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211 Cards in this Set

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what are the components of innate immunity?
epithelial barrier, phagocytic cells, dendritic cells, NK cells, plasma proteins (complement)
what are the two major actions of innate immunity?
inflammation and anti-viral defense
what are the components of adaptive immunity?
lymphocytes and their products, including antibodies
what are the two types of adaptive immunity?
humoral and cell-mediated immunity
what is humoral immunity?
B-cell and antibody response that protects against extracellular microbes and their toxins
what enzyme mediates the maturation of T-lymphocytes?
RAG-1 and RAG-2
(recombination activating genes; mediate rearrangement of antigen receptor genes)
how can you differentiate between non-neoplastic and neoplatic T-cell proliferations?
non-neoplastic proliferations should have unique TCRs, whereas neoplastic proliferations will be monoclonal (all TCRs will be similar b/c derived from one progenitor)
which parts of T-cells are identical in all T-cells?
the CD3 complex and the ζ-chain dimer
(these transmit signals into the T cell after TCR has bound the antigen)
what cells display CD4 proteins?

what antigen-display proteins do they respond to?
cytokine-secreting helper T-cells
(help macrophages and B cells combat infections)

MHC 2
what cells display CD8 proteins?

what antigen-display proteins do they respond to?
cytotoxic T cells

MHC 1
which membrane-bound antibodies are present on the surface of all mature, naive B cells?
IgM and IgD
what happens to B cells after stimulation by antigen?
develop into plasma cells that secrete antibodies
what portions of the B cell are important for signal transduction through the antigen receptor?
Igα and Igβ
which APCs are located under the epithelia and in the interstitia of all tissues?
Dendritic cells
what are follicular dendritic cells?
dendritic cells located in germinal centers of lymphoid follicles in the spleen and LNs; have Fc receptors for IgG and receptors for C3b and trap antigen bound to Ab's or complement proteins; they select the B cells that have the highest affinity for the antigen
what cell surface molecules are used to identify NK cells?
CD16 and CD56
(CD16 is an Fc receptor for IgG, giving it the ability to lyse IgG-coated target cells)
what do NK cell inhibitory receptors recognize?
self-class 1 MHC molecules

(may be either killer cell Ig-like receptors or CD94-family lectins)
what is the relationship between NK cells and cytokines?
NK cells secrete IFN-γ: activates macrophages to destroy ingested microbes

they are regulated by IL-2, IL-15: stimulate proliferation of NK cells; IL-12: activates killing and secretion of IFN-γ
what happens to B-cells after development into plasma cells?
they remain in lymphoid organs b/c they secrete Ab's that are carried to distant tissues
where do differentiated effector T cells go?
they ultimately leave the LN, enter circulation and migrate into tissues that harbor their antigen
what is the function of MHC molecules?
display peptide fragments of proteins for recognition by antigen-specific T cells
what do class I MHC molecules display?
peptides from cytoplasmic pathogens (e.g. viruses)
what do class II MHC molecules display?
antigens that are internalized into vesicles, typically derived from extracellular microbes and soluble proteins
what diseases are associated with inheritance of HLA-B27?
Inflammatory diseases (Ankylosing spondylitis, postinfectious arthropathies)
What diseases are associated with inheritance of DR alleles?
Autoimmune diseases (e.g. autoimmune endocrinopathies)
What disease is associated with inheritance of HLA-BW47?
21-hydroxylase deficiency
what disease is associated with inheritance of HLA-A?
hereditary hemochromatosis
which cytokines are part of innate immunity; are made in response to microbes by macrophages, dendritic cells, and NK cells, and mediate inflammation and anti-viral defense?
TNF, IL-1, IL-12, type I IFNs, IFN-γ, chemokines
what cytokines are made by CD4+ T cells to promote lymphocyte proliferation and differentiation, and to activate effector cells?
IL-2, IL-4, IL-5, IL-17, IFN-γ
what happens to a dendritic cell after capture of Ag?
transport to lymphoid organ; maturation and expression of MHCs and costimulators; Ag recognition by naive T-cells and activation (proliferate and differentiate); effector T-cells migrate to sites of infection
what are the principal costimulators for T cells?

