Immuno 2

Question 1

Acute Rheumatic Fever/Heart Disease

1. Type of hypersensitivity?
2. Abs to?
3. Pathology is characterized by?
4. Inflammatory cells?
5. What focal development in the heart? Other heart manifestations?

Answer 1

1. Type II
2. M. proteins of S. pyogenes that cross react with cardiac and other antigens
3. Exudative and proliferative inflammatory lesions in CT of heart, joints, and subcutaneous tissue
4. lymphocytes, plasma cells, and giant cells
5. Perivascular inflammatory lesions (Aschoff’s nodules); pericarditis, myocarditis and/or endocarditis, residual rheumatic valvular disease with murmur

Question 2

Acute Rheumatic fever/Heart disease cont.

1. Paryarthritis involves?
2. Can have symptoms of syndeham’s chorea: what are these symptoms? When do they occur?
3. Highest occuring symptoms?

Answer 2

1. Fibrinous exudate and effusion without erosions or pannus, disabeling arthritis
2. Occurs after other symptoms have resolved - involuntary movement of limbs/face
3. 75% polyarthritis, 50% carditis, 15% chorea

Question 3

Type III Hypersensitivity

1. What is this associated with?
2. What is the arthus reaction?
3. Difference in the way large vs. small ICs are dealt with?
4. IC mediated acute necrotizing vasculitis often results in?

Answer 3

1. Immune complexes that either form in tissue or deposit from the circulation: Ag may be endogenous or exogenous
2. Ab is injected IV and diffuses to tissue, then the Ab specific Ag is injected into the skin and the Ag-Ab complex forms –> compliment is activated, inflammatory cells are recruited, mast cells degranulate and cause inflammation with increased vascular permeability –> vasculitis with erythema, edema, and hemorrhage
3. Large ICs are removed by macrophages in the liver, small may circulate and have greater chance of depositing in tissue
4. fibrinoid necrosis

Question 4

Systemic IC diseases

1. What is polyarteritis nodosa? Onset associated with?
2. What is a characteristic of this? Common morphology?
3. What causes serum sickness? Symptoms?

Answer 4

1. systemic vasculitis of kidney, heart, GI, and CNS (lungs are spared); infection
2. All stages of inflammation coexist at the same time; fibrinoid necrosis with occluded lumen
3. Large doses of any high molecular weight compound (venom/abx); pruritic rash first followed by fever, arthritis, GN, lymphadenopathy, splenomegaly, and myalgia

Question 5

IC glomerulonephritis

1. Ags: Exogenous associated with? Endogenous?
2. Common characteristic of all IC-GNs?
3. 2 variations of pathogenesis?
4. What determines location of deposit?
5. 2 clinical similar syndromes associated with IC-GNs and differences?
6. Difference between anti-GBM GN vs IC-GN?

Answer 5

1. components of infectious agents/certain tumor Ags; Lupus
2. Granular IC deposits
3. In situe rxn of Ab with Ag: intrinsic or extrinsic Ag in GBM and Deposition of circulating ICs: deposit in areas of increased pressure and turbulence
4. Charge and size also increased vas. perm
5. Nephritic syndrome (mild proteinuria/edema/hypertension) Nephrotic syndrome (extensive proteinuria/edema/hypertension)
6. Anti-GBM: Ag in BM only IC: larger in subendo.

Question 6

Acute diffuse proliferative GN

1. Post infectious associated with? Nonpostinfection associated with?
2. Pathology? Deposit location? Type of deposits?
3. Children post infection present with?
4. Post-infectious adults causes?
5. Most common cause of nephrotic syndrome?

Answer 6

1. streptoccal pharyngitis or impetigo; lupus
2. Diffuse hypercellularity with inflammatory cells; granular deposit in subepithelium
3. Nephritic syndrome with edema, mild hypertension, hematuria, RBC casts, and hypocomplementemia
4. Some will resolve, some develop chronic GN, others: RPGN
5. membranous GN

Question 7

RPGN

1. Causes? If IC where?
2. What forms from proliferation of epithelial cells and inflammatory infiltrate? What does this cause?
3. What occurs to the GBM? This allows what?
4. What GNs are supepithelial? Subendothelial?

