Inflammation & Autoimmune Disorders

Question 1

Acute inflammation is characterized by presence of ____ and _____ in tissue

It arises in response to ______ or _____ _____ with the goal to eliminate pathogen or clear debris. Also important to note is that it is an immediate response with LIMITED specificity — which is a hallmark of innate immunity.

Answer 1

Edema; neutrophils

Infection; tissue necrosis

Question 2

Innate immunity is mediated by several factors. ______ are present on cell of innate immune system including macrophages and dendritic cells, and recognize and are activated by PAMPs

Answer 2

TLRs

Question 3

Pathogen-associated molecular patterns (PAMPs) are commonly shared by microbes. _____ is an example of a PAMP on the outer membrane of gram-negative bacteria that is recognized by CD14 on macrophages

Answer 3

LPS

Question 4

Activation of a TLR upon recognition of a PAMP results in upregulation of ______, which activates immune response genes and leads to production of multiple immune mediators.

Answer 4

NF-kB

Question 5

T/F: TLRs are only present on cells of innate immunity

Answer 5

False — they are also present on cells of adaptive immunity in which case they mediate chronic inflammation

Question 6

______ _____ is an immune mediator released from the phospholipid cell membrane by phospholipase A2.

It is then acted on by _______ or ________

Answer 6

Arachidonic acid

Cyclooxygenase; 5-lipooxygenase

Question 7

Arachidonic acid is an immune mediator released from the phospholipid cell membrane by phospholipase A2. It is then acted on by cyclooxygenase or 5-lipooxygenase.

Cyclooxygenase produces ________.

Of these, ___________ (3) mediate vasodilation and inceased vascular permeability. ______ also mediates fever and pain

Answer 7

Prostaglandins

PGI2, PGD2, PGE2; PGE2

[NOTE vasodilation occurs at the level of the ARTERIOLE and the increased vascular permeability occurs at the level of the POST-CAPILLARY VENULE]

Remember EEEEEEE2 controls feeeeeeeever

Question 8

Arachidonic acid is an immune mediator released from the phospholipid cell membrane by phospholipase A2. It is then acted on by cyclooxygenase or 5-lipooxygenase.

5-lipoxygenase produces _______.

Of these, _____ attracts and activates neutrophils and __________ (3) mediate vasoconstriction, bronchospasm, and increased vascular permeability

Answer 8

Leukotrienes

LTB4; LTC4, LTD4, LTE4

[increased vascular permeability is d/t contraction of pericytes]

Question 9

Mast cells are an inflammatory mediator widely distributed throughout connective tissue of the body. What are the 3 ways in which mast cells are activated?

Answer 9

Tissue trauma

Complement proteins C3a and C5a

Cross-linking of cell-surface IgE by antigen

Question 10

Immediate response of mast cell activation involves release of preformed ____ granules which mediate vasodilation of arterioles and increased vascular permeability. The delayed response involves production of _____ _____ metabolites, particularly ______

Answer 10

Histamine; arachidonic acid; leukotrienes

Question 11

Complement are proinflammatory serum proteins that enhance inflammation. They circulate as inactive precursors. What are the 3 ways in which complement activation can occur?

Answer 11

Classical pathway — C1 binds to IgG or IgM that is bound to antigen

Alternative pathway — Microbial products directly activate complement

Mannose-binding lectin pathway — MBL binds mannose on microorganisms and activates complement

Question 12

The result of complement activation by any of the 3 pathways is generation of C3 convertase, C5 convertase, and formation of MAC. Key products generated by complement include C3a and C5a, C3b, and the MAC.

What is the specific function shared by C3a and C5a?

Answer 12

C3a and C5a trigger mast cell degranulation

Question 13

The result of complement activation by any of the 3 pathways is generation of C3 convertase, C5 convertase, and formation of MAC. Key products generated by complement include C3a and C5a, C3b, and the MAC.

C3a and C5a trigger mast cell degranulation. What is the other function of C5a?

