So named as they were initially found in the Bursa of Fabricius, B cells produce antibodies and are associated with humoral immunity (T cells are part of the cell-mediated immune response), and are an integral part of the adaptive immune system. They represent 20-30% of circulating lymphocytes.
Basophils are derived from the same stem cell line as mast cells and while they are similar to mast cells, they are not identical (they are thought by some to be immature mast cells). They are the least common of all the leukocytes, are a similar size to neutrophils and eosinophils and are characterised by the large number of basophilic staining granules in their cytoplasm. They are present in the circulation but rarely found in tissue.
Mature B cells that undergo stimulation by an antigen undergo class switching, and differentiate into either plasma or memory cells. In the paracortex region of the lymph node binding to MHC II in the presence of IL-4 produced by the CD4+ T cells (TH2 type) causes the B cells to differentiate; most will become plasma cells, however a small number will become memory cells. Follicular dendritic cells present in the germinal centers of peripheral lymphoid organs can absorb intact antigen onto their surface to present to B cells to stimulate differentiation.
Blood cells develop in the bone marrow from a common stem cell in the process known as haematopoiesis. Once mature, cells are divided into groups that reflect their morphological and functional characteristics including the erythrocytes, or red blood cells, the granulocytes, the agranulocytes and the megakaryocytes.
It is important that all aspects of haemostasis can be independently evaluated. This will help to identify the phase affected and to pinpoint what the abnormality is. There are tests available to assess primary haemostasis, secondary haemostasis and fibrinolysis.
Complement is so called because it complements the function of antibody. It is a triggered enzyme cascade and there are more than 20 different proteins in the complement cascades, with most being enzymes or pro-enzymes. It can be activated by both the innate and adaptive immune systems and is one of the main innate protective mechanisms of invertebrates. Due to its destructive potential the complement system is heavily regulated but when activated it works largely by forming pore complexes as well as triggering acute inflammation and by promoting phagocytosis by macrophages and neutrophils.
Eosinophils are a similar size to neutrophils, have a bilobed nucleus and are characterised by the large eosinophilic granules present in their cytoplasm. Produced in the bone marrow they migrate into circulation briefly before moving into tissue where they survive for around six hours. The proportion of eosinophils circulating depends on the state of the animal. Normally numbers are very low but will rise considerably during a parasitic infection or allergic reaction.
Also known as red blood cells (RBCs). Erythrocytes deliver oxygen to, and remove carbon dioxide from tissues. Erythrocytes are derived from the stem cell (CFU-GEMM) and formed in a process known as erythropoiesis.
Erythrocytes contain no nucleus and are thus only produced from stem cells. During the fetal stage production is in both the liver and spleen however production is transferred to the bone marrow (red marrow) in the final stages of gestation. Initially erythropoiesis occurs in all bones, however after puberty production is limited to membranous bones (ribs, vertebrae, pelvic bones etc.) as the long bones contain adipose tissue in place of red marrow.
Transfer of passive immunity in the bovine neonate occurs solely through maternal colostrum. This is in contrast to humans where placental transfer of immunity via specific Fc receptors is the predominant mechanism. However, inadequate transfer of immunity is a relatively commonly diagnosed problem affecting young stock. This is particularly the case in modern Holstein dairy herds, where large milk yields dilute the antibody concentration in the colostrum meaning relatively more must be consumed to have the same immunity transferred. Due to the lower yields and possibly other genetic reasons, this tends to be less of a problem in suckler herds.
Haematopoiesis is also known as haemopoiesis or hemopoiesis and describes the process of blood cell formation. All blood cells are derived from the initial pluripotent stem cell (PPSC) which gives rise to colony forming units (CFUs). These CFUs further differentiate to give rise to their final stage of development where they become the various forms of blood cells or those cells which migrate from the circulation into tissues, such as mast cells and macrophages.
Heterophils are the most abundant granulocyte in most avian species and occur alongside lymphocytes, monocytes, eosinophils and basophils in avian blood. These cells are also found in some reptile and mammalian species.
