Immune Disorders: Hypersensitivities, Autoimmunity, and Immunodeficiency

Immune Disorders

Overview of Immune Disorders

Immune disorders arise when the immune system malfunctions, leading to exaggerated, insufficient, or misdirected immune responses. These disorders are classified into hypersensitivities, autoimmune diseases, and immunodeficiency diseases. Understanding these categories is essential for recognizing the mechanisms and clinical implications of immune dysfunction.

Hypersensitivities

Definition and Types of Hypersensitivity

Hypersensitivity refers to any immune response against a foreign antigen that is exaggerated beyond the norm. There are four main types, each with distinct mechanisms and clinical manifestations:

• Type I (Immediate) – Allergy, mediated by IgE and mast cell degranulation

• Type II (Cytotoxic) – Antibody-mediated cell destruction

• Type III (Immune Complex-Mediated) – Immune complex deposition and inflammation

• Type IV (Delayed or Cell-Mediated) – T cell-mediated tissue damage

Type I (Immediate) Hypersensitivity

Type I hypersensitivity is a rapid, antibody-mediated reaction to allergens, resulting in the release of inflammatory mediators. It is commonly known as an allergy and can be localized or systemic.

• Mechanism: Involves two steps: Sensitization (initial exposure to allergen) and Degranulation (release of mediators upon re-exposure).

• Key Cells: Mast cells, basophils, and eosinophils play central roles in mediating allergic responses.

• Clinical Manifestations: Range from mild (hay fever, hives) to severe (anaphylactic shock).

Inflammatory Molecules Released from Mast Cells

Molecule	Role in Hypersensitivity Reactions
Histamine	Causes smooth muscle contraction, increased vascular permeability, and irritation
Kinins	Cause smooth muscle contraction, inflammation, and irritation
Proteases	Damage tissues and activate complement
Leukotrienes	Cause slow, prolonged smooth muscle contraction, inflammation, and increased vascular permeability
Prostaglandins	Some contract smooth muscle; others relax it

Common Allergens and Clinical Signs

• Allergens include pollen, fungal spores, dust mites, animal dander, and certain foods.

• Localized reactions depend on the portal of entry (e.g., hay fever from inhaled allergens, hives from skin contact).

• Systemic reactions can cause anaphylaxis, a life-threatening emergency requiring epinephrine.

Diagnosis, Prevention, and Treatment

• Diagnosis: Detection of allergen-specific IgE (e.g., ImmunoCAP test) and skin testing.

• Prevention: Avoidance of allergens, elimination diets, and immunotherapy (allergy shots).

• Treatment: Antihistamines, glucocorticoids, bronchodilators, and epinephrine for severe reactions.

Type II (Cytotoxic) Hypersensitivity

Type II hypersensitivity involves the destruction of cells by antibodies and complement, often seen in blood transfusion reactions and hemolytic disease of the newborn.

• Mechanism: Antibodies bind to antigens on cell surfaces, leading to cell lysis via complement activation.

• Examples: ABO blood group incompatibility, Rh incompatibility in pregnancy.

ABO Blood Group System

ABO Blood Group	ABO Antigen(s) Present	Antibodies Present	Can Donate To	Can Receive From
A	A	Anti-B	A or AB	A or O
B	B	Anti-A	B or AB	B or O
AB	A and B	None	AB	A, B, AB, or O (universal recipient)
O	None	Both anti-A and anti-B	A, B, AB, or O (universal donor)	O

Rh System and Hemolytic Disease of the Newborn

• Rh antigen is present in most humans (Rh+).

• Rh− mothers carrying Rh+ fetuses may develop antibodies that attack fetal red blood cells in subsequent pregnancies.

• Prevention with RhoGAM (anti-Rh immunoglobulin) is effective.

Type III (Immune Complex–Mediated) Hypersensitivity

Type III hypersensitivity is caused by the formation and deposition of immune complexes, which trigger inflammation and tissue damage.

• Mechanism: Immune complexes activate complement and attract neutrophils, leading to tissue injury.

• Examples: Hypersensitivity pneumonitis, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus (SLE).

Clinical Manifestations

• Hypersensitivity pneumonitis: Inhaled antigens cause immune complex formation in the lungs.

• Glomerulonephritis: Immune complexes deposit in kidney glomeruli, leading to renal failure.

• Rheumatoid arthritis: Immune complexes in joints cause chronic inflammation and joint deformity.

