Disorders in Immunity: Hypersensitivities, Autoimmunity, and Immunodeficiencies

Disorders in Immunity

Section 17.1: The Immune Response: A Two-Sided Coin

The immune system protects the body from pathogens, but dysfunction can lead to disease. Immunopathology is the study of diseases caused by abnormal immune responses, which can be categorized as overreactivity (hypersensitivity and autoimmunity) or underreactivity (immunodeficiency).

• Immunopathology: Study of diseases resulting from abnormal immune responses.

• Overreactivity: Includes allergies, hypersensitivity, and autoimmunity.

• Hyposensitivity (Immunodeficiency): Immune function is incomplete, suppressed, or destroyed.

Section 17.2: Hypersensitivity Reactions

Hypersensitivity refers to exaggerated or inappropriate immune responses to antigens. Antigens causing hypersensitivity can be exogenous (e.g., pollen, microbes) or endogenous (self-antigens in autoimmunity). There are four major types:

• Type I: Immediate (IgE-mediated) – common allergies and anaphylaxis.

• Type II: Antibody-mediated cytotoxicity (IgG/IgM) – cell damage.

• Type III: Immune complex-mediated – immune complex formation and deposition.

• Type IV: Delayed-type (cell-mediated) – T cell-mediated reactions.

Type I Hypersensitivity: Allergy and Anaphylaxis

• Allergy: Exaggerated immune response causing inflammation.

• Allergens: Antigens that provoke allergic reactions in susceptible individuals.

• Atopy: Chronic local allergy (e.g., hay fever, asthma, eczema).

• Anaphylaxis: Severe, systemic allergic reaction that can be fatal due to airway obstruction and circulatory collapse.

• Common Allergens: Peanuts, shellfish, pollen, antibiotics (e.g., penicillin), and insect stings.

Genetic Predisposition: Allergic susceptibility is often inherited, favoring IgE production and mast cell reactivity.

Hygiene Hypothesis: Suggests that reduced microbial exposure in industrialized societies leads to increased allergy rates.

Chemical Mediators of Allergy

• Produced by: Mast cells and basophils.

• Key Mediators: Histamine, serotonin, leukotrienes, prostaglandins, bradykinin, platelet-activating factor.

• Effects: Cause symptoms such as rashes, itching, sneezing, diarrhea, and systemic effects like altered blood pressure and respiration.

Diagnosis and Treatment of Allergy

• Diagnosis: Blood tests for allergen-specific IgE, tryptase levels, leukocyte histamine-release test, and skin testing.

• Treatment: Avoidance of allergens, drugs blocking immune mediators, desensitization (controlled exposure), and emergency use of epinephrine for anaphylaxis.

Section 17.3: Type II Hypersensitivities – Antibody-Mediated Cytotoxicity

Type II hypersensitivity involves IgG or IgM antibodies binding to cell surface antigens, leading to cell lysis via complement activation. The ABO blood group system is a classic example.

• ABO Blood Types: Determined by glycoprotein antigens (A, B, AB, O) inherited as alleles.

• Transfusion Reactions: Occur when incompatible blood is transfused, causing hemolysis, shock, kidney failure, and potentially death.

Genotype	Blood Type
AA or AO	A
BB or BO	B
AB	AB
OO	O

Universal Donor: Type O Universal Acceptor: Type AB

Section 17.4: Type III Hypersensitivities – Immune Complex Reactions

Type III hypersensitivity is mediated by immune complexes (antigen-antibody aggregates) that deposit in tissues, activating complement and attracting neutrophils, leading to inflammation and tissue damage.

• Key Features: Involves IgG, IgM, or IgA; requires large antigen doses; delayed onset (hours to days).

• Example: Acute post-streptococcal glomerulonephritis (APSGN) – immune complexes deposit in kidney glomeruli after Streptococcus pyogenes infection, causing inflammation and damage.

Section 17.5: Type IV Hypersensitivities – Cell-Mediated (Delayed) Reactions

Type IV hypersensitivity is mediated by T cells, not antibodies. Symptoms appear 2–3 days after antigen exposure. Classic examples include the tuberculin skin test and contact dermatitis.

• Delayed-Type Hypersensitivity: Seen in the tuberculin reaction (e.g., PPD test for tuberculosis).

• Contact Dermatitis: Caused by exposure to substances like poison ivy, metals, or cosmetics; requires prior sensitization.

• Graft Rejection: T cells recognize foreign MHC molecules on transplanted tissue, leading to rejection.

Type of Graft	Description
Autograft	From the same individual
Isograft	From an identical twin
Allograft	From a genetically different individual of the same species
Xenograft	From a different species (e.g., swine heart valve)

Section 17.6: Autoimmunity – Inappropriate Response Against Self

Autoimmune diseases occur when the immune system attacks self-antigens. They can be systemic (affecting multiple organs) or organ-specific. Over 80 autoimmune diseases are recognized.

• Genetic Factors: Certain MHC genes increase susceptibility; diseases often cluster in families.

• Molecular Mimicry: Microbial antigens resemble self-antigens, triggering cross-reactive immune responses (e.g., rheumatic fever).

• Infection: Viral infections may alter self-antigens, leading to autoimmunity (e.g., type 1 diabetes, multiple sclerosis).

• Gut Microbiome: Changes in microbiome composition may disrupt immune tolerance.

Disease	Target	Key Features
Systemic Lupus Erythematosus (SLE)	Multiple organs	Autoantibodies against various tissues; butterfly rash
Rheumatoid Arthritis	Joints (and sometimes other organs)	Immune complexes in synovial membrane; joint damage
Type 1 Diabetes	Pancreatic beta cells	Cytotoxic T cells destroy insulin-producing cells
Multiple Sclerosis	Myelin sheath of neurons	T cells and autoantibodies damage myelin; neurological symptoms

Section 17.7: Immunodeficiency Diseases – Hyposensitivities

Immunodeficiency diseases result from insufficient immune responses. They are classified as primary (congenital) or secondary (acquired).

• Primary Immunodeficiencies: Genetic defects present at birth (e.g., agammaglobulinemia, DiGeorge syndrome, SCID).

• Secondary Immunodeficiencies: Acquired after birth due to infection (e.g., HIV/AIDS), metabolic disease, chemotherapy, or radiation.

Disorder	Defect	Clinical Features
Agammaglobulinemia	B cell deficiency	Recurrent bacterial infections
DiGeorge Syndrome	T cell deficiency (thymic development)	Severe infections by fungi, protozoa, viruses
SCID (Severe Combined Immunodeficiency)	B and T cell deficiency	Severe, recurrent infections; often fatal without treatment
AIDS	T helper cell depletion (HIV infection)	Opportunistic infections, cancers

Therapies: May include bone marrow transplantation, gene therapy, or enzyme replacement (e.g., for ADA deficiency in SCID).

Additional info: This summary expands on the provided notes with definitions, examples, and tables for clarity and completeness, as would be expected in a microbiology textbook study guide.