The “old view.” so to speak, is not without its merits. Many components of the immune system simply don’t operate in the brain at the same capacity as they do in the rest of the body, and there are plenty of good reasons for this. For instance, although new neurons can be produced over the course of a person’s lifetime, this generally happens at an incredibly slow pace,2 and so any nerve cells that are destroyed as collateral damage in an immune response — very much a possibility, considering that the immune system sometimes likes to carpet‐bomb the body to get rid of threats — would be difficult to replace.
Instead, to protect itself from disease, the nervous system relies mainly on physical barriers like the aforementioned BBB, which consists of cells like astrocytes and pericytes that surround blood vessels in the brain and have extremely narrow gaps between them. The idea is that the brain doesn’t need to bother with massive immune responses if germs are too fat to squeeze through the gaps in the BBB and enter the brain in the first place.

This micrograph shows the layers of cells coating blood vessels that comprise the BBB.
Credit: Podjaski et al., 2015.
Generally, the BBB does quite a good job, keeping out not only pathogens but all kinds of other things — acting, if you will, like an invisibility cloak for the brain. For instance, the BBB was first noticed by scientists who found that dyes injected into the blood would seemingly touch every part of the body but the brain.3 And we have pretty solid indications that the brain relies on the BBB doing its job. Factors such as aging and exposure to chemical weapons can lead to a permanent deterioration of the BBB, allowing inflammatory responses from the immune system to intrude upon the brain and bring about cognitive decline.4; 5 Such BBB dysfunction is even believed to be a significant contributor to cognitive decline in Alzheimer’s disease. The exact reasons for this are under investigation and up for interpretation, but it at least partially has to do with inflammatory responses that enter the brain as the BBB falls apart.5; 6 The fact that this doesn’t normally happen is a testament to the BBB’s importance and how well it does its job in healthy individuals.
As foolproof as the BBB’s approach may seem, it has one insidious weakness. By necessity, the brain is connected to the rest of the body by nerves. Also by necessity, many of these nerves are not as well‐shielded from disease as the brain itself. A particularly determined pathogen could, therefore, enter a nerve and gradually work its way up into the brain.
The most infamous examples of this are lyssaviruses, such as the one that causes rabies. Upon entering a nerve, they crawl along the intracellular transport networks of the neurons there, hopping slowly but determinedly from cell to cell until they reach the brain7. A similar approach can be used by herpes simplex virus, resulting in encephalitis.5; 8
Furthermore, the brain can face threats from within. Normal cellular functions produce massive amounts of waste that can prove toxic if allowed to accumulate, and that therefore need to be cleaned up somehow. Just like any other part of the body, the brain is also subject to physical injury, which can cause cell damage that needs to be cleaned up. And, of course, there can always be more extreme conditions like rogue cancerous cells. When problems like these occur, the BBB is powerless to do anything — at the end of the day, it is just a passive barrier. The brain needs an active helper, and so the various components of the immune system must enter the brain to take care of disease, waste disposal, and other tasks.
So how do they get there? As is typical for seemingly simple questions, the answer to that question is … it depends.