Br Pathology: Immunopatholgy

Front 1

What is the function of TLRs? What are examples of molecules they bind

Back 1

1) membrane proteins on host cells that bind foreign molecules
2) endotoxin and peptidoglycan in gram + bacteria

Front 2

What intracellular molecule is activated when TLRs bind antigen? What is end result?

Back 2

1) NFkB
2) release of NO, TNF, IL-1, peroxide, antimicrobial peptides, chemokines and increased adhesion molecules like selectins on neutrophils

Front 3

When does IgM synthesis begin? What does its presence at birth indicate?

Back 3

1) at birth
2) cytomegalovirus

Front 4

When does IgG synthesis begin?

Back 4

~2 months

Front 5

What chromosome is the MHC gene on?

Back 5

short arm of chromosome 6

Front 6

What cell are MHCs not expressed on?

Back 6

RBCs

Front 7

What are class 1 antigens? What cell recognizes them? When are they altered?

Back 7

1) HLA, B,C proteins
2) recognized by CD8 and NK cells
3) viral infection

Front 8

What are class 2 antigens? Which cells express them? Which cells recognize them

Back 8

1) HLA-DP, DQ, DR
2) present on B cells, macrophages, dentritic cells
3) recognized by CD4 cells

Front 9

is ankylosing spondylitis associated with a class I or class II antigen?

Back 9

class I HLA-B27

Front 10

HLA-DR2 is seen in what disease?

Back 10

MS

Front 11

Type I diabetes is associated with what HLA antigens?

Back 11

HLA-DR3 and DR4

Front 12

In a transplantation work-up what is it important to match up?

Back 12

HLA-A, B, D in donor and graft recipient

Front 13

In a type I hypersensitivity APC present to what type of T cell?

Back 13

TH2 which release interleukins to activate B cells

Front 14

What does IL-4 induce?

Back 14

IgM to IgE switch

Front 15

What activates eosinophils?

Back 15

IL-5

Front 16

What is the pathway that induces mast cells to release histamine in a type I hypersensitivity?

Back 16

they bind Fc portion of IgE and on second exposure they are activated when antigen binds IgE to release histamine, chemotactic factors for eosinophils and proteases

Front 17

What happens in the late phase of a type I hyersensitivity?

Back 17

Mast cells release prostaglandins and leukotrienes which prolongs inflammatory response

Front 18

On the molecular level what occurs during desensitization of allergen?

Back 18

there is a switch to IgG from IgE which prevents mast cell activation

Front 19

CD4 cells release IL-2 what is the result? They also release IFN-gamma. What happens?

Back 19

1) proliferation of CD4/CD8 cells
2) activation of macrophages

Front 20

What cytokine do NK cells release?

Back 20

IFN-gamma to activate macrophages to clean up the mess

Front 21

Which test has the highest sensitivity to evaluate a type I hypersensitivity? what is the result?

Back 21

1) scratch test
2) if positive see a wheel and flare reaction on skin

Front 22

What are atopic reactions seen in type I hypersensitivity?

Back 22

hay fever, eczema, hives, asthma

Front 23

Type II hypersensitivity is also known as?

Back 23

cytotoxic hypersensitivity

Front 24

What examples of IgM mediated cell lysis?

Back 24

1) IgM types of cold immune hemolytic anemia
2) transfusion of group A blood into group B

Front 25

How are the complement dependent- antibody dependent reactions of IgM and IgG different?

Back 25

1) IgM binds and cell membrane activates complement forming MAC
2) IgG attaches to basement membrane/matrix, C5a produced which recruits neutrophils that release enzymes and ROS
3) IgG can also cause opsonization and therefore phagocytosis

Front 26

What are examples of cytotoxic hypersensitivities that involve IgG cell lysis?

Back 26

1) good pasutres
2) acute rheumatic fever where antibodies bind heart, skin , brain, SQ tissue and joints

Front 27

What are examples of Type II hypersensitivity that involve IgG mediated phagocytosis?

Back 27

1) warm IgG immune hemolytic anemia
2) ABO hemolytic disease of newborn (mother has O baby has A or B)

Front 28

What are type II hypersensitivity complement-independent reactions?

Back 28

1) cells are coated with IgG activate neutrophils, monocytes and NK cells to cause lