TOPIC: INNATE IMMUNITY

Key Knowledge:
• The innate immune response including the steps in an inflammatory response and the characteristics
and roles of macrophages, neutrophils, dendritic cells, eosinophils, natural killer cells, mast cells,
complement proteins and interferons
• The role of the lymphatic system in the immune response as a transport network and the role of
lymph nodes as sites for antigen recognition by T and B lymphocytes

INNATE IMMUNE SYSTEM

The second line of defence against infectious disease is the innate immune system, which is non-specific:
• It does not differentiate between different types of pathogens (it does not recognise antigens)
• It responds to an infection the same way every time (i.e. it has no immunological memory)

The principal components of the innate immune system include phagocytic leukocytes, the inflammatory
response, complement proteins, cytokines and fever.

PHAGOCYTOSIS
Certain types of white blood cells (leukocytes) can engulf foreign bodies.
These phagocytes are non-specific, but can detect generic characteristics
called pathogen-associated molecular patterns (PAMPs). After infected
tissues release chemotactic chemicals to recruit phagocytic leukocytes,
the phagocyte will engulf the pathogen by surrounding it with cellular
extensions (pseudopodia) and internalising it within a vesicle. The vesicle
is then fused to the lysosome and the pathogen is digested. The antigenic
fragments from the pathogen may then be presented on the surface of
the phagocyte in order to stimulate the third line of defence (adaptive).
Neutrophils are short-lived phagocytes that respond rapidly to infection,
while monocytes (macrophages) are longer lived and capable of sustained
action. Finally, a dendritic cell is a type of phagocyte that is particularly
suited to the role of antigen presentation (more so than macrophages).

COMPLEMENT PROTEINS
Complement proteins are a group of antimicrobial chemical agents that are produced in an inactive form
that circulates within the bloodstream. In response to immune activation, a cascade of reactions will ensue
that help to protect the body from infection. Complement proteins function in a variety of ways:
• Chemotaxis: They can function as chemical signals to attract the phagocytes to sites of infection
• Opsonisation: They will coat pathogens to enhance their identification by the phagocytic leukocytes
• Membrane attack: They will form a porous complex in a bacterial cell wall, causing the cell to rupture
• Inflammation: They can intensify the inflammatory response to improve phagocyte recruitment

While complement proteins are part of the innate immune system, they can also be activated by specific
antibodies that are generated as part of the adaptive immune response.
INFLAMMATION
The inflammatory response is a non-specific mechanism by which the body improves leukocyte access to
sites of infection. When tissue damage occurs, mast cells (localised) or basophils (circulating) release a
chemical called histamine. Histamine causes local vasodilation and increased capillary permeability to
improve the recruitment of white blood cells to the damaged region. While inflammation is necessary to
allow phagocytes to access infected tissue, there are unavoidable side effects. Increased blood flow causes
redness and heat, while increased permeability releases fluids that cause swelling and tenderness (pain).

Vasodilation (blood flow) Capillary Permeability

Causes redness and heat Causes swelling and pain

CYTOKINES
Cytokines are proteins that are released from white blood cells (leukocyte) and function to regulate
immune activity. Cytokines are used to activate lymphocytes in response to pathogenic entry and also
increase the resistance of surrounding body cells to infection. For example, interferon is released from
virally-infected cells and functions to recruit natural killer cells and reduce susceptibility of neighbouring
cells to infection by activating endogenous antiviral agents.

FEVER
A fever is an abnormally high temperature associated with infection. Fevers may help to combat infection
by reducing the growth rate of microbes. It may also increase the metabolic activity of body cells and
activate heat shock proteins to strengthen the immune response. Fevers are triggered by the release of
prostaglandins, which stimulate the hypothalamus to raise the core body temperature. Up to a certain
point a fever may be beneficial, but beyond a tolerable limit it can cause damage to the body’s own cells.

LYMPHATIC SYSTEM
Node
The lymphatic system is a secondary transport system that functions to
drain fluid from all around the body. The fluid within this system is called
lymph and is rich in white blood cells. The lymphatic system functions to
filter the fluid in the body and remove pathogens to prevent infections.
When a phagocytic leukocyte engulfs a pathogen and become an antigen
presenting cell, it will be transported to the lymphatic system in order to
present the antigenic fragment to lymphocytes (adaptive immune cells).
These lymphocytes are produced by primary lymphoid organs (e.g. bone
marrow) and reside in secondary lymphoid organs (i.e. lymph nodes). The
lymphatic system therefore functions as an important link between the
innate and adaptive immune responses. Artery Vein
TYPES OF IMMUNE CELLS
There are a variety of white blood cells (leukocytes) that are involved in coordinating an immune response:

NEUTROPHILS MONOCYTES

Most abundant type of leukocyte and functions Monocytes are also involved in phagocytosis –
as the first responder to a microbial infection they are slower to respond but are longer lasting
Neutrophils destroy pathogens via phagocytosis Unlike neutrophils, monocytes are involved in
but are not involved in antigen presentation antigen presentation (link to the adaptive system)
They are short-lived with a circulating life span of Monocytes include macrophages and dendritic
less than a day (forms pus when destroyed) cells (specialised for antigen presentation)

EOSINOPHILS BASOPHILS / MAST CELLS

Function as the primary responder to large Release the chemical histamine to initiate an
multicellular parasites (e.g. helminths) inflammatory response (e.g. allergic reactions)
Do not phagocytose, but instead release chemical Mast cells and basophils are similar, but mast
products that perforate cell membranes cells are localised while basophils will circulate

LYMPHOCYTES NATURAL KILLER CELLS

Are responsible for the adaptive response (will Natural killer (NK) cells are a type of non-specific
specifically target the antigens on pathogens) lymphocyte (do not target particular antigens)

B cells produce antibodies, while TC cells target NK cells respond to interferon release and will
intracellular pathogens (cancers and viruses) target and destroy virally-infected or cancer cells

Helper T cells (TH) reside in the lymph nodes and They function in a manner that is analogous to
release cytokines to activate the lymphocytes cytotoxic T cells (but are non-specific in action)

IMMUNE CELLS ANALOGY

Neutrophils are like street cops (first responders), while monocytes are longer lasting (durable riot police).
Eosinophils deal with larger pathogens by releasing chemicals (like fumigators), while mast cells / basophils
trigger inflammatory responses (firemen). Natural killer cells are responsible for compromised tissues (like
a bomb disposal technician), while lymphocytes target specific pathogens (as well-trained special forces).

INNATE (NON-SPECIFIC) IMMUNE RESPONSE ADAPTIVE RESPONSE

Neutrophil Eosinophil Basophil Monocytes Natural Killer Lymphocytes (B + T)

Street cop Fumigator Fireman Riot police Bomb disposal Special forces soldiers