What receptor recognizes them?
the B7 proteins (CD80 and CD86)

CD28 receptor on T cells
what do T cells express when they recognize antigens displayed by macrophages or B cells?
CD40L, which engages CD40 on the macrophages or B cells to activate them.
What causes differentiation of T cells to Th1 cells?
IFN-γ, IL-12
What cytokine do Th1 cells produce?
IFN-γ (macrophage activator)
What cytokine do Th2 cells produce?
IL-4 (stimulates B cells to differentiate into IgE plasma cells)
IL-5 (activates eosinophils)
What causes differentiation of T cells to Th2 cells?
IL-4
What causes differentiation of T cells to Th17 cells?
TGF-β, IL-6, IL-1, IL-23
What cytokine do Th17 cells produce?
IL-17 (recruit neutrophils, monocytes),
IL-22
chemokines
What is the role of Th1 cells?
macrophage activation, stimulation of IgG production; defense against intracellular microbes; can cause immune-mediated chronic inflammatory dzs
What is the role of Th2 cells?
stimulation of IgE production, activation of mast cells and eosinophils; defense against helminths; cause allergies
what is the role of Th17 cells?
recruitment of neutrophils, monocytes; defense against extracellular bacteria, fungi; can contribute to immune-mediated chronic inflammatory dzs
which cytokines induce isotype switching of B cells?
IL-4 and IFN-γ
phagocytes have Fc receptors for what antibody type?
IgG
IgA is secreted from what anatomic site?
mucosal epithelia (neutralizes microbes in lumen of resp and/or GI tracts
what antibody crosses the placenta and protects the newborn until maturation of the immune system?
IgG
MOA of Type 1 hypersensitivity?
(Immediate)

production of IgE --> immediate release of vasoactive amines, protamines, leukotrienes, prostaglandins from mast cells and later recruitment of inflammatory cells
Pathologic reactions to Type 1 hypersensitivity?
vascular dilation
edema
sm muscle contraction
mucus production
tissue injury
inflammation
MOA of Type 2 hypersensitivity?
production of IgG, IgM --> bind Ag on target cell or tissue --> phagocytosis/lysis of target cell by activated complement or Fc receptors; recruitment of leukocytes
Pathologic lesions created by Type 2 hypersensitivity?
phagocytosis/lysis of cells; inflammation; in some dzs, functional derangements w/o cell or tissue injury
(Autoimmune hemolytic anemia, Goodpasture syndrome)
MOA of Type 3 hypersensitivity?
deposition Ag-Ab complexes --> complement activation --> recruit leukocytes by complement products and Fc receptors --> release enzymes and other toxic molecules
Pathologic lesions created by Type 3 hypersensitivity?
inflammation
necrotizing vasculitis (fibrinoid necrosis)
MOA of Type 4 hypersensitivity?
activated T cells --> release of cytokines (--> inflammation and macrophage activation) and T cell-mediated cytotoxicity
Pathologic lesions created by Type 4 hypersensitivity?
perivascular cellular infiltrates
edema
granuloma formation
cell destruction
what mediates immune response in type 1 hypersensitivity?
Th2 cells, IgE, mast cells
what are the results of type 1 hypersensitivity?
mediators (from mast cells) act on vessels and sm muscle
pro-inflammatory cytokines recruit inflammatory cells
what mediates immune response in type 2 hypersensitivity?
IgG and IgM antibodies promote phagocytosis/lysis and induce inflammation
what are the results of immune response in type 3 hypersensitivity?
IgG and IgM antibodies bind Ag in circulation and are deposited in tissues --> inflammation. Recruited leukocytes produce tissue damage (neut, mono)
what mediates the immune response in type 4 hypersensitivity?
sensitized T lymphocytes (Th1, Th17 and CTLs)
examples of type 1 hypersensitivity reactions?
localized cutaneous swellings (e.g. hives)
nasal and conjunctival discharge (rhinitis, conjunctivitis)
hay fever
bronchial asthma
allergic gastroenteritis (food allergy)
what characterizes late-phase reaction?
infiltration with eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells as well as tissue destruction, typically in the form of mucosal epithelial cell damage
where are mast cells made?

