Failures of the Immune Response

Failures of the Immune Response

• The immune response has failures including immunodeficiencies, autoimmune disease, and allergic reactions (hypersensitivities).

Syllabus Content

• Immunodeficiencies
• Autoimmune disease
• Allergic reactions (Hypersensitivities)

Immunodeficiencies

• Immunodeficiency can be caused by infection (e.g., HIV) or by primary immunodeficiency diseases.
• Primary immunodeficiency diseases are genetic abnormalities that result in improper immune system function from birth. These defects lead to a lack of proper host defense. These defects can occur in B-cells (Antibody defects), T-cells (T-cell defects), or phagocytic cells, complement, or cytokine receptors. Defects in phagocytic cells or complement cascade can also lead to an increase in the occurrence of infectious disease.

Immunodeficiency Caused by Infection (HIV)

• HIV stands for Human Immunodeficiency Virus.
• HIV is a lentivirus (a subgroup of retrovirus).
• It causes AIDS (Acquired Immunodeficiency Syndrome) over time, decreasing the body's ability to fight off infections and illnesses.
• HIV infects human beings.
• The virus replicates inside living cells.
• In primary HIV infection, symptoms are often mistaken for influenza or a cold.
• Symptoms may occur between 2 and 6 weeks after infection and may include, fever, headache, sore throat, fatigue, body aches, weight loss, swollen lymph nodes, rashes, mouth or genital ulcers, diarrhea, nausea and vomiting, and thrush.
• Initial infection can last several days to weeks.
• HIV infects immune cells like CD4+ T cells, macrophages, and microglial cells.
• HIV-1 entry to macrophages and CD4+ T cells is facilitated by interaction of virion envelope glycoproteins (gp120) with CD4 molecules on target cells, and chemokine co-receptors (CCR5).
• The virion enters cells by adsorbtion of gp120 on receptors (CD4, CCR5).
• HIV capsid releases into cells initiating replication and transcription of viral RNA.
• Reverse transcriptase makes a complementary DNA copy of the viral RNA.
• This DNA is integrated into the host cell's DNA and used to produce new viral RNA
• Then new HIV virions assemble at the plasma membrane of the host cell and bud out.
• Acute phase: virus produced in large quantities, killing infected cells. The asymptomatic phase is also called clinical latency, the HIV provirus is latent.
• Symptomatic phase: the clinical symptoms of AIDS develop, and Th and Tc cells count decreases dramatically. When Th counts drop below 200 per microliter, the patients are considered to have AIDS.

Autoimmune Disease

• Autoimmune diseases result from the immune system attacking the body's own tissues.
• Some people are genetically predisposed to autoimmune diseases to these diseases influenced by environmental factors.
• Autoimmune diseases are caused by production of autoantibodies, with various parts of the immune response involved.
• Causes of autoimmunity include genetic predisposition, environmental factors (chemicals, heavy metals, infections, stress), and drugs or toxins.
• Types include type 1 diabetes mellitus, Hashimoto's thyroiditis, Grave's disease, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus (SLE).
• The immune system reacts to self-antigens.
• B cells are activated by T cells, differentiating into plasma cells.
• Self-antigen-specific antibody initiates an inflammatory response causing cell injury.

Allergic Reactions (Hypersensitivity)

• Allergic reactions are an immune response to allergens (antigens) like peanuts, pollen, dust mites, etc.
• Allergies may cause discomfort and distress for the patient and not all allergic reactions are life-threatening.
• Allergic reactions can sometimes result in a condition called anaphylaxis which is life threatening.
• Allergic reactions have various forms of transmission that include skin contact, injection, ingestion, or inhalation. Allergens can cause degranulation of mast cells and release of inflammatory mediators. This leads to immediate increases in local blood flow, vessel permeability and enzyme production that often results in inflammation.
• Allergic reactions are categorized into Type I IgE mediated Hypersensitivity, where IgE antibodies bind to mast cells and trigger degranulation when exposed to specific allergens causing release of variety of inflammatory mediators.

Primary Immunodeficiency Diseases

• Result from genetic abnormalities at birth.
• Characterized by an abnormally functioning immune system.
• Can be caused by mutations in immune response genes.
• Inherited immunodeficiencies affect T cells and B cells.
• Defects in phagocytic cells, complement, or cytokine receptors can result in lack of proper host defense.