Answer 7

1. immune mediated: either IC or Anti-GBM; subepith
2. crescents form causing compression of the glomerular tuft
3. thickens and ruptures - allows cells, inflammatory mediators, and protein into urinary space
4. RPGN, Acute diffuse proliferative GN, Membranous GN; primary MPGN type I and secondary MPGN

Question 8

Membranous GN

1. Where does IC deposit? What does this cause?
2. Idiopathis vs secondary form?
3. What eventually happens to the GBM? Classic tell?
4. Inflammatory infiltrate? GBM damage associated with?
5. Clinical: 85% present with? 25% present with?

Answer 8

1. subepithelial - GBM spikes and effacement of epithelial foot processes
2. I: autoimmune Abs to renal Ags S: drugs, tumor Ags, lupus, other autoimmune diseases
3. Grows over the deposit –> universal thickening with “wire loop” lesions
4. not much; complement activation and activation of mesangial cells
5. nephrotic syndrome with mild edema; end stage renal failure

Question 9

Membranoproliferative GN (MPGN)

1. Primary MPGN Type I location? TYpe II? (deposits where)
2. Secondary MPGN presentation? Association?
3. Immune pathogenesis?
4. ____ from inflammatory infiltrate, mesangial, and ___ proliferation. The GBM is thickened often showing a “___ ___” especially in ____.
5. Clinical manifestation? 50% progress to?

Answer 9

1. subendothelial (and some mesangial IC); intramembranous
2. like Type I; various infections, neoplasms, lupus, and other autoimmune diseases
3. Pre-formed IC deposit or In situ formation
4. Hypercellularity; endothelial; double contour; Type I (because of extra GBM synthesis)
5. nephritic or nephrotic syndrome with edema, hypertension, and hematuria; end stage renal failure

Question 10

Type IV hypersensitivity

1. DTH: role of TH1?
2. DTH: role of TH17?
3. CMI: role of TH1?

Answer 10

1. secrete IFN gamma that activates macrophages to kill microbes in phagolysosomes
2. secreted IL-17/22: recruits/prolongs survival of neutrophils and induces activation/proliferation of fibroblasts and keratinocytes
3. Secrete IFNgamma and IL-2 that activates Tc to lyse targets with intracellular microbes (viruses) and tumor cells. Also activates NK cells via cytokines

Question 11

DTH

1. Ultimate effector? What does DTH hypersensitivity occur?
2. The model is Tuberculin-type hypersensitivity rxn to purified protein derivative (PPD) from M. tuberculosis: Steps?
3. If macrophage fails to eliminate the stimulus, ____ inflamation occurs and may involve?

Answer 11

1. Activated macrophage; when Ag is not a microbe (eg. plant catechols)
2. initial recognition of PPD –> sentitization –> TH1 memory cells…. 2nd encounter –> elicitation phase –> inflammation and induration (hardening) [increased vas perm allows leakage of fibrinogen to tissue and converted to fibrin and mononuclear infiltrate = induration)…. followed by resolution/healing
3. chronic; Granuloma (epithelial most common) and fibrosis

Question 12

DTH: Allergic Contact dermatitis

1. Ags? What is sensitization?
2. What is elicitation? Infiltrate?
3. What is down-regulation?
4. Acute symptoms?
5. Chronic symptoms?
6. Treatment?

Answer 12

1. chemicals (drugs/plat catechols); Ag-tissue protein processed by langerhans cells –> presented to TH1/TH17 (become memory cells)
2. Ag contact –> activated TH1/TH17 –> secretion of cytokines –> activation of endothelial cells and keratinocytes; basophils, eosinophils, and monocytes
3. PGs from keratinocytes/APCs block TH1 cytokine release
4. pruritic vesicular rash
5. pruritic crusty lesions
6. corticosteroids

Question 13

CMI: Role of Tc

1. What are Tc important for eliminating?
2. Tc released from the ___ must bind Ag via class __ proteins and activated by ___ and ___ (from TH1) to become cytolytic.
3. ___ from APCs stimulates IFNgamma production from ___ cells, ___, and ___.
4. Tc degranulates what? Mechanism?
5. 2 alternative mechanisms?

