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219 Cards in this Set
- Front
- Back
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What type of hypersensitivity casuses anaphylaxis?
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Type I
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What type of hypersensitivity causes Allergic rhinitis?
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Type I
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What type of hypersensitivity causes Hemolytic anemia?
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Type II
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What type of hypersensitivity causes Idiopathic thrombocytopenic purpura?
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Type II
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What type of hypersensitivity causes Erythroblastosis fetalis?
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Type II
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What type of hypersensitivity causes Rheumatic fever?
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Type II
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What type of hypersensitivity causes Goodpasture's syndrome?
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Type II
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What type of hypersensitivity causes Bullous pemphigoid?
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Type II
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What type of hypersensitivity causes Graves' Disease?
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Type II
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What type of hypersensitivity causes Myasthenia gravis?
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Type II
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What type of hypersensitivity causes SLE?
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Type III
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What type of hypersensitivity causes Rheumatoid arthritis?
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Type III
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What type of hypersensitivity causes Polyarteritis nodosum?
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Type III
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What type of hypersensitivity causes Poststreptococcal glomerulonephritis?
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Type III
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What type of hypersensitivity causes Serum sickness?
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Type III
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What type of hypersensitivity causes Arthus reaction?
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Type III
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What type of hypersensitivity causes Hypersensitvity pneumonitis?
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Type III
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What type of hypersensitivity causes Type 1 diabetes mellitus?
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Type IV
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What type of hypersensitivity causes Multiple sclerosis?
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Type IV
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What type of hypersensitivity causes Guillain-Barre' syndrome?
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Type IV
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What type of hypersensitivity causes Hashimoto's thyroiditis?
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Type IV
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What type of hypersensitivity causes Graft-versus-host disease?
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Type IV
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What type of hypersensitivity causes PPD response?
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Type IV
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What type of hypersensitivity causes contact dermatitis?
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Type IV
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What disease is associated with recurrent bacterial infections after 6 mo of age in boys?
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Bruton's agammaglobulinemia
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What is the genetic defect of Bruton's agammaglobulinemia?
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X-linked recessive defect in tyrosine kinase
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What cardiovascular presentation would be expected in a pt with DiGeorge syndrome?
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Tetany due to hypocalcemia (decreased PTH)
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Bruton's agammaglobulinemia is a defect in what cell type?
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B Cells
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Disease associated with recurrent viral and fungal infections?
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DiGeorge syndrome (T cell deficiency)
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Associated with 22q11 deletion?
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DiGeorge syndrome (T cell deficiency)
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In what disease are both B and T cells deficient?
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Severe combined immunodeficiency (SCID)
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What do pts with SCID present with?
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Recurrent viral, bacterial, fungal, and protozoal infections
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What causes SCID?
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Defect in early stem-cell differentiation
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What is the result of an IL-12 receptor deficiency?
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Pt presents with dissemenated mycobacterial infections due to decreased Th1 response
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What is IgM syndrome?
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Defect in CD40 ligand on CD4 T helper cells, inability to class switch. Therefore high IgM, all others low.
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What defect causes pt to present with severe pyogenic infections?
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IgM syndrome
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X-linked defect in ability to mount an IgM response to capsular polysaccharides of bacteria.
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Wiskott-Aldrich syndrome
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What disease presents with this triad: infections, thrombocytopenic purpura, eczema?
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Wiskott-Aldrich syndrome
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What immune deficiency presents with increased levels of IgA
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Wiskott-Aldrich syndrome
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What is Job's syndrome?
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Failure of IFN-gamma productions by helper T cells therefore neutrophils fail to respond, presents with coarse facies, cold staph abscesses, retained primary teeth, increased IgE, and dermatologic problems.
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What syndrome presents with eczema, increased IgE, and staph abscess?
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Job's syndrome
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What deficiency presents with recurrent bacterial infections, absent pus formation, and delayed seperation of umbilicus?
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Leukocyte adhesion deficiency
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Defect in LFA-1 integrin proteins on phagocytes.
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Leukocyte adhesion deficiency
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What immune cell is deficient in Leukocyte adhesion deficiency?
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Phagocyte
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What disease presents with recurrent pyogenic infections by staph and strep, partial albinism, and peripheral neuropathy?
