Pathogen is any organism that can produce disease. Pathogens could be virus, bacteria, fungi, parasites etc. All pathogens need to thrive and survive in a host. Once the pathogen sets itself up in a host., it manages to avoid the body’s immune response and use the body’s resource to replicate before exiting and spreading to a new host.
Immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. The immune system recognizes foreign substances by repeating pattern of molecular structure on the microbial surface known as pathogen-associated molecular patterns (PAMPS). PAMPs are unique substances present in microbes. They are absent in humans and only present on microbial surface and they inform the immune system that microbes have invaded the body. The best-characterized microbial sensors are the so-called pattern recognition receptors (PRRs) of the innate immune system, which detect relatively invariant molecular patterns found in most microorganisms. PRRs can also recognize host molecules containing damage-associated molecular patterns (DAMPs), molecules that are often released from necrotic cells damaged by invading pathogens.
PRRs that can be broadly categorized into secreted, transmembrane, and cytosolic classes. Secreted PRRs (including collectins, ficolins, and pentraxins) bind to microbial cell surfaces, activate classical and lectin pathways of the complement system, and opsonize pathogens for phagocytosis by macrophages and neutrophils.
The transmembrane PRRs include the Toll-like receptor (TLR) family and the C-type lectins. TLRs in mammals are either expressed on the plasma membrane or in endosomal/lysosomal organelles. Cell-surface TLRs recognize conserved microbial patterns that are accessible on the cell surface, such as lipopolysaccharide (LPS) of Gram-negative bacteria (TLR4), lipoteichoic acids of Gram-positive bacteria and bacterial lipoproteins (TLR1/TLR2 and TLR2/TLR6), and flagellin (TLR5), whereas endosomal TLRs mainly detect microbial nucleic acids, such as double-stranded RNA (dsRNA) (TLR3), single stranded RNA (ssRNA) (TLR7), and dsDNA (TLR9). Dectin-1 and -2 are transmembrane receptors of the C-type lectin family that detect b-glucans and mannan, respectively, on fungal cell walls.
The cytosolic PRRs include the retinoic acid– inducible gene I (RIG-I)–like receptors (RLRs) and the nucleotide-binding domain and leucine rich repeat–containing receptors (NLRs). RLRs detect viral pathogens. RIG-I and melanoma differentiation factor 5 (MDA5) recognize viral RNA through their helicase domain and signal through their caspase recruitment domain. RLRs use a common adaptor molecule mitochondria antiviral signaling protein (MAVS). RIG-I is a sensor for both ssRNA viruses and some dsDNA viruses (via Pol III). MDA5 preferentially recognizes long dsRNA structures in the cytosol, a PAMP associated with positive ssRNA virus infections.
NLRs represent a large family of intracellular sensors that can detect pathogens and stress signals. NLRs are multidomain proteins that contain a C-terminal leucine-rich repeat domain, a central nucleotide-binding oligomerization domain (NOD), and an N-terminal effector domain. They can be divided into three subfamilies depending on their N-terminal domains. NLR family members detect degradation products of peptidoglycans, various forms of stress, microbial products, and noninfectious crystal particles.
Activated PRRs trigger distinct transcriptional programs and induce multiple downstream pathways that are involved in pathogen clearance. However, excessive activation is deleterious as it can cause systemic inflammation and disease.
MALARIA AND IMMUNE RESPONSE
Malaria, one of the most life-threatening diseases of human history, has infected about 219 million people over 90 countries with around 1 million deaths per year. Plasmodium, an intracellular protozoan parasite, is the causative agent of malaria. It is transmitted by infected female Anopheles mosquito biting, and four species of Plasmodium are responsible for human malarial infection. Among Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae, P. falciparum is the deadliest.
The malaria infection has two stages. The first stage of malaria infection is referred to as the liver stage or the tissue stage infection where the sporozoites that enter the blood target liver, where they exclusively infect liver cells (hepatocytes), they further develop and release merozoites. The second stage of infection is the blood stage infection where matured merozoite invade the red blood cells.