where do they reside?
bone marrow-derived cells

widely distributed in the tissues, but abundant especially near blood vessels and nerves and in subepithelial tissues
what things activate mast cells to degranulate?
cross-linking of high-affinity IgE Fc receptors
complement C5a and C3a (anaphylatoxins)
some chemokines (IL-8)
some drugs (codeine, morphine and adenosine)
mellitin (in bee venom)
physical stimuli (heat, cold, sunlight)
what is the relationship between basophils and mast cells?
basophils are essentially mast cells in the circulation (in extremely small numbers) rather than in tissues
what is the role of Th2 T-cells in type 1 hypersensitivity?
initiation and propagation of the reaction by stimulating IgE production and promoting inflammation
what do Th2 cells produce upon subsequent encounter with its antigen, and what is the function of each?
IL-4: stimulates B cell class switching to IgE, promotes development of more Th2 cells
IL-5: development and activation of eosinophils
IL-13: enhances IgE prodution and stimulates mucus secretion from epithelial cells
what is the function of FcεRI on mast cells/basophils?
binds the Fc portion of IgE to coat mast cells/basophils with IgE, which, upon exposure to antigen, will stimulate the mast cell to secrete its preformed mediators and synthesize and release secondary mediators
what are the preformed mediators in mast cells/basophils?
vasoactive amines (histamine)
enzymes (neutral proteases, acid hydrolases)
proteoglycans (heparin, chondroitin sulfate)
effects of histamine?
intense smooth muscle contraction
increased vascular permeability
increased mucus from nasal, bronchial, and gastric glands
effects of proteases released from mast cells?
tissue damage, generation of kinins, and activated complement components
effects of proteoglycans released from mast cells?
package and store the amines in the granules
what is the function of lipid mediators in mast cell response?
activate phopholipase A2 which converts mast cells membrane phospholipids to arachidonic acid which is converted into leukotrienes and prostaglandins, and, in some mast cells, to activate the synthesis of platelet activating factor (PAF)
what mediators are produced in response to activation of phospholipase A2 and what are their functions?
Leukotrienes C4, D4: potent vasoactive and spasmogenic activity
Leukotriene B4: highly chemotactic for neutrophils, eosinophils, monocytes
PGD2: intense bronchospasm, increased mucus
PAF: plt aggregation, histamine release, bronchospasm, increased vascular permeability, vasodilation, chemotactic for neutrophils and eosinophils, activates inflammatory cell degranulation (not a product of arachidonic acid metabolism)
which cytokines promote the leukocyte recruitment of late-phase reactions?
TNF, IL-1, chemokines
which cytokines amplify the TH2 response?
IL-4
what cells produce chemicals that are chemotactic for eosinophils?
epithelial cells, TH2 cells, and mast cells
which cytokines activate eosinophils that have been recruited to sites of inflammation?
IL-3, IL-5, and GM-CSF (granulocyte-macrophage colony-stimulating factor)

IL-5 is most potent
what is the function of eosinophils in the late-phase reaction?
release proteolytic enzymes, major basic protein and eosinophil cationic protein (all kill epithelial cells)

