Chapter 4 - Immunopathology Flashcards
List the different types of effector cells in innate immunity.
Effector cells: phagocytic cells, NK cells, mucosal/endothelial cells
What is innate immunity?
Innate immunity: nonadaptive immune response to microbial pathogens
What do TLRs do?
TLRs: recognize nonself antigens on pathogens and damaged tissue antigens
What are PAMPs?
PAMPs: pathogen-associated molecular patterns
What are DAMPs?
DAMPs: damage-associated molecular patterns
What is NFκβ?
NFκβ: “master switch” to nucleus for induction of inflammation
What are NLRs?
NLRs: cytosolic receptors in monocytes/macrophages, dendritic cells
NLRs function in concert with what?
NLRs: function in concert with TLRs
What do activated NLRs form?
Activated NLRs: form multiprotein inflammosome complexes
What do inflammasomes activate resulting in what?
Inflammosomes activate caspase-1 → ↑secretion IL-1β and IL-18 → attract immune cells to sites of infection
What does hepcidin do?
Hepcidin: keeps iron away from bacteria
What is IL-6?
IL-6: key cytokine for stimulating APR synthesis/release from liver
Name four protective APRs.
Protective APRs: CRP, C3b, C5a, ferritin
What do protective gut bacteria do?
Protective gut bacteria: limit dominance, compete for nutrients, activate host defenses
What do defensins do?
Defensins: attract neutrophils, prevent microbial colonization of mucosa
Name two physical barriers.
Physical barriers: skin, mucous membranes
What does fever inhibit?
Fever: inhibits viral/bacterial reproduction
What does IFN-γ activate?
IFN-γ: activates macrophages
What do IFN-α and IFN-β inhibit?
IFN-α and IFN-β: inhibit viral growth
What do B lymphocytes produce?
B lymphocytes: humoral response (antibodies)
What do antibodies do?
Antibodies: destroy extracellular microbial pathogens
What do naive B cells produce?
Naïve B cells produce IgM and IgD
Class (isotype) switching to produce other Igs involves what?
Class (isotype) switching to produce other Igs involves changes in the heavy chain locus in the constant region of the gene
What is involved in isotype switching?
CD40 ligands, cytokines, and CD4 helper T cells are involved in isotype switching
CD4 and CD8 T lymphocytes are part of what type of immunity?
CD4 and CD8 T lymphocytes: cell-mediated immunity
What does CMI do?
CMI: destroys intracellular microbial pathogens
Where is MHC located and what is it collectively known as?
MHC: HLA system; chromosome 6
MHC is located on what cells?
MHC: located on all nucleated cells/platelets except RBCs
HLA genes are transmitted from whom to whom?
HLA genes: transmitted from parents to child
Class I molecules are encoded on what three loci?
Class I molecules: HLA-A, HLA-B, and HLA-C loci
How molecules encoded by the HLA-A, HLA-B, and HLA-C loci are expressed?
HLA-A, HLA-B, and HLA-C loci: molecules codominantly expressed
What two cell types recognize class I molecules?
Class I molecules: recognized by CD8 T cells/NK cells
Where are class II molecules encoded?
Class II molecules: HLA-D region (DP-DQ-DR subregions)
Class II molecules are located on what cell types?
Class II molecules on APCs: B cells, macrophages, dendritic cells
Name two applications of HLA testing.
HLA testing: transplantation workup for graft compatibility, disease risk
Developing anti-HLA antibodies can occur in what three scenarios?
Developing anti-HLA antibodies: pregnancy, blood transfusion, previous transplant
What is type I hypersensitivity?
Type I: IgE activation of mast cells/basophils
In type I HSR, allergens are first processed by what?
Allergens first processed by APCs (macrophage/dendritic cells)
APCs interact with what cell type?
APCs interact with CD4 TH2 cells
What does IL-4 do?
IL-4: plasma cells switch from IgM to IgE synthesis
What does IL-5 do?