Answer 13

Chemotactic for neutrophils

Question 14

The result of complement activation by any of the 3 pathways is generation of C3 convertase, C5 convertase, and formation of MAC. Key products generated by complement include C3a and C5a, C3b, and the MAC.

What is the specific function of C3b?

Answer 14

Opsonin for phagocytosis

[opsonins basically tag things for destruction]

Question 15

The result of complement activation by any of the 3 pathways is generation of C3 convertase, C5 convertase, and formation of MAC. Key products generated by complement include C3a and C5a, C3b, and the MAC.

What is the specific function of the MAC?

Answer 15

Lyses microbes by creating holes in the cell membrane

[MAC is formed by C5b joined with C6-9]

Question 16

Inactive proinflammatory protein produced in the liver; activated upon exposure to subendothelial or tissue collagen

Answer 16

Hageman factor

[plays an important role in DIC]

Question 17

Hageman factor activates coagulation and fibrinolytic systems (role in DIC), complement, and kinin system. What is the role of the kinin system?

Answer 17

Cleaves HMWK to bradykinin, which mediates vasodilation, increased vascular permeability, and pain

Question 18

The cardinal signs of inflammation include redness (rubor), warmth (calor), swelling (tumor), pain (dolor), and fever. What is the physiology behind redness and warmth (including key mediators)?

Answer 18

Due to vasodilation which results in increased blood flow via relaxation of arteriolar smooth muscle

Key mediators are histamine, prostaglandins, and bradykinin

Question 19

The cardinal signs of inflammation include redness (rubor), warmth (calor), swelling (tumor), pain (dolor), and fever. What is the physiology behind swelling (including key mediators)?

Answer 19

Due to leakage of fluid from postcapillary venules into interstitial space

Key mediators are histamine and tissue damage

Question 20

The cardinal signs of inflammation include redness (rubor), warmth (calor), swelling (tumor), pain (dolor), and fever. What is the physiology behind pain (including key mediators)?

Answer 20

Bradykinin and PGE2 sensitize sensory nerve endings

Question 21

The cardinal signs of inflammation include redness (rubor), warmth (calor), swelling (tumor), pain (dolor), and fever. What is the physiology behind fever (including key mediators)?

Answer 21

Pyrogens cause macrophages to release IL-1 and TNF

Increase COX activity in perivascular cells of hypothalamus

Increased PGE2 raises temperature set point

Question 22

Step one of neutrophil arrival and activation is ______ which is characterized by vasodilation which slows blood flow in postcapillary venules and cells move to periphery of flow

Answer 22

Margination

Question 23

Step one of neutrophil arrival and activation is margination. Step two is rolling, which requires selectin upregulation on endothelial cells. What are the 2 important selectins?

Answer 23

P-selectin is released from Weibel-Palade bodies (in endothelial cells); mediated by histamine

E-selectin is induced by TNF and IL-1

[Remember Weibel-Palade bodies contain P-selectin and vWF]

Question 24

Step one of neutrophil arrival and activation is margination. Step two is rolling, which requires selectin upregulation on endothelial cells. Selectins bind __________ on leukocytes, an interaction which then results in rolling of leukocytes along the vessel wall

Answer 24

Sialyl Lewis X

Question 25

Step one of neutrophil arrival and activation is margination. Step two is rolling, which requires selectin upregulation on endothelial cells. Step three is adhesion, which is an interaction resulting in firm adhesion to the vessel wall. This requires cell adhesion molecule upregulation on the endothelium by ____ and ____. In addition, integrins are upregulated on leukocytes by ____ and ____

Answer 25

TNF; IL-1 C5a; LTB4

Question 26

Leukocyte adhesion deficiency is an _____ ____ inherited defect of _______

Answer 26

Autosomal recessive; integrins (CD18 subunit)

Question 27

3 key clinical features of Leukocyte Adhesion Deficiency

Answer 27

Delayed separation of umbilical cord Increased circulating neutrophils Recurrent bacterial infections that LACK pus formation

Question 28

Step one of neutrophil arrival and activation is margination. Step two is rolling, which requires selectin upregulation on endothelial cells. Step three is adhesion via integrins and cell adhesion molecules. Step four is transmigration and chemotaxis. During step four, leukocytes transmigrate across the endothelium of postcapillary venules and move toward chemical attractants. What are the 4 key chemoattractants for neutrophils?

