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The immune system must overcome daily challenges from pathogens to protect the body from infection. The success of the immune response to infection relies on the ability to sense and evaluate microbial threats and coordinate their elimination all the while limiting damage to host tissues. This delicate balance is achieved through coordinated action of innate and adaptive arms of the immune system. The main distinguishing characteristic of these two branches of the immune response is the way they recognize antigens. Whereas innate immunity relies on germline-encoded receptors to sense the presence of pathogens, adaptive immunity employs a highly diverse set of receptors generated through somatic mutation and recombination that are tailored to specific pathogens. The second major defining characteristic of the adaptive immune system is the development of immunological memory that manifests with increased functionality and frequency of responding cells upon re-exposure to the same antigen. Several immune cell subsets play a critical role in mediating innate immune responses. These include neutrophils, natural killer (NK) cells, dendritic cells (DC), and macrophages. These cells are alerted to the presence of pathogens via recognition of microbial non-self, missing self, or altered self (Medzhitov and Janeway 2002). Recognition of microbial entities relies on the detection of conserved molecular patterns referred to as pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) of the innate immune system. The three best-characterized families of PRRs are the toll-like receptors (TLR), the NOD-Like Receptors (NLR) and the retinoic acid-inducible gene (RIG-I)-like RNA helicases (RLHs). Following PAMP encounter, these receptors initiate signaling cascades that drive production of several anti-microbial molecules that ultimately limit pathogen replication and spread. Furthermore innate immune cells activate the adaptive arm of the immune system through the action of soluble mediators and antigen processing and presentation (Kabelitz and Medzhitov 2007; Medzhitov 2007). DCs can be divided into myeloid (mDC) also known as conventional DCs and plasmacytoid DCs (pDCs) (Sallusto and Lanzavecchia 1994; Olweus, BitMansour et al.

Modulation of Immune Senescence by Menopause and Hormone Therapy