produce leukotriene C4 and PAF to activate mast cells.
What is atopy?
genetic predisposition to developing immediate hypersensitivities d/t higher serum IgE and more IL-4-producing TH2 cells
what characterizes anaphylaxis?
vascular shock, widespread edema, difficulty breathing
what is type 2 hypersensitivity?
antibodies reacting with antigens on cell surfaces or in ECM
how do antibodies direct the inflammatory process?
Abs deposited in fixed tissues activate complement which produce chemotactic agents. PMNs, monocytes and anaphylatoxins increase vascular permeability. The leukocytes release pro-inflammatory substances (PG's, vasodilator peptides, chemotactic substances), as well as lysosomal enzymes.
what are examples of disorders produced by type 2 hypersensitivity that do not involve tissue injury or inflammation?
Graves dz (antibodies to TSH receptor stimulate the receptor)
Myasthenia gravis (antibodies to ACh receptor in muscle end plate bind and block the receptor)
Type 2 Diabetes (Ab binds and blocks insulin receptor)
what is the Arthus reaction?
a localized area of tissue necrosis from acute immune complex vasculitis - the complexes precipitate in vessel walls and cause fibrinoid necrosis and superimposed thrombosis worsens the ischemia
which cytokines, produced by APCs, induce differentiation of CD4+ cells to the Th1 subset?
IL-12 and IFN-ϓ
which cytokines, produced by APCs, induce differentiation of CD4+ cells to the Th17 subset?
IL-1, IL-6, IL-23, and TGF-β
How do Th1 cells respond to repeat exposure to an antigen?
Secrete cytokines, mainly IFN-ϓ, which activates macrophages to kill more efficiently and express more MHCII molecules (thus facilitating more Ag presentation), they secrete TNF, IL-1, and chemokines, which promote inflammation, and they produce IL-12, which amplifies the Th1 response
How do Th12 cells respond to repeat exposure to an antigen?
they secrete IL-17, IL-22, chemokines and other cytokines. These cytokines recuit neutrophils and monocytes, thus promoting inflammation. They also produce IL-21, which amplifies the Th17 response.
Morphology of delayed-type hypersensitivity?
accumulation of mononuclear cells, mainly CD4+ cells and macrophages around venules (perivascular cuffing)
what is a granuloma?
an aggregation of epithelioid cells (macrophages transform into epithelium-like cells after a long period of activation)
what is the principal mechanism of CTL-mediated killing?
CTL recognizes MHC I, secretes perforin/granzyme/serglycin complex; in cytoplasm, perforin activates granzymes, which cleave and activate caspases which induce apoptosis of target cell.
What is presented by MHC II?

What cells recognize it?
antigens that have been endocytosed; typically extracellular microbes and soluble proteins

CD4+ T lymphocytes
What is presented by MHC I?

What cells recognize it?
peptides from antigens located in the cytoplasm, such as viruses

CD8+ T lymphocytes
what is central tolerance?
the elimination of T and B cells with high-affinity receptors for self-antigens in the central lymphoid organs (thymus and bone marrow)
what are the fates of self-reactive T cells?
1. escape from thymus --> peripheral tolerance --> anergy or activation-induced apoptosis
2. reacting with self-Ag triggers thymic APC --> apoptosis (central tolerance)
3. reassignment as regulatory T cell to suppress abnml immune reactions to self-antigens in periphery
what are the mechanisms of peripheral tolerance?
1. anergy
2. suppression by regulatory T cells
3. deletion by activation-induced apoptosis
how do regulatory T cells work?
CD4+ cells that also express CD25 (α-chain of the IL-2 receptor) inhibit lymphocyte activation and effector functions by secreting cytokines IL-10 and TGF-β
autoimmunity arises from a mixture of what?
inheritance of susceptibility genes (contribute to breakdown of self-tolerance) and environmental tirggers (e.g. infxn, tissue damage; promote activation of self-reactive lymphocytes)
what gene is most frequently implicated in autoimmunity?

what diseases is it associated with?
PTPN-22 (encodes a protein tyrosine phosphatase, which control activity of tyrosine kinases which are involved in lymphocyte responses)

Rheumatoid arthritis, type 1 diabetes
what is the paradox involved in infection and development of autoimmunity?
infections may protect against some autoimmune diseases, possibly because infections promote IL-2 production, which is essential for maintaining regulatory T cells
how do infections contribute to development of autoimmune diseases?
1. molecular mimicry
2. up-regulation of expression of costimulators (esp. on self-Ag-presenting APCs)
3. some viruses pcause polyclonal B-cell activation --> more autoantibodies
4. tissue injury releases structurally altered self-Ag's that T cells are not tolerant to
5. production of cytokines that recruit lymphocytes to sites of self-Ag's
disease characterized by anti-dsDNA and anti-Smith antigen antibodies?
SLE
female-to-male ratio of SLE?
9:1 during childbearing years,
2:1 during childhood or after age 65
what are the patterns of nuclear fluorescence recognized in SLE?
1. homogeneous (Ab's to chromatin, histones, dsDNA)
2. peripheral (Ab's to dsDNA)
3. Speckled (Ab's to non-DNA nuclear components)
4. Nucleolar (Ab's to RNA)
In what disease, other than SLE, is a nucleolar staining pattern seen on nuclear fluorescence?
systemic sclerosis
Other than ANA, what is the most common autoantibody seen in SLE?
antiphospholipid antibodies
(against prothrombin, annexin V, beta-glycoprotein I, protein S & C, and cardiolipin)
Lupus pts may have abnormal results with what tests?
Anticardiolipin antibody test for syphilis serology
PTT (interfere w/ in vitro clotting)
With what disease is secondary antiphopholipid antibody syndrome associated?

