Diseases Flashcards
C3 deficiency
Increase risk of severe recurrent pyogenic sinus and respiratory infections
increases susceptibility to type III hypersensitivities
C5-C9 deficiency
Increase susceptibility to Neisseria bacteremia
DAF (GPI anchored enzyme deficiency)
Causes complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (purple color or dark urine)
C1 deficiency
Increased susceptibility to encapsulated organisms
SLE
C1 esterase inhibitor deficiency
AD
Causes hereditary angioedema-ACE inhibitors contraindicated
Episodes of painless, non pitting, well circumscribed edema
Manifests as abdominal pain, vomiting and diarrhea
C1 esterase blocks activation of complement and kalikrein which derives into bradykinin (decreasing their effects of increased vasodilation and vascular permeability)
Excess bradykinin + C3a and C5a lead to angioedema
if affecting tracheobronchial tree leads to death
Type I Hypersensitivity
Anaphylactic and atopic-free antigen cross links IgE on presensitized mast cells and basophils, triggers immediate release of vasoactive amines that act at postcapillary venules (histamine, proteases, heparin, leukotrienes and PGs)
Increased tryptase from mast cells
Reaction develops rapidly after Ag exposure due to preformed Ab
Delayed response due to production of arachidonic acid metabolites (leukotrienes)
Leads to systemic vasodilation, brnchioconstriction and inflammation
Wheal-single lesion of uriticaria described as erythematous plaque or papule with central pallor
Test: skin test for specific IgE
Treat with epineprhine
Examples: anaphylaxis-Bee sting, food/drug allergy,
allergic and atopic disorders-rhinitis, hay fever, eczema, hives, asthma
Type II Hypersensitivity
Cytotoxic-Ab mediated
IgM, IgG bind to fixed Ag on enemy cell leading to cellular destruction
3 mechanisms
Opsonization leading to phagocytosis or complement activatiotn
Complement mediated lysis (C5-C9)
Ab-dependent cell mediated cytotoxicity usually due to NK cells or marcophages
Decreased C3 in drawn serum
Tests:
Direct Coombs:detect Abs that HAVE adhered to patient’s RBCs
Indirect Coombs: detects Abs that CAN adhere to other RBCs
Examples: autoimmune hemolytic anemia, pernicious anemia, idophathic throbocytopenic purpura, erythorblastosis fetalis, Acute hemolyic transfusion reactons-ABO incompatibility
Rheumatic fever, Goodpasture, Bullous pemphigoid, Pemphigus vulgaris, myasthenia gravis
Type III Hypersensitivity
Immune complex: Ag-Ab (IgG) complexes activate complement which attracts neutrophils
neutrophils release lysosomal enzymes
Decreased C3 in drawn serum
Examples: Lupus, Polyarteritis nodosa, Poststreptococcal glomerulonephritis, serum sickness, arthrus reaction
Serum Sickness
An immune complex disease in which Abs to the foreign proteins are produced (takes 5 days)
Immune complexes form and are deposited in membranes where they fix complement leading to tissue damage
Fibrinoid necrosis and neutrophil infiltration
Most serum sickness is caused by drugs acting as haptens
fever, uriticaria, arthralgias, proteinuria, lymphadenopathy (5-10 days after Ag exposure)
Hypocomplimentemia
(Chimeric Abs, non human Igs-venom, penicillin, cefactor and trimethoprim-sulfamethoxale)
Arthurs Reaction
Local subacute mediated hypersensitivity reaction
Intradermal infection of Ag induces Ab which form Ag-Ab complexes in the skin
Characterized by: edema, necrosis and activation of complement
Test: immunofluorescent staining
Type IV hypersensitivity
Delayed (T cell mediated)
Sensitized T lymphocytes encounter Ag and then release lymphokines (leads to macrophage activation-NO Abs)
Occurs 1-2 days later-meidated by Th1 lymphocytes releasing IFN-y
Examples: transplant rejection, TB skin tests, contact dermatitis, MS, Guillain Barre, GVH,
Allergic Reaction to blood transfusion
Type I hypersensitivity
Against plasma proteins in transfused blood
Clinical: uriticaria, pruritus, wheezing, fever
Treatment: antihistamines
Anaphylactic Blood transfusion reaction
Severe allergic reaction
IgA deficient individuals must receive blood products that lack IgA