Answer 13

1. viruses, bacteria, fungi, allogenic transplants, and tumors
2. thymus, I, IL-2 and IFNgamma
3. IL-12; NK; Tc and TH1
4. Perforin and granzyme - induces apoptosis/lysis
5. FasL on Tc to Fas on target cell; TNFbeta from Tc–<both></both>

</both>

Question 14

1. Tissue derivation for: Autograft? Syngraft? Allograft? Xenograft?
2. Graft rejection depends on?
3. Rejection mediated by Ab =? By T cells =?
4. Direct vs. indirect pathway of rejection?

Answer 14

1. same person; genetically similar person; genetically different person; different species
2. Recognition of foreign MHC Ags by host immune system
3. humoral rejection; cellular rejection
4. D: recipient T cells react to donot MHC (dendritic cells) NO ANTIGEN I: donor Ag processing and presentation occurs by recipients dendritic cells

Question 15

Rejection mechanisms

1. Hyperacute: time? Occurs from? Induces?
2. Acute humoral: Time? What occurs?
3. Acute cellular: Infiltrate? what occurs in kidney? Endothelium?
4. Chronic: Time? What occurs in kidneys? Vasculature?

Answer 15

1. min/hrs; from preexisting Abs to MHC or mismatched blood type; damage endothelium –> inflammation, thrombosis, and infarction
2. days/weeks; Ab to endothelial Ags –> necrotising vasculitis, lumen narrows, infarction
3. Extensive T cells; invasion of tubules –> necrosis; injury
4. months/years; intersitial fibrosis, tubular atrophy, loss of renal parenchyma from ischemia; intimal fibrosis and smooth muscle proliferation

Question 16

1. What is graft vs. host disease? Most common? how can it be controlled?
2. Acute GVH involves what organs? Chronic?
3. What is prolong immunodeficiency associated with? Results in?
4. What occurs in Host vs. Graft disease?
5. Kidney transplant: rare rejection? most common?
6. Heart: what occurs with chronic rejection? Most common recurrent disease?

Answer 16

1. Donor cells mount a response; allogenic bone marros; corticosteroids and cyclosporin
2. skin, liver, GI; same but more severe
3. Chemo or delay in repopulating lymphatic organs; Increased risk of infection
4. NK and T cells of recipient attack transplant
5. hyperacute; chronic
6. Arteriopathy in distal epicardial and intramiocardial branches; atherosclerosis

Question 17

1. Liver transplant: rare rejection? What does acute cellular rejection involve? Chronic? Most common recurrent disease?
2. Long term complications in transplantation
3. What is central tolerance? Reculator of +/- selection?
4. Peripheral tolerance: when are self reactive cells induced to be anergic (unresponsive)?
5. How are self reactive cells suppressed?
6. When do self reactive cells undergo apoptosis?

Answer 17

1. Hyperacute/acute humoral; portal inflammation, bile duct injury, and endothelial venous inflammation; arteriopathy; HBV and HCV
2. post-transplantation lymphoproliferative disorder
3. self reactive B and T cells induced to undergo Apoptosis; AIRE
4. when Ag is presented without costimulatory molecule
5. by Tregs through secretion of TGFbeta and IL-10
6. by repeated and persistant activation via Fas

Question 18

Systemic Lupus Erythematosus

1. Characterized by? Hallmark of active diesease?
2. Criteria for diagnosis? (must have 4+)
3. Most common manifestations and %?
4. Kidney manifestations? Highest %?
5. Symptoms of active disease?
6. What is CREST? Occurs with positive ___ test.

Answer 18

1. Formation of auto-Ab reactive to numerous cellular Ags; Anti-dsDNA Ab
2. malar rash, discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder (w/ seizures), hematologic disorder (HA), immune disorder, Anti-nuclear Ab/Anti-dsDNA
3. 100%: HA, 90% arthritis, 85% photosensitivity, 50% GN, 50% pneumonitis, 50% depression/seizures
4. Mesangial, focal proliferative, diffuse proliferative, and membranous GN
5. fever, fatigue, anorexia, joint pain, and nephritic s.
6. Calcinosis - raynauds - esophageal dismotility - sclerodactyly - telangeictasia; ANA

Question 19

Rheumatoid Arthritis

1. Begins as? Turns into? Most common cutaneous manifestation? Systemic?
2. What does the Ag activate? This causes what?
3. Role of ICs?
4. Role of TH17? TH1?