IL-5: stimulates production/activation of eosinophils
What happens during mast cell activation?
Mast cell activation: allergens cross-link allergen-specific IgE antibodies
Describe what occurs during the early phase reaction of type I HSR.
Early phase: release preformed histamine, eosinophil chemotactic factor
Describe how the mediators released by mast cells differ between the early phase and late phase.
Mast cell releases mediators: early phase preformed, late phase synthesized
Name three late phase mediators.
Late phase mediators: PGs, LTs, PAF
List two test used to evaluate for type I HSR.
Type I testing: scratch test, RAST test
What is type II HSR?
Type II: antibody directed against antigens on cell membrane/in extracellular matrix
Give two clinical examples of cell lysis IgM-mediated.
Cell lysis IgM-mediated: cold IHA, ABO mismatch
Give two examples of cell-lysis that is IgG-mediated.
Cell lysis IgG-mediated: Goodpasture syndrome, acute rheumatic fever
Give two examples of phagocytosis in type II HSR.
Phagocytosis: warm autoimmune hemolytic anemia, ABO hemolytic disease of newborn
Give two examples of ADCC that is IgG-mediated.
ADCC IgG-mediated: NK attaching to IgG in virally infected cell or cancer cell
Give an example of IgE-mediated ADCC.
ADCC IgE-mediated: eosinophil destruction of IgE-coated helminth
Give two examples of IgG autoantibodies against cell surface receptors.
IgG autoantibodies against cell surface receptor: myasthenia gravis, Graves disease
Name two tests to evaluate type II HSR.
Type II tests: indirect/direct Coombs tests
What is type III HSR?
Type III: circulating antigen-antibody complexes that damage tissue
Describe the mechanism of tissue damage in type III HSR.
Type III: ICs activate complement that attract neutrophils, leading to tissue damage
What is an Arthus reaction?
Arthus reaction: localization of ICs
Give an example of an Arthus reaction.
Arthus reaction: farmer’s lung
Which types of HSRs are antibody-mediated?
Antibody-mediated HSRs: types I, II, III
What is type IV HSR?
Type IV: T cell-mediated immunity; often delayed
Name three functions of CMI.
CMI functions: infection control (e.g., TB), graft rejection, tumor surveillance
What cell types are involved in DTH?
DTH: involves macrophages (APCs) and CD4 T cells
In DTH, macrophages interact with what cell type via what?
Macrophages interact via their class II antigen sites with naïve CD4 T cells
In DTH, Naïve CD4 cells differentiate into what cell type? What is the stimulus for this differentiation? How do these cells continue to differentiate?
Naïve CD4 cell → CD4 TH1 memory cells: IL-12 activated macrophage, γ-IFN memory T cell
What do activated CD4 TH1 cells release? What results?
Activated CD4 TH1 cells release IFN-γ: ↑macrophage phagocytosis/killing phagocytosed pathogen
What do activated macrophages become?
Activated macrophages become epithelioid cells
In DTH, what does a granuloma consist of?
Granuloma: epithelioid cells, multinucleated giant cells, rim CD4 T cells
A PPD reaction is an example of what type of HSR?
PPD reaction: example of DTH
What are Langerhans cells?
Langerhans cells: APC of skin; dendritic cell
PPD reaction is dependent on what?
PPD reaction dependent on CMI competency
CMI is diminished in what types of people?
CMI diminished in elderly/people with AIDS
The CD4 TH17 subset secretes what in order for what to occur?
CD4 TH17 subset: cytokines recruit neutrophils/monocytes
DTH in chronic asthma involves what cell types?
DTH chronic asthma: macrophages, CD4 TH2 subset cells, eosinophils
Give four examples of what may cause allergic contact dermatitis.
Allergic contact dermatitis: poison ivy, topical drugs, rubber, chemicals
Describe what occurs during the induction phase of contact dermatitis.