Clinical: dyspnea, bronchospasm, hypotension, respiratory arrest, shock
Febrile nonhemolytic transfusion reaction
Type II hypersensitivity reaction
Host Abs against donor HLA Ags and leukocytes
Clinical: fever, headache, chills, flushing
Acute hemolytic transfusion reaction
Type II hypersensitivity
Intravascular hemolysis (ABO group incompatibility) or extravascular hemolysis (host Ab reaction against foreign Ag on donor RBCs)
Clinical: fever, hypotension, tachypnea, tachycardia, flan pain, hemoglobinemia, jaundice
Chest and or back pain
DIC or rneal failure
X-linked agammaglobulinemia
Defect: defect in BTK-tyrosine kinase
No B cell maturation
X linked recessive-Boys
Presentation: recurrent bacterial and enteroviral infections after 6 months (decreased maternal IgG)
Giardia Lamblia gastroenteritis due to decreased Abs
Findings: decreased CD19 and CD20
Decreased pro-B, decreased Ig of all classes
Absent scanty lymph nodes and tonsils-no germinal centers or follicles
Increased risk of encapsulated bacteria
Selective IgA deficiency
Majority ASYMPTOMATIC
Can see airway and GI infections, autoimmune diesease, Atopy-predisoposition to allergic reactions
Anaphylaxis to IgA containing products-blood transfusions!
Normal IgM and IgG
Common variable immunodeficiency
Defect in B cell differentiation
Can be acquired in 20s and 30s
Increased risk of autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections (in adults and children)
Decreased plasma cells and immunoglobins
thymic aplasia (DiGeorge Syndrome)
22q11 deletion-failure to develop 3rd and 4th pharyngeal pouches-absent thymus and parathyroids (detected by FISH)
Presentation: tetany (hypocalcemia), recurrent viral/fungal infections, conotruncal abnormalities (tetraology of Fallot/truncus arteriosus0
Findings: decreased T cells, decreased PTH, decreased Ca
Absent thymic shadow on Chest X ray
Decreased paracortex
IL-12 receptor deficiency
AR
Decreased TH1 response
Presentation: disseminated mycobacterial and fungal infections
May present after administration of BCG vaccine
Findings: decreased IFN-y
AD hyper IgE syndrome (Job Syndrome)
Deficiency of TH17 cells due to STAT3 mutation leading to impaired recruitment of neutrophils to sites of infection
Presentation: Staph AbscEES, retained baby TEETH, EczEma, coarse FacEEEs-widened bridging head
Findings: increased IgE
Decreased IFN-y
Chronic mucocutaneous candidiasis
T cell dysfunction
Presentation: noninvasive Candida albicans infections of skin and mucous membranes
Findings: absent T cell proliferation in response to candida Ags
Absent cutaneous reaction to Candida Ags
Severe Combined Immunodeficiency
Defective IL-2R gamma chain-(most common-X-linked)
Adenosine deaminase deficiency (AR)-toxic accumulation of deoxyadenosine affects dividing T lymphocytes
Presentation: failure to thrive, chornic diarrhea, thrush (candidiasis),
Recurrent bacterial, viral, fungal, and protozoal infections
Treatment: bone marrow transplant (no concern for rejection)
Findings: decreased T cell receptors excision circles (CD3)
Absence of thymic shadaw
No germinal centers-hypogammaglobinemia
Anergy to candidiasiss test-no macrophages, CD4, CD8 or NK cells)
Ataxia Telangiectasia
Defects in ATM gene leadign to DNA double strand breaks and cell cycle arrest
Increased cancer risk
Presentation: cerebellar defects (atrophy), spider angiomas, IgA deficiency-repeated sinopulmonary infections
Findings: Increased AFP
Decreased IgA, IgG, and IgE
Lymphopenia
Hyper IgM syndrome
Most commonly due to defective CD40L on TH cells leading to class switching defect
X linked receessive-Boys
Presentation: severe pyogenic infections early in life,
opportunistic infection with pneumocystis, Cryptosporidium, CMV
Recurrent sinus and airway infections-decreased IgA
Findings: increased IgM, decreased IgG, IgA, and IgE
Treatment: IV gamma globulin
Wiskott-Aldrich syndrome
Mutation in WAS gene
T cells unable to reorganize actin cytoskeleton
X linked recessive-Boys
Presentation: Thrombocytopenic purpura (bleeding, petechiae, hematemesis), Eczema, recurrent infections
