Features of the immune response to specific types of pathogens within the CNS


Viruses invade the CNS through hematogenous dissemination or by retrograde transport up neurons that have processes extending into sites of infection in the periphery. As intracellular pathogens, their tropism for different neural cells and effect on host cell function determine the severity of disease. The paucity of MHC antigen expression within the CNS can make the cytotoxic T lymphocyte (CTL)-mediated clearance of viruses difficult and may predispose to chronic or relapsing infections. Their capacity to establish latency also allows viruses to avoid detection by the immune system. In other circumstances, antiviral antibodies can shut off virus production by infected neurons in a noncytolytic manner and promote recovery from disease. During chronic CNS infection caused by human immunodeficiency virus (HIV), the long-term production of inflammatory mediators such as tumor necrosis factor a (TNFa) may promote the development of neurological symptoms.


Bacteria require specific virulence factors to allow invasion of the CNS and production of disease. Organisms that cause acute meningitis are usually encapsulated; this inhibits phagocytosis and activation of complement through the classical pathway. As a result, these bacteria survive in the bloodstream longer and are more likely to invade the CNS. Once in the subarachnoid space, favorable conditions (i.e. limited intrinsic host defense, abundant nutrients) allow for rapid bacterial multiplication. Cytokines, particularly IL-1 and TNFa, are secreted in response to bacterial products and induce endothelial expression of adhesion molecules important for neutrophil egress. The production of other chemotactic stimuli including IL-8 also recruits neutrophils, but low levels of opsonins, antibody and complement in the CSF limit bacterial phagocytosis by these infiltrating cells. These responses combine to produce BBB dysfunction, leakage of protein and cerebral edema. Slow-growing bacteria adapted to survive inside macrophages, such as mycobacteria, induce mononuclear inflammatory responses and cause subacute or chronic disease.


Fungi are generally avirulent pathogens; most individuals with fungal infections of the CNS have some underlying immune deficiency. The greater frequency of these disorders in patients with impaired cell-mediated rather than humoral immunity implies that the former is the primary means of host defense against fungal pathogens that invade the CNS. In the setting of deficient cellular immunity, fungi can grow unchecked in the CSF without eliciting an inflammatory response. As a result, these infections are difficult to eradicate from the CNS completely and require long-term antifungal therapy. Mortality in general is high.


Only a few parasites frequently invade the nervous system. Free-living amoebae that cause acute meningitis enter the CNS by crossing the olfactory mucosa. All other parasites are assumed to enter from the bloodstream. Intracellular pathogens such as Toxoplasma may establish latent infections which reactivate in the face of acquired deficiencies of cellular immunity. The cysticerca of Tania solium induces an intense inflammatory reaction which may induce seizures. The organisms are eventually killed, leaving behind calcified nodules. Malaria, on the other hand, induces a toxic encephalopathy associated with ICAM-1-mediated adhesion of parasitized erythrocytes to cerebral capillary endothelial cells and induction of local cytokine production.

See also: Acquired immune deficiency syndrome (AIDS); Acute inflammatory reaction; Adhesion molecules; Antigen-presenting cells; Bacillus, infection and immunity; Borrelia, infection and immunity; Bun-yavirus, infection and immunity; Chemotaxis; Coronavirus, infection and immunity; Cryptococcus, infection and immunity; Cysticercosis; Cytokines; Cytomegalovirus, infection and immunity; Endothelium; Fungi, immunity to; Haemophilus, infection and immunity; Herpes simplex virus, infection and immunity; Herpesvirus-6, infection and immunity; Histoplasma, infection and immunity; Human immunodeficiency viruses; Immune surveillance; Transmissible spongiform encephalopathies, infection and immunity; Listeria, infection and immunity; Lymphocyte trafficking; Malaria; Monocytes; Mycobacteria, infection and immunity; Neisseria, infection and immunity; Nocardia, infection and immunity; Opportunistic infections; Opsonization; Picornavirus, infection and immunity; Rhabdovirus, infection and immunity; Rickettsia, infection and immunity; Streptococcus, infection and immunity; Togavirus, infection and immunity; Toxoplasmosis; Treponema, infection and immunity; Trypanosomiasis, African; Viruses, infection of immune cells by.

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