Aging and Adaptation in Infectious Diseases II/Session I: Immune System: Architecture and Dynamics
April 30, 2019
9:30 am - 12:00 pm
Mercedes Pascual (Univ. Chicago)
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- John Doyle (Caltech)
Effective layered architectures such as in brains and organisms seamlessly integrate high level goal and decision making and planning with fast lower level sensing, reflex, and action and facilitate learning, adaptation, augmentation (tools), and teamwork, while maintaining internal homeostasis. This is all despite the severe demands such actions can put on the whole body’s physiology, and despite being implemented in highly energy efficient hardware that has distributed, sparse, quantized, noisy, delayed, and saturating sensing, communications, computing, and actuation. Similar layering extends downward into the cellular level, out into ecological and social systems, and many aspects of this convergent evolution will increasingly dominate our most advanced technologies. Simple demos using audience’s brains can highlight universal laws and architectures and their relevance to tech, bio, neuro, med, and social networks. This suggests conjectures about senescence, and tradeoffs in the evolution of cancer, wound healing, degenerative diseases, auto-immunity, parasitism, and social organization, and potential animal models to explore these tradeoffs.
With this motivation, we’ll sketch progress on a new unified theory of complex networks that integrates communications, control, and computation with applications to cyberphysical systems as well as neuroscience and biology. Though based on completely different constraints arising from different environments, functions, and hardware, such systems face universal tradeoffs (laws) in dimensions such as efficiency, robustness, security, speed, flexibility, and evolvability. And successful systems share remarkable universals in architecture, including layering, localization, and diversity sweet spots, to effectively manage these tradeoffs, as well as universal fragilities, particularly to infectious hijacking.
I have videos of some introductory material and posted it in my public dropbox folder:
Some new neuro stuff (with videos) is in the subfolder 1.New_CDS141\2.2.UCSDneuro
There are lots of videos and papers on biology and medicine (and lots of tech) in the subfolder 0.Intro2Research.
Given the limited time and that I’m an extreme outlier, I’ll try to post videos (need to organize them) of some additional background material on aging, cancer, immune systems, wound healing, microbiome, etc that give some background on our approach to these topics.
Some videos/slides relevant to this meeting are in the subfolder: 1.New_CDS141\4.2.AgingSFI
A key lesson from allometric scaling perspectives has been that a variety of physiological processes and timescales systematically change with body size. These have important implications for interpreting a variety of ecological processes and for normalizing physiology across diverse organisms. Applying these concepts to infectious disease may, on the practical side, make it possible to scale interventions between organisms of very different size, and on scientific side, help us to systematize the ecology and evolution of hosts and parasites. In this talk we will discuss: 1) how various immune dynamics can be systematically scaled with body size and what implications this may have for organism physiology, 2) the time-scales of infection across diverse organisms, 3) the consequences of infection on lifetime reproduction across organisms of different size and across different broad taxonomic groups, and 4) the efficacy of vaccines and the timescales of immunity.
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- Kempes-Slides-4-30-1019.pdf (x)
The innate and adaptive components of the immune system do not age independently. We consider a mathematical model that couples these two complementary responses, and demonstrate a mechanism in which the progression of immunosenescence in the adaptive response leads to aging in the inflammatory response. We analyze the innate-adaptive interface of this coupled immune model by studying cytomegalovirus infection, a persistent infection that interacts with both components of the immune system.
- Pamela Martinez (Harvard)
Two kinds of immunity underlie pathogen competition for hosts as a function of history of exposure: specific immunity depending on memory of specific variants that have been seen before, and generalized immunity resulting only from the number of previous infections regardless of their antigenic identity. The role of immune selection remains unclear in rotavirus, the most common cause of diarrheal disease worldwide which contributes 40% of total hospitalizations in young children. With a process-based model that allows for both demographic and measurement noise, we analyzed over 10 years of monthly incidence data at the serotype level from Dhaka, Bangladesh. We specifically investigated the role of specific and generalized immunity in temporal patterns of antigenic diversity by fitting and comparing models that represent these different hypotheses, including consideration of variation in the two antigenic determinants on the surface of the virus. Our findings show that strong generalized immunity is needed to recover the serotype dynamics of rotavirus in Dhaka, a process dominated by exposure to VP4 (P-type), the outer layer protein that mediates cell attachment. Our results further indicate a role of specific immunity via the VP7 (outer capsid protein, G-type), whose effect is weak by comparison to that of VP4 but is nevertheless required to capture the epidemiological dynamics and antigenic diversity patterns of the virus.