Inflammation and Immunity

  1. Diseases Associated with hypersensitivity
    • Transfusion Reactions
    • Atopic Allergies
    • Allergic Asthma
    • Rh disease
    • Serum Sicknes
    • Food Allergies
    • Contact dermatitis
    • Anaphylaxis
  2. Diseases associated with Autoimmune Problems
    • (Coombs +) Hemolytic Anemia
    • Type I diabetes
    • Multiple Sclerosis
    • Rheumatoid arthritis
    • SLE
    • Pemicious Anemia
    • Myasthenia Gravis
    • Graves Disease
    • Goodpasture's Syndrome
    • Celiac Disease
    • Sjoren syndrome
    • SSS
    • Polymyositis/Dermatomyositis
    • Hashimoto thydroitis
    • Pemphigus vulgaris
    • MCTD
  3. Infection Related Diseases
    • Septic Shock
    • Toxic Shock
    • Crohn's Disease
    • Rheumatic Fever
    • SIRS (not really, but sort of)
    • Candidas
    • Cytalomegalovirus pneumonia
    • Histoplasmosis
    • Kaposi Sarcoma
    • MAI
  4. Transplantation Related Diseases
    • Hyperacute Allograft Rejection
    • Acute rejection
    • Chronic Rejection
    • GVHD
    • Xenograft Rejection
  5. Monoclonal Diseases
    • Multiple Myeloma
    • MGUS
    • Waldenstrom's Macroglobulinemia
  6. Diseases associated with immune deficiencies
    • BLS (Type I and II)
    • LAD
    • XLA
    • CVID
    • AIDS
    • Hyper IgM syndrome
    • Chediak-Higashi Syndrome
    • Selective IgA deficiency
    • IgH chain Locus deletion
    • Transient Hypogammoglobulinemia
    • SCID (ADA, Gamma-C, RAG 1/2, JAK3 deficiencies)
    • TCR-Initiated signaling defects
    • Hereditary hemochromatosis
    • Wiscott-Alrdich Syndrome
    • Neonatal Neutropenia
    • Chronic Granulomatus
    • MPO deficiency
    • IFNgamma deficiency
    • Hereditary angioedema
    • PNH
    • C2 deficiency
    • Factor B deficiency
    • MBP deficiency
  7. Define Hypersensitivity
    an undesirable reaction produced by a normal immune system
  8. Selective IgA deficiency, transient hypogammaglobulinemia, XLA, and IgH chain locus deletion are best classified as what type of deficiency?
  9. DiGeorge syndrome, CD3 deficiency, ZAP-70 deficiency, BLS 1/2, IL-12 (R), IFNgamma receptor deficiencies, hyper IgM syndrome types 1/2 are best classified as what type of deficiency?
    T cell
  10. Gamma chain deficiency, adenosine deaminase deficiency, RAG 1/2, and Wiscott-Aldrich syndrome are best classified as what type of deficiencies?
    Combined immune deficiencies
  11. Cyclic neutropenia, LAD (1,2,3 and 4), Chediak-Higashi syndrome, chronic granulomatus disease, and neutrophil granule deficiency are best classified as what type of deficiencies?
    Phagocytic cell deficiencies
  12. MBL and C2 deficiencies, Factor I and H deficiencies, HAE, C4b-BP deficiency, and PNH are best classified as what type of deficiencies?
  13. IRAK-4 mutations, MBL deficiencies, Defensin deficiencies, and Nod2 deficiency are best classified as what types of deficiencies?