Answer 19

1. small joins of hands/feet as synovitis; collagen destruction, cartilage erosion, bone resorption, and loss of function; rheumatoid nodule; vasculitis that resembles polyarteritis nodosa as well as fatigue, weight loss, and fever
2. CD4 T helper cells –> activate B cells –> production of RF –> initiates ICs
3. activate compliment –> inflammatio and neutrophil recruitment
4. Neutrophil recruitment and survival; activate macrophages

Question 20

RA cont:

1. What do macrophages release?
2. What do TNF and IL1 stimulate?
3. What happens to the synovium?
4. End result?
5. Non-articular manifestations?

Answer 20

1. Proinflammatory cytokines: TNFalpha, IL-1/6/8
2. Synovial cells to proliferate –> produce PG and metalloproteinases
3. Thickens –> CT replaces cartilage and bone forming a pannus (granulation tissue)
4. Bone/cartilage destruction, bone erosion/resorption
5. Rheumatoid nodules, lung - pleurisy/pneumonitis, pericarditis, vasculitis

Question 21

Sjogrens Syndrome

1. Characterized by? Due to?
2. Hallmark? Infiltrate?
3. What happens to the ducts? Rest of the gland?
4. Tested findings?
5. Symptoms?
6. Increased risk of what malignancy?

Answer 21

1. Dry eyes and mouth; auto-Ab destruction of lacrimal and salivary glands
2. lymphocytic infiltrate; CD4, B, and plasma cells
3. hyperplasia (occusion); fibrosis, atrophy of acini, fat deposition
4. Antiribonuclear protein Abs
5. Blurred vision, ulcerated cornea, difficulty swallowing, mouth ulcers/fissures, dental caries, enlargement of salivary glands, dry nose, dysuria
6. lymphoid

Question 22

Mixed CT disease

1. Describes the coexistance of what diseases?
2. Abs to? Therapy?

Progressive systemic sclerosis

3. Type of disease? Characterized by?
4. Immunopathogenesis?
5. Localized vs. limited vs. diffuse?

Answer 22

1. SLE, polymyositis, RA, and systemic sclerosis
2. Ribonuclear proteins; corticosteroids
3. collagen-vascular; fibrosis in skin and other organs
4. abnormal BV physiology, dysfunctional endothelium, immune activation
5. Local - isolated in skin (kids) limited- skin confined to face, neck, and areas distal to elbows/knees with slow visceral involvement diffuse - widespread skin and rapid progression to viscera

Question 23

Progessive systemic sclerosis (Scleroderma)

1. First clinical manifestation? Progression?
2. Diffuse clinical manifestation?
3. Some also develop what syndrome?

Answer 23

1. Raynauds; cutaneous fibrosis (begins with soft tissue edema)
2. CT infiltration of small arteries, lung, heart, kidney, muscles, bon, joints, and GI –> arthralgia, pulmonary fibrosis, cardiac arrhythmia, and diarrhea
3. CREST

Question 24

Polymyositis Dermatomyocitis

1. Disease of?
2. CMI directed at? This causes?
3. Presents with?
4. Describe rash?
5. What is found in blood? Urine? Disease course characterized by?

Answer 24

1. skeletal muscle with or without a rash (acute/chronic)
2. Skeletal muscle Ags –> muscle cell atrophy and necrosis
3. symmetric proximal muscle weakness and pain
4. photosensitive on face, hands, and chest
5. muscle enzymes; creatinine; remissions and exacerbations

Question 25

Primary Immunodeficincies 1. How are they determined? 2. Manifestations? 3. B cell IDs: infection with? 4. T cell IDs: infection with? 5. Complement IDs? MAC deficiencies? 6. Clinical evaluation?