What is it?
SLE

antibodies against phospholipid clotting factors somehow induce clotting in vivo, produce thrombi that are associated with miscarriages, and cerebral ischemia
what is the fundamental defect in SLE?
failure of mechanisms that maintain self-tolerance
what is the cause of most of the visceral lesions in SLE?
immune complexes (type III hypersensitivity)
what are the common organs involved in SLE?
kidneys
joints
skin
CNS (Ab against synaptic protein or occlusion of small vessels)
Pericardium
Heart (LSE, coronary atherosclerosis)
Spleen
Lungs
What differentiates Libman-Sachs endocarditis from rheumatic heart disease?
LSE vegetations are larger, and can appear anywhere on the valve, on either side
(RHD vegs occur on lines of closure)
presence of what in the bone marrow is strongly indicative of SLE?
LE (hematoxylin) bodies
Presentation: young woman w/ rash on face, fever, pain (but no deformity) in peripheral joints, pleuritic CP, and photosensitivity. Diagnosis?
SLE
what clues point toward renal involvement in SLE?
hematuria, RBC casts, proteinuria, classic nephrotic syndrome
what are the patterns of lupus nephritis?
Class I: minimal mesangial GN (rare)
Class II: mesangial proliferative GN
Class III: focal proliferative GN
Class IV: diffuse proliferative GN
Class V: membranous GN
what characterizes Class II lupus nephritis?
10-25%; mesangial cell proliferation, immune complex deposition w/o involvement of glomerular capillaries. Minimal hematuria/proteinuria. Granular mesangial deposits of Ig and complement are always present.
what characterizes Class III lupus nephritis?
20-35%; involvement of fewer than 50% of all glomeruli; recurrent hematuria, moderate proteinuria, mild renal insuff. Focal and segmental glomerular swelling w/ endothelial and mesangial proliferation, neutrophils, sometimes fibrinoid deposits and capillary thrombi.
what characterizes Class IV lupus nephritis?
most severe form; 35-60% of pts; entire glomerulus frequently affected; >50% glomerular involvement; Pts usually have sxs (hematuria and proteinuria); HTN, mild-severe renal insufficiency.
what characterizes Class V lupus nephritis?
10-15% of pts; diffuse thickening of capillary walls, severe proteinuria or nephrotic syndrome; antibody complexes are subepithelial.
What classes of lupus nephritis have subendothelial deposits?

What do they look like?
Proliferative types (classes III and IV)

Homogeneous thickening of capillary wall seen by light microscopy as "wire-loop" lesion
What is the difference between rheumatoid arthritis and lupus arthritis?
Lupus causes nonerosive synovitis with little deformity
Most common cause of death in SLE pts?
renal failure and intercurrent infections
What is chronic discoid lupus erythematosus?
dz w/ skin lesions mimicking SLE but w/o systemic manifestations;

35% have positive ANA, but dsDNA antibodies are rare.
What is subacute cutaneous lupus erythematosus?