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Chediak-Higashi disease
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What is Chediak-Higashi disease?
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Autosomal recessive defect in microtubular function and lysosomal emptying of phagocytic cells.
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What immune deficiencies result in decreased production?
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Bruton's agammaglobulinemia, DiGeorge syndrome, Severe combined immunodeficiency
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What immune deficiencies result in decreased activation?
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IL-12 receptor deficiency, IgM syndrome, Wiskott-Aldrich syndrome, Job's syndrome
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What immune deficiencies result in phagocytic cell deficiency?
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Leukocyte adhesion deficiency, Chediak-Higashi disease, Chronic granulomatous disease
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Lack of NADPH oxidase.
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Chronic granulomatous disease
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What is chronic granulomatous disease?
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Defect in phagocytosis of neutrophils due to lack of NADPH oxidase, marked susceptibility to opportunitstic infections.
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How do you confirm chronic granulomatous disease?
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Nitroblue tetrazolium dye reduction test (doesn't turn blue if they lack NADPH oxidase)
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What disease is the nitroblue tetrazolium dye reduction test used to diagnose?
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Chronic granulomatous disease
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Pt presents with recurrent skin and mucous membrane Candida infections
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Either immunocompromised state OR idiopathic chronic mucocutaneous candidiasis
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What is chronic mucocutaneous candidiasis?
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Idiopathic T cell dysfunction specifically against Candida albicans
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What is the most common selective immunoglobulin deficiency?
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Selective IgA deficiency, presents with sinus and lung infections, milk allergies, and diarrhea.
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Defect in DNA repair enzymes with associated IgA deficiency.
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ataxia-telangectasia, presents with cerebellar problems and spider angiomas
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Normal numbers of circulating B cells, decreased plasma cells, decreased Ig
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Common variable immunodeficiency, defect in B cell maturation
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What immune defieincies are idiopathic dysfunctions of B cells?
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Selective IgA deficiency, Ataxia-telangectasia, and Common variable immunodeficiency
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Antinuclear antibody
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SLE
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What autoantibodies are associated with SLE?
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Antinuclear antibody, Anti-dsDNA, and anti-Smith
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Anti-Smith antibody
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SLE
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Anti-dsDNA antibody
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SLE
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Antihistone antibody
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Drug induced lupus
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Anti-IgG antibody
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Rheumatoid arthritis
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Anticentromere antibody
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Scleroderma (CREST)
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Anti-scl-70 antibody
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Scleroderma (diffuse)
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Antimitochondrial antibody
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Primary biliary cirrhosis
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Antigliadin antibody
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Celiac Disease
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Anti-basement membrane antibody
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Goodpasture's syndrome
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Anti-epithelial cell antibody
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Pemphigus vulgaris
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Antimicrosomal antibody
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Hashimoto's thyroiditis
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Antithyroglobulin antibody
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Hashimoto's thyroiditis
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Anti-Jo-1 antibody
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Polymyositis, dermatomyositis
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Anti-SS-A
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Sjogren's syndrome
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Anti SS-B
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Sjogren's syndrome
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What antibody is associated with Drug induced lupus?
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Antihistone antibody
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What antibody is associated with Rheumatoid arthritis?
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Anti-IgG antibody
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What antibody is associated with Scleroderma (CREST)?
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Anticentromere antibody
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What antibody is associated with Scleroderma (diffuse)?
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Anti-scl-70 antibody
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What antibody is associated with Primary biliary cirrhosis?
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Antimitochondrial antibody
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What antibody is associated with Celiac Disease?
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Antigliadin antibody
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What antibody is associated with Goodpasture's syndrome?
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Anti-basement membrane antibody
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What antibody is associated with Pemphigus vulgaris?
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Anti-epithelial cell antibody
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What antibody is associated with Hashimoto's thyroiditis?
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Antimicrosomal antibody, Antithyroglobulin antibody
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What antibody is associated with Polymyositis, dermatomyositis?
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Anti-Jo-1 antibody
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What antibody is associated with Sjogren's syndrome?
