Innate vs Adaptive Immunity

By Eva Amsen

The immune system that protects our bodies from disease can be roughly divided into two separate
components: the innate immune system and the adaptive immune system. The innate immune system
is quick to kick into action, but it acts equally on all foreign material it encounters. The adaptive immune
system is slower but more specific to its target – it can distinguish antigens with only minor differences.

The innate and adaptive immune systems complement each other very well, and researchers are still
learning how the two interact. For example, recent studies have shown that both systems play a role in
vaccine response, autoimmunity and immunotherapy.

In this list we explore six key areas that highlight differences and similarities of the innate and adaptive
immune system.

Cell types of the innate and adaptive immune system

Cells of the innate immune system include:

• macrophages
• dendritic cells
• mast cells
• natural killer cells
• granulocytes
– eosinophils
– basophils
– neutrophils

Together, these cells form a first response to any infection. They act by quickly targeting and removing
foreign material.

The adaptive immune system includes fewer cell types, but their functions are a lot more specialized. T cells
express T cell receptors on their surface, as well as either one of CD4 or CD8 glycoproteins. CD8+ T cells are
cytotoxic, killing their targets. CD4+ T cells are helper cells, which, among other roles, influence the activation

INNATE VS ADAPTIVE IMMUNITY 1

of B cells to produce antibodies against specific antigens, and differentiation of B cells into memory B cells
which make it possible for the immune system to recognize the same infection if it happens again.

The cells of the innate and adaptive immune systems come from two different origins. Myeloid progenitor
cells are the source for most of the cells of the innate immune system, whilst all cells of the adaptive
immune system originate from lymphoid stem cells.

The only exceptions are three cell types that are not strictly part of the adaptive immune system, despite
being derived from lymphoid stem cells. These are natural killer (NK) cells, natural killer T cells and γδT cells.
Of these three, NK cells are part of the innate immune response, whilst the other two share characteristics
with both innate and adaptive systems.

Immune response
The immune response is a combination of both the innate and the adaptive immune system.1 Upon
encountering an infection, the first line of defense is the innate immune system.

Mast cells in skin and endothelial tissue activate inflammatory pathways when they detect pathogens. At the
same time, macrophages and granulocytes respond by phagocytosing the foreign body.

The innate immune response is also supported by the complement cascade. Complements are proteins
circulating in blood and in the fluid between cells in tissues. Once activated, they initiate a signaling cascade
that triggers mast cell activation, attracts macrophages and neutrophils, promotes inflammation, and
destroys micro-organisms. They also activate cells to release cytokines.

Cytokines are produced by a range of different cells, including immune cells, and act as a communication
signal between cells. In immune signaling, cytokines include for example interferons, which act as
antiviral agents, and chemokines, which control cell migration. Through this mechanism, mast cells and
macrophages recruit other immune cells to the site of infection.

Meanwhile, natural killer cells stop the spread of disease by destroying infected host cells. These responses
all rely on the innate immune system’s ability to distinguish our own cells from foreign cells, for example by
detecting pathogen-associated molecular patterns (PAMPs) on the surface of microbes.

When dendritic cells and macrophages encounter a pathogen, they initiate a process of phagocytosis, after
which they display pathogen-specific antigens bound to the major histocompatibility complex (MHC) class II
on the surface of their cells.

This process then activates the adaptive immune system, as CD4+ T cells recognize these MHC class II-
bound foreign antigens. This activates the T cells and encourages proliferation by clonal selection to expand
the pool of T cells that all recognize the same antigen through identical T cell receptors.

B cells initially recognize antigens via antigen receptors on their cell surface. They then internalize the
antigen and break it down into peptides which the cell displays on the external cell membrane, bound
to MHC class II. When CD4+ T cells recognize the antigen displayed on B cells, they release cytokines to
stimulate the B cell to produce antibodies against the specific antigen they’ve been exposed to.

Whilst the MHC class II complex on dendritic cells, macrophages and B cells responds to extracellular
antigens (such as PAMPs), many other cell types have an MHC class I complex, which display intracellular
antigens, such as those from viruses inside the cell. When these cells are infected by a virus, they present

INNATE VS ADAPTIVE IMMUNITY 2

viral antigens on the MHC class I complex. This is recognized by CD8+ cytotoxic T cells, that directly target
and kill infected host cells that present the antigen to limit further spread of the disease.

