All multicellular organisms have evolved various defense mechanisms that protect themselves from invading pathogens. The ancient immune defense mechanism is conserved between plants and animals and is called innate immunity. In animals, detection of pathogens is performed by various receptors belonging to two diverse receptor families: the Toll-like receptor family and the Nod protein (or NBD-LRR protein) family. In vertebrates, the innate immune system is used to activate a more evolved form of immunity called the adaptive immune system, which is composed of T and B lymphocytes (See figure and table). Frequently, the term PAMPs (pathogen-associated molecular patterns) is used for the characteristic structures present in microorganisms. These structures are detected by innate immune receptors such as the Toll-like receptors and Nod proteins. Innate immunity is important for numerous diseases, including infectious diseases, inflammatory diseases and cancer.
Differences between
innate and adaptive immunity |
||
| Innate Immunity | Adaptive Immunity | |
| Action Time | Early (hours) | Late (Days) |
| Cell Types | Macrophages, Dendritic cells, Neutrophils | B, T Lymphocytes |
| Receptors | Fixed in genome |
Gene rearrangement necessary e.g., B cell receptor, T cell receptor |
| Recognition | Conserved molecular patterns e.g., LPS | Wide variety of molecular structure (proteins, peptides) ~1,000,000,000,000,000,000 |
| Evolution | Evolutionarily conserved (plants, animals) | Only vertebrates (jawed fish-human) |
1. Toll-like receptors (TLRs)
2. Nod proteins (or NBD-LRR or NBS-LRR proteins)
3. Complement system
Complement proteins exist in blood serum.
They coat pathogens and form pores on pathogen membranes, causing lysis of
pathogens with the help of antibodies. Complement
fragments called opsonins adhere to pathogen surface (opsonization)
and promote phagocytosis and microbial killing by leukocytes.
4. Phagocytosis
Animals have cells that engulf pathogens
at high efficiency. They are called professional phagocytes (e.g. macrophages
and neutrophils in humans) and have phagocytosis receptors (e.g. CR3, FcgR,
mannose receptors, scavenger receptors) on their cell surface to facilitate
phagocytosis and kill pathogens by protease enzymes and/or reactive oxygen
species.
5. Cytoplasmic viral receptors
There are proteins inside
cells that detect viral products (such as double-stranded RNA) directly.
The detection of viruses by these receptors leads to the production of anti-viral
proteins (e.g. Interferons) or programmed cell death. e.g. PKR, RIG-I
6. Antimicrobial peptides
Antimicrobial peptides (e.g. defensins,
cathelidins) are small cationic molecules secreted from animals and plants
that kill pathogens such as bacteria, fungi or viruses (Some antimicrobial
peptides even kill cancer cells). In humans, antimicrobial peptides are secreted
to the body surface such as the skin or intestinal epithelium. They kill
pathogens by disrupting their membranes.
7. Programmed cell death
Animal cells infected by virus have
a “suicide” program
called programmed cell death or apoptosis. By death of the virus-infected
cells, a host can limit the proliferation of viruses and reduce propagation
of the virus to the other cells. Plants have a similar mechanism called
the hypersensitive response (HR). Tissues infected with pathogens such
as bacteria or viruses undergo suicide to prevent further infection.
Innate immune response:
1) Antigen-presenting cells (APCs) are activated through recognition of pathogens (or PAMPs) by receptors such as TLRs or NBD-LRR proteins.
2) This activation leads to the production of inflammatory cytokines and the expression of co-stimulatory molecules on the cell surface.
Adaptive immune response:
3) Antigens will be presented by
MHC molecules on APCs to T lymphocytes (Signal 1). This is not sufficient
to activate T lymphocytes and they need an additional signal from co-stimulatory
molecules (Signal 2), of which expression on APCs is induced by TLR (or
NBD-LRR) stimulation.
4) Activated T lymphocytes become further differentiated to effector T lymphocytes by stimulation with cytokines such as IL-12.