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Anti-SS-A, Anti SS-B
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Anti-U1 RNP antibody
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Mixed connective tissue disease
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Anti-smooth muscle antibody
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Autoimmune hepatitis
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Anti-glutamate decarboxylase
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Type I diabetes mellitus
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c-ANCA antibody
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Wegner's granulomatosis
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p-ANCA antibody
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Vasculitities other than Wegner's, ex: microscopic polyangitis
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What diseases are associated with HLA subtype B27?
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PAIR - Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter's syndrome
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What diseases are associated with HLA subtype B8?
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Graves' disease, celiac sprue
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What diseases are associated with HLA subtype DR2?
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Mutiple sclerosis, hay fever, SLE, Goodpasture's
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What diseases are associated with HLA subtype DR3?
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Diabetes mellitus type I
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What diseases are associated with HLA subtype DR4?
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Rheumatoid arthritis, diabetes mellitus type I
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What diseases are associated with HLA subtype DR5?
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Pernicious anemia due to B12 deficiency, Hashimoto's thyroiditis
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What diseases are associated with HLA subtype DR7?
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Steroid-responsive nephrotic syndrome
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A graft from self
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Autograft
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What is an allograft?
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Graft from nonidentical individual of same species
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Graft from identical twin or clone?
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Syngeneic graft
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What is a xenograft?
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Graft from different species
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What is the MOA of cyclosporine?
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Binds to cycophilins, the complex inhibits calcineurin, stopping IL-2 production (end result blocks clonal expansion of T cells)
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What is the clinical use of cyclosporine?
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suppress organ rejection, some autoimmune disorders
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What is an alternative to cyclosprine that is less toxic and more potent?
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Tacrolimus
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What drug binds FK-binding protein and inhibits IL-2 production?
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Tacrolimus
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Antimetabolite precursor of 6-mercaptopurine, toxic to proliferating lymphocytes
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Azathioprine (cytotoxic agent)
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What are the toxic effects of Azathioprine?
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Bone marrow suppression, can be increased if taken with allopurinol
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Monoclonal antibody that binds to CD3 on T cells used for immunosuppression after kidney transplatation.
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Muronomonab-CD3
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What is the MOA of Sirolimus?
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Binds mTOR(mamallian target of rapamycin), inhibits T cell proliferation in response to IL-2.
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What are the toxic effects of Sirolimus?
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Hyperlipidemia, thrombocytopenia, and leukopenia
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What immunosuppressant inhibits de novo guanine synthesis?
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Mycophenolate mofetil
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What is the MOA for Daclizumab?
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Monoclonal antibody with high affinity for the IL-2 receptor on activated T cells.
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What are the toxic effects of Cyclosporine?
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Predisposes pts to viral infections and lymphoma, nephrotoxic.
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What are the toxic effects of Tacrolimus?
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Nephrotoxicity, peripheral neuropathy, hypertension, pleural effusion, and hyperglycemia
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What is Aldesleukin (IL-2) used for clinically?
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Renal cell carcinoma, metastatic melanoma
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What recombinant cytokine might you give a pt for anemia, especially associated with renal failure?
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Erythropoietin (epoetin)
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What is Filgrastim?
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Granulocyte colonys-stimulating factor, used for recovery of bone marrow
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What is Sargramostim?
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Granulocyte macrophage colony stimulating factor, used for recovery of bone marrow
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What recombinant cytokines might you give a pt for recovery of bone marrow?
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Filgrastim, Sargamostim (Granulocyte colony stimulating factors)
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What is the clinical use of alpha-interferon?
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Hepatitis B and C, Kaposi's sarcoma, leukemias, malignant melanoma
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What recombinant cytokine is used clinically for Kaposi's sarcoma?
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alpha-interferon
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What recombinant cytokine is used clinically for Hepatitis B and C?
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alpha-interferon
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What is beta-interferon used for clinically?
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Multiple sclerosis
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What recombinant cytokine is used clinically for Multiple sclerosis?
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beta-interferon
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What is the clinical use of gamma interferon?
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Chronic granulomatous disease
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What recombinant cytokine is used clinically for Chronic granulomatous disease?
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gamma-interferon
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What is the clinical use of Oprelvekin (IL-12)?
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Thrombocytopenia
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What is the clinical use of Thrombopoietin?