With what genetic morphologies is it associated?
skin lesions of SLE with mild systemic sxs consistent with SLE

anti SS-A antibodies and HLA-DR3 genotype
what drugs are associated with lupus-like syndrome?
hydralazine
procainamide
isoniazid
D-penicillamine
what are the manifestations of drug-induced SLE?
Development of ANAs, and less commonly, systemic lupus-like sxs. Renal and CNS involvement is RARE. Extremely high frequency of HISTONE Ab's.
manifestation of Sjögren syndrome?
dry eyes, dry mouth
(immunologically mediated destruction of lacrimal and salivary glands)
With what diseases does Sjögren syndrome occur most frequently?
RA (most common)
SLE, polymyositis, scleroderma
what is rheumatoid factor?
an antibody reactive with self-IgG
Disease associated with RF (w/o RA) and ANAs against ribonucleoproteins SS-A and SS-B?
Sjögren syndrome
Disease that may be initiated by chronic inflammatory dzs, EBV, or HCV?
Sjögren syndrome
What test helps differentiate between lacrimal and salivary gland enlargement caused by Sjögren syndrome and that caused by sarcoidosis/leukemia/lymphoma?
Lip bx
In what demographic is Sjögren syndrome most often seen?
Women age 50-60
Clinical sxs of Sjögren syndrome?
blurry vision, burning, itching, thick secretions in conjunctival sac; difficulty swallowing solid foods, decreased taste, oral cracks/fissures.
Sjögren syndrome confers a higher risk of what disease?
B-cell lymphoma (in involved glands)
what is the CREST syndrome?

with what autoimmune disease is it associated?
Calcinosis (formation of calcium deposits in soft tissue)
Raynaud's phenomenon (vasospasm of periphery, discoloration of fingers and toes)
Esophageal dysmotility
Sclerodactyly (thickening and tightening of skin on fingers and toes)
Telangiectasia (small, dilated BVs near surface of skin, usually on face)

Localized systemic sclerosis
What ANAs are associated with diffuse and localized scleroderma?
Diffuse: DNA topoisomerase I ANA

Localized: anticentromere antibody
What complication is consistently present early in the course of systemic sclerosis?
microvascular disease -- intimal proliferation in 100% of digital arteries of scleroderma pts
Which disease initially presents with symmetric edema and thickening skin of hands and fingers or with Raynaud phenomenon?
Systemic sclerosis
Progression of skin disorder in scleroderma?
begins with edema --> fibrotic fingers become tapered and claw-like, face becomes drawn --> focal obliteration of vessels leads to ulceration and sometimes autoamputation
GI involvement of what disease causes inflexibility of the esophagus with GERD and Barrett's; thinned, ulcerated mucosa w/ excessive mural collagen, and loss of villi/microvilli?
Scleroderma
What causes malabsorption in scleroderma?
loss of villi/microvilli in small bowel
Involvement of musculoskeletal system in scleroderma?
inflammatory synovitis progresses to fibrosis; mimics RA but w/o joint destruction; muscle edema and mononuclear infiltrate begins proximally, myofibers progressively degenerate
most common causes of death in scleroderma?
renal failure, cardiac failure, pulmonary insufficiency, intestinal malabsorption
what is the immune abnormality that initiates scleroderma?
Exogenous agent --> CD4+ response, accumulate in the skin, release cytokines --> activate inflammatory cells and fibroblasts.
Exogenous agent also --> vascular injury and plt aggregation --> release of PDGF, TGF-β --> trigger perivascular fibrosis
Kidney involvement in scleroderma is associated with what complications?
- Vascular lesions (interlobular arteries have intimal thickening, concentric proliferation of intimal cells)
- HTN in 30% (fibrinoid necrosis of arterioles w/ thrombosis and infarction)
- 50% of deaths
Demographic at highest risk for scleroderma?
50-60 y.o., female:male = 3:1
What complications arise from pulmonary fibrosis seen in scleroderma?
R-sided cardiac dysfxn, respiratory difficulties
What complications arise from myocardial fibrosis seen in scleroderma?
Arrhythmias, cardiac failure
Pts with CREST syndrome have less occurrence of what sxs of scleroderma?
Less involvement of skin, confined to fingers, forearms and face, and calcification of SQ tissues
CREST syndrome is associated with high levels of what ANA?
anticentromere antibodies
Which inflammatory myopathies occur with other immune-mediated diseases, esp scleroderma?
Dermatomyositis, polymyositis, and inclusion-body myositis
What characterizes mixed CT disease?
Mixture of features of SLE, scleroderma and polymyositis