Lysozyme is one of the major bactericidal agents in secretions and particularly helps to protect vulnerable sites such as the eyes and nasal passages. The lysoszyme exerts bactericidal effects by digesting bacterial cell walls. The complement system is a group of about 30 proteins within the body fluids of all vertebrates and some invertebrates. The main functions of complement are to promote phagocytosis or causes lysis of an invading organism.
IgA is present at low concentrations in plasma, and has minimal function inside the body. However, it is specially adapted for action at mucosal surfaces and as such, is present in high concentrations in mucosal secretions and in colostrum (and milk). In many species (dogs, cats and pigs), it is the major antibody in
IgD is present in ruminants, pigs, dogs and rodents but has not been identified in horses, cats, rabbits and chickens. It is mainly expressed on the surface of B-cells i.e. it is never secreted.
Unlike IgM, IgG and IgA, IgE does not function as a soluble antibody, with binding to Fc? receptors required before it can bind to the target antigen, and is found in low levels in blood plasma. Like IgA, it is produced by plasma cells and is mainly localised to mucosal surfaces.
IgG is the major antibody in blood plasma, and constitutes at least 80% of all antibodies in the body. It is the smallest immunoglobulin, so can readily leave the blood plasma and enter tissues. They can also cross the placenta, providing adaptive immunity to the foetus when the mother is under attack. IgG is also present in breast milk.
IgM is the primordial antibody and, although a monomer, is secreted as a pentamer (five monomers joined by disulphide bonds with two monomers joined by a J chain). This gives it ten identical antigen binding sites although IgM usually has relatively low affinity for its antigen. Its heavy chain is type mu (ľ).
Also called antibodies, Immunoglobulins (Ig) are the soluble form of B cell receptors (BCR) released by plasma cells after they have been activated. Immunoglobulins have to bind to a number of different antigens in a variety of environments and as such there are several different immunoglobulin classes. Each class has an optimum environment of action.
Both the innate and adaptive immune systems use receptors to recognise foreign organisms. The innate immune system uses pattern recognition receptors which acts as an early warning system. The adaptive immune response is highly specific for each organism, as B and T cells have specialist surface immunoglobulin receptors which detect specific antigens on foreign pathogens. The Innate immune system is the body's first barrier of defence to infection. It relies on an older, more generic, and faster acting set of tools than the adaptive system. While the adaptive system is essential for a specific response to infection, it is ultimately the innate system that conquers foreign attackers through means of phagocytosis.
The simplest way to avoid infection is to prevent microorganisms gaining access to the body. The skin has an external coating of dead cells (cuticle) that, when intact, is impermeable to most infectious agents as very few pathogens are capable of penetrating the thick stratified squamous epithelium of the skin (and lower urinary tract).
Pathogens can invade the body if a breach occurs in the barriers formed by the skin and mucus membranes, for example a wound, they must be detected and destroyed by cellular and humoral means. The cells involved in the cellular response to a wound are mast cells, macrophages, granulocytes, and monocytes.
The innate response to bacterial infection lies in its first-response role of detection of a foreign organism. By using the tools of Pattern-Recognition Receptors (PRRs), the innate response flags up problems while the adaptive response gets itself organized.
Because viruses invade host cells to take over a host's cellular machinery, the innate system has a more difficult time detecting viruses as foreign agents. However, there is a give-away element of the viral attack that the innate system can recognize: the double-stranded RNA (dsRNA) produced by a virus in its replication phase. Because mammalian cells only ever produce single-stranded RNA, the presence of dsRNA signals a foreign intruder. dsRNA can be detected by TLR-3R on the cell surface or intracellularly by the presence of dsRNA-dependent protein kinase.
Leukopoiesis is the process of formation of leukocytes (white blood cells) from stem cells in haematopoietic organs. Leukocytes develop from either multipotential myeloid stem cells (CFU-GEMM) or multipotential lymphoid stem cells (CFU-L).
Macrophages are large, round cells that contain a central round nucleus and have abundant clear, often vacuolated, cytoplasm. Macrophages acts as sentinel cells; they have a role in destroying bacteria, protozoa and tumour cells, and release substances that act upon other immune cells. They are also responsible for clearing dead and damaged cells and tissue through the process known as efferocytosis. Macrophages are phagocytic, long lived and are found throughout the body.