    Inherited defects in innate immunity; result in infectious diseases
  14. Transfusion reaction
    • Hypersensitivity
    • Abs against ABO carbohydrate antigens
    • Type II
    • Igm/IgG mediated
  15. Atopic Allergies
    • Hypersensitivity; Type I
    • IgE mediated
    • APC presents an Ag to The2 cells; produces IL-4 and IL-13 (promotes class switchign to IgE)
    • Overreaction of immune system to non-pathogenic substance
  16. Allergic asthma
    • Hypersensitivity; type I
    • IgE mediated
    • Lumgs and airways primarily; mucous plugging and expiratory wheezing; hyperinflated lungs when having an attack
    • Common in developed world
    • Controlled with steroids and bronchodilators
  17. Rh disease
    • Hypersensitivity
    • Rh- mom; if not given Rhogan during first pregnancu (assuming Rh+ child), will become sensitized to Rh Ag and produce anti-Rh Abs
    • Normal first pregnancy; subsequent Rh+ babies are attacked by mom's anti-Rh IgG Abs that cross placenta
    • Give Rhogan during pregnancy (regardless of phenotype of fetus) and after delivery (if baby is RH+)
  18. Serum sickness
    • Hypersensitivity; Type III
    • Ag-Ab immunes complex reaction acts as anaphylatoxins; cause mast cell degranulation and anaphylactoid shock
    • Induced by anti-thymocyte globulin (post-transplant), ant-toxin therapy (for hepatitis), and certain drugs (penicillin)
    • Symptoms=fever, urticaria (hives), hypotension, vasculitis, hemorrhage, lymphdenopathy, arthralagia, and glomerulonephritis
  19. Food allergies
    • Hypersensitivity; type I
    • Similar to atopic allergies
    • Loss of tolerance
  20. Contact dermatitis
    • Hypersensitivity; type IV
    • CAn be induced by poison ivy, metal, etc
    • Localized reaction
    • CTLs, macrophages, and NK cells cause production of TNFalpha, prostaglandinds (contraction and relaxation of smooth muscle), and leukotrienes
  21. Anaphylaxis
    • Serious type I hypersensitivity; occurs upon 2nd exposure to Ag
    • Systemic shock form of allergy that can occur in response to insect venoms, certain foods, radiocontrast media, latex (cross-reactivity with banana, avocado, and chestnut), and drugs (penicllin cross reaction with cephalosporin)
    • IgE mediated; mast cell mediators include histamine, proteases (tryptase, chymase), PGs, Leukotrienes, Cytokines, and platelet activating factor
    • cardiovascular, pulmonary, GI, and cutaneous systems involved; can have difficulty breathing due to allergic reaction inducing angioedema blocking of lungs; generalizd prurutis, apprehension, hypotension, abdominal crampling, tachycardia, tachypnea, and hives
    • Treat (remember your ABCs): maintain airway, reverse bronchoconstriction, and ensure adequate circulation; timely injection of epinephrine is life saving
  22. (Coombs +) Hemolytic Anemia
    • Autoimmune disease
    • Auto-Abs to RBCs
    • Decreased hemoglobin, hematocrit, and increased bilirubin
    • Symptoms of anemia; fatigue, shortness of breath, pale skin due to poor O2 circulation; also hepatosplenomegaly, jaundice, etc.
  23. Type I diabetes
    • Autoimmune disease
    • Auto-Abs to beta cells in the pancreas that produce insulin
    • Inability to produce insulin in order to lwoer blood sugar leads to hyperglycemia and subsequent diabetes
  24. Multiple Sclerosis
    • Autoimmune disease
    • Auto-Ab to myelinated cells in the CNS (Schwann cells); decreased production of myelin
    • Scars in white matter of the brain and spinal cord which are normally filled with myelin
    • Neurological symptoms; physical and cognitive disability
  25. Rheumatoid arthritis
    • Autoimmune disease
    • Ag-Ab complexes deposit in the sinovial joints (bilaterally); deformations of hands and joints; destruction of articular cartilage and ankylosis of joint
    • Onset between 40 and 50; better with exercise, worse with rest
    • Treat with anti-TNFalpha drugs; decrease impact of body's inflammatory response
  26. SLE
    • Autoimmune disease; type III hypersensitivity
    • Systemic lupus erythematosus; more common in females and African Americans
    • Soluble immune complexes deposit in kidney, joints, capillaries, etc.; causes systemic issues
    • Ab against DS-DNA
    • Symptoms=butterfly rash on face (20%), fatigue, arthritis (90%), weight loss/gain, nephritis, and vasculitis (20%; bad prognosis)
    • Tests for ANA and anti-DSDNA Ab are diagnostic
  27. Pernicious Anemia
    • Autoimmune disease
    • Auto-Ab against parietal gastric cells; causes lack of intrinsic factor and inability to absorb B12; leads to megaloblastic anemia (continued cell growth without division)
    • Treated with B12 injections; NOT orally because no ability to absorb through GI tract
  28. Myasthenia Gravis
    • Autoimmune disease
    • Auto-Ab to ACh (acetylcholine) receptors; blocks transmission of NTs
    • Muscle weakness, difficulty swallowing, etc.