Autoimmunity and autoimmune disorders

The immune system is fine-tuned to detect foreign threats, but leave the body’s own, healthy cells alone.
However, this mechanism can go off-course, and cause the body to attack its own tissues, leading to
autoimmune disorders such as rheumatoid arthritis, type I diabetes, or celiac disease.2

In the normal development of T cells, there will be some that have the capability to detect the body’s own
cells. However, T cells that display this kind of autoimmunity are usually eliminated from the system. In
autoimmune disorders, these cells remain in circulation and continue to respond to the body’s own cells as
if they were a threat.

Even though autoimmune reactions appear to be mostly limited to the adaptive immune system, recent
research suggests that innate immunity also plays a role in autoimmune diseases.3 For example, there is a
subset of B cells that more closely resembles the innate immune system than the adaptive system. Their
response is not as selective and strong as that of most B cells, but they’re much faster. Some produce
low affinity antibodies; others resemble NK cells. Now, it appears that innate-like B cells may be partly
responsible for auto-inflammatory effects.4

Vaccines
Vaccines take advantage of the specificity of the adaptive immune system, and in particular memory B cells
and memory T cells that make it possible to maintain long-term immunity to antigens. But immunologists
are now starting to recognize that vaccination also influences the innate immune system.

For example, in one study researchers compared two established vaccines against human papillomavirus
(HPV).5 Both vaccines target similar antigens, but they are produced in different ways and contain different
adjuvants. When researchers measured cytokine levels related to the early innate immune response, they
found a notable difference between the two vaccines, suggesting that the innate immune system may play a
role in mediating the effect of these vaccines.

The innate immune system is also implicated in the development of non-specific effects of the bacilli
Calmette-Guérin (BCG) vaccine, which protects against pathogens other than the targeted antigen.6
Researchers have also proposed targeting the innate immune system in the development of new
tuberculosis vaccines.7

Understanding the role of the innate immune system in the vaccine response is a relatively new area of
research, so many questions have not yet been answered. What is clear, however, is that the adaptive
immune system isn’t the only route to protection after vaccination.

Immunotherapy
Immunotherapy is gaining traction as a treatment for certain cancers. The therapy works by targeting
“immune checkpoints”, usually receptors like CTLA-4 or PD-1 on T cells. These receptors receive the signal
that a cell is healthy and does not need to be attacked. However, if the receptors are blocked through
immunotherapy, they then enable the immune system to recognize and target tumor cells.8

INNATE VS ADAPTIVE IMMUNITY 3

However, focusing only on T cells does not always make for an effective immunotherapy treatment. For
ovarian cancer and breast cancer, for example, researchers are now exploring ways to target both the
adaptive and innate immune systems, to allow for more efficient therapies.9,10 In both those examples,
a therapy that targeted both PD-1 and cells that inhibit the innate immune system appears to be more
effective at killing cancer cells than one that only targets the adaptive immune system.

Genetics and environment

The cells of the immune system need to carry out many diverse and complicated tasks that rely on
maintaining different innate cell populations to respond quickly, maturing naive B and T cells into
specialized cells, and forming memory cells to deal with recurring infections. Balancing these intricate
functions of the immune system is shaped by both genetic factors and environmental factors.

For example, people who live together have a more similar immune profile to each other than to people
who do not live with them, suggesting that environment plays a big part.11 On the other hand, genetics
appears to influence the levels of specific immune cells that people may have.12

Although both genetic and environmental factors play a role in maintaining the immune system, it
appears that they don’t affect the innate and adaptive branches of the immune system in equal manners.
By studying sets of adult twins, researchers found which aspects of the immune system are shaped by
genetics and which were influenced by environment.13 They learned that overall, distinctive differences in
the adaptive immune system were mostly determined by genetics. On the other hand, the innate immune
system was largely shaped by environmental factors such as diet or exposure to pathogens.

References

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2). https://doi.org/10.1186/s13223-018-0278-1
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Investigation, 125(6), 2228–2233. https://doi.org/10.1172/JCI78088
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