Induction phase: CD4 TH1 subset memory cells in lymph nodes; effector cytotoxic CD8 memory T cells in circulation
Describe the elicitation phase of contact dermatitis.
Elicitation phase: cytokine release from circulating effector T lymphocytes
Describe the key clinical findings of allergic contact dermatitis.
Allergic contact dermatitis: pruritus, erythema, edema, vesicles
In CD8 T cytotoxicity, what do T cells interact with?
CD8 T cytotoxicity: T cells interact with altered class I antigen sites
In CD8 T cell cytotoxicity, which cell types are lysed?
CD8 T cell cytotoxicity: lysis of neoplastic, virus-infected, donor graft cells
What test is used to confirm allergic contact dermatitis?
Patch test: confirm allergic contact dermatitis
What is anergy?
Anergy: no response to mitogenic assays and/or skin response to Candida
What is the most important requirement for successful transplantation?
ABO blood group compatibility: most important requirement for successful transplantation
List two factors that enhance graft viability.
Graft viability: absence preformed anti-HLA antibodies; close matches for HLA-A, HLA-B, HLA–C-DR loci
What is an autograft? How does the survival rate compare to other types of grafts?
Autograft: self to self; best survival rate
What is a syngeneic graft?
Syngeneic graft: graft between identical twins
What is an allograft?
Allograft: graft between genetically different individuals of same species
What is a xenograft?
Xenograft: graft between two different species
Hyperacute rejection is what type of reaction and what type of HSR?
Hyperacute rejection: irreversible; type II
Describe the pathogenesis of hyperacute rejection.
Hyperacute rejection: small vessel vasculitis; neutrophils, fibrinoid necrosis, thrombosis
Name two causes of hyperacute rejection.
Causes: ABO mismatch, anti-HLA antibodies
What is the most common type of rejection? Is it reversible? What type of HSR is this type of rejection?
Acute rejection: most common (MC) rejection; reversible; type II/IV
What is the key cell in donor grafts?
Key cell in donor graft: dendritic cells with classes I and II MHC molecules
Acute rejection type IV is characterized by what?
Acute rejection type IV: endothelialitis, interstitial tissue inflammation
What are the key cells in the recipient in type IV HSR?
Key cells in recipient in type IV: CD4 T cell (DTH), CD8 T cell (cytotoxicity)
What is acute rejection type II caused by?
Acute rejection type II: anti-HLA antibodies
Describe a finding of less severe/late onset acute rejection.
Acute rejection less severe/late onset: vessels show thicker intima similar to atherosclerosis
Describe chronic rejection.
Chronic rejection: irreversible; months/years; previous acute rejection immunosuppression
What is the most common infection in transplantation recipients?
CMV: MC infection in transplantation recipients
What is the most common infection in solid organ transplantation?
Solid organ transplantation: Candida MC infection
What is the most common infection in bone marrow transplantation?
Bone marrow transplantation: Aspergillus MC infection
HLA matching of the donor and recipient is very important in what types of transplantations, preventing what?
HLA matching donor/recipient: very important in kidney/bone marrow transplants; prevents hyperacute rejections
How do you test for compatibility of the recipient and donor class II antigens?
Compatibility donor/recipient lymphocytes: mix together to see if mitoses occur (incompatible)
Describe lymphocyte cross-match.
Lymphocyte cross-match: recipient serum against donor lymphocytes; test for anti-HLA antibodies (concept similar to blood transfusion cross-match)
Describe three key prerequisites for GVH.
GVH reaction: graft has T cells; recipient immunocompromised; recipient has foreign MHC antigens
List four different causes of GVH.
Causes GVH: bone marrow/liver transplant; blood transfusion to T cell–immunodeficient patient, newborn
What occurs during acute GVH?
Acute GVH: donor CD8 cells attack foreign MHC antigens
List four clinical findings of acute GVH.