    • Treat with cholinesterase inhibitors, immunosuppressors, and sometimes thymectomy
  29. Graves disease
    • Autoimmune disease
    • Auto-Ab to TSH; hyperthyroidism; elevated T4; decreased TSH (thyroid stimulating hormone)
    • more common in females
  30. Goodpasture's syndrome
    • Autoimmune disease; type II hypersensitivity
    • Only one that's more common in M than F
    • Auto-Ab against basement membrane collagen
    • Glomerulonephritis and pneumotitis; can see the aut-Ab using fluorescence; linear design as opposed to lumpy design
  31. Celiac disease
    • Autoimmune disease; probably Ab-mediated hypersensitivity though some research says cell-mediated (role of MHC)
    • Abormal reaction to gluten; damage to GI tract and destruction of villae; decrease in body's ability to absorb nutrients
    • Presents with variety of symptoms
    • Treat with gluten free diet; villi reform after time
  32. Sjoren Syndrome
    • Autoimmune disease
    • 90% women; most >40
    • Dry eyes; dry mouth; neutrophil infiltration in salivary glands and conjunctiva results in decreased secretions
    • 40 fold increased risk of lymphoma
    • Infection by virus or bacteria may trigger (hypersensitivity)
    • Testing; ANA for rheumatoid factor is usually (+)
  33. SSS
    • Autoimmune disease
    • Systemic Sclerosis Syndrome
    • Female 3:1; >50
    • Sclerosis of skin; Raynaud's phenomenon caused by vasoconstriction in fingers (70%); sclerodactaly; fragile skin; GI fibrosis; difficulty swallowing; renal failure caused by glomeruli closing (70%)
    • Positive ANA in low titer; hypergammaglobulinemia; glomeruli closing visible on histo
  34. Polyositis/Dermatomyositis
    • Autoimmune disease
    • Females 2:1
    • Joint pain without inflammation (Arthralgias); malar skin rash (facial); systemic vasculitis
    • Associated with internal malignancies
    • HLA linked; serum Abs against myosin, myoglobin, and ANA
    • Abnormal EMG (proximal muscle groups and extremities); abnormal skin biopsy with elevated creatinine phosphokinase (MM fraction)
  35. Hashimoto thyroiditis
    • Autoimmune disease
    • Females 10:1
    • Initial presentation of hyperthyroidism with end stage hypothyroidism (similar to Graves disease)
    • Most common cause of goiters
    • Anti-thyroglobulin staining; also, thyroid is large and disfigured
  36. Pemphigus Vulgaris
    • Autoimmune disease
    • Large, easily ruptured bullae; most common on scalp and mucous membranes
    • Progress; fatal if untreated as a result of infection of exposed skin
    • Abs to epidermal surface Ag (desmoglein)
    • skin biopsy with immunofluorscence is diagnostic
  37. MCTD
    • Autoimmune disease
    • Mixed connective tissue disease
    • 80% females
    • Overlapping clinical and lab features of different autoimmune disease
    • High titers to RNP (ribonuleic acid protein)
    • Treat with corticosteroids
  38. Septic shock
    • Infection-related
    • Systemic reaction to LPS on surface of gram (-) bacteria; recognized by TLRs and NLRs; inflammatory cytokines (TNFalpha and AA metabolies PG and leukotrienes) are increased
    • Symptoms=fever, severe hypertension, coagulopathies (DIC), impaired organ perfusion, hypoxia; death if left untreated
  39. Toxic shock syndrome
    • Infection-related
    • SuperAg binds TCR and MHC outside of peptide-Ag binding site; polyclonal activation of T cells and cytokine storm
    • Symptoms=fever, diarrhea, coagulopathies (DIC), hypotension, rash, exfoliation of skin; death if left untreated
  40. Crohn's Disease
    • Infection-related
    • (aka Inflammtory bowel disease; IBS)
    • Abs against normal flora in GI tract; loss of epithelial function; Macrophages and Th1 cells produce excess IL-12, IFNgamma, TNFalpha
    • Chronic inflammation due to sustained macrophage and neutrophil activation
  41. Rheumatic Fever
    • Infection-related
