- Assist the immune system in building an immune response

- House of lymphocytes (B cell and T cell)

- B-cell lymphocytes become activated due to presence of antigen – release of antibodies

- T-cell lymphocytes responsible for cell mediated immunity and destruction of pathogens

Differential blood count is also used along with leukocyte count (WBC) to generate an absolute value for each type of white blood cells (eg, absolute neutrophil count, absolute lymphocyte count, or absolute eosinophil count), which usually gives more meaningful information than the percentage of each, since relative percentage can be misleading. Expressing absolute values are also useful for monitoring (eg, monitoring neutropenia during chemotherapy or bone marrow transplantation). ^[1] Using absolute values, conditions such as neutropenia, neutrophilia, lymphopenia, lymphocytosis, monocytopenia, monocytosis, eosinophilia, and basophilia can be identified, whichcanhelp differential diagnosis of patient’s underlying disorders. 

Differential blood count is not a part of complete blood count (CBC) but is interpreted together with CBC to help support or exclude a suspected diagnosis. For example, the presence of anemia along with thrombocytopenia with a low or high white blood cell count may suggest bone marrow involvement by leukemia

Source: Medscape

· Alcohol abuse

· Drug abuse, either intravenous or other (appears related to associated factors i.e. poor diet, use of infected/dirty needles, poor exercise, stress/depression)

· Medications (particularly the use of anti-cancer drugs, corticosteroids, and antibiotics)

· Radiation

· Exposure to certain environmental toxins, whether naturally occurring or from pollution. These include:

· Cigarette smoke

· Stress/Depression - Research shows that psychological stress can greatly increase your susceptibility to colds and other viral diseases, namely through an increase in serum corticosteroid levels

· Age - Ability of the immune system to respond is decreased at early and old age.

· Disease or medications (i.e. Diabetes, corticosteroids, immune suppressant drugs), causing constant exposure to infectious agents without natural defense (intact skin)

· Inadequate sleep at the Delta brain wave level.

· Lack of exercise as well as excessive exercise resulting in physiological stress

· Long-term weightlessness

· Diseases either infectious or other causing more depression on the immune system like:

o Cancer, and hematological malignancy (such as leukemia, lymphoma and myeloma) in particular.

o Diabetes Mellitus

o Cystic fibrosis

o Lupus Erythematosus

o Nephrotic syndrome

o Viral infections i.e. viral respiratory infections then allowing for bacterial pneumonia to develop.

o HIV

o Ulcerative colitis

o Bulimia (due to malnutrition, stress, depression).

o Sickle-cell disease.

o Liver disease/cirrhosis

o Cushing's syndrome

                                                             ii.      Elimination

Diseases can be eliminated locally without global eradication of the causative microorganism. In four of six WHO regions, substantial progress has been made in measles elimination; transmission no longer occurs indigenously and importation does not result in sustained spread of the virus. Key to this achievement is more than 95% population immunity through a two-dose vaccination regimen. Combined measles, mumps and rubella (MMR) vaccine could also eliminate and eventually eradicate rubella and mumps. Increasing measles immunization levels in Africa, where coverage averaged only 67% in 2004, is essential for eradication of this disease. Already, elimination of measles from the Americas, and of measles, mumps and rubella in Finland has been achieved, providing proof in principle of the feasibility of their ultimate global eradication. It may also be possible to eliminate Haemophilus influenzae type b (Hib) disease through well implemented national programmes, as experience in the West has shown.

Local elimination does not remove the danger of reintroduction, such as in Botswana, polio-free since 1991, with importation of type 1 poliovirus from Nigeria in 2004, and in the United States of America (USA) with measles reintroduced to Indiana in 2005 by a traveller from Romania.

For diseases with an environmental reservoir such as tetanus, or animal reservoirs such as Japanese encephalitis and rabies, eradication may not be possible, but global disease elimination is a feasible objective if vaccination of humans (and animals for rabies) is maintained at high levels.

 

                                                               i.      Efficacious vaccines protect individuals if administered before exposure. Pre-exposure vaccination of infants with several antigens is the cornerstone of successful immunization programmes against a cluster of childhood diseases. Vaccine efficacy against invasive Hib disease of more than 90% was demonstrated in European, Native American, Chilean and African children in large clinical studies in the 1990s. In the United Kingdom, no infant given three doses developed Hib disease in the short-term (boosters may be required for long-term protection), and recent postmarketing studies have confirmed the high effectiveness of vaccination of infants against Hib in Germany and pertussis in Sweden.

