Whether it’s fighting the coronavirus or the common cold, the body’s immune system
has several mechanisms to combat viral infection. So, how does the immune system respond to
viruses? Before we explore this question in more detail,
let’s take a look at viruses and their effects on the human body. A virus needs to invade
a living cell to replicate. A viral infection is when a virus invades the body and can lead
to a spectrum of symptoms. The virus particle, which is called the virion,
consists of a viral genome that is made up of either DNA or RNA and is enclosed in an
outer protein shell, called a capsid. Some viruses have an envelope around the capsid
that contains lipids and proteins, including glycoproteins and viral receptor proteins
known as spikes.
The virion uses surface proteins in the capsid or glycoproteins in the envelope to attach
to the host cell. After entering the cell, the virion turns it into a virus factory.
The virus utilizes the host's protein formation and replication functions, which it uses to
assemble into new viruses. Multiple copies of the virus are released from the host cell
and spread to nearby cells, where they repeat the cycle.
So, what strategies does the immune system use to prevent or curb infection?
The first response to a viral infection is the rapid-onset innate response. There are
several mechanisms involved in innate immunity: interferons, natural killer cells, and antigen
presenting cells.
When a virus infects a cell, the cell produces and releases signaling proteins called interferons,
which are a type of cytokine. Interferons act as a warning signal to neighboring cells.
They act by binding to interferon receptors on nearby uninfected cells. In response, the
cells start producing antiviral proteins, which prevent the virus from replicating in
the cell in the event of infection.
Interferons also play another important role in the immune response. They induce nearby
cells to increase the expression of major histocompatibility class I molecules, or MHC
class I, on their surface. MHC class I molecules have two important signaling functions, for
which they display endogenous viral fragments, known as antigens. First, they present antigens
to adaptive immune cells, which we’ll discuss later. Second, MHC class I molecules present
antigens to innate immune cells. Let’s look at this in detail:
Infected cells are removed by specific lymphocytes that patrol the body. These natural killer
cells, or NK cells, have receptors that recognise the antigens on MHC class I molecules. The
absence of MHC class I molecules plays an important role in the immune response of NK
cells. Usually, cells express sufficient MHC class I on their surface for T cells to be
able to recognize them if they become infected. However, viruses can prevent infected cells
from synthesizing these molecules. As a result, there are too few MHC class I molecules on
the cell surface, which causes the infected cell to evade capture by T cells. The patrolling
NK cells recognize the absence of MHC class I and release toxic substances, such as granzymes
and perforin, which kill the virus-infected cell.
Infected cells can also be removed via macrophages. These large leukocytes ingest free viruses
in a process called phagocytosis. First, the macrophage surrounds and engulfs the virus.
The macrophage then breaks the virus down by mixing it with digestive enzymes stored
in vesicles called lysosomes. The degraded virus material is then released from the cell
as waste.
Macrophages are antigen-presenting cells, which means they’re able to capture, process,
and present antigens from pathogens. Another type of antigen-presenting cell is dendritic
cells, which bridge the innate and adaptive immune responses.
If the innate immune response is unable to curb an infection, the adaptive immune response
becomes involved. Let’s take a closer look at how the adaptive immune system helps the
body fight viruses. The adaptive immune system includes lymphocytes
such as T cells and B cells, as well as antibodies. Viral fragments presented on MHC class I molecules
on the surface of infected cells attract cytotoxic T cells. These cells, also known as CD8+ T
cells, are able to kill infected cells. With their specific T cell receptors, cytotoxic
T cells interact with the antigen-loaded MHC complex. In response, the complex releases
cytotoxic factors that induce either cell lysis or apoptosis, that is, programmed cell
death of the infected cell. Macrophages then engulf the dead cell and release it as waste.
Let’s move on to the B cell response. B cells also fight viral antigens. However,
rather than targeting antigens and killing infected cells, B cells produce specific antibodies.
Antibodies are proteins that are produced in response to a specific pathogenic protein,
the antigen. Let’s take a look at this process:
Before antibodies are produced, B and T cells need to interact. The B cell needs to undergo
several steps to present the viral antigen on its surface.
First, the B cell receptor recognizes the viral antigen. The B cell then internalizes
the antigen and presents it on MHC class II molecules on the B cell surface.
Before T cell recognition can occur, CD4+ T cells, also known as T helper cells, need
to interact with viral antigens of the same specificity. The antigen is presented on the
surface of the dendritic cell by MHC class II molecules. This entire process is termed
priming and stimulates the maturation of the CD4+ T cells.
Finally, the B cell with the presented antigen binds to the T cell receptor on the CD4+ T
cell. This interaction is called linked recognition, and is the final step required to fully activate
the B cell. The activated B cell gives rise to long-lasting memory B cells and plasma
cells.
Another type of long-lasting immune cell is the memory T cell, a specialised T cell that
remains in the body after being produced during an innate immune response. Memory cells ensure
a swift and effective response when the body is exposed again to a specific virus, and
usually provide lasting protective immunity. Importantly, memory cells form the basis of
immunological memory, the ability of the immune system to recognize antigens after an initial
exposure and to mount a quick and efficient response in subsequent exposures. Immunological
memory provides the rationale for vaccination. Plasma cells also secrete antibodies specific
to the viral antigen encountered. So, antibodies developed in response to a
virus will eliminate that virus on subsequent encounters. There are several ways in which
antibodies help destroy viruses: First, antibodies can neutralize free virus
particles so that they’re unable to infect host cells.
Second, antibodies can mark free viruses for phagocytosis in a process called opsonization.
Third, antibodies can activate the complement system, also known as the complement cascade.
The complement system is made up of a series of proteins. It helps antibodies and phagocytic
cells to clear pathogens. Together, the series of proteins generate the membrane attack complex,
which is abbreviated as MAC. The MAC causes infected cells to lyse and die.
Fourth, antibodies can bind to infected cells, resulting in the activation of natural killer
cells. The antibody binds to the viral antigen on the target cell surface. Special receptors
on NK cells, called Fc receptors, recognize the bound antibodies. This binding signals
the NK cell to release cytotoxic factors that kill the target cell. This process is called
antibody-dependent cell-mediated cytotoxicity.
So, in short, the innate immune response comprises cellular and biochemical defense mechanisms
that the host uses immediately or shortly after exposure to the virus. The innate immune
response is present before infection. In contrast, the adaptive immune response is antigen-specific
and acquired, taking several days to endow protection. The immunological memory developed
in the adaptive immune response is long-lasting, sometimes even life-long. The practice of
vaccination is based on the development of immunological memory.