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Thrombocytopenia
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What recombinant cytokine is used clinically for Thrombocytopenia?
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Oprelvekin (IL-11), Thrombopoietin
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What recombinant cytokine is used clinically for malignant melanoma?
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alpha-interferon
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What recombinant cytokine is used clinically for leukemias?
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alpha-interferon
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What part of antibody recognizes antigens
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Variable part of L and H chains
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What types of antibody fix complements
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The Fc regions of IgM and IgG
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What portions of the antibody does heavy chain contribute to
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Both Fab and Fc regions
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What are the characteristics of the Fc region
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Constant, Carboxy terminal, Complement binding (IgG + IgM), Carbohydrate side chains
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What are some benefits of the antibody
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(1) Promote opsonization (2) Prevent bacterial adherence to cells (3)Activate complement and enhances opsonization and lysis
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What factors are responsible for antibody diversity
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(1) Random recombination of VJ (light-chain) or VDJ (heavy-chain) regions (2) Random recombination of heavy chains and light chains (3) Somatic hypermutation (4) Addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase
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What types of antibodies to mature B lymphocytes express on their surface
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IgM and IgD. These may differentiate by isotype switching (mediated by cytokines and CD 40 ligands) into plasma cells that secrete IgA, IgE, or IgG
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What are the characteristics of IgG
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(1) The main antibody in secondary response (2) Most abundant (3) Fixes complement (4) Opsonizes bacteria (5) Neutralizes bacteria toxins and viruses (6) Crosses the placenta
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What are the characteristics of IgA
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(1) Prevents the attachment of bacteria and viruses to mucus membrane (2) Does not fix complement (3) Is a monomer of a dimer (4) Found in secretions (5) Picks up secretory component from epithelial cells before secretion
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What are the characteristics of IgM
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(1) Produced in the primary response to an antigen (2) Fixes complement (3) Does not cross the placenta (4) Is the antigen receptor on the surface of B Cells (5) Is a monomer on B Cell or Pentamer
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What are the characteristics of IgD
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(1) Found on the surface of many B Cells and in serum (2) Its function is unclear
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What are the characteristics of IgE
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(1) Mediates immediate (Type 1) hypersensitivity by inducing the release of mediators from mast cells and basophils when exposed to allergen (2) Mediates immunity to warms by activating eosinophils (3) Has the lowest concentration in serum
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What is an allotype (Polymorphism)
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An Ig epitope that differs among members of the same species. Can be on a light chain or heavy chain. (ALLotypes represent different ALLeles
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What is an Isotype
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An Ig epitope common to a single class of Ig. There are 5 classes of Igs (IgA, IgD, IgE, IgG, IgM) and the difference is determined by the heavy chain. Isotype = iso (same); common to same class
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What is an idiotype
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An Ig epitope determined by antigen binding site. It is specific to a given antigen. (Idiotype = idio (unique); hypervariable region is unique)
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What are the characteristics of IL-1
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(1) Secreted by macrophages (2)Cause acute inflammation (3) Induces cytokine production to recruit leukocytes (4) Activates endothelium to express adhesion molecules (5) Is an endogenous pyrogen
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What are the characteristics of IL-2
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(1) Secreted by Th Cells (2) Stimulates grow of helper and cytotoxic T Cells. (IL-2: Stimulates T Cells)
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What are the characteristics of IL-3
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(1) Secreted by activated T Cells (2) Supports the growth and differentiation of bone marrow stem cells (3) Has a function similar to GM-CSF. (IL-3: Stimulates bone marrow growth)
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What are the characteristics of IL-4
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(1) Secreted by Th2 Cells (2) Promotes growth of B Cells (3) Promotes class switching to IgE and IgG. (IL-4: Stimulates IgE production)
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What are the characteristics of IL-5
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(1) Secreted by Th2 Cells (2) Promotes differentiation of B Cells (3) Promotes class switching to IgA (4) Stimulates production and activation of eosinophils. (IL-4: Stimulates IgA production)
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What are the characteristics of IL-6
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(1) Secreted by Th cells and macrophages (2) Stimulates production of acute phase reactants and immunoglobulins
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What are the characteristics of IL-8
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(1) Secreted by macrophages (2) Major chemotactic factor for neutrophils. ('Clean up on aisle 8' - Neutrophils are recruited by IL-8 to clear infections)
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What are the characteristics of IL-10
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(1) Secreted by regulatory T Cells (2) Inhibits action of activated T Cells
