Aging related decline of the Immune system
Aging is defined as a time-dependent decline of all of the body systems, yet its effects on immune system are probably the most devastating. For instance, lymphoid cells, which are responsible for memorizing how to respond to infectious agents, and therefore persist for almost the length of body’s lifespan, through all this extended existence accumulate environmental insults resulting in loss of their functionality: aged T-cells have reduced ability to proliferate in response to the antigen, in our study we will test ability of T-cells to activate in response to stimulation and produce cytokines (ELISpot assay- please, click to enlarge)
Aged B cells show abridged antibody production. This explains why vaccination is less efficient in the elderly and why they are in general more susceptible to infectious agents. We will assess our dogs for susceptibility to immunization (dogs will be vaccinated against leptospirosis and titre of antibodies will be then regularly analyzed).
With age macrophages - cells responsible for clearance of both infectious agents and dead/broken cells - lose their phagocytic abilities (the amount of potentially hazardous objects they can engulf as well as the speed of this process decline). THis phenomenon is well studied for humans and mice, not so much is known about dogs. We will collect macrophages from dogs at different time points within our project and check their potential for phagocytosis.
Cytokines are regulatory proteins mediating activity of immune cells. They are being released by various cell types upon numerous stimuli in order to trigger immune response. Ability of body to release a specific set of cytokines in response to certain stimulation is a striking characteristic of health status and gets compromised with age. We will check cytokine production timeline upon stimuli: besides infection encounter, cytokines are being released as a natural response to exercising. The timeline of their release and disappearance is described in young dogs. Here we will analyze this timeline for elder dogs and check, whether proposed treatment can mitigate defects of cytokine response in elder animals.