
The most common drugs used for these applications are the alkylating agent cyclophosphamide and the antimetabolites methotrexate, mycophenolate, azathioprine, and 6-mercaptopurine. Other drugs with predominant use in autoimmune disorders are sulfasalazine, hydroxychloroquine, and leflunomide. These compounds interfere with the synthesis of DNA, arresting the cell cycle and inducing apoptosis. Generally, they inhibit both T- and B-cell proliferation and therefore any new immune responses. In addition, depending on the dose used, they inhibit cellular and antibody responses resulting from previous sensitizations. The major limitation of the use of these agents is their toxicity to other hematopoietic and nonhematopoietic cells, with development of cytopenias, gastrointestinal mucosa, and skin deterioration. These cytopenias contribute to the state of secondary immunodeficiency and susceptibility to infections.
What type of virus is HIV
a dsRNA lentivirus with tropism for CD4+ expressing cells (T cells and macrophages)
How long does the acute phase of HIV last?
1 to 6 weeks after infection, with nonspecific symptoms, such as fever, fatigue, myalgia, and headaches.
How long is the latency period of HIV
characterized by a virtual absence of signs or symptoms until symptomatic disease occurs and can last as long as 10 years
What are a small proportion of HIV-infected patients remain asymptomatic and do not have AIDS?
long-term nonprogressors and have been the focus of multiple studies to understand the basis of their protection.
What are those who maintain low levels of HIV (ie, <50 RNA copies/mL) without treatment called?
elite controllers
An inherited defect in which gene may explain immunity when talking about HIV?
inherited defect in the gene encoding the CCR5 receptor, a T-cell surface molecule that is necessary for HIV cell entry
Besides CCR5 what other factors have been identiified for long term nonprogressors in HIV?
low number of activated CD8+ T cells,49 the presence of particular HLA haplotypes, and viral mutations that result in low virulence.
How do you diagnose HIV?
Initially? and then to confirm?
sensitive ELISA to detect antibodies against the HIV protein p24.
A positive HIV ELISA result is confirmed by using the more specific Western blot, which detects antibodies to several HIV proteins, or the detection of HIV DNA sequences by PCR.
How should you diagnose infants and children born to HIV infected mothers up to 18 months?
HIV DNA PCR test because the presence of passively acquired maternal antibodies in the serum of the child can result in a positive HIV ELISA test result, even if the child is not infected with HIV.
What is HIV genotyping?
identifies HIV mutations that confer viral resistance to antiretroviral drugs
