Immunodeficiency: The 2 Types of Important Immunodeficiency Disorders

SCID is a Primary Immunodeficiency Disorder

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Immunodeficiency is a situation where the immune system is unable to mount enough immune response to clear attacking antigens. This defect makes people having them become vulnerable to nearly all types of infections.

Scientists have established an interesting relationship between immunodeficiency and autoimmunity. Approximately 25% of all people suffering from immunodeficiency also have autoimmunity. For instance, this has at least been found to be the case among people suffering from immune thrombocytopenia.

Immunodeficiency Analogy

To better understand immunodeficiency compared to hypersensitivity and normal immune response, we shall employ a simple analogy here. When doing mathematics dealing with integers, you use a number line.

At the center of the number line, the line is zero, moving to the right are higher and higher positive numbers while moving to the left are higher and higher negative numbers. In immunology, you can assume that at zero is the normal immune response.

That means, the extreme right (Positive) can be compared to hypersensitivity while the extreme left of the number line (Negative) can be compared to immunodeficiency.

Both too much immune response (Hypersensitivity) and too little immune response (immunodeficiency) are undesirable. The ideal is a normal immune response because it is protective of the body.  

There are two types of immunodeficiency disorders.

  • Primary immunodeficiency disorders
  • Secondary immunodeficiency disorders

Let’s discuss each of them in detail:

Primary immunodeficiency disorders (PIDs)

Primary immunodeficiency disorders are hereditary in nature and mostly manifest in childhood. However, there are some that can manifest in adulthood (e.g., common variable immunodeficiency).

Being hereditary means, they are passed down through familial lineage. You are bone with such a disorder because some relatives had it. Although PIDs are relatively rare, they are very dangerous when they occur. 

Primary disorders are mostly caused by mutations in an individual’s genes. These mutations may affect the X or Y chromosomes. When they are on the X-chromosomes, the disorders are referred to as X-linked and that means males will be affected in a higher proportion (Approx. 60%) than females.

Disorders affecting Humoral immunity

This affects the B cells making them not able to produce antibodies. Individuals suffering from these disorders will frequently suffer from bacterial infections. These are the commonest of all immunodeficiency disorders having a frequency of about 50-70%.

B cell abnormalities may be caused by primary immunodeficiency
B cells’ failure to produce antibodies may be a result of primary immunodeficiency disorders (istock photos)

Disorders affecting cellular immunity

These disorders affect the T cells among other cellular immunity components. If the CD4 T cells are affected then this will, in turn, affect the entire immune system that relies upon the cytokines that are produced by these subsets of the T cells. The disorders affecting T cells have an occurrence frequency of 30%.

Disorders that affect both Humoral and Cellular Immunity

Here the patients will have a non-functional adaptive immunity. That means that they will not produce both the B cells and the T cells. These are very problematic disorders.

Severe combined immunodeficiency (SCID) manifests in childhood
Severe combined immunodeficiency is a primary immunodeficiency disorder (istock photos)

A good example is severe combined immunodeficiency (SCID). People having this condition may not survive to adulthood – they are highly vulnerable to infections.

Disorders affecting Complement proteins

These disorders will affect the genes that encode the complement proteins. The complement cannot be activated. Such individuals will frequently suffer from bacterial infections.  These disorders are quite rare (2% frequency of occurrence) but are dangerous.

Disorders affecting Phagocytic Cells

Phagocytic cells include neutrophils, eosinophils, basophils, macrophages, and dendritic cells. They are important in the effector functions of the immune system. They are encoded in the germline.

This means that a genetic defect that affects them will affect the eventual elimination of unwanted antigens. These types of disorders have an 18% frequency of occurrence.

Secondary immunodeficiency disorders (SID)

Secondary immunodeficiency disorders occur at a later stage in your life. They are not hereditary. They may be a result of another problem like HIV infection or prolonged use of chemotherapy in cancerous disorders which eventually weaken the immune system.

SIDs are generally more common than PIDs. Some SIDs are fatal and can be lifelong but do not affect the life span of an individual. The secondary immunodeficiency disorders are caused by:

Human Immune Virus (HIV)

HIV is perhaps the most researched cause of secondary immunodeficiency disorders. Additionally, it is the most dreaded cause of immunodeficiency. HIV is a retrovirus that infects the CD4+ T-Helpers cells, multiplies inside them, and lyses them to release millions of virions that continue with the same cycle over and over.

HIV causes secondary immunodeficiency
HIV test showing positive results – HIV infection causes secondary immunodeficiency (istock photos)

As a result, this will cause the count of the CD4+ T cells to drastically drop. When they drop to very low levels the individuals have Acquired Immune Deficiency Syndrome (AIDS). They become too weak and suffer from many opportunistic infections.

The CD4+ T cells are arguably the most important cells in the immune system. We can only equate them to pillars of a storey building without which the building loses its integrity and eventually collapses.

The T cells are called helper cells because they help the CD8+ T cells and the B cells to be activated and perform their functions. The CD4+ T-Helper cells also produce interferon-gamma among other cytokines that activate the macrophages (Antigen Presenting Cells).

Other cytokines produced by these cells are pro-inflammatory and inflammation is a vital immune response in the human body.

Prolonged diabetes

Prolonged disorders like diabetes can impair the immune system and cause SID. Research has demonstrated that those with diabetes mellitus are also vulnerable to several bacterial infections which is evidence of a diminished immune system ability.


These immunosuppressants will in the long run impair the immune system. Their use is sometimes inevitable in transplant patients where the doctors work to prevent rejection of the transplanted organ.

Remember it is not easy to get an organ transplant (E.g., a Kidney) and so you would really want to protect it from the immune system if donated to you. This is where corticosteroids come in handy.

Unfortunately, they will protect your new organ but at the same time weaken the general strength of your immune system against foreign antigens (Like viruses, bacteria, protozoa, fungi, etc.).


Some types of cancers especially blood cancers like leukemia and lymphomas impair the immune system. This is because these types of cancers affect the bone marrow which is the site where all types of immune cells originate. As a result, one will not produce enough normal immune cells.


When one lacks important nutrients like calcium and zinc in their body, they will not make enough immune cells. These cells may also be defective and that means that they will not able to deal with unwanted antigens as they ought to. Individuals in such a situation will be overly vulnerable to infections.


Immunodeficiency is the lack of enough immune response that can keep you safe from foreign antigens. It can be an inborn disorder (Primary immunodeficiency) or an acquired disorder (Secondary immunodeficiency). Secondary immunodeficiency disorders are more common but much easier to manage compared to their primary counterparts.

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