Clinical: jaundice, diarrhea, dermatitis, hepatosplenomegaly
Define autoimmune.
Autoimmune: lose self-tolerance; host tissue considered foreign
List four types of self-antigens.
Self-antigens: class I/II MHC, nuclear/cytoplasmic
In autoimmune diseases, class I-related diseases and class II-related diseases are more common in men or women?
Autoimmune: class I–related men > women; class II-related women > men
In genetically susceptible individuals, what is required to initiate an autoimmune disease?
Autoimmune: genetic predisposition involving HLA system + environmental trigger
If an infection is the environmental trigger for autoimmune disease, what does the infection do?
Infections as trigger: upregulates co-stimulators on APCs
What are co-stimulators?
Co-stimulators: APCs with both class I and II antigens
What are self-reactive lymphocytes?
Self-reactive lymphocytes: IL-2 causes clonal proliferation of CD4 and CD8 T cells
What is molecular mimicry? Provide an example.
Sharing antigens between host and pathogen: S. pyogenes−rheumatic fever
Name three polyclonal B cell activators. Polyclonal activation of B lymphocytes results in what?
Polyclonal B cell activators: EBV, HIV, CMV; produces autoantibodies
Name six viruses that may act as a trigger for autoimmune disease.
Viruses as triggers: coxsackievirus, measles virus, CMV, EBV, HHV-6, influenza virus
Name four bacterial triggers for autoimmune disease.
Bacterial triggers: S. pyogenes, C. trachomatis, M. pneumoniae, C. jejuni
How can procainamide and hydralazine act as an environmental trigger for autoimmune disease?
Procainamide, hydralazine: autoantibodies against histones; lupus-like syndrome
Give an example of drug alteration resulting in autoimmune disease.
Drug alteration: methyldopa alters Rh antigens on RBCs; AIHA
Describe the role of hormones as a trigger for autoimmune disease.
Autoimmune disease women > men: ? role of estrogen
List four tissues with sequestered antigens.
Tissues with sequestered antigens: sperm, lens, uveal tract, CNS
Name two types of intracellular sequestered antigens.
Intracellular sequestered antigens: DNA, histones
Describe how UV light may trigger autoimmune disease.
UV light: apoptosis keratinocytes; autoantibodies against nuclear antigens with formation of ICs
What do non-MHC genes do?
Non-MHC genes: interfere with immune regulation and self-tolerance
The PTPN-22 gene is implicated in what two autoimmune diseases?
PTPN-22 gene: rheumatoid arthritis, type 1 DM
The NOD-2 gene is implicated in what autoimmune disease?
NOD-2 gene: implicated in Crohn disease
List two important markers of autoimmune disease.
IRF5, STAT4: important markers of autoimmune disease
List two organ-specific autoimmune disorders.
Organ-specific: Addison disease, pernicious anemia
List three systemic autoimmune disorders.
Systemic: SLE, rheumatoid arthritis, systemic sclerosis
What are serum ANA?
Serum ANA: antibodies against DNA, histones, acidic proteins, nucleoli
What is the most useful screening test in autoimmune disease?
Serum ANA: most useful screening test in autoimmune disease
Anti-dsDNA is positive in patients with what disease?
Anti-dsDNA: SLE with glomerulonephritis
Anti-histone antibodies are present in what disease?
Anti-histone: drug-induced lupus
Anti-Sm antibodies are present in what disease?
Anti-Sm: SLE
Anti-RNP antibodies are present in what two diseases?
Anti-RNP: systemic sclerosis, SLE
Anti-nucleolar antibodies are present in what disease?
Anti-nucleolar: systemic sclerosis
Describe the serum ANA test.
Serum ANA: fluorescent antibody test; pattern and titer
The presence of a rim pattern of fluorescence in a serum ANA test is associated with what?
Rim pattern: associated with anti-dsDNA antibodies
Who does SLE primarily affect?
SLE: women of childbearing age
List two genetic factors in SLE.
