Pathology and Immunology
Septicemia is a life-threatening disease that can affect all horses;
however, foals are very prone to illness when compared to adult horses.
Commonly, foals are considered neonates when less than seven days old
but in some studies foals are considered neonates until 30 - 60 days of
age (Marsh and Palmer 2001; Wilson and Madigan 1989). Normal foals are
very active and oscillate between nursing, sleeping, and playing. Foals
can become very ill rapidly (within hours), and as such prompt treatment
is necessary. At birth, foals are immunologically naive and depend on
two main methods of fighting infection, the innate and the adaptive
immune systems (Mealey and Long 2018). Due to the equine placental
structure (epitheliochorial, diffuse, microcotyledonary), no antibodies
are passed in utero and as such foals depend on adequate amounts
of colostrum intake for the antibodies needed for initial protection
(Madigan 2013a; Senger 2005). These antibodies act as the acquired
immune system until the foal is able to mount their own immune responses
to pathogens. The colostral antibodies also help to opsonize neutrophils
and make them more able to respond to infection (Mealey and Long 2018).
The initial antibodies ingested by the foal from the dam’s colostrum are
assessed by measuring immunoglobulin G (IgG) levels in the blood
(Madigan 2013a). Adequate levels of IgG are > 800 mg/dL and
this is considered “adequate passive transfer”. Levels below 800 g/dL
indicate complete or partial failure of passive transfer and make the
foal more susceptible to infection (Madigan 2013a). Once the foal has
absorbed immunoglobulins in the first 6 - 24 hours after birth they are
used to fight against environmental organisms that may cause infection.
Maternal, colostral-derived antibodies reach their lowest levels in the
foal between one and two months of age due to usage consumption but can
still interfere with a foal’s endogenous antibody production.
A foal will take weeks to months to develop a functional initial
acquired immune system (Barton 2006). Specifically, IgGa starts being
produced by nine weeks of age, but IgGb does not begin to rise until
after four months of age. The effectiveness of IgG protection is also
dependent on secondary signals from the inflammatory cascade which may
not be mature enough to respond properly before four months of age
(Mealey and Long 2018). The acquired (or adaptive) immune system is
mediated by activation of B and T cell lymphocytes and develops due to
exposure and recognition of the body to antigens. B cells are produced
in the bone marrow after a 3 day maturation process and recognize
antigens in solution or on cell surfaces. T cells are produced in the
thymus and respond to antigens that are associated with self-molecules
called major histocompatibility complex molecule, found on most cell
surfaces. These exposures create primed cells that can rapidly respond
when needed in the future by creating specific antibodies, cytokine, and
cell proliferation responses in the form of plasma cells, memory B
cells, CD4 T cells, or CD8 T cells (Mealey and Long 2018). This acquired
response takes weeks to “learn” each new organism and the complete
ability to respond to antigens in foals can take up to one year after
birth (Perkins and Wagner 2015). An adult-level immune response using
lymphoproliferation can be mounted starting at three months of age in
foals. Prior to that major, histocompatibility complex II presentation
may be compromised (Mealey and Long 2018). The innate immune system
requires weeks to months to develop into full function (Perkins and
Wagner 2015). Foals are born with neutrophils that are completely
functional at birth, however for full effectiveness they require
opsonization by colostral antibodies and as such may have reduced
killing ability in the first two weeks of life (Mealey and Long 2018).
Cell-based molecules such as Toll-like Receptors recognize molecular
patterns on the bacterial cell wall or viral structure and lead to an
intracellular cascade which in turn signals the adaptive innate response
as well as releasing pro-inflammatory cytokines. These cytokines
stimulate the production of acute phase proteins from the hepatocytes,
cause clinical signs of inflammation, and activate complement. The
complement cascade activation leads to neutrophil chemotaxis, activation
of mast cells, neutrophil degranulation, and the release of reactive
oxygen species (ROS) from neutrophils. These ROS play a key role in
bacterial and viral killing (Mealey and Long 2018). Band neutrophils are
produced when the granulopoiesis in the bone marrow is not sufficient to
keep up with the tissue demand and the cells are released prematurely
(Webb and Latimer 2011). Band cells, which are immature neutrophils,
have a longer half-life but are less effective against infectious
organisms due to decreased phagocytosis and ROS production (Sheats
2019).
The adaptive immune response uses specific interactions between antigens
and antigen-specific receptors on lymphocytes. In foals, it is
incomplete through the first year of life, but an attempted immune
response is seen to pathogens starting at three months of age. B and T
cell lymphocytes have specific receptors that interact with cell
surfaces either alone or in conjunction with the host’s cell receptors
to create antibodies against specific pathogens (Mealey and Long 2018).
These lymphocytes have memory, which allows them to rapidly respond to
previously recognized insults. If adequate, the immune system is able to
eradicate the infecting organism without becoming uncontrolled. When
there is an inadequate (whether excessive or deficient) response, the
uncontrolled immune response can turn against itself or allow an
infection to flourish. Foals have been shown to have a reduced
interferon Ɣ levels in the prenatal period. This makes them more
susceptible to intracellular organisms as interferon Ɣ assists in the
normal major histocompatibility complex response of T cells. (Mealey and
Long 2018).