Answer 28

LTB4 C5a IL-8 Bacterial products

Question 29

Step one of neutrophil arrival and activation is margination. Step two is rolling, which requires selectin upregulation on endothelial cells. Step three is adhesion. Step four is transmigration and chemotaxis. Step five is phagocytosis which involves consumption of pathogens or necrotic tissue. This process is enhanced by opsonins ____ and _____. The way by which phagocytosis occurs is that pseudopods from the leukocytes extend to form phagosomes. The phagosomes are internalized and merged with lysosomes to form phagolysosomes

Answer 29

IgG; C3b

Question 30

Protein trafficking defect characterized by impaired phagolysosome formation; clinical features include increased risk of pyogenic infection, neutropenia, giant granules in leukocytes, defective primary hemostasis, albinism, and peripheral neuropathy

Answer 30

Chediak-Higashi syndrome [can be thought of as a microtubule defect]

Question 31

Inheritance of Chediak Higashi syndrome

Answer 31

Autosomal recessive

Question 32

Destruction of phagocytosed material occurs by one of two mechanisms: oxygen-dependent or oxygen-independent. The oxygen-dependent mechanism is most effective. What is this mechanism?

Answer 32

HOCl generated by oxidative burst in phagolysosomes destroys phagocytosed microbes [generation of HOCl occurs by the following: O2 is converted to O2* by NADPH oxidase — this is the oxidative burst! O2* is then converted to H2O2 by SOD. H2O2 is then converted to HOCl by MPO]

Question 33

Disease characterized by poor O2-dependent killing due to NADPH oxidase defect

Answer 33

Chronic granulomatous disease

Question 34

Inheritance of chronic granulomatous disease

Answer 34

X-linked or autosomal recessive

Question 35

Key type of bacteria that those with chronic granulomatous disease are at risk for

Answer 35

Catalase-positive organisms! Most bacteria naturally produce a little bit of H2O2, so we can still generate HOCl using that, so CGD pts don’t have a problem with those. Catalase destroys H2O2, so catalase-producing organisms. ``` Important catalase-positive organisms to be aware of include: **Pseudomonas cepacia** S. aureus S. marcescens Nocardia Aspergillus ```

Question 36

Test used to screen for chronic granulomatous disease

Answer 36

Nitroblue tetrazolium test Turns blue if NADPH oxidase can convert O2 to O2*. Remains colorless if NADPH oxidase is defective [allows you to differentiate from MPO deficiency, which would have a negative NBT test]

Question 37

_____ deficiency results in defective conversion of H2O2 to HOCl*. These pts are typically asymptomatic, but are considered at increased risk for ____ infections

Answer 37

MPO; candida

Question 38

The 2 ways in which organisms are killed after phagocytosis are O2-dependent killing and O2-independent killing (less effective). What is the mechanism of O2-independent killing?

Answer 38

Occurs via enzymes present in leukocyte secondary granules (e.g., lysozyme and major basic protein)

Question 39

Neutrophils undergo _____ and disappear within 24 hours after resolution of inflammatory stimulus

Answer 39

Apoptosis

Question 40

What cell type predominates after neutrophils (i.e., peaks 2-3 days after inflammation begins)?

Answer 40

Macrophages [derived from monocytes in the blood; arrive via margination, rolling, adhesion, and transmigration sequence identical to neutrophils. They then ingest via phagocytosis and destroy phagocytosed material using enzymes (lysozyme!) in the secondary granules]

Question 41

Macrophages are responsible for managing next steps in acute inflammatory process. They promote resolution and healing via _____ and _____. They can allow continued acute inflammation via _____. They are also involved in abscess formation and chronic inflammation

Answer 41

IL-10; TGF-B; IL-8

Question 42

Chronic inflammation is characterized by lymphocytes and plasma cells in tissues. It is a delayed response, but more specific (adaptive immunity). Stimuli for chronic inflammation include persistent infection (most common), infection with viruses, mycobacteria, parasites, and fungi, autoimmune disease, foreign material, and some cancers. Lymphocytes can be divided into T cells and B cells. Describe basic development of T cells

Answer 42

T cells form in the bone marrow from T cell progenitors Further develop in thymus where TCR undergoes rearrangement. Progenitor T cells become CD4+ helper T cells or CD8+ cytotoxic T cells

Question 43

T cells use TCR complex for antigen surveillance. The TCR complex recognizes antigens presented on MHC. What is the difference between MHC recognized by CD4 vs. CD8?

