03/13a Hypersensitivity III & IV, Granulomas Flashcards
What is autoimmune thrombocytopenic purpura? Describe its symptoms, mechanisms, and treatments
Caused by IgG against platelet membrane glycoproteins
Leads to opsonization and phagocytosis by splenic macrophages
Symptoms - thrombocytopenia, petechiae
Treatment - steroids, immunosuppression, splenectomy
What is pemphigus vulgaris? Describe its symptoms and mechanisms
Caused by antibodies against desmosome proteins of keratinocytes
Leads to loss of attachment of epidermal keratinocytes
Symptoms - blisters, mucocutaneous erosions
What is Goodpasture’s Syndrome? Describe its mechanisms and symptoms
Caused by IgG against type IV collagen, which react with the capillary basement membrane of the kidney and lung
Stimulates inflammation
Leads to renal failure due to glomerulonephritis and pulmonary hemorrhage
What is a Type III hypersensitivity?
An immune complex-mediated disease
What causes the clinical manifestations of Type III hypersensitivity reactions?
Immune complexes, composed of antibodies bound to self or foreign antigen, which deposit in tissues activate complement
Symptoms reflect the site of immune complex deposition, not the cellular source of the antigen
Affects multiple organs and tissues, particularly the kidneys and joints
What are two important physical characteristics of pathogenic immune complexes? Why are they important?
Small size - small complexes penetrate tissue better and persist in circulation longer (avoid phagocytosis better) than large ones
Positive charge - bind tightly to negatively charged components of the basement membranes of blood vessels and kidneys
Why are neutrophils attracted by immune complexes? Why is this significant?
Activation of complement by immune complexes leads to the release of C5a, a chemoattractant
Attracts neutrophils, which can cause tissue damage
What are six examples of immune complex diseases?
Arthrus reaction Serum sickness Systemic lupus erythematosus Polyarteritis nodosa Poststreptococcal glomerulonephritis Farmer's Lung
What is the Arthrus Reaction? Describe its mechanisms and effects
A response to a subcutaneous injection of antigen into a previously immunized host
Circulating antibodies bind rapidly to the antigen
Complexes are deposited in the walls of small arteries, complement is activated, neutrophils are recruited
Symptoms - local cutaneous vasculitis, possible tissue necrosis
What is serum sickness? Describe its mechanisms
A response to an intravenous injection of foreign protein, serums, or haptens (due primarily to drug exposure)
Antibody response occurs after about 14 days
Immune complexes form in circulation and deposit in the walls of blood vessels, stimulating inflammation and causing systemic symptoms
What are the symptoms of serum sickness?
Rash Joint pain Fever Lymphadenopathy Glomerulonephritis Proteinuria
What is SLE?
Systemic lupus erythematosus - the Prototypic Immune Complex-Mediated Disease!
What causes lupus?
Autoantibodies, particularly anti-DNA antibodies
Immune complexes cause vasculitis involving small arteries throughout the body
What are the symptoms of lupus?
Rashes ("butterfly" pattern on the face)
Arthritis
Glomerulonephritis ("Lupus Nephritis")
Hemolytic anemia
Thrombocytopenia
Pericarditis, myocarditis, endocarditis
Photosensitivity
CNS involvementWhat is the diagnostic test for SLE?
Test for antinuclear antibodies, particularly antibodies against double-stranded native DNA
What types of genetic characteristics can lead to SLE?
Being female
Deficiencies in complement proteins, especially C1q, C2, and C4
HLA-DR3 allele
What is polyarteritis nodosa? Describe its mechanisms and symptoms
Immune complex deposition in small and medium arteries, resulting in ischemic damage
Affected organs can include the skin, heart, kidneys, and nervous system
Generalized symptoms - fever, fatigue, weakness
Skin - rashes, swelling, ulcers, lumps
With what other disease is polyarteritis nodosa associated?
Active hepatitis B infection (30% of patients)
What is poststreptococcal glomerulonephritis? Describe its mechanisms and symptoms
Lodging of immune complexes in the glomerular basement membrane, as a result of streptococcal skin infection
Complexes also activate complement - causes destruction of the basement membrane
Symptoms - hematuria, oliguria, edema, hypertension, heavy proteinuria, nephritic syndrome
What is Farmer’s Lung? Describe its mechanisms
Hypersensitivity pneumonitis induced by the inhalation of biologic dusts
Sensitization to dusts leads to production of IgG, which binds to antigens upon subsequent exposure
Immune complexes deposit in the alveoli, leading to complement activation, inflammation, cell damage, and fibrosis
What are the three types of Farmer’s Lung? Describe their symptoms and differences?
1) Acute - develops after large exposure to antigen and causes fever, chills, cough, dyspnea, chest tightness, possible acute respiratory failure
2) Subacute - less antigen over a longer period and causes dough, dyspnea, anorexia, and weight loss
3) Chronic - prolonged and continuous exposure to antigen and can cause irreversible lung damage, sever dyspnea
What is a type IV hypersensitivity reaction?
Cell-mediated hypersensitivity - does NOT involve antibodies
What is delayed-type hypersensitivity? What are the steps in the development of such a reaction?
Model of type IV hypersensitivity
Step 1 - sensitization by immunization, infection, or contact with chemical or environmental antigens
Step 2 - wait about 2 weeks for adaptive immunity to develop
Step 3 - elicitation by subsequent exposure to the same antigen alone, which activates local memory and effector T cells, which make cytokines
What is the classic clinical application of the delayed-type hypersensitivity reaction?
Tuberculin purified protein derivative (PPD) test
Tests for T cells that have been activated by PPD antigens