(Raynaud, esophageal dysmotility, myositis, leukopenia-anemia, fever, lymphadenopathy, hypergammaglobulinemia)
Pharmacological tx for mixed CT disease?
Excellent response to corticosteroids
What is the serological difference between SLE and mixed CT disease?
Mixed CT disease = High titers of Ab's to ribonucleoproteins, but no Ab's to dsDNA or Smith antigens (as in SLE)
what is the initial target of antibodies in acute humoral rejection?
Graft vasculature (resulting in rejection vasculitis)
What predisposes a pt to hyperacute rejection?
- prior rejection of similar transplant
- multiparous women receiving grafts from husband or children
- prior blood transfusions
what is the MOA of direct rejection?
host T cells recognize DONOR HLA on DONOR dendritic cells;

host CD8+ recognize donor MHC 1, mature into CTL

host CD4+ recognize donor MHC 2, proliferate and differentiate to form Th1 effector cell population
what is the MOA of indirect rejection?
host T cells recognize donor HLA after they have been processed and presented on the HOST APCs (just like any exogenous antigen);

Delayed-type hypersensitivity reaction mediated by CD4+ T cells
What predisposes a pt to hyperacute rejection?
preformed antidonor antibodies present in recipient:
- prior txp rejection
- multiparous woman receiving graft from husband or children
- prior blood transfusion
appearance of hyperacutely rejecting organ (kidney)?
cyanotic, mottled, flaccid;
Ig and complement deposits in vessel walls with endothelial injury, microthrombi, neutrophil infiltrates, and arteriolar fibrinoid necrosis --> cortical necrosis from infarction
appearance of acute cellular rejection of kidney?
Interstitial mononuclear cell infiltrate (macrophages, plasma cells, CD4+ & CD8+ T cells);
CTLs damage endothelium and parenchymal cells, CD4+ damage by inducing delayed hypersensitivity
appearance of acute humoral rejection?
Rejection vasculitis:
- necrotizing vasculitis w/ endothelial cell necrosis, neutrophils
- Ig, complement, and fibrin deposits
- thrombosis
What is the most useful indicator of humoral rejection?
C4d (product of degradation of activated C4b complement protein)
appearance of chronic rejection?
progressive organ dysfxn; arteries show dense obliterative intimal fibrosis, causing ischemia
what is usually present in chronically rejecting kidneys?
interstitial mononuclear cell infiltrates of plasma cells and numerous eosinophils
MOA of cyclosporine?
blocks activation of txn factor, nuclear factor of activated T cells (NFAT), which is needed for txn of cytokine genes (esp. gene for IL-2)
MOA of azathioprine?
inhibits leukocyte development from bone marrow precursors
Drugs used in immunosuppressive therapy?
Cyclosporine
Azathioprine
Steroids
Rapamycin, mycophenolate mofetil
Monoclonal anti-T-cell antibodies
MOA of rapamycin and mycophenolate mofetil?
inhibit lymphocyte proliferation
Immunosuppressed pts are at increased risk for what diseases?
EBV-induced lymphomas
HPV-induced squamous cell carcinomas
Kaposi sarcoma
What are the problems associated with txp of hematopoietic cells?
Graft-vs-host disease
Immunodeficiency
Major clinical manifestations of acute GVH dz?
Generalized rash --> desquamation (severe)
Destruction of small bile ducts --> jaundice
Mucosal ulceration of gut --> bloody diarrhea
Major clinical manifestations of chronic GVH dz?
Extensive cutaneous injury (destruction and fibrosis)
Chronic liver dz (cholestatic jaundice)
GI damage (esophageal strictures)
Immune system damage (involution of thymus, depletion of lymphocytes in LNs)
loss of chromosome 22q11?
DiGeorge (thymic and parathyroid aplasia)
imm. def. resulting from mutation of common gamma chain of cytokine receptors?
SCID (Xlinked type)
AR type of SCID is deficiency of what enzyme?
adenosine deaminase
male infants w/ this imm def syndrome get recurrent bacterial infxns (otitis media, pneumonia, bronchitis, pharyngitis)
Bruton's X linked agammaglobulinemia
male and female children have recurrent bacterial infxns, esp Giardiasis, in what imm def syndrome?