Answer 43

CD4+ T cells recognize MHC class II CD8+ T cells recognize MHC class I

Question 44

Activation of T cells requires 2 things: binding of antigen/MHC complex and additional 2nd signal. Describe these 2 events in the context of CD4+ T-cell activation

Answer 44

EXTRACELLULAR antigen is phagocytosed, processed, and presented via MHC class II (APCs — macrophages, dendritic cells, B cells) B7 on APC binds CD28 on CD4+ T cells, providing the 2nd activation signal

Question 45

CD4+ T-cells are divided into what 2 subtypes and their major products?

Answer 45

Th1 — secrete IL-2 and IFN-y Th2 — secrete IL-4, IL-5, and IL-10

Question 46

Major functions of IL-2 and IFN-y produced by Th1 CD4+ T-cells

Answer 46

IL-2 = T-cell growth factor and CD8+ T cell activator IFN-y = macrophage activation

Question 47

Major functions of IL-4, IL-5, and IL-10 secreted by Th2 CD4+ T-cells

Answer 47

IL-4 = class switching to IgG and IgE IL-5 = eosinophil chemotaxis and activation, matruation of B cells to plasma cells, and class switching to IgA IL-10 = inhibits Th1 phenotype

Question 48

Activation of T cells requires 2 things: binding of antigen/MHC complex and additional 2nd signal. Describe these 2 events in the context of CD8+ T-cell activation

Answer 48

Intracellular antigen is processed and presented on MHC I IL-2 from CD4+ Th1 cell provides 2nd activation signal

Question 49

CD8+ T cells mediate cell killing by secretion of ____ and ____ — inducing apoptosis of target cell. This is mediated by expression of _____, which binds ____ on target cell activating apoptosis

Answer 49

Perforins; granzyme; FasL; Fas

Question 50

Describe general development of B lymphocytes

Answer 50

Immature B cells are produced in bone marrow Undergo Ig rearrangement to become naive B cells that express surface IgM and IgD

Question 51

Mechanisms for B cell activation

Answer 51

Antigen binding surface IgM or IgD (becomes Ab-secreting plasma cell) B-cell antigen presentation to CD4+ helper T cells via MHC II; CD40 receptor on B cel binds CD40L on helper T cell providing 2nd activation signal

Question 52

One way in which B-cell activation occurs is B-cell antigen presentation to CD4+ helper T cells via MHC II; CD40 receptor on B cel binds CD40L on helper T cell providing 2nd activation signal. The helper T cell then secretes IL-4 and IL-5 which serve what purpose?

Answer 52

IL-4 and IL-5 mediate B-cell isotype switching, hypermutation, and maturation to plasma cells

Question 53

A subtype of chronic inflammation is granulomatous inflammation. This is characterized by formation of a granuloma. The key cell of a granuloma is a(n) _____ _____ surrounded by giant cells and a rim of lymphocytes. Granulomas are divided into noncaseating and caseating subtypes

Answer 53

Epithelioid histiocyte (macrophages with abundant pink cytoplasm)

Question 54

Noncaseating granulomas lack central necrosis. What are some clinical scenarios in which you see noncaseating granulomas?