T-cells rely on Major Histocompatability Complexes (MHC), which are molecules manufactured within cells for the purpose of presenting antigen fragments so that they can be detected by the immune system. MHC has evolved to form two classes for antigen presentation: MHC I presents digested fragments from antigen in cellular cytoplasm, and MHC II presents digested fragments from antigen in the tissue fluid (extracellular). MHC I tends to bind slightly smaller peptides (~9 amino acids) than MHC II (~15 amino acids).
Mast cells are derived from the same stem cell line as basophils and while they are similar to basophils they are not identical. Mast cells are found in connective tissue and are larger than other leukocytes at 15-20ľm. They have cytoplasm containing a high number of large, intensely staining basophilic granules which mask the nucleus.
Monocytes are the largest leukocytes. They have a large indented nucleus, few granules and constitute about 5% of circulating leukocytes. Monocytes are precursors to a number of cells that make up the mononuclear phagocytic system. Developing in the bone marrow, monocytes migrate into the circulation where, after approximately three days, they migrate into tissues and differentiate.
NK cells can be classified as lymphocytes because they are capable of recognising antigen, however they are more often associated with the innate immune response. They target cells by monitoring MHC production, which is expressed by healthy cells to present antigen to T-cells. Low MHC levels can be used as a marker for a cell whose machinery is compromised by a replicating virus. When MHC levels drop, it acts as a danger signal to the NK cells, which then release enzymes to kill the infected cells.
Neutrophils represent up to 70% of all leukocytes in the blood stream (in humans there are approximately 4.4 million neutrophils / millilitre of blood) and are distinguished by their irregular multi-lobed nucleus and indistinct granular appearance. They are 10-12ľm and circulate in the blood for minutes to hours (average 6-8 hours) and lasting for 1-2 days in tissue. Although the most abundant leukocyte in the blood, the vast majority of neutrophils are found in the bone marrow (5x more) mostly as functionally immature precursor cells, although this varies between species with mice having a large pool of functional neutrophils in their bone marrow.
Phagocytosis is a very primitive system of defence against infection, having even been shown to exist in invertebrates and single cell organisms. The discovery was made in starfish larvae by Elle Metchnikoff who subsequently won the Nobel Prize for Medicine or Physiology in 1908. The process of phagocytosis itself is a form of endocytosis (cell eating), with vesicular internalisation being the method of removal of pathogens and dead cells (those that have undergone apoptosis, or Programmed Cell Death). This internalised vesicle is referred to as the "phagosome".
The innate immune system recognises components of pathogens which are intrinsically foreign (i.e. not present on normal mammalian cells), such as Lipolysaccharides, Peptidoglycans and D-isoform amino acids.
T cells are so named as they differentiate in the thymus. They are long lived and are involved in cell mediated immunity. They represent 60-80% of the circulating lymphocytes and all express the markers CD2, CD3 and CD7 as well as having T cell receptors (TCR). Each T cell has 30,000 TCRs each of which is identical and recognises antigens and major histocompatability complex (MHC) II.
T cells are long lived and are involved in cell mediated immunity. Functionally they are divided by the expression of CD4+ or CD8+ markers. CD4+ T helper cells recognise antigens bound to MHC II complexes and are involved with the control of intracellular and extracellular pathogens; they can interact with CD8+, NK and dendritic cells or with B cells. Cytotoxic CD8+ T cells recognise the MHC I complex and destroy infected or neoplastic cells.
Thrombocytes are small anuclear fragments of megakaryocytes. They are membrane bound portions of the megakaryocyte cytoplasm and have a finely granular cytoplasm; they are much smaller than other blood cells at 2-3ľm and have a lifespan of around 10 days in the circulation.
As with erythrocytes, thrombocytes are derived from multipotential myeloid stem cells (CFU-GEMM). In the bone marrow CFU-GEMM cells differentiate into the megakaryocyte precursor cell the megakaryocyte CFU (CFU-Meg), under the influence of cytokines CFU-CSF and IL-3. Unlike other blood cells which undergo mitosis in the first few developmental stages, once the CFU-GEMM has differentiated into the CFU-Meg there is no further mitosis. The CFU-Meg then develops into the megakaryoblast.