    • Abs against strep (M protein) cross-react with Ags on cardiac valves (myosin, keratin, and laminin)
    • 2-4 weeks post-strep pharyngitis infection
    • Patient must take full dose of Abs when diagnosed with S. pharyngitis (common) to prevent activation of B cells; don't want too many Abs because may begin cross-reacting
  42. Candidas
    • Infection-related
    • Opportunistic infections
    • Thrush in infants
  43. Ctyomegalovirus pneumonia
    • Infection related
    • Member of the herpes family-latent but always present in T cells
    • Virus infects cells and makes it bigger
    • Life-threatening in immunocompromised
  44. Histoplasmosis
    • Infection related
    • Intracellular yeast; it's a mold in the environment, but a yeast in your body
    • Common in Missouri river
    • Histo, looks like gunk in cell
  45. PCP
    • Infection related
    • Pneumocystis jiroveci pneumonia
    • Inside a cyst-can see with silver stainm
    • Can be protozoa or fungi
  46. Toxoplasmosis
    • Infection related
    • Protozoan parasite; in cat feces
    • When you do a CT of the brain, you can see ring enhancing lesions with edema surrounding
    • Present with headaches and neurological problems
  47. Kaposi Sarcoma
    • Infection related
    • Tumor caused by virus (Herpes 8); tumor of the blood vessels
    • Looked at mouth and arm tumors in class
  48. MAI
    • Infection related
    • Mycobacterium avium intracellulare
    • Histologically, looks like cytoplasm contains webs
    • Can infect normal people; required bird contact
  49. Hyperacute allograft rejection
    • Transplantation related
    • Occurs within minutes; Type II hypersensitivity; mediated by IgG, complement, neutrophils, and platelets
    • Preformed ABO Abs react with MHC of nonself tissue
    • Prevented by not allowing exposure to blood when transplanting organs (common in liver but not other organs now; NOT seen in kidney because donor's blood cells are washed out prior to transferring)
  50. Acute Rejection
    • Transplantation-related
    • Weeks to months; Type II (?); mediated by Th1, CTLs, NK cells, and macrophages that infiltrate the graft in response to all-MHC I and II, but enhanced by IgG Ab (ADCC)
    • Watch for fever, mononuclear cell infiltrate, organ tenderness, and loss of organ function
    • Treat with immunosuppressants
  51. Chronic rejection
    • Transplantation-related
    • Months to years
    • Tendency to form fibrosis, infarction, and ischemic injury
  52. GVHD
    • Transplantation-related
    • Graft vs. Host Disease: up to 80% of allogeneic HSCT
    • Donor T cells attack host MHC I and II; problem in hematopoietic stem cell transfers where recipient expresses MHC not seen in donor
    • Symptoms=rash, blistering, loss of epithelium, mucosal problems, pain, diarrhea, vomiting, anorexia, hepatomegaly, elevated bilirubin, and jaundice
  53. Xenograft rejection
    • Transplantation-related
    • Hyperacute rejection; transplant of organ from another species; increased risk of zoonotic infection
    • membrane complement regulatory proteins (DAF) of animal do not inhibit the human C3 convertase; uncontrolled complement-mediated damage (Type II hypersensitivity)
  54. Multiple Myelomaq
    • Monoclonal disease
    • Cancer of the plasma cells; causes bone lesions; suppressed hematopoiesis
    • Pancytopenia and Bence-Jones proteins (L chain) in the urine; spike in the gamma region of SPE
    • Treat with IVIG
  55. MGUS
    • Monoclonal disease
    • Monoclonal gammopathy of undetermined significance
    • Benign monoclonal gammopathy; age-related; no bone lesions; no Bence-Jones proteins or other symptoms
    • Lower plasma cell and IgG levels than multiple myeloma; spike in gamma region is less distinct
  56. Waldenstrom's Macroglobulinemia
    • Monoclonal disease
    • Malignant IgM monoclonal gammopathy