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What are the characteristics of IL-12
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(1) Secreted by macrophages and B Cells (2) Activates NK and Th1 Cells
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What are the characteristics of gamma interferon
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(1) Secreted by Th1 cells (2) Stimulates macrophages
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What are the characteristics of TNF
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(1) Secreted by macrophages (2) Mediated septic shock (3) Causes leukocyte recruitment and vascular leak
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What cell surface proteins are on Helper T Cells
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CD4, TCR, CD3, CD28, CD40L
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What Cell surface proteins are on Cytotoxic T Cells
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CD8, TCR, CD3
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What Cell Surface proteins are on B Cells
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IgM, B7, CD19, CD20, CD27, CD40, MCH II
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What Cell surface proteins are on macrophages
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MCH II, B7, CD40, CD14. Receptors for Fc and C3b
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What Cell surface proteins are on NK Cells
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Receptors for MHC I, CD 16, CD56
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What Cell surface receptor is on all cells except mature red cells
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MHC I
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What is the definition of Complement
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Complement is a system of proteins that interact to play a role in humoral immunity and inflammation
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What is the function of the Membrane attack complex of complement
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To defend against gram negative bacteria
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How is complement activated
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(1) Complement is activated in the Classic pathway by IgG and IgM. (GM makes classic cars) (2) Complement is activated by molecules on the surface of microbes (especially endotoxins) in the alternative pathway
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What are the primary opsonins in bacterial defense
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C3b and IgG (C3b = opsonization - Bind Bacteria)
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How is complement activation in self-cells prevented
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By Decay Accelerating Factor (DAF) and C1 esterase inhibitor
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What is C3a and C5a known for
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Anaphylaxis
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What is a function of C5a
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Neutrophil chemotaxis
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What is the function of the C5b - 9 complement
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Cytolysis by membrane attack complex (MAC)
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What causes hereditary angioedema
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Deficiency of C1 esterase inhibitor
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What is the problem associated with C3 complement deficiency
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Severe, recurrent pyogenic sinus and respiratory tract infections
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What is the problem associated with C6 - C8 complement deficiency
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Neisseria bacteremia
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What is the problem associated with deficiency of Decay accelerating Factor (DAF)
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Complement-mediated lysis of RBC and paroxysmal nocturnal hemoglobinemia (PNH)
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What interferon place an uninfected cell in an antiviral state
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Interferons alpha, beta, and gamma
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What is the function of interferons
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(1) Interferons induce the production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA (but not host mRNA) (2) They activate NK Cells to kill virus-infected cells - Interferons INTERFERe with viruses
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What is the function of interferons alpha and beta
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They inhibit viral protein synthesis
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What is the function of interferon gamma
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They increase MHC I and II expression and antigen presentation in all cells
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What are the characteristics of ACTIVE immunity
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(1) Induced after exposure to foreign antigens (2) Slow onset (3) Long-lasting protection (memory)
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What are the characteristics of PASSIVE immunity
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(1) Based on receiving pre-formed antibodies from another host (2) Rapid onset (3) Short lifespan of antibodies (half-life = 3 weeks) - After exposure of Tetanus Toxin, Botulinum Toxin, HBV, or Rabies, patients are given preformed antibodies (passive) - To Be Healed Rapidly
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What are some examples of antigen variations in bacteria
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(1) Salmonella has two flagella variants (2) Borrelia has relapsing fever (3) Neisseria gonorrhoeae has pilus protein
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What are some examples of antigen variations in virus
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(1) Influenza (major variation = shift, minor variation = drift)
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What are some examples of antigen variations in parasites
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Programmed rearrangement in Trypanosomes
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What are some examples of mechanisms of antigen variation
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DNA Rearrangement and RNA segment reassortment (e.g. influenza major shift)
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What is anergy
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Anergy is a condition where self-reactive T Cells become non-reactive without co-stimulatory molecule. B Cells also become anergic, but tolerance is less complete than in T Cells
