Alessandra Tomasi received her B.A. from Cornell University and is now a first-year medical student.
The immune system comprises a uniquely vast network of organs, tissues, and cells that work together to fight off foreign bodies in a host. Any foreign body—a bacterium, virus, parasite, or even a damaged host cell— that in this way elicits an immune response is known as an ‘antigen.’ Specifically, an invader such as a microbe or tumor cell will contain unique structural features that are recognized by the host immune system as foreign; that is, as something that does not belong.
An understanding of the many intricacies of the immune system therefore begins with the discrimination between “self” and “non-self.” Simply put, the body's immune system will ignore any cell that carries a "self" marker molecule, but will instead be triggered as soon as a cell or organism presents with a "non-self" (or, foreign) marker. Again, these antigens can be anything from invading microbes to damaged host cells. And, since “self” markers are unique to each individual, any transplanted tissue can even act as an antigen: this is the molecular foundation for donor rejection.
The capacity to distinguish between “self” and “non-self” is one that pervades throughout the two types of responses that are mounted by mammalian immune systems: the innate and the adaptive. Over time, it has become increasingly clear that the two responses are intricately interconnected.
The role of the innate immune system is simply to recognize “self” from “non-self.” It is the first line of defense against any damage, invasion, or disruption to host homeostasis — whether infectious or non-infectious. The innate immune system, unlike its adaptive counterpart, does not recognize specific agents; rather, it acts solely to recognize patterns that are associated with “non-self.” As soon as a host comes in contact with any substances associated with antigenicity, innate immune cells are immediately released to initiate attack.
There are two main classes of molecules that are in this way recognized: damage-associated molecular patterns (DAMPs), which are released by damaged or dying host cells, and pathogen-associated molecular patterns (PAMPs), which instead are molecular patterns that are associated with foreign microbes. Both DAMPs and PAMPs are recognized by host proteins known as pattern recognition receptors (PRRs), which are typically expressed on leukocytes (white blood cells). Examples of PRRs include toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I-like receptors (RLRs). Various PRRs are classified according to their specificities; that is, based on the specific damage or pathogen- associated patterns that they recognize as "non-self." Following binding of DAMPs or PAMPs to PRRs, innate immune cells are activated to help clear the foreign agent through phagocytosis, target-cell lysis, and/or the initiation of inflammation.
Given its ability to recognize “self” vs. “non-self” through pattern recognition rather than the specific identification of foreign agents, the innate immune system is readily able to act quickly in response to infection or damage. Conversely, the adaptive immune system is instead characterized by its specificity and even memory, and takes time (upwards of 2 weeks) to become active.
The main cell types associated with adaptive immunity are known as lymphocytes (read more about the lymphatic system and its role in immunity here): B-lymphocytes (also known as B cells) and T-lymphocytes (T cells). Each of these lymphocytes is capable of expressing thousands of copies of a single unique antigen receptor protein, which interact with antigens to trigger lymphocyte activation. Unlike their innate immune counterparts, B cell receptors (BCRs) and T cell receptors (TCRs) recognize specific molecules that are unique to a single pathogen. The two differ in that B cell receptors are able to identify whole pathogens, whereas T cells can only recognize fragments thereof— that is, antigen peptides.
When a B cell recognizes and binds to a whole antigen (whether soluble or present on a pathogen surface), it induces the production of plasma cells. These plasma cells then secrete antibodies, which help clear the pathogen. Given this mechanism, B cells help to fight off extracellular pathogens.
The T cell response instead is different. There are two main classes of T cells involved in antigen recognition: cytotoxic T cells (Tc) and helper T cells (Th). Given that T cells cannot recognize whole pathogens, they instead rely on the presence of a major histocompatibility complex (MHC) for recognition and binding. Briefly, MHCs are cell surface proteins that exist as two classes, and they help display antigenic peptides on the surface of dendritic cells— aptly known as antigen-presenting cells— to recruit T cells. Tc cells recognize MHC Class I proteins, whereas Th cells recognize MHC Class II proteins. When a TCR on a Tc cell recognizes an antigenic peptide that is presented on an MHC Class I molecule of a cell, the Tc cell is activated to produce cytotoxic T lymphocytes that lyse any host cells infected by the particular pathogen. Because of this, Tc cells are able primarily to recognize intracellular pathogens. When a TCR on Th cell instead recognizes an antigenic peptide that is presented on an MHC Class II molecular of a cell, Th cells are activated to produce effector cells that then secrete cytokines to activate and recruit B cells and Tc cells. Consequently, Th cells are able to help fight off both extracellular and intracellular pathogens.