    • Similar to Hodgkin's lymphoma
  57. XLA
    • Immune deficiency
    • X-linked Agammaglobulinemia
    • Mutation in Btk results in no B cell development and no Ab production
    • Onset at 6 months-1 year; cogenital; males only
    • Recurrent extracellular, encapsulated bacterial infections
    • Symptoms=otitis media, diarrhea, pneumonia, sinusitis
    • Treat with Abs and IVIG
  58. Hyper IgM Syndrome
    • Immune deficiency
    • CD154 absent on T cells; poor signaling for class switching; elevated IgM levels with little to no IgA/G
    • Recurrent bacterial infections (because normal levels of T cells, poor B cell activation)
    • Treat with Abs, IVIG, and gene therapy
  59. Selective IgA deficiency
    • Immune deficiency (most common 1/330)
    • Either block in plasma cell differentiation to make IgA or a defect in IgA secretion
    • 50% patients show no symptoms because IgM compensates
    • Present with sinopulmonary infections and diarrhea; increased incidence of atopic allergies
    • Treat with Abs; NOT IVIG (leads to serum sickness)
  60. IgH chain locus deletion
    • Immune deficiency
    • Normal number of B cells with no detectable IgG1, IgG2, IgG4, or IgA
    • No increased risk of bacterial infections because one Ig class can compensate for absence of another
  61. Transient hypogammaglobulinemia
    • NOT an immune disease
    • Normal in 6-9 months olds; delayed IgM and IgG production and no more maternal IgG
    • Increased sinopulmonary infections; not necessary to give IVIG; should have normal levels of Ig by 1 year old
  62. CVID
    • Immune deficiency
    • Common variable immune deficiency
    • Defect in humoral and cell-mediated immunity; normal B and T cell levels; poor Ab production; decreased cellular immunity
    • Increased risk of general bacterial infections
    • Similar to XLA (but autosomal)
  63. Chediak-Higashi Syndrome
    (drunken cell syndrome)
    • Immune deficiency
    • Mutation in lysosomal trafficking regulation; cells show poor chemotaxis and impaired NK cells function
  64. AIDS
    • Immune deficiency (msot prevalent one in US)
    • Acquired immunodeficiency syndrome
    • Depleted CD4 (Th) cells
    • Opportunistic infections; commonly seen with the following diseases; Kaposi sarcoma, cytomegalovirus, PCP, etc.; also, common cause of thrush in infants
  65. DiGeorge Syndrome
    • Immune deficiency
    • Mutation in third and fourth pharyngeal pouches results in loss of thymus; parathyroid deficiency and heart defects
    • Lack of T cells causes early onset of fungal and viral infections; lymphopenia; mderate hypogammaglobulinemia; calcium imbalance; cardiac disease
    • Treat with thymic transplant and anti-microbial agents
  66. SCID
    • Immune deficiency
    • Severe Combined Immunodeficiency
    • Combination of B, T, NK cell deficiencies; includes gamma chain, ADA, RAG 1/2, and JAK3 deficiency
    • Avoid live viral vaccines
  67. Gamma C deficiency
    • Immune deficiency: subset of SCID
    • X-linked recessive; most common cause of SCID
    • Absence of gamma chain of receptors for IL-2, 4, 7, 9, and 15
    • Phenotype: T-/B+/NK-
  68. ADA deficiency
    • Immune deficiency: subset of SCID
    • (Adenosine Deaminase deficiency)
    • Excess adenosine due to inability to break it down causes absent T, B, and NK cells
    • Phenotype: T-/B-/NK-
  69. RAG 1/2 Deficiency
    • Immune deficiency: Subset of SCID
    • Blocks B and T cell development by preventing rearragement of heavy and light chains
    • Phenotype: T-/B-/NK+
  70. JAK3 deficiency
    • Immune deficiency: Subset of SCID
    • Lack of receptor signaling; T and NK cells are present but fail to respond to cytokines; same phenotype as gamma chain deficiency, but it's different
    • Phenotype: T-/B+/NK-
  71. LAD
    • Immune deficiency
    • Leukocyte adhesion defect