Genetic factors: HLA associations; complement deficiencies
List four environmental triggers for SLE.
Environmental triggers: EBV, UV light, estrogen, medications
Describe two mechanisms of injury in SLE.
Mechanism injury: ICs (type III); autoantibodies (type II)
Name four constitutional symptoms in SLE.
Constitutional: fatigue (MC), fever, arthralgia, weight loss
Name four hematologic findings in SLE.
Hematologic: anemia, neutropenia, lymphopenia, thrombocytopenia
Name two lymphatic findings in SLE.
Lymphatic: generalized lymphadenopathy, splenomegaly
Describe two features of arthralgias in SLE.
Arthralgia (joint pain): very common initial complaint; morning hand stiffness
Describe four features of arthritis in SLE.
Arthritis: symmetrical; hands (PIP, MCP), wrist; nonerosive, nondeforming
Describe three features of a malar rash.
Malar rash: photosensitive; cheeks/bridge of nose, sparing nasolabial folds
What do immunofluorescence studies of a malar rash show?
IF: basement membrane involved/uninvolved skin
What is the most common visceral organ involved in SLE?
Kidney MC visceral organ involved
What is the most common cardiac manifestation in SLE?
Fibrinous pericarditis with/without effusion: MC cardiac manifestation
What are two features of Libman-Sacks endocarditis?
Libman-Sacks endocarditis: sterile vegetations MV; MV regurgitation
Give two examples of serositis, a key finding in SLE.
Pleuritis, pericarditis: example is serositis, key finding in SLE
In SLE, interstitial fibrosis leads to what?
Interstitial fibrosis: restrictive lung disease, hypoxemia
List four CNS findings in SLE.
CNS: headache (MC), psychosis, stroke (APL), seizures
Name two pregnancy-related findings in SLE.
Pregnancy: complete heart block in newborn (IgG anti-SS-A antibodies); recurrent spontaneous abortions (placental vessel thrombosis; APL)
What is the most common drug involved in drug-induced lupus?
Procainamide: MC drug in drug-induced lupus
List three ways drug-induced lupus differs from SLE.
Drug-induced lupus vs SLE: antihistone antibodies, ↓incidence renal/CNS disease, symptoms disappear when drug removed
What is the best screening test for SLE?
Serum ANA best screen for SLE
How can you confirm the diagnosis of SLE?
Confirm SLE: anti-dsDNA/anti-Sm antibodies; high specificity
APL antibodies may be present in the SLE patient with what two clinical findings?
APL antibodies: strokes, recurrent abortions
What is an LE cell?
LE cell: neutrophil containing phagocytosed altered DNA
What is the band test?
Band test: IF along basement membrane skin biopsy; ICs
What are the two most common causes of death in SLE?
MC causes of death: infection, CRF
List three features of systemic sclerosis.
Systemic sclerosis: vascular dysfunction, fibrosis skin/visceral organs, immune dysfunction
What are the two major forms of systemic sclerosis?
Types: diffuse/limited systemic sclerosis
Describe the epidemiology of systemic sclerosis.
Systemic sclerosis: female dominant, ↑black females
Describe the etiology of systemic sclerosis.
Systemic sclerosis: ↑CD4 TH2 cells; ↑DNA-topoisomerase, centromere antibodies
What is the earliest manifestation of systemic sclerosis? What does this manifestation lead to?
Endothelial dysfunction: earliest manifestation; vasculitis
Describe the role of vasoconstrictors and vasodilators in endothelial dysfunction in systemic sclerosis.
Endothelial dysfunction: ↓NO, PGI2; ↑endothelin
Describe the mechanism of fibrosis in systemic sclerosis.
Mechanism of fibrosis: ↑PDGF, TGF-β
What is the most common initial sign of systemic sclerosis?
Raynaud phenomenon: MC initial sign of systemic sclerosis
List two digital findings in systemic sclerosis.