• Systemic lupus erythematosus (SLE): Autoantibodies against DNA and other cell components cause widespread tissue damage.

Type IV (Delayed or Cell-Mediated) Hypersensitivity

Type IV hypersensitivity is mediated by T cells and occurs 12–24 hours after antigen exposure. It is characterized by inflammation and tissue damage at the site of antigen contact.

• Mechanism: Involves antigen-presenting cells and T cells; delay is due to migration and activation of T cells and macrophages.

• Examples: Tuberculin skin test, allergic contact dermatitis, graft rejection, graft-versus-host disease.

Summary Table: Characteristics of the Four Types of Hypersensitivity

Descriptive Name	Cause	Time Course	Characteristic Cells Involved
Immediate (Type I)	IgE on sensitized cells binds antigen, causing degranulation	Seconds to minutes	Mast cells, basophils
Cytotoxic (Type II)	Antibodies and complement lyse target cells	Minutes to hours	Plasma cells (antibodies)
Immune Complex-Mediated (Type III)	Antibody-antigen complexes trigger complement, inflammation	Several hours	Neutrophils
Delayed (Type IV)	T cells attack body cells	Several days	Activated T cells

Immunosuppressive Drugs in Transplantation

Class	Examples	Action
Glucocorticoids	Prednisone, methylprednisolone	Anti-inflammatory; kill T cells
Cytotoxic drugs	Cyclophosphamide, azathioprine, etc.	Block cell division nonspecifically
Cyclosporine	Cyclosporine	Blocks T cell responses
Lymphocyte-depleting therapies	Antilymphocyte globulin, monoclonal antibodies	Kill T cells nonspecifically or inhibit IL-2 reception

Autoimmune Diseases

Causes of Autoimmune Diseases

Autoimmune diseases occur when the immune system attacks the body's own tissues. They are more common in the elderly and in women, and may be triggered by genetic, hormonal, environmental, or infectious factors.

• Estrogen may stimulate cytotoxic T cell activity.

• Maternal or fetal cells crossing the placenta can trigger autoimmunity.

• Environmental triggers include viral infections and molecular mimicry.

• Genetic predisposition (e.g., certain MHC genes).

• Failure of immune regulation mechanisms.

Examples of Autoimmune Diseases

• Systemic autoimmune diseases: Affect multiple organs (e.g., SLE, rheumatoid arthritis).

• Single-organ autoimmune diseases: Target specific tissues (e.g., blood cells, endocrine glands, nervous tissue).

Autoimmunity Affecting Blood Cells

• Autoimmune hemolytic anemia: Antibodies against red blood cells cause severe anemia. May follow viral infection or drug treatment.

Autoimmunity Affecting Endocrine Organs

• Type 1 diabetes mellitus: Immune destruction of pancreatic islets leads to insulin deficiency.

• Graves' disease: Autoantibodies stimulate the thyroid, causing hyperthyroidism and goiter. Treated with antithyroid drugs, radioactive iodine, or surgery.

Autoimmunity Affecting Nervous Tissue

• Multiple sclerosis (MS): Cytotoxic T cells destroy myelin sheaths, impairing neural function.

Immunodeficiency Diseases

Types of Immunodeficiency Diseases

Immunodeficiency diseases result from defective immune mechanisms and are classified as primary (congenital) or acquired.

• Primary immunodeficiency: Genetic or developmental defects, manifesting in infancy or childhood.

• Acquired immunodeficiency: Result from external factors such as infections (e.g., HIV/AIDS), aging, stress, or malnutrition.

Examples of Primary Immunodeficiency Diseases

Disease	Defect	Manifestation
Chronic granulomatous disease	Ineffective phagocytes	Uncontrolled infections
Severe combined immunodeficiency disease (SCID)	Lack of T and B cells	No resistance to infection; rapid death
DiGeorge syndrome	Lack of T cells	Overwhelming viral infections
Bruton-type agammaglobulinemia	Lack of B cells	Overwhelming bacterial infections

Acquired Immunodeficiency Diseases

• Caused by aging, severe stress, malnutrition, or infection (e.g., HIV/AIDS).

• HIV infection leads to AIDS, characterized by low CD4 T cell counts and opportunistic infections.

Micro Matters: Meningococcal Meningitis

Meningococcal meningitis is an infection of the meninges caused by Neisseria meningitidis. Rapid antibiotic treatment is critical to prevent permanent CNS damage or death.

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