Answer 25

1. genetically 2. skin lesions, chronic diarrhea, impaired growth, and failure to thrive 3. H influenzae, strep pneumonia, staph aureus, echovirus, and giardia 4. herpes, myco. tb, candida, pneumocystitis, cryptococcus, fungi 5. bacteria like B cell IDs; Nisseria 6. measure cell # and Ab levels, DTH skin test, measure chemotaxis, adhesion O2 metabolism, and microbial killing of phagocytes

Question 26

X linked Agammablobulinemia 1. Age? Presentation 2. Hypoplasia of? Results in? 3. Defect and Result? Treat? Common Variable ID 4. Age? Presentation? 5. Occurs due to? Lymph node size? Treat?

Answer 26

1. 5/6 months; chronic/recurrent infections: otitis, conjunctivitis, rash, dental deday 2. Nodes with lack of follicles (NO B CELLS) but normal T cells 3. Tyrosine Kinase results in failure of Pre-B to mature; IvIg 4. 13-35yr; chronic sinopulmonary infection and increased risk of autoimmune disease 5. B cells _dont_ differentiate to plasma cells; normal; IvIg

Question 27

1. Selective IgA deficiency: most common: presents with? 2. Selective IgA deficiency: deficiency results from? Results in? 3. Hyper-IgM syndrome: defect in what cells? Results in deficiency of? 4. Hyper-IgM syndrome: main problem? presentation?

Answer 27

1. recurrent infections (especially sinopulmonary and GI) and an increased risk for allergies/autoimmune d. 2. Isotype switch failure or a secretion failure; no IgA 3. TH1 and TH2; Ab and CMI deficiency 4. Failure of T cells to produce cytokins for IgM class switching; excess IgM, recurrent pyogenic infections and infections caused by intracellular microbes

Question 28

_Congenital Thymic Aplasia (DiGeorge)_ 1. What is this? 2. Early presentation? Time? what occurs? 3. Treatment? 4. _Primary combined immunodeficiencies_: characterized by? 5. What occurs in _X-linked SCID?_ 6. Most common deficiencies of _autosomal recessive SCID_? Result?

Answer 28

1. incomplete development of thymus and parathyroid gland 2. 24hrs: hypoparathyroidism resulting in hypocalcemia; chronic infections 3. marrow or stem cell transplants 4. total absence of immune function with thymus and/or node hypoplasia 5. defective cytokine receptors especially IL-1 needed for T cell maturation 6. Adenosine deaminase and purine nucleoside phosphorylase; impaired lymphoid stemm cell development bc ribonucleotide reductase is inhibited and toxic metabolites accumulate

Question 29

Primary Phagocyte Deficiencies _Chronic Granulomatous disease_ 1. Defects in? 2. Presentation? Treatment? _Leukocyte adhesion deficiency_ 3. No expression of? Results in? 4. Presentation?

Answer 29

1. NADPH oxidase 2. recurrent infection with lymphadenopathy, skin lesions, and sinopulmonary infection; IFNgamma 3. LFA-1 and MAC1; defective chemotaxis and cytotoxic activity 4. Recurrent skin, vaginal, and sinopulmonary infection

Question 30

_Primary complement deficiencies_ 1. Cause? 2. What is _Proxysmal nocturnal hemoglobinuria_? 3. What causes _hereditary angioedema_? 4. Defects in _MAC_ from infection of what?

Answer 30

1. Decreased phagocytosis and chemotaxis --\> recurrent infections and increased risk of auto-IDs 2. Deficiency in DAF and CD59 (MAC inhibitor) --\> pancytopenia 3. C11NH deficiency 4. Nisseria

Question 31

Secondary IDs _AIDS_ 1. General retroviral characteristics: enveloped? Genetic material? Replication? 2. HIV initially infects what cells? Where do these migrate? 3. What occurs in the node? 4. Eventually what occurs? 5. What binds CD4? Induces HIV-host fusion?

Answer 31

1. enveloped; 2 + polarity ssRNA; reverse transcriptase 2. mucosal CD4 T cells and macrophages; draining lymph node 3. viral replication --\> viremia --\> controlled and thus a latent infection is promoted 4. CD4 declines and allows opportunistic infection 5. GP120; GP41

Question 32

_AIDS cont_ 1. What activates transcription of HIV genes? Where? 2. Most important effect? What occurs to macrophages? 3. What happens to B-cells? 4. Acute infection: stage? incubation? Acute retroviral syndrome with what symptoms? What occurs after? 5. Chronic phase (stage 2): persistant symptoms? 6. Crisis phase (stage 3): As immune system declines there is onset of?