Digital findings: sclerodactyly, infarction
What is the most common target organ in systemic sclerosis?
Skin: MC target organ
List four skin findings in systemic sclerosis.
Skin: edema, fibrosis, dystrophic calcification, radial furrowing around mouth
List four esophageal findings in systemic sclerosis.
Esophagus: dysphagia solids/liquids, dysmotility, strictures/ulceration, Barrett esophagus
List two stomach findings in systemic sclerosis.
Stomach: dysmotility/bloating
List three small intestine findings in systemic sclerosis.
Small intestine: malabsorption, dysmotility, diverticula
List two large intestine findings in systemic sclerosis.
Large intestine: dysmotility, constipation
List two respiratory findings in systemic sclerosis.
Respiratory: PH, interstitial fibrosis
What is the most common cause of death in systemic sclerosis?
Systemic sclerosis: respiratory failure MCC death
List two renal findings in systemic sclerosis.
Renal: hyperplastic arteriolosclerosis, malignant hypertension
What is CREST syndrome?
CREST: calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia
What tests are positive in systemic sclerosis?
Systemic sclerosis: +ANA, anti-topoisomerase/centromere antibodies
What tests are positive in CREST syndrome?
CREST syndrome: centromere antibodies, +ANA
Name two noninfectious inflammatory myopathies.
Noninfectious inflammatory myopathies: PM, DM
Describe the epidemiology of polymyositis.
PM: female dominant; ↑blacks; ↑risk malignancies (lung, bladder, lymphoma)
Describe the etiology and pathogenesis of polymyositis.
PM: CD8 T cells/CD4 TH1, viruses (HIV, HTLV-1), environmental triggers → autoantibodies
List the muscles involved in polymyositis.
PM muscle involvement: upper/lower extremity, trunk, shoulders/hips, neck extensors
Describe the dysphagia present in PM.
PM: oropharyngeal/upper esophagus dysphagia solids/liquids
Respiratory difficulties in PM are related to what?
PM: interstitial fibrosis
What are the lab findings in PM?
PM: ↑serum CK/aldolase; +ANA; ↑anti–Jo-1
In PM, what do the EMG and biopsy show?
PM: EMG (myopathic dysfunction); biopsy (lymphocytic/macrophage infiltrate, atrophy not prominent)
What is the first-line treatment for PM?
PM: corticosteroids first-line treatment
Describe the etiology and pathogenesis of DM.
DM: CD4 T cells target skeletal muscle capillaries; antibody/complement involvement
List two cutaneous findings in DM.
DM: Gottron patches over knuckles/PIP joints; heliotrope eyes
What do muscle biopsies show in DM?
DM: muscle atrophy; lymphocytic infiltrate
What is MCTD?
MCTD: signs/symptoms ∼SLE, systemic sclerosis, PM
Describe the epidemiology of MCTD.
MCTD: female dominant, renal disease uncommon
Describe the etiology and pathogenesis of MCTD.
MCTD: B/T cell activation; antibodies against ribonucleoprotein
List two vascular findings in MCTD.
MCTD: Raynaud phenomenon, sclerodactyly
List two MSK findings in MCTD.
MCTD: arthralgia/arthritis hands
List one GI finding in MCTD.
MCTD gastrointestinal: esophageal dysmotility
List two MCTD respiratory findings.
MCTD respiratory: pulmonary hypertension, pleuritis
List one cardiovascular, hematologic, and CNS finding in MCTD.
MCTD: pericarditis, leukopenia, trigeminal neuralgia
List two lab findings in MCTD.
MCTD: +ANA, anti-ribonucleoprotein (U1-RNP antibodies)
List four risk factors for immunodeficiency disorders.
Risk factors: prematurity, autoimmune disease, lymphoma, HIV, immunosuppressive agents
What is the most common cause of death due to infection worldwide?
AIDS: MCC death due to infection worldwide
Name two features of HIV.