                                                             ii.      Many vaccines can also protect when administered after exposure – examples are rabies, hepatitis B, hepatitis A, measles and varicella.

 

c.       Mitigation of disease

  i.      Disease may occur in previously vaccinated individuals. Such breakthroughs are either primary – due to vaccine failure – or secondary. In such cases, the disease is usually milder than in the non-vaccinated. In a German efficacy study of an acellular pertussis vaccine, vaccinated individuals who developed whooping cough had a significantly shorter duration of chronic cough than controls. Such findings were confirmed in Senegal. Varicella breakthroughs exhibit little fever, fewer skin lesions and fewer complications than unvaccinated cases. Milder disease in vaccinees was also reported for rotavirus vaccine.

d.       Prevention of infection
                                                              i.      Many vaccines are primarily intended to prevent disease and do not necessarily protect against infection. Some vaccines protect against infection as well. Hepatitis A vaccine has been shown to be equally efficacious (over 90% protection) against symptomatic disease and asymptomatic infections. Complete prevention of persistent vaccine-type infection has been demonstrated for human papillomavirus (HPV) vaccine. Such protection is referred to as “sterilizing immunity”. Sterilizing immunity may wane in the long term, but protection against disease usually persists because immune memory minimizes the consequences of infection

  i.      Efficacious vaccines not only protect the immunized, but can also reduce disease among unimmunized individuals in the community through “indirect effects” or “herd protection”. 

                                                             ii.      “Herd protection” of the unvaccinated occurs when a sufficient proportion of the group is immune. The decline of disease incidence is greater than the proportion of individuals immunized because vaccination reduces the spread of an infectious agent by reducing the amount and/or duration of pathogen shedding by vaccinees, retarding transmission.

f.        Prevention of related diseases and cancer

i.      Vaccines will also protect against diseases related to the targeted disease. For example, in Finland, the USA and elsewhere, influenza vaccination has been found protective for acute otitis media in children, with a vaccine efficacy of more than 30%. Measles vaccination protects against multiple complications such as dysentery, bacterial pneumonia, keratomalacia and malnutrition.An enterotoxic Escherichia coli vaccine demonstrated protection against diarrhoea due to Salmonella enterica.

                                                             ii.      infective agents cause several cancers. Chronic hepatitis B infection leads to liver cancer. Vaccination against such pathogens should prevent the associated cancer as already observed for hepatocellular carcinoma. Reduction of the incidence of cervical cancer is expected with the use of HPV vaccines against serotypes 16 and 18, responsible for over 70% of the global cervical cancer burden, as reduction in precancerous lesions has been demonstrated in vaccinees.

-          Without this, T cells cannot recognise the antigen

-          The secretion of cytokines by APCs activated by antigen presentation that further activates antigen-specific T cells

-          This interaction between APCs and T cells is strongly influenced by a group of molecules called co-stimulators

-          The absence of co-stimulators leads to T-cell unresponsiveness

-          Processed antigen is presented to the T cells in the context of the MHC complex present on the surface of APCs

-          Most efficient APCs are the dendritic cells. 

-          These dendritic cells have high concentrations of MHC class I and II antigens, co-stimulatory molecules, and adhesion molecules on their surface

-          Dendritic cells on the skin – Langerhans cells = important role in immune defences, mobile, can capture antigen in the periphery and migrate to secondary lymph nodes where dendritic cells become mature and interact with naïve T cells

-          The follicular dendritic cells reside in the follicular germinal center (B-cell area) of a lymph node 

-          These cells have receptors for complement and immunoglobulins and their function is to trap immune complexes and feed them to B cells 

-          Closely associated with MHC class II molecules on the APC surfaces and thus activates B cells

●An increased total serum protein concentration

 and/or the presence of a monoclonal protein in the urine or serum

●Systemic signs or symptoms suggestive of malignancy, such as unexplained anemia

●Hypercalcemia, which is either symptomatic or discovered incidentally

The revised IMWG criteria allow, in addition to the classic CRAB features, three myeloma defining events (MDEs). The presence of at least one of these markers is considered sufficient for a diagnosis of multiple myeloma, regardless of the presence or absence of symptoms or CRAB features. Each of these markers has been shown in two or more independent studies to be associated with an approximately 80% or higher risk of developing myeloma-related organ damage within two years.

Recommended exam, tests, and imaging studies for the diagnosis of myeloma

1. History and Physical Examination

2. Routine Testing

3. Bone Marrow Testing: Obtain an aspirate plus trephine biopsy with testing for cytogenetics, fluorescent in situ hybridization (FISH) and immunophenotyping.

4. Imaging