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).