HIV: retrovirus; reverse transcriptase
What is reverse transcriptase?
Reverse transcriptase: converts viral RNA to proviral dsDNA
What is the most common virus causing AIDS in the U.S.?
HIV-1: MC virus causing AIDS in U.S.
Describe two features of HIV-2.
HIV-2: more restricted than HIV-1; most prevalent in Western Africa
HIV cannot penetrate what?
HIV cannot penetrate intact skin/mucosa
What does the gag gene in HIV do?
Gag gene: synthesis p24 core antigen
What does the env gene in HIV do?
Env gene: synthesis gp120
What does the pol gene in HIV do?
Pol gene: synthesis of reverse transcriptase, integrase, protease
What is the most common cause of AIDS?
Sexual transmission MC cause AIDS
What increases the risk for HIV?
STDs ↑risk for HIV
What is the second most common cause of AIDS?
IVDA: 2nd MCC AIDS
What is the most common cause of pediatric AIDS?
Pediatric AIDS: MC due to vertical transmission
What is the most common cause of HIV in health-care workers?
Accidental needlestick: MCC HIV in health-care workers
How do blood banks screen blood products for HIV?
Blood products: blood bank screens for HIV with p24 antigen assay
List four body fluids with HIV.
Body fluids with HIV: blood, semen/vaginal secretions, breast milk
List the different cell types that can be infected by HIV.
Cells infected by HIV: CD4 T cells, macrophages, dendritic cells, astrocytes
HIV is cytotoxic to what cell type?
HIV cytotoxic to CD4 T cells
What two cell types are important reservoirs for HIV?
Macrophages/dendritic cells: reservoirs for HIV
How does HIV enter the body?
HIV enters interrupted mucosal surfaces genital tract/anus
What cell type is the major reservoir for HIV during latency?
Follicular dendritic cells: major reservoir for HIV during latency
Describe the process of HIV binding.
HIV binding: gp120, chemokine co-receptors
What does viral protease do?
Viral protease: uncoats virus, releasing RNA
What does reverse transcriptase do?
Reverse transcriptase: viral RNA → dsDNA
What does viral integrase do?
Viral integrase: inserts viral DNA into host DNA; provirus
In HIV infection, activation of the host cell leads to what?
Activation of host cell: transcription for IL-2 + receptor
Describe the role of cytokines in the HIV life-cycle.
Cytokines: HIV genome transcribes viral RNA
What is the HIV core structure?
HIV core structure: protein surrounding viral RNA
Describe the role of the HIV core structure in the life-cycle of HIV.
HIV core structure: acquires lipid bilayer from cell membrane → forms bud → detaches as infective viral particle
Describe the acute phase of HIV infection.
Acute phase: 3–6 weeks postinfection; flu-like symptoms; greatest risk coital contraction HIV
Describe the asymptomatic carrier phase of HIV infection.
Asymptomatic carrier phase: virus replicates in follicular dendritic cells/macrophages
Describe the early symptomatic phase of HIV infection.
Early symptomatic phase: lymphadenopathy, hairy leukoplakia, oral candidiasis
What are the criteria for AIDS?
AIDS: CD4 T-cell count ≤200 cells/mm3 and/or AIDS-defining lesion
List four AIDS-defining malignancies.
AIDS-defining malignancies: Kaposi sarcoma, Burkitt lymphoma 1° CNS lymphoma, cervical carcinoma
What is the cause of death in AIDS?
Death in AIDS: disseminated infection (CMV, MAI)
In AIDS, hypergammaglobulinemia results from what?
AIDS: hypergammaglobulinemia due to polyclonal B cell stimulation by EBV/CMV
In AIDS, decreased CD4 T cells results in what?
↓CD4 T cells: lymphopenia, anergy, CD4/CD8 ratio <1
What treatment can be given to pregnant women with AIDS in order to decrease transmission to newborns?