Answer 54

``` Reaction to foreign material Sarcoidosis Beryllium exposure Crohn disease Cat scratch disease (Bartonella henselae) ``` [Note cat scratch disease shows stellate granulomas, usually in neck]

Question 55

Caseating granulomas exhibit central necrosis. These are characteristic of what 2 clinical scenarios?

Answer 55

Tuberculosis infections Fungal infections [AFB stain looks for TB, GMS stain looks for fungus]

Question 56

Steps involved in granuloma formation

Answer 56

1. Macrophages present antigen via MHC II to CD4 T cells 2. Macrophages secrete IL-12, inducing CD4 cells to differentiate into Th1 subtype 3. Th1 cells secrete IFN-y, which converts macrophages to epithelioid histiocytes and giant cells [Note — these steps are the same for caseating and noncaseating granuloma formation]

Question 57

DiGeorge syndrome results from developmental failure of the ____________________ due to a ____ microdeletion

Answer 57

3rd and 4th pharyngeal pouches; 22q11

Question 58

Clinical presentation of DiGeorge Syndrome

Answer 58

T-cell deficiency (lack of thymus) Hypocalcemia (lack of parathyroids) Abnormalities of heart, great vessels, and face

Question 59

Severe combined immunodeficiency (SCID) involves defective cell-mediated and humoral immunity, characterized by susceptibility to fungal, viral, bacterial, and protozoal infections including opportunistic infections and live vaccines. What are the 3 major etiologies of SCID?

Answer 59

Cytokine receptor defects **Adenosine deaminase deficiency** MHC class II deficiency

Question 60

Treatment of SCID pts

Answer 60

Sterile isolation Stem cell transplant

Question 61

Immunodeficiency characterized by complete lack of immunoglobulin due to disordered B-cell maturation, so naive B cells cannot become plasma cells

Answer 61

X-linked agammaglobulinemia

Question 62

Genetic basis for X-linked agammaglobulinemia

Answer 62

Mutation in bruton tyrosine kinase (BTK)

Question 63

Clinical presentation of X-linked agammaglobulinemia including age at presentation, types of infections seen, and considerations regarding vaccination

Answer 63

Presents after 6 months of life Recurrent bacterial, enterovirus, and Giardia infections Live vaccines (e.g., polio) must be avoided [enterovirus and Giardia d/t lack of IgA protection of mucosal surface of the gut]

Question 64

Common variable immunodeficiency (CVID) is characterized by low immunoglobulin due to B-cell or helper T-cell defects. What complications are these pts at risk for in childhood vs. adulthood?

Answer 64

Increased risk for bacterial, enterovirus, and Giardia infections (usually in late childhood) Increased risk for autoimmune disease and lymphoma (usually later into adulthood)

Question 65

What is the most common single Ig deficiency?

Answer 65

IgA deficiency — characterized by low serum and mucosal IgA leading to increased risk for mucosal infections, especially viral

Question 66

In which GI disease is there a high incidence of IgA deficiency?

Answer 66

Celiac disease

Question 67

Hyper-IgM syndrome is characterized by elevated IgM. What causes this condition?

Answer 67

Mutated CD40L or CD40 receptor Thus the second signal cannot be delivered to the helper T cell during B cell activation — so cytokines necessary for Ig class switching are not produced. Low IgA, IgG, and IgE result in recurrent pyogenic infections, especially at mucosal sites.

Question 68

Triad associated with Wiskott-Aldrich syndrome

Answer 68

Thrombocytopenia Eczema Recurrent infections (defective humoral and cellular immunity)

Question 69

Inheritence and genetic basis for Wiskott Aldrich syndrome

Answer 69

X-linked Mutation in WASP gene

Question 70

A complement deficiency affecting anything from C5 to C9 increases the risk for ______ infection

Answer 70

Neisseria

Question 71

Consequence of C1 inhibitor deficiency

Answer 71

Hereditary angioedema characterized by edema of skin (especially periorbital) and mucosal surfaces

Question 72

Autoimmune disease results from a loss of self-tolerance. Where is central vs. peripheral tolerance usually generated?

Answer 72

Central occurs in generative organs: Thymus or bone marrow Peripheral occurs in peripheral tissues (via anergy or apoptosis) [note: negative selection in the medulla of the thymus removes self-reactive CD4 or CD8 lymphocytes by apoptosis prior to release of naive mature lymphocytes into circulation. Central tolerance in bone marrow allows the opportunity for receptor editing, followed by apoptosis if B cell is still self-reactive]

Question 73

Autoimmune polyendocrine syndrome is associated with a _____ mutation that results in a breakdown in central tolerance, leading to hypoparathyroidism, adrenal failure, and recurrent candida infections

Answer 73

AIRE [transcription factor in thymic medullary epithelial cells required to present self antigen to naive lymphocytes to check for tolerance]

Question 74

What is autoimmune lymphoproliferative syndrome (ALPS) and how does it affect peripheral tolerance?

Answer 74

Mutations in Fas (CD95) apoptosis pathway — can’t undergo apoptosis in the periphery which eventually allows the survival of self-reactive lymphocytes [may present with anemia or thrombocytopenia due to IgG against pts blood cells, generalized LAD, HSM, lymphoma]

Question 75

Immunophenotype of regulatory T cells

Answer 75

CD4+ CD25+ FoxP3+ [CD25 is IL-2R]

Question 76

2 types of mutations affecting regulatory T cells and their effects

Answer 76

CD25 polymorphisms — autoimmunity (e.g., multiple sclerosis and type 1 DM) FOXP3 mutations — IPEX syndrome (immune dysfunction, polyendocrinopathy, enteropathy, x-linked)

Question 77

Autoimmune disorders are more common in women and classically affect women of childbearing age, reflecting possible role of estrogen in pathogenesis. Autoimmune disorders are also thought to involve environmental triggers in genetically susceptible individuals, evidenced by increased incidence in twins. There is an association with ____ subtypes and ____ polymorphisms. Triggers lead to bystander activation or molecular mimicry

Answer 77

HLA; PTPN22 [note: strongest association with HLA subtypes is HLA B27 and its association with ankylosing spondylitis]

Question 78

Systemic Lupus Erythematosus (SLE) is a chronic systemic autoimmune disease of which flares and remissions are common. SLE is often associated with nonspecific findings like fever, weight loss, fatigue, LAD, and Raynaud. What are the clinical features more specific to SLE?

Answer 78

Malar “butterfly” rash or discoid rash, especially upon sun exposure Oral or nasopharyngeal ulcers Arthritis Serositis Psychosis or seizures Renal damage — diffuse proliferative glomerulonephritis (most common; type of nephritic syndrome), membranous glomerulonephritis (nephrotic syndrome) Anemia, thrombocytopenia, or leukopenia (this is due to type II HSR, while lupus itself is type III HSR) Libman-Sacks endocarditis — vegetations on BOTH sides of the valve [only need 4 of the more specific criteria to make dx]

Question 79

Pt populations most affected by SLE

Answer 79

Tends to affect middle aged females (10:1 F/M); More common in African Americans and Hispanics Female bias is less dramatic in children and older adults

Question 80

Pathogenesis and lab results suggestive of SLE

Answer 80

Antigen-antibody complex deposition in multiple tissues [Type III HSR] Antibodies are often directed against host nuclear material. Activation of complement damages tissues (labs: decreased CH50, decreased C3, decreased C4) Thus pts with early complement deficiencies (C1q, C4, C2) are associated with developing SLE because these are required for initiating clearance of the Ag-Ab complexes

Question 81

What is the significance of looking for ANA antibody in pts suspected of having SLE? What is a better test?

Answer 81

ANA antibody is sensitive but not specific — used to screen for SLE Anti-dsDNA and anti-Sm are specific to SLE Antiphospholipid antibodies can also be tested

Question 82

Which antibody associated with SLE can be used to assess prognosis because it predicts renal involvement (common cause of death in SLE)?

Answer 82

Anti-dsDNA

Question 83

Antiphospholipid antibodies are autoantibodies against proteins bound to phospholipids. What are the 3 major antiphospholipid antibodies?

Answer 83

Anticardiolipin (associated with false positive VDRL and RPR for syphilis) Lupus anticoagulant (associated with falsely elevated PTT) Anti-b2-glycoprotein I