cause?
Common variable immune deficiency (CVID)

B-cell maturation defect -> hypogammaglobulinemia
defects caused by malformation of 3rd and 4th pharyngeal pouches?
DiGeorge = CATCH - 22
Cardiac anomalies (esp ToF)
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia (parathyroid aplasia)

22q11 deletion
Mixed CT dz is a mix of features of which other syndromes?
SLE, scleroderma, and polymyositis
associated with high titers of anti-U1-ribonucleoprotein-antibody?
Mixed CT disease
Young child gets infxns with candida, CMV, P. jiroveci. What standard procedure must be avoided by the physician in this child?
must not give live attenuated virus vaccinations (SCID)
Young child gets infxns with candida, CMV, P. jiroveci. Caused by defective maturation of what cells?
Stem cells

(humoral and cell-mediated maturation deficiency)
cause of imm. def. in male child that gets recurrent infxns, has severe thrombocytopenia, and eczema?
progressive depletion of T cells, no Ab's to polysaccharide antigens

(d/t mutation in Wiskott-Aldrich syndrome protein)
imm def with low IgM, normal IgG, elevated IgA and IgD?
Wiskott-Aldrich
deficiency of C2 complement results in increased risk of what?
SLE-like autoimmune disease
deficiency of C5-9 complement results in increased risk of what?
Neisserial infection
imm def caused by defective CD40-CD40L interactions d/t mutation in CD40L?
hyper IgM syndrome
chronic inflammation, damage to small BVs, and progressive interstitial and perivascular fibrosis is indicative of what autoimmune disease?
Scleroderma
visceral manifestations of diffuse scleroderma?
dysphagia, malabsorption, non-destructive synovitis, HTN (renal vascular fibrosis), pulm HTN & fibrosis, pericarditis
other name for DiGeorge?
velo-cardio-facial syndrome
AIDS pts are at greatest risk for development of which 2 cancers?
B-cell NHL, Kaposi sarcoma
what tissues are most often attacked in GVH dz?
liver, skin, GI epithelium
what type of hypersensitivity causes tissue injury in SLE?
type II and III
pathogenesis of hyper-IgM syndrome?
abnormal interaction of CD40-CD40L leads to lack of isotype switching
antibody in diffuse scleroderma?
anti-DNA-topoisomerase-1
hemoptysis, hematuria, glomerular damage and linear pattern of immunofluorescence with labeled anti-complement and anti-IgG antibody?
Goodpasture
predisposing factor for Reiter syndrome?
GI infxn (SSYC) and/or GU infxn (Chlamydia)
dz associated with deposition of β2-microglobulin proteins?
hemodialysis-associated amyloidosis
dz associated with deposition of transthyretin proteins?
senile cardiac amyloidosis
dz associated with deposition of light chain subunits of Ig's?
primary amyloidosis

(plasma cell disorders, e.g. mult myeloma, B-cell lymphomas)
non-severe sinopulmonary infxns and diarrhea - imm deficiency?
selective IgA deficiency
cause of recurrent episodes of edema of the skin and mucosal surfaces (e.g. larynx, GI tract)?
hereditary angioedema

Dominant deficiency of C1 complement inhibitor
surface markers for NK cells?
CD16 (recognizes complement, allows cell to lyse opsonized particles)
CD 56
what are Langerhans cells?
dendritic cells in epithelia
what are follicular dendritic cells?
dendritic cells within germinal centers
what are Langhans giant cells?
groups of activated macrophages organized as part of a granulomatous response
which cytokine, released from CD4 T cells, recruits neutrophils and monocytes in delayed type hypersensitivity?
IL-17
which cytokine activates eosinophils as part of the Th2 response?
IL-5
NK cells secrete ____ in response to stimulation by ____, which also serves to induce the Th1 immune response.
IFN-γ
IL-12