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Anaphylactic and Atopic hypersensitivity
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Hypersensitivity Type I - Free antigen cross-links IgE on presensitized mast cell and basophils, triggering release of vasoactive amines (i.e. histamine). Reaction develops rapidly after antigen exposure due to preformed antibody. (First and Free (anaphylaxis))
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Antibody-mediated hypersensitivity
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Hypersensitivity Type II - IgM or IgG bind to fixed antigen on enemy cell, leading to lysis (by complement) or by phagocytosis - Cyt-2-toxic. Antibody and Complement lead to membrane attack complex (MAC)
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Delayed (T-Cell mediated) type hypersensitivity
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Hypersensitivity Type IV - sensitized T lymphocytes encounter antigen and then release lymphokines (leads to macrophage activation). 4th and last = delayed. Cell-mediated, so not transferable by serum. 4T's = T lymphocytes, Transplant rejections, TB skin tests, Touching (contact dermatitis)
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Mnemonic for Hypersensitivity Reactions
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ACID = Anaphylactic and Atopic (Type I), Cytotoxic - antibody-mediated (Type II), Immune complex (Type III), and Delayed - cell mediated (Type IV)
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An immune complex disease in which antibodies to the foreign protein are produced
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Serum Sickness - Type III hypersensitivity. Takes 5 days. Immune complexes form and are deposited in membranes, where they fix complement (leads to tissue damage). More common than Arthus reaction
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Antigen-antibody complexes activate complement, which attracts neutrophils; neutrophils release lysosomal enzymes
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Immune complex - Type III hypersensitivity
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A local subacute antibody-mediated hypersensitivity reaction. Characterized by edema, necrosis, and activation of complement
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Arthus reaction = Type III hypersensitivity. Intradermal injection of antigen induces antibodies, which form antigen-antibody complexes in the skin.
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Imagine 3 things stuck together: Antigen-Antibody-Complement. Most serum sickness is now caused by drugs, not serum. Characterized by fever, urticaria, arthralgia, lymphadenopathy, proteinuria 5 - 10 days after exposure to antigen. Antigen-Antibody complexes cause the Arthus reaction
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Type III hypersensitivity
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What occurs in a lymph node follicle?
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B-cell localization and proliferation
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What occurs in a lymph node Medulla?
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Communicate with lymphatics, contains reticular cells and macrophages
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What occurs in a lymph node Paracortex?
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Houses T cells; enlarges in an immune response; not well developed in Di George
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Spleen-Periarterial lymphatic sheath (red pulp)
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T cell location in spleen
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Spleen-Follicles (white pulp)
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B-cell localization
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Site of T-cell maturation?
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Thymus
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Site of B-cell maturation?
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Bone Marrow
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What is innate immunity?
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Receptors that recognize pathogens encoded in the germline. Response is fast and nonspecific with no memory. (PMN, Macrosphages, NK cells, complement)
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What is adaptive immunity?
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Receptors that undergo recombination during lymphocyte development; has memory (T cells and B cells, Antibody)
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MHC
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Major histocompatibilty complex encoded by Human Leukocyte Antigen genes (HLA)
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MHC I-Location
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All nucleated cells, loaded in RER, mediates viral immunity
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MHC II- Location
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Antigen presenting cells, loaded in acidified endosome
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MHC II- Types
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HLA-DR, HLA-DP, HLA-DQ
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B-cell function
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Make antibody
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T-cell function-CD4+
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CD4+ T cells help B cells make antibody, and produce gamma-interferon
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T-cell function-CD8+
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Kill virus-infected cell
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Natural killer cells-Killing mechanisms
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Uses perforin and granzymes to induce apoptosis
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How to activate a NK cell?
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IL-12, INF-beta, INF-alpha
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What is a superantigen?
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Cross-links Beta-region of TCR to the MHC class II on APC
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How many signals are required for T and B cell activation?
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Two
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T cell activation-Helper
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1)Antigen on MHC II and Costimulatory (B7-CD28)
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B cell activation
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1) IL-4, IL-5, IL-6 2) CD40 and CD40 ligand on Th Cell
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T-cell activation- Cytotoxic
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1)TRC-MHC I (with antigen) 2)IL-2 from Th cell
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