IMMUNODEFICIENCY
DISORDERS
INTRODUCTION
• As expected in any complex multicomponent system, the immune
system can be subject to failures of some or all of its parts.
• These failures can have severe or life threatening consequences
• Immunodeficiency is the condition where the immune system fails to
protect the host from disease causing agents due to certain defects.
• This can be due to abnormalities of specific or non specific
components
The B- The T-
• The deficiencies can be either congenital or lymphocyte lymphocyte
acquired (PRIMARY or SECONDARY) system system
• Immunodeficiency can occur in any of the 4
components of the immune system
The The
Phagocytic Complement
system system
PRIMARY IMMUNODEFICIENCY
• Immunodeficiency resulting from an inherited genetic or
developmental defect in the immune system is called a primary
immunodeficiency
• In such a condition, the defect is present at birth, although it may not
manifest until later in life
• These diseases can be caused by defects in virtually any gene
involved in immune development or function, innate or adaptive,
humoral or cell mediated, plus genes not previously associated with
immunity
• Over 400 different types of primary, or inherited immunodeficiency have been identified
• Theoretically, any component important to immune function that is defective can lead to some form of
immunodeficiency.
• These are usually called Primary Immunodeficiency Disorders ( PIDs)
• Most of these disorders are believed to be monogenic ( caused by a single gene defect)
• Over 100 primary immune deficiency diseases have been identified in humans.
• Most primary immune deficiencies become apparent at about 6 months of age, when the maternally
derived antibodies that entered the fetal circulation in utero begin to disappear and the infant becomes
dependent on his or her own immune system .
• Primary immunodeficiency diseases vary in severity from mild to nearly fatal
• The disease manifestation of a particular gene disruption depend on the specific immune system
component involved and the severity of the disruption.
• There are several categories of PIDs depending on the component of immune system affected
CLASSIFICATION OF PIDs
• Primary immunodeficiencies are classified BROADLY by the main component of the immune system that is
deficient, absent, or defective:
• These classes are:
Humoral immunity
Cellular immunity
Combined humoral and cellular immunity
Phagocytic cells
Complement proteins
• They can be further sub-classified more specific components
CLASSIFICATIONS OF PIDs
Combined T and B–cell immunodeficiencies
Predominantly antibody deficiencies
Other well defined immunodeficiency syndrome
Diseases of immune dysregulation
Congenital defects of phagocyte number, function, or both
Defects in innate immunity
Autoinflammatory disorders
Complement deficiencies
Phenocopies of primary immune deficiencies
• Important signs that may indicate a PID include:
Recurrent, unusual or difficult to treat infections
Poor growth or loss of weight
Recurrent pneumonia, ear infections or sinusitis
Multiple courses of antibiotics or IV antibiotics necessary to clear infections
Recurrent deep abscesses of the organs or skin
A family history of PIDD
Swollen lymph glands or an enlarged spleen
Autoimmune disease
SECONDARY IMMUNODEFICIENCY
• Secondary immunodeficiency also known as acquired immunodeficiency, is the loss of immune function
that results from exposure to an external agent, often an infection.
• Secondary immunodeficiencies (SID) are not genetic, but are caused by environmental or external
exposures.
• SIDs are more common and can be resolved by treating the causative factor.
• SIDs are caused by many conditions, agents or factors
• Causes of SIDs include:
Systemic disorders (eg, diabetes, undernutrition, HIV infection)
Immunosuppressive treatments (eg, cytotoxic chemotherapy, bone marrow ablation before transplantation,
radiation therapy)
Prolonged serious illness
Malnutrition,
Aging,
Many types of cancer
Radiation,
Chemotherapy,
Burns,
Etc
DRUGS
• Drugs can cause reduced functioning of the immune system. This is known as immunosuppression and can
have both beneficial and adverse effects.
• Immunosuppression is a common side-effect of most chemotherapies used in cancer treatment.
• Immunosuppressive drugs are used in the prevention of transplant rejection, where medication is required
to suppress the transplant recipient’s immune system and prevent it from targeting the transplanted tissue.
NUTRITION
• Traces elements, iron, selenium, copper and zinc are important in immunity.
• Lack of these elements can lead to diminished neutrophil killing of bacteria and fungi, susceptibility to viral
infections and diminished antibody responses.
• Vitamins A, B6, C, E and also folic acid are important in overall resistance to infection.
• Carotenoids are antioxidants like vitamin C and E and can enhance NK cell activity, stimulate the production
of cytokines and increase the activity of phagocytic cells.
AGING
• Some decrease in immunity occurs with aging.
• For example, in older adults, the thymus tends to produce fewer naive T cells; thus, fewer T cells are available to
respond to new antigens.
• The total number of T cells does not decrease but these cells can recognize only a limited number of antigens.
• Also, helper T cells may be less likely to signal B cells to produce antibodies.
• The number of neutrophils does not decrease, but these cells become less effective in phagocytosis and
microbicidal action.
MALNUTRITION –
• Protein-calorie malnutrition is the biggest global cause of SIDs
• T cell numbers and function decrease in proportion to levels of protein deficiency, which leaves the patient
particularly susceptible to diarrhoea and respiratory tract infections.
CHRONIC INFECTIONS –
• There are a number of chronic infections which can lead to SID disorders, the most common of which is
acquired immune deficiency syndrome (AIDS), resulting from HIV infection.
• Many types of cancer, particularly those of the bone marrow and blood cells (leukemia, lymphoma, multiple
myeloma) cause SIDs
• Chemotherapy treatments can cause a secondary immunodeficiency called neutropenia.
• In leukemia and multiple myeloma, cancerous immune cells crowd out the normal stem cells of the bone
marrow.
• These abnormal cells reduce the number of B-cells and lead to hypogammaglobinemia, another type of
secondary immunodeficiency.
HIV/ AIDS
• HIV attacks certain cells in the immune system and prevents them from carrying out their proper functions
against microbes.
• When the immune system is sufficiently weakened, infected people catch atypical and severe infections.
This is then called the Acquired Immunodeficiency Syndrome, or AIDS.
• The virus attacks CD4+ T cells, a type of white blood cell that plays a critical role in preventing infection, and
gradually depletes their numbers.
• Once the T cell count is less than 200 cells per ml of blood, symptoms of AIDS begin to manifest and the
patient is at high risk of recurrent infections that will eventually lead to death.
• Patients with acquired immunodeficiency syndrome (AIDS) present with opportunistic infections caused by
certain bacteria, viruses, fungi, and protozoa.
• AIDS patients also have a high incidence of tumors such as lymphomas, which may be the result of a failure
of immune surveillance.
• Anti-viral therapies, such as the HAART regimen (Highly Active Antiretroviral Therapy), allow the T cell
population a chance to recover and resume normal function.
• However, these drugs must be taken every day for life as they are not curative