Pregnant woman AIDS: Rx reverse transcriptase inhibitors ↓transmission to newborns
How does early treatment of AIDS affect survival?
Rx AIDS: early Rx improves survival
What is the principal treatment to prevent immune deterioration in AIDS?
HAART: principal Rx to prevent immune deterioration
Describe two features of complement.
Complement: liver synthesis; innate immunity
Complement is only functional in what form?
Complement: cleavage factors functional
What are the anaphylatoxins of complement?
C3a, C5a anaphylatoxins
What is the role of C3b?
C3b opsonization
What does C5a do?
C5a: activate neutrophil adhesion molecules, chemotaxis
What do C5-C9 do?
C5-C9 cell lysis
Describe the classical pathway of complement.
Classical pathway: C1, C4, C2; activated by ICs; requires antibody for activation
What does C1 esterase inhibitor do?
C1 esterase inhibitor: inactivates protease activity of C1
What are the components of the alternative pathway? How is it activated?
Alternative pathway: factor B, properdin, factor D; activated by endotoxins
What is the importance of the lectin pathway?
Lectin pathway: important in destruction of bacteria, fungi, viruses
What does the membrane attack complex consist of?
MAC: C5-C9
What does decay accelerating factor do? It is deficient in what disease?
DAF: enhances degradation C3 and C5 convertase in classical/alternative pathways; deficient in PNH
Describe how deficiencies in complement predispose to infection via two mechanisms.
Complement deficiencies: ineffective opsonization, defects in cell lysis
How do opsonization defects present? What type of organism is responsible?
Opsonization defects: recurrent pyogenic infections; encapsulated bacteria
How do deficiencies in C1, C4 and C2 present? What is the most common presentation?
Deficiencies in C1, C4, C2: autoimmune disease; SLE MC
How does MAC deficiency present?
MAC deficiency: recurrent infection N. gonorrhoeae/meningitidis
What is CH50?
CH50: functional ability complement systems
Describe test results indicating activation of the classical pathway.
Classical pathway activation: decreased C4, C3; normal factor B
Describe test results indicating activation of the alternative pathway.
Alternative pathway activation: decreased factor B, C3; normal C4
What is amyloid?
Amyloid: fibrillar protein; deposited in interstitial tissue; pressure atrophy
Describe the composition of amyloid.
Amyloid: linear filament; β-pleated sheet
Describe Congo red staining of amyloid.
Amyloid: Congo red +; apple green birefringence when polarized
What are the tree major precursor proteins of amyloid?
Major precursor proteins: λ light chains, SAA, APP
List three other amyloid precursor proteins.
Other precursor proteins: transthyretin, β2-microglobulin, prion proteins
Describe the pathogenesis of amyloidosis.
Pathogenesis: misfolded proteins in most cases; monocyte enzyme defects
Describe kidney involvement in amyloidosis.
Kidney: proteinuria with nephrotic syndrome
List two gastrointestinal findings in amyloidosis.
Gastrointestinal: malabsorption, macroglossia
List three cardiac findings in amyloidosis.
Heart: restrictive cardiomyopathy, diastolic dysfunction LHF, conduction defects
Describe nervous system involvement in amyloidosis.
CNS: dementia, peripheral/autonomic neuropathy
Describe liver involvement in amyloidosis.
Liver: hepatomegaly, functional impairment uncommon
Describe spleen involvement in amyloidosis.
Spleen: splenomegaly; white pulp sago spleen, red pulp lardaceous spleen
List one clinical finding in hemodialysis-associated amyloidosis.
Hemodialysis-associated amyloidosis: carpal tunnel syndrome
Describe three hemostasis abnormalities of amyloidosis.
Hemostasis: factor X deficiency, pinch purpura, periorbital hemorrhage
List six techniques used to diagnose amyloidosis.
Diagnosis: serum/urine electrophoresis, BM aspirate, nuclear imaging, echocardiography, tissue biopsy
