Disorders Associated with the Immune System

Introduction

This chapter explores disorders resulting from abnormal immune responses, including autoimmune diseases and immunodeficiencies such as AIDS. Understanding these conditions is essential for recognizing how the immune system can malfunction and the consequences for human health.

Autoimmune Diseases

Mechanisms and Classification

Autoimmune diseases occur when the immune system mistakenly attacks the body's own tissues, failing to distinguish self from nonself. This loss of self-tolerance leads to organ and tissue damage. Autoimmune diseases are classified based on the immune mechanisms involved:

• Cytotoxic autoimmune diseases

• Immune complex diseases

• Cell-mediated autoimmune diseases

Self-tolerance is the immune system's ability to avoid attacking its own cells. Breakdown of self-tolerance results in autoimmunity.

Cytotoxic Autoimmune Reactions

These reactions involve antibodies and immune cells attacking specific cell types, leading to tissue damage.

• Multiple sclerosis (MS): Autoantibodies, T cells, and macrophages attack the myelin sheath of nerves, compromising nerve impulse transmission. Symptoms range from fatigue and weakness to severe paralysis. The exact cause is unknown but may involve genetic and environmental factors.

Immune Complex Autoimmune Reactions

In these diseases, antibodies form complexes with antigens and deposit in tissues, causing inflammation and damage.

• Graves' disease: Abnormal antibodies stimulate the thyroid to produce excessive hormones, leading to hyperthyroidism.

• Myasthenia gravis: Antibodies coat acetylcholine receptors at neuromuscular junctions, preventing muscle activation and causing muscle weakness.

• Systemic lupus erythematosus (SLE): Immune complexes deposit in the kidney glomeruli, causing nephritis and systemic symptoms.

• Rheumatoid arthritis: Immune complexes form in the joints, leading to chronic inflammation and joint damage.

Cell-Mediated Autoimmune Reactions

These disorders are mediated by T cells that directly attack body tissues.

• Insulin-dependent diabetes mellitus (Type 1 diabetes): T cells destroy insulin-secreting pancreatic beta cells, resulting in high blood glucose levels.

• Psoriasis and psoriatic arthritis: T cell-mediated autoimmune disorders affecting the skin and joints.

Immunodeficiencies

Types and Causes

Immunodeficiencies are conditions where the immune system's ability to fight infections is compromised or absent.

• Congenital immunodeficiencies: Result from defective or missing genes present from birth.

• Acquired immunodeficiencies: Develop during life due to external factors such as drugs, cancers, or infections.

Acquired Immunodeficiency Syndrome (AIDS)

Origin and Epidemiology

Human immunodeficiency virus (HIV) is the causative agent of AIDS. HIV originated in west and central Africa, crossing into humans from chimpanzees around 1908. The virus spread due to urbanization and increased sexual transmission. The earliest known sample is from Kinshasa, DRC, in 1920.

Discovery and Impact

• 1981: Cluster of cases of Pneumocystis pneumonia, Kaposi's sarcoma, and immune dysfunction in the US.

• 1983: HIV identified as the cause of AIDS, selectively infecting T helper cells.

The Structure of HIV

HIV is a retrovirus of the genus Lentivirus. Its structure includes:

• Two identical + stranded RNA genome molecules

• Reverse transcriptase enzyme

• Phospholipid envelope

• gp120 glycoprotein spikes (for cell attachment)

HIV Structure Table

Attachment and Entry into Host Cells

HIV infects cells by binding its gp120 spike to the CD4 receptor and a co-receptor (CCR5 or CXCR4) on T helper cells, macrophages, and dendritic cells. The virus fuses with the cell membrane and enters the cell.

HIV Replication Cycle

• Viral RNA is reverse transcribed into DNA:

• Viral DNA integrates into host chromosomal DNA.

• Active infection: new viruses bud from the host cell.

• Latent infection: viral DNA remains hidden as a provirus; some infected cells become memory T cells, serving as reservoirs.

Stages of HIV Infection

HIV infection progresses through three phases:

• Phase 1: Asymptomatic or lymphadenopathy (swollen lymph nodes).

• Phase 2: Steady decline in CD4+ T cells; mild symptoms such as persistent infections, fever, and oral leukoplakia.

• Phase 3: AIDS develops when CD4+ T cell count falls below 200 cells/μl; indicator conditions appear.

Stages of HIV Infection Table

Immune Response and Challenges

• Initial immune response is strong; CD8+ T cells suppress viral replication.

• Latently infected CD4+ T cells make eradication impossible.

• Developing an effective vaccine is challenging due to high mutation rates and lack of natural immunity models.

Diagnosis, Transmission, and Epidemiology of HIV/AIDS

Diagnostic Methods

• Seroconversion: Time between infection and appearance of antibodies (up to 3 months).

• HIV antibodies detected by ELISA.

• Viruses detected by Western blotting or RNA testing.

Transmission Routes

• Sexual contact

• Breast milk

• Transplacental infection of fetus

• Blood-contaminated needles

• Organ transplants

• Artificial insemination

• Blood transfusion

HIV survives up to 6 hours outside a cell and more than 1.5 days inside a cell.

Global Epidemiology

• 36 million people infected worldwide; 70% in Africa.

• Heterosexual transmission is the most common mode globally.

• In Eastern Europe and Central/Southeast Asia, a significant proportion of cases are due to injected drugs.

Prevention and Treatment of AIDS

Intervention Strategies

• Biomedical interventions: Condoms, HIV testing, needle exchange programs, medication.

• Behavioral interventions: Sex education, safe infant feeding, counseling.

• Structural interventions: Changes in social, economic, political, and environmental factors.

Antiretroviral Therapy

In developed countries, AIDS is now considered a treatable chronic disease due to Highly Active Antiretroviral Therapy (HAART). HAART uses combinations of drugs to minimize the survival of resistant HIV strains.

Drugs Targeting HIV Life Cycle Table

Challenges in HIV Vaccine Development

• No model of natural immunity to mimic

• Lack of suitable research animals

• Limited understanding of retrovirus mechanisms

• High mutation rate leads to resistant strains

• An ideal vaccine would induce immunity before latent reservoirs are established, stimulate CD8+ cell production, and be affordable.

Summary Table: Autoimmune Diseases vs. Immunodeficiencies

Key Terms

• Self-tolerance: Ability of the immune system to avoid attacking its own tissues.

• Autoimmunity: Immune response against self-antigens.

• Immunodeficiency: Reduced or absent immune function.

• HIV: Human immunodeficiency virus, a retrovirus causing AIDS.

• CD4+ T cells: Main target cells for HIV infection.

• HAART: Highly active antiretroviral therapy.

Example Applications

• Diagnosis: ELISA and Western blotting are used to detect HIV infection.

• Treatment: HAART combines multiple drugs to suppress HIV replication and prevent resistance.

• Prevention: Education, safe practices, and biomedical interventions reduce HIV transmission.

Additional info: The notes expand on the mechanisms of immune dysfunction, provide context for diagnostic and therapeutic strategies, and include tables for comparison and drug classification.