Increased risk of autoimmune disease and malignancy
Findings: decreased to normal IgG and IgM
Increased IgE and IgA (WEskott Aldrich)
Fewer and smaller platelets
Encapsulated and opportunistic organisms
Leukocyte adhesion deficiency type 1
Defect in LFA-1 integrin (CD18) on phagocytes
Impaired migration and chemotaxis
AR
Presentation: recurrent bacteria skin and mucosal infections Absent pus formation Impaired wound healing Delayed separation of umbilical cord Gingivitis and peridontitis
Findings: increased neutrophils but absence at infection sites
Inability to synthesize beta-2 integrins-Mac1 and LFA affecting tight adhesion, crawling and transmigration
Chediak Higashi syndrome
Defect in lysosomal trafficking gene
Microtubule dysfunction in phagosome-lysosome fusion
AR
Presentation: recurrent pyogenic infections by staphylococci and streptococci Partial albinism Peripheral neuropathy Progressive neurodegeneration Inflitrative lymphohistocytosis Nystagmus
Findings: giant granules in neutorphils and platelets
Pancytopenia
Mild coagulation defects
abnormal melanin storage in melanocytes-albinism
Chronic granulomatous disease
Defect of NADPH oxidase leading to decreased reactive oxygen species
Absent respiratory burst in neutrophils
Decrease activation of granule proteases
Increased susceptibility to catalase + organisms which can destroy own H202 production by metabolism
Recurrent infections: pneumonia, skin and organ abscesses, suppurative adenitis, and osteomyelitis
Diffuse granuloma formation
Findings: abnormal dihydrohodamine (flow cytometry test)-no fluorescence=CGD
Nitroblue tetrazolium blue test-no blue (yellow is normal)
Hyperacute Transplant rejection
Within minutes
Pre-existing recipient Abs react to donor Ag (type II hypersensitivity) and activate complement
Widespread thrombosis of graft vessels leading to ischemia and necrosis-becomes cyanotic and mottled
Fibrinoid necrosis and thrombotic occlusion
Graft must be removed
Acute Transplant rejection
Weeks to months
Mediated by host T cell lymphocyte sensitization against graft MHC Ags
Generally asymptomatic but can develop fevers, chills, malaise and arthralgias
Increased creatinine, hypertension, decreased urine output
Neutrophilic inflitrate with necrotizing vasculitis
Cellular: CTLs activated against donor MHCs
Humoral: Abs develop after transplant
Vasculitis of graft vessels with dense interstitial lymphocytic inflitrate (cell mediated)
Prevent/reverse with calcineurin inhibitors or corticosteroids
Chronic transplant rejection
Months to years
FIBROSIS-collagen in vessels
Recipient T cells perceive donor MHC as recipient MHC and react against donor Ags presented
Both cellular and humoral components
Scant inflammatory cells and interstitial fibrosis
Parenchyma atrophy
Vascular wall thickening and luminal narrowing
Organ specific:
Kidney: Worsening hypertension, increased creatinine, proteinuria
Vascular fibrosis, glomerulopathy
Heart: atherosclerosis
Lungs: bronchiolitis obliterans-fibrotic obstruction, fibropurlen exudate and granulation tissue, replaced by CT
Liver: vanishing bile ducts
Irreversible
Graft Vs. Host disease
Bone marrow and liver transplants
Grafted immunocompetent T cells proliferate in the immunocompromised host and reject host cells with “foreign” proteins-severe organ dysfunction
CD4 and CD8 cells destroy tissue
Maculopapular rash, jaundice, diarrhea, hepatosplenomegaly
Leprosy
Caused by mycobacterium leprae-Acid fast
Likes cool temperatures-infects skin and superficial nerves- invades Scwann cells
Testicular destruction and blindness, paresis and regional anesthesia
Resevoir: Armadillos
Lepramatous: presents diffusely over the skin with lion like facies
Communicable by low cell mediated immunity with humoral Th2 response
-lepromin test
Increased bacteria load within macrophages
Tuberculoid:
Limited to few hairless skin plaques
Characterized by high cell mediated immunity with a largely Th1 response
+ lepromin test-indurated nodule
Treatment: dapsone and rifampin for 6 months for tuberculoid
Dapsone, rifampin and clofazamine for 2-5 years for lepoamtions
