Overview of the Innate Immune System
The innate immune system is a relatively broad-acting rapid reaction force that recognizes “nonself ” foreign substances, proteins, or lipopolysaccharides. The innate response can be thought of as a preprogrammed reaction that is immediate, requires no prior exposure to the foreign substance, and is similar for all encountered triggers. The result is the generation of biochemical mediators and cytokines that recruit innate effector cells, especially macrophages and neutrophils, to remove the offending stimulus through phagocytosis or enzymatic degradation. The innate response also alerts the cells of the adaptive immune system to reinforce and refine the attack. In endophthalmitis, bacteria-derived toxins or host cell debris stimulates the recruitment of neutrophils and monocytes, leading to the production of inflammatory mediators and phagocytosis of the bacteria. Responses to Staphylococcus organisms are nearly identical to those mounted against any other bacteria.
An array of highly conserved pattern recognition receptors (PRRs) and proteins detect similarly conserved molecular motifs, pathogen-associated molecular patterns (PAMPs), on triggering stimuli. PAMPs include proteins found only in bacterial, fungal, and viral nucleic acids. Cell-associated PRRs may be extracellular, endosomal, or cytoplasmic and include toll-like receptors (TLRs), C-type lectin receptors (CTLRs), nucleotide-binding oligomerization domain-like receptors (NOD-like receptors, or NLRs), and retinoic acid-inducible gene-I-like receptors (RIG-I-like receptors, or RLRs), among others. Since each PRR has evolved to respond to a different PAMP, engagement of a specific PRR subtype conveys information regarding the type of infection (ie, bacterial, fungal, or viral) and the location (ie, extracellular or intracellular). In humans, there are 10 members of the TLR family. Those that respond to bacterial products (TLR1/2, TLR2/6, TLR4, TLR5) are localized in the plasma membrane of innate immune cells and sense extracellular microbes. The TLRs that detect viral nucleic acids (TLR3, TLR7, TLR9) are in endosomal compartments and interact with membrane proteins.
Immunity Versus Inflammation
An immune response is the process for removing an offending stimulus. An immune response that becomes clinically evident is termed an inflammatory response. Immunity (innate or adaptive) triggers this response and consists of a sequence of molecular and cellular events resulting in 5 cardinal clinical manifestations: pain, hyperemia, edema, heat, and loss of function. These signs are the consequence of 2 physiologic changes within a tissue: cellular recruitment and altered vascular permeability.
The following pathologic findings are typical in inflammation:
infiltration of effector cells resulting in the release of biochemical and molecular mediators of inflammation, such as cytokines (eg, interleukins and chemokines) and lipid mediators (eg, prostaglandins, leukotrienes, and platelet-activating factors)
production of oxygen metabolites (eg, superoxide and nitrogen radicals)
release of granule products as well as catalytic enzymes (eg, proteases, collagenases, and elastases)
activation of plasma-derived enzyme systems (eg, complement components and fibrin)
These effector systems are described in greater detail later in this chapter.
Adaptive and innate immune responses are a constant presence, though usually at a subclinical level. For example, ocular surface allergen exposure, which occurs daily in humans, or the nearly ubiquitous event of bacterial contamination during cataract surgery is usually cleared by innate or adaptive mechanisms without overt inflammation. The physiologic changes induced by innate and adaptive immunity may be indistinguishable. Compare the hypopyon of bacterial endophthalmitis, which results from innate immunity against bacterial toxins, with the hypopyon of lens-associated uveitis (excluding phacolytic glaucoma), presumably a result of an adaptive immune response against lens antigens. These hypopyons cannot be distinguished clinically or histologically.
Delves PJ, Martin SJ, Burton DR, Roitt IM. Roitt’s Essential Immunology. 13th ed. Hoboken, NJ: Wiley-Blackwell; 2017.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.