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1. #FIRST AID 2017 DRUGS USMLE STEP 1 DRIVERS#
2. #FIRST AID 2017 DRUGS USMLE STEP 1 SKIN#
3. #FIRST AID 2017 DRUGS USMLE STEP 1 SERIES#

Dendritic cells (DCs) represent the third of the mononuclear phagocyte trinity and act as immune sentinels capable of triggering adaptive immunity. Early work by Ralph van Furth and Zanvil Cohn founded the paradigm wherein bone marrow promonocytes differentiate into monocytes that enter the bloodstream and become macrophages as they extravasate into tissue ( van Furth and Cohn, 1968). Monocytes appear in early circulation several days after the first macrophages ( Schulz et al., 2012).

#FIRST AID 2017 DRUGS USMLE STEP 1 SKIN#

In contrast, the skin and intestine are continuously replaced by circulating macrophage precursors known as monocytes ( Baron et al., 2012). Hematopoiesis thus establishes populations of long-lived and self-replenishing resident phagocytes (aka histiocytes) in the brain (microglia), liver (Kupffer cells), and lungs (alveolar macrophages). Metchnikoff characterized macrophages’ phagocytic function as not only instrumental to tissue remodeling of tadpoles, but in taking up and killing foreign materials in starfish larvae as well (Reviewed in Gordon, 2016). The pervasiveness of these amoeboid cells throughout the body led the early founder of cellular immunity, Ilya Metchnikoff, to postulate their utility in engulfing debris. Each of these locations supplies waves of primordial myeloid cell migration to the periphery, giving rise to the first tissue resident macrophages ( McGrath et al., 2015).

#FIRST AID 2017 DRUGS USMLE STEP 1 SERIES#

Human hematopoiesis occurs at a series of sites including the yolk sac by 17 days post-conception, fetal liver and spleen, and finally within bones (Reviewed in Baron et al., 2012). The MP’s story is how a cell, when given opportunities, can protect and defend, elicit disease or be harnessed for therapeutic drug delivery ( Edagwa et al., 2017).įrom their inception during embryonic development, MP exemplify the principal that ontogeny recapitulates function. When opportunities come available they can affect a functional change for the innate immune system ( Moorjani et al., 1996 Kadiu and Gendelman, 2011b). How the immune system affects its environment and vice versa characterize its multifaceted roles. A discussion of the multifaceted MP in all its roles in health and disease has become the subject of this review with an eye towards how natural functions may be harnessed or even enhanced for the benefit of the host ( Li et al., 2016). That role rests in utilizing the cell’s own “high cytoplasmic content” to carry disease fighting drugs encased into stable nanoparticles ( Edagwa et al., 2017). Over the past decade yet another role for the MP has been uncovered. This is certainly true for a host of viral, bacterial and parasitic infections where MPs serve as reservoirs of infectious agents, sites for microbial persistence, and inducers of end organ disease ( Koziel et al., 1999 Langford et al., 2002 Buckner et al., 2011). However, the same MPs that protect the host can also, under pathological and infectious circumstances incite the very disease states that they were designed to thwart ( Bocchino et al., 2001 Giralt et al., 2009).

All serve in organ and body maintenance (Reviewed in Martinez and Gordon, 2014). Each and all enable intracellular killing, cell mobility, tissue and cellular repair and antigen presentation to maintain tissue homeostasis and affect T cell immunity for microbial and cancer surveillance ( van Furth et al., 1972 Pistoia, 1991 Mindell, 2012). Mononuclear phagocytes (MP monocytes, macrophages and dendritic cells) serve as surveyors and protectors of the tissue microenvironment, secretors of inflammatory, growth and regulatory factors. These undiscovered cellular functions can lead to reductions in persistent infection and may potentially facilitate the eradication of residual virus to eliminate disease. These phagocytic and intracellular killing sensing mechanisms can also be used in service as macrophages serve as cellular carriage depots for antiretroviral nanoparticles and are able to deliver medicines to infectious disease sites with improved therapeutic outcomes.

A hidden and often overlooked resource of the macrophage rests in its high cytoplasmic nuclear ratios that allow the cell to sense its environment and rid it of the cellular waste products and microbial pathogens it encounters. However, each of these events are held in check by antiretroviral therapy.

Virus replicates in tissue reservoir sites that include the nervous, pulmonary, cardiovascular, gut, and renal organs. These herald viral spread from macrophages to neighboring CD4 + T cells and end organ damage. However, the cellular microenvironment changes as a consequence of viral infection with aberrant production of pro-inflammatory factors and promotion of oxidative stress. Low-level viral persistence continues in these cells in the absence of macrophage death.

#FIRST AID 2017 DRUGS USMLE STEP 1 DRIVERS#

Macrophages serve as host cells, inflammatory disease drivers and drug runners for human immunodeficiency virus infection and treatments.