The communication between innate and adaptive immunity

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In this article, I briefly explain the communication between innate immunity and adaptive immunity.

Innate immunity

Innate immunity accounts for the first line of defense against harmful pathogens. It gives a uniform response to all types of harmful pathogens, therefore, also known as non-specific immunity. Innate immunity is quite important to keep us healthy. However, it is not adequate to give us full protection against many infectious diseases.

As many microbes have evolved different strategies to evade innate immunity, antigen-specific responses are required to wipe out infections. The antigen-specific responses are produced by adaptive immunity, which is initiated and regulated by our innate immunity.

Adaptive immunity

An adaptive immune response is started when the pathogen is delivered to lymphoid tissues. T cells and B cells, respond to the pathogen after recognizing it in the lymphoid tissues. The dendritic cells, act as a key intermediate between innate and adaptive immunity. The immature dendritic cells carry the microbes through the lymphatic vessels to nearby secondary lymphoid tissues, either attached to it, or in phagosomes.

In the secondary lymphoid tissues, the dendritic cells transfer the microbes to other cells. The dendritic cell internalizes the phagocytosed microbes and degrades them. The peptides from the microbes come up the cell surface, attached with MHC class-II proteins.

The cytoplasm replicating pathogens, e.g., viruses, some bacteria, and protozoan parasites are processed in the cytosol, and their peptide fragments come up to the surface, bound to MHC class-I proteins.

The dendritic cell is matured by the binding of microbial pathogen-associated molecular patterns (PAMPs) to the dendritic cell’s pattern recognizing receptors (PRRs). The binding makes it a sturdy antigen-presenting cell as it begins to express higher levels of MHC class-II proteins.

The mature dendritic cells, also switch on the costimulatory membrane protein, CD80 or CD86, which is identified by receptors on T-helper cells (TH cells), and causes their activation. The mature dendritic cells are the most productive antigen-presenting cells, which activate naïve T cells.

Differentiation of T-helper cell gets impacted by pathogen recognition by dendritic cells

Different types of pathogens bind distinct pathogen recognition receptors (PRRs) on dendritic cells and accordingly activate signaling pathways. These signaling pathways control the secretion of specific cytokines by dendritic cells. This causes the differentiation of naïve T helper cells to mature T helper cells. These processes aid the immune system to produce a precise response for each invading pathogen.

Dendritic cells help to differentiate naïve T cells into several T-helper cell subsets like TH1, TH2, TH17, and T-regulatory cells. These subsets of T cells produce different cytokines and function differently in the immune system. Each T-helper cell subset functions to eliminate the pathogen causing the activation of the dendritic cell.

Internalized bacteria and viruses produce endosomal nucleic acids. These activate dendritic cells to secrete the cytokine IL-12, which helps the differentiation of T cell into different T-helper cell subsets. TH1 cells secrete the cytokine IFN-γ, which in turn activates NK cells and macrophages to eradicate pathogens and infected cells.

Parasitic worms having pathogen-associated molecular patterns (PAMPs) and some bacteria and fungi attached to pattern recognition receptors of plasma membrane and cytoplasm activate dendritic cells. These activated dendritic cells produce the cytokine IL-10, which along with cytokines IL-13 and IL-4 activate TH cells to become TH2 cells. Other leukocytes get activated by the cytokines of TH2 cells, and release mediators that eliminate pathogens.

T cells become differentiated into TH17 cells when the fungal pathogen-associated molecular patterns bind to the CLR dectin-1 and activate it. TH17 cells produce IL-17, which induces the production of mediators. These mediators, take on inflammatory cells to the infection site to clear fungal infections.

The antigens having PAMPs can activate B cells

B cells not encountered with any antigen, are also called naïve B cells. These get activated by receiving multiple signals, e.g., from helper T cells, antigen binding to B-cell receptor, T-cell produced cytokines, and cell-cell interactions. After activation, they get differentiated into plasma cells secreting antibodies.

Toll-like receptors (TLRs), expressed by B cells get attached with PAMPs. Thus, they activate signaling pathways that can provide the same signals required for B cell activation.

Mouse B cells express TLR4, which when bound with LPS (lipopolysaccharide), can activate optimum signals to induce proliferation in B cells and their differentiation into antibody-secreting plasma cells. However, human B cells do not synthesize TLR4, instead produce TLR9, and can get activated by microbial CpG DNA.

Adjuvants activate the innate immunity that enhances the adaptive immunity

An adjuvant accelerates an immune response when used in combination with certain specific vaccines. The effects of a vaccine are augmented by an adjuvant, which stimulates the immune system. Thus, it responds to the vaccine more vigorously and renders increased immunity to a specific disease.

Adjuvants do this work by mimicking pathogen-associated molecular patterns (PAMPs). These include liposomes, lipopolysaccharides, components of bacterial cell walls, and endocytosed nucleic acids.

An adjuvant included with a vaccine enhances the innate immune response by accelerating the activities of dendritic cells, lymphocytes, and macrophages by imitating a natural infection.

Aluminum salts, oils, and virosomes are some mainly used known adjuvants. Immunization with aluminum salts generally aids in the conversion of activated T cells to TH2 cells and accelerates antibody responses.

Many vaccines function as built-in adjuvants as they contain their own PAMPs by consisting of killed or attenuated viruses or bacteria. However, some new vaccines containing protein antigens, do not possess the power to boost immunity to a certain extent.

An effective vaccine for a pathogen protein can be produced by fusing the protein with a TLR ligand by applying genetic engineering.

Innate and adaptive immunity adapt the same pathogen elimination mechanisms

Opsonins are soluble proteins, that recognize microbial surface components. When opsonins bind to surfaces of microbes, they are marked by phagocytic receptors, that proceed with enhanced phagocytosis.

Some antibodies serve as opsonins and bind to microbial surfaces. After binding, these antibodies can be recognized by the immunoglobulin FC receptor, expressed by macrophages and leukocytes enhancing phagocytosis.

Both innate and adaptive immunity activate the complement system. Soluble proteins like MBL (mannose-binding lectin) and the complement component C1 recognize components on microbial surfaces. This leads to the activation of the complement pathway. Similarly, when certain antibodies get attached to microbial surfaces, they are recognized by the C1 component of complement, thus setting off the complement pathway.

The complement cascade gets activated by any one of the above-specified ways, and after its activation, it produces certain protective processes. These processes include opsonization, lysis of membrane-attached microbes, and generation of proinflammatory and chemoattractant fragments.

The adaptive immunity along with the innate immunity opted for the same pathogen eliminating pathways like opsonization and complement activation. Thus, both contribute to antibody-mediated clearance of pathogens.

Conclusion

Innate immunity is the first line of defense against harmful pathogens. Whereas, adaptive immunity is a form of acquired immunity, which is built up gradually as we are exposed to pathogens or get vaccinated. Innate immunity is specific, whereas adaptive immunity is non-specific in nature.

The communication between innate and adaptive immunity is established by antigen-presenting cells.

The dendritic cells act as a key intermediate between innate and adaptive immunity. Various pathogens bind distinct pathogen recognition receptors on dendritic cells. Thus, they activate many signaling pathways, that eventually control the secretion of specific cytokines by dendritic cells. These cytokines help to differentiate naïve T helper cells into mature T helper cells.

An adjuvant included with a vaccine enhances the innate immune response by accelerating the activities of dendritic cells, lymphocytes, and macrophages by imitating a natural infection.

The same pathogen elimination mechanisms like complement activation and opsonization are adapted by both innate and adaptive immunity.

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