    • Poor leukocyte adhesion to endothelial lining of blood vessels; defective complement-mediated opsonophagocytosis
    • Delayed wound healing and poor pus formation because neutrophils are unable to exit vessels
    • Recurrent pyogenic bacterial infections with no pus formation
  72. BLS: Type I
    • Immune deficiency
    • Bare lymphocyte syndrome
    • No MHC class I due to defect in TAP (transport associated with Ag processing)
    • No production of CTLs; lymphopenia
  73. BLS: Type II
    • Immune deficiency
    • Bare lymphocyte syndrome
    • No MHC class II due to defect in CIITA (required for class II expression)
    • No production of Th cells; lymphopenia
    • First rule out HIV as it is the most common reason for decreased Th cells
  74. CD3 deficiency
    • Immune deficiency
    • No T cells; normal B and NK cells
  75. ZAP-70 deficiency
    • Immune deficiency
    • (responsible for T cell signaling)
    • No T cells; normal B and NK cells
  76. Lck Deficiency
    • Immune deficiency
    • No T cells; normal B and NK cells
  77. HAE
    • Immune deficiency
    • Herediatary Angioedema
    • Autosomal dominant
    • Defect in C1 inhibitor; constitutive activation of the classical complement pathway
    • Symtpoms=Acute, non-painful, non-pruitic, non-erythematous swelling of skin and mucous
  78. Hereditary Hemochromatosis
    • Immune deficiency
    • Excessive iron accumulation; body absorbs and stores too much iron; toxic levels damage and destroy organs
    • HLA-H regulates function of transferring (involved in iron absorbency)
  79. Wiscott-Aldrich syndrome
    • Immune deficiency
    • Thrombocytopenia; causes bloody diarrhea and bruising; small non-functional platelets
    • Defect in CD43 and decreased overall Ab production; decreased IgM; increased IgA and IgE\
    • Recurrent extracellular bacterial infections
  80. Neonatal neutropenia
    • Immune deficiency
    • Defect in receptor for G-CSF; not responsibve to G-CSF therapy because of this
    • Abormal number of neutrophils in peripheral circulation when no infection; bands on CBC; WBC will typically be normal
  81. Chronic granulomatus disease
    • Immune deficiency
    • Defective respiratory burst oxidase (NADPH); Granulomas form in liver, spleen, and lung
    • Recurrent bacterial and fungal infections
    • Diagnose with negative result on nitroblue tetrazoliumyde reduction test; presence of Langhan's giant cells
    • Treat with prophylactic Abs, recombinant IFNgamma, and granulocyte transfusions
  82. MPO deficiency
    • Immune deficiency (myeloperoxidase)
    • Block in production of hypothalous acid; impaired intracellular killing
    • Similar presentation to CGD, but positive NBT dye test because cells have NADPH oxidase activity, just incapable of forming bleach
  83. IFNgamma deficiency
    • Immune deficiency
    • Recurrent viral and intracellular pathogens
    • Same phenotype as IL-12, IL-12R deficiencies because these are important inducers of IFNgamma
  84. PNH
    • Immune deficiency
    • Paroxysmal Nocturnal Hemoglobinuria
    • Failure to express CD59 and CD55 for DAF causes RBCs to lyse (MAC from complement)
    • Bloody urine in the morning
  85. C2 deficiency
    • Immune deficiency
    • Autosomal recessive
    • Increased risk of bacterial infections due to defective complement cascade
  86. Factor B deficiency
    • Immune deficiency
    • Increased risk of bacterial infections due to defect in complement cascade
  87. MBP (MBL) deficiency
    • Immune deficiency
    • Increased risk of bacterial infections due to defect in complement cascade
  88. Cyclic Neutropenia
    • Immune deficiency
    • Neutrophil elastase deficiency; occurs periodically
    • Gingivitis, periodontal disease, cuaneous infections, abscesses, pneumonias, and granulomas
    • Treat with recombinant G-CSF therapy
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Inflammation and Immunity