Answer 32

1. NF-kB binding LTR; memory T cells 2. CD4 T cell death; Decreased Ag presentation and cytokine production 3. Polyclonal activation causing hypergammaglobulinemia, ICs, and inability to mount response to new Ags 4. 1; 1-6 weeks; fever, lymphadenopathy, pharyngitis, rash, myalgia, and decrease CD4; latency 5. lymphadenopathy, splenomegaly, fatigue, fever, wt loss, oral diseases (hairy oral leukoplakia) 6. opportunistic infection of GI, skin, genital tract, renal, respiratory, and CNS

Question 33

_Amyloidosis_ 1. This is a group of diseases with what in common? 2. What is amyloid? how is it visualized? 3. What occurs as it collects? conformation? Proteins involved: 4. _Ig light chains_ from what cells? Called what in tissue? condition? 5. _Serum amyloid associated protein A_ condition? 6. _Transthyretin:_ normal protein? 'mutant' in what type of amyloidosis?

Answer 33

1. deposition of fibril proteins in intersitial tissue tissue 2. proteinaceous substance btwn cells; H/E or congo 3. Pressure atrophy of adjacent cells; Beta pleated sheet 4. neoplastic plasma cells; amyloid light chains; Primary amyloidosis (AL) 5. secondary amyloidosis (AA) 6. thyroxine and retinol transport protein; hereditary amyloidosis

Question 34

_Amyloidosis cont_ 1. What is _senile amyloidosis_? 2. Who accumulates beta2-microglobulin? why? 3. 2 other main proteins? 4. Amyloidosis is a combination of what?

Answer 34

1. Normal transthyretin (TTR) deposited in a number of organs 2. patients on long term hemodialysis bc cant pass through the dialysis membrane 3. Alzheimer disease beta-amyloid and prion proteins 4. abnormal protein folding and abnormal proteolytic activity that normally degrades misfolded proteins

Question 35

_Primary amyloidosis_ 1. Associated with ___ cell dyscrasias, often ___ \_\_. The amyloid protein (AL) is usually an __ chain. Not all patient with ___ chain multiple myeloma develop \_\_\_. 2. Most patients with AL amyloid dont have what symptoms? But have detectable ___ protein. Where? 3. Secondary: protein? deposits where? 4. Secondary: associated with? most frequent association?

Answer 35

1. plasma; multiple myeloma; L; L; amyloidosis 2. systemic symptoms; M proteins; serum or urine 3. AA protein (from serum amyloid-associated protein); multiple organs 4. Chronic inflammatory diseases or disease resulting in necrosis; rheumatoid arthritis

Question 36

Heredofamilial amyloidosis 1. _Familal mediterrenian fever_: protein? presentation? 2. _Familial amyloid polyneruopathy_: amyloid protein? Deposits where? results in?

Answer 36

1. AA protein; fever and serosal inflammation mostly involving the pleura, peritoneum, and synovial membranes 2. Mutant tranthyretin that deposits in nerves resulting in progressive peripheral and autonomic neuropathy

Question 37

_Localized Amyloidosis_ 1. Infiltrate? responsible for? 2. associated with what tissue? frequently seen in what cancer? 3. May also occur in what other disease?

Answer 37

1. mononuclear infiltrate; M protein secretion 2. endocrine tissue; medullary carcinoma of the thyroid 3. Type II diabetes

Question 38

_Generalized amyloidosis_ 1. Most common organ? What can develop? 2. Spleen deposition pattern? 3. Deposits in the liver cause? 4. GI involvement?

Answer 38

1. kidney; nephrotic syndrome and renal failure 2. splenic follicles or walls of sinuses 3. hepatomegaly and loss of hepatocytes by pressure atrophy 4. Any part; involvement of the tongue may hamper speech/swallowing

Question 39

1. Major organ of senile amyloidosis? What occurs? 2. Prognosis of patients with generalized amyloidosis?

Answer 39

1. _heart_; interrupts contractile function/electrical conduction, CHF, monocyte necrosis ==\> systolic ventricular dysfunction, valvular insufficiency, myocardial ischemia from infiltration of vessels 2. poor prognosis