1. Immunodeficiency Disorders

Immunodeficiency refers to a state in which the immune system is unable to mount an adequate response against pathogens, leading to increased susceptibility to infections, malignancies, and sometimes autoimmune phenomena. These disorders can be classified as:

Primary Immunodeficiencies (PIDs)

Primary immunodeficiencies are typically genetic and often manifest early in life. They affect specific components of the immune system:

• B-cell defects (e.g., X-linked agammaglobulinemia) result in impaired antibody production.
• T-cell defects (e.g., Severe Combined Immunodeficiency, SCID) affect cell-mediated immunity.
• Combined immunodeficiencies involve both humoral and cellular immunity.
• Phagocytic defects (e.g., Chronic Granulomatous Disease) impair pathogen killing.
• Complement deficiencies compromise opsonization and immune complex clearance.

Secondary Immunodeficiencies

These are acquired due to external factors such as:

• Viral infections (e.g., HIV infection leading to AIDS)
• Malnutrition
• Chemotherapy or immunosuppressive drugs
• Chronic diseases (e.g., diabetes, renal failure)

Pathophysiology: Defects in immune cell development, signaling pathways, or effector functions lead to inadequate pathogen clearance and opportunistic infections.

2. Autoimmune Diseases

Autoimmunity arises when the immune system fails to distinguish self from non-self, leading to an immune attack on host tissues. This breakdown of self-tolerance involves both genetic predisposition and environmental triggers.

Mechanisms of Autoimmunity

• Central tolerance failure: Inadequate elimination of self-reactive T and B cells in the thymus and bone marrow.
• Peripheral tolerance breakdown: Defects in regulatory T cells (Tregs) or immune checkpoints.
• Molecular mimicry: Pathogens share antigenic similarities with host proteins, triggering cross-reactivity.
• Epitope spreading: Progressive immune recognition of additional self-antigens.

Examples

• Systemic lupus erythematosus (SLE): Multisystem autoimmune disease with autoantibody production.
• Rheumatoid arthritis (RA): Chronic inflammation of synovial joints.
• Type 1 diabetes mellitus: Autoimmune destruction of pancreatic β-cells.
• Multiple sclerosis (MS): Demyelination of the central nervous system.

Pathogenesis: Autoantibodies, immune complexes, and autoreactive T cells mediate tissue damage via complement activation and cytokine release.

3. Neoplastic Diseases (Cancer)

Neoplastic diseases involve uncontrolled cellular proliferation due to genetic and epigenetic alterations. The immune system plays a dual role in both suppressing and promoting tumor growth.

Hallmarks of Cancer

• Sustained proliferative signaling
• Evading growth suppressors
• Resisting cell death (apoptosis)
• Enabling replicative immortality
• Inducing angiogenesis
• Activating invasion and metastasis

Immune Surveillance and Escape

The concept of cancer immunoediting describes three phases:

1. Elimination: Immune system detects and destroys tumor cells.
2. Equilibrium: Tumor variants persist under immune pressure.
3. Escape: Tumor cells evade immune detection.

Tumors evade immunity through:

• Downregulation of MHC molecules
• Secretion of immunosuppressive cytokines (e.g., TGF-β, IL-10)
• Expression of immune checkpoint molecules (e.g., PD-L1)

Immunotherapy

Modern cancer treatment includes:

• Immune checkpoint inhibitors (e.g., anti-PD-1, anti-CTLA-4)
• CAR-T cell therapy
• Cancer vaccines

4. Infectious Diseases

Infectious diseases are caused by pathogenic microorganisms such as bacteria, viruses, fungi, and parasites. The outcome of infection depends on host immunity and pathogen virulence.

Host Defense Mechanisms

• Innate immunity: Rapid, non-specific defense (barriers, phagocytes, complement system).
• Adaptive immunity: Specific, memory-based response (B cells and T cells).

Pathogen Strategies

• Immune evasion (antigenic variation, latency)
• Intracellular survival (e.g., viruses, intracellular bacteria)
• Toxin production
• Biofilm formation

Examples

• Viral infections: HIV, influenza, hepatitis viruses
• Bacterial infections: Tuberculosis, sepsis
• Parasitic infections: Malaria
• Fungal infections: Candida, Aspergillus