Question 84

What is antiphospholipid antibody syndrome?

Answer 84

Antiphospholipid antibody plus hypercoagulable state (note this is paradoxical because PTT will appear to be prolonged) Prone to deep vein, hepatic vein, placental, and cerebral thrombosis Requires lifelong anticoagulation

Question 85

_____ antibody is characteristic of drug-induced SLE

Answer 85

Antihistone

Question 86

Drug-induced SLE usually goes into remission when drug is removed. CNS and renal involvement are rare in these cases, and they are considered ANA+ to anti-histone antibody. What 3 drugs are commonly associated with drug-induced SLE?

Answer 86

Hydralazine Procainamide Isoniazid

Question 87

Treatment for SLE

Answer 87

Avoid sunlight Glucocorticoids (flares) Other immunosuppressive agents

Question 88

Prognosis of SLE and common causes of death

Answer 88

Px is good with >90% 5-year survival Renal failure and infection are most common causes of death; accelerated coronary atherosclerosis (late)

Question 89

Autoimmune destruction of lacrimal and salivary glands due to lymphocyte-mediated damage with fibrosis

Answer 89

Sjogren syndrome

Question 90

What type of HSR is Sjogren syndrome?

Answer 90

Type IV HSR — because it is lymphocyte-mediated damage

Question 91

Classic presentation of Sjogren syndrome

Answer 91

Dry eyes, dry mouth, and recurrent dental caries in older woman Pts may complain that they can’t chew a cracker and feel like they have dirt in their eyes Extraglandular manifestations are common — Lymphocytic sialadenitis seen on bx of lip [this is very important for dx of Sjogrens!]

Question 92

Sjogren’s syndrome can be primary, or associated with another autoimmune disorder. It is commonly associated with ____ _____

Answer 92

Rheumatoid arthritis [Note: rheumatoid factor is often present, even in primary disease where rheumatoid arthritis is absent]

Question 93

Sjogrens is characterized by ANA and ___________, classically _____ and _____

Answer 93

Anti-ribonucleoprotein; Anti-SSA; Anti-SSB

Question 94

Presence of Anti-SSA and Anti-SSB antibodies in Sjogren’s syndrome is associated with extraglandular manifestations, risk of neonatal ____, and congenital _____ _____. These antibodies are also seen in a subset of _____ patients, and it is important to screen pregnant women with this condition

Answer 94

lupus; Heart block; SLE

Question 95

Complication of Sjogrens syndrome that presents as unilateral enlargement of parotid gland late in disease course

Answer 95

B-cell lymphoma

Question 96

Autoimmune disorder more common in middle-aged females presenting with sclerosis of the skin and visceral organs

Answer 96

Systemic sclerosis (scleroderma)

Question 97

Pathogenesis of systemic sclerosis involves _____ activation leading to deposition of ______

Answer 97

Fibroblast; collagen [this leads to autoimmune damage to mesenchyme, endothelial dysfunction, perivascular fibrosis, and organ damage]

Question 98

Systemic sclerosis can be divided into a limited type and a diffuse type. In the limited type there is limited skin with late visceral involvement. The prototype of this is CREST syndrome — what are the components of this syndrome?

Answer 98

Calcinosis/anti-Centromere antibodies Raynaud phenomenon Esophageal dysmotility Sclerodactyly Telangiectasias of skin

Question 99

Systemic sclerosis can be divided into a limited type and a diffuse type. The diffuse type diffusely involves the skin with early visceral involvement. What aspects of viscera are typically involved and what Abs are characteristically seen?

Answer 99

Vessels, GI tract, lungs, kidneys, heart (but any organ can be involved) DNA topoisomerase I antibodies [note: GI tract is most commonly involved viscera. Lung involvement is most common cause of death — due to pulmonary hypertension or interstitial fibrosis; kidney is second most common cause of death — due to scleroderma renal crisis]

Question 100

Mixed connective tissue disease involves autoimmune-mediated tissue damage with mixed features of SLE, systemic sclerosis, and polymyositis. What antibodies are seen in this condition?

Answer 100

ANA with serum antibodies against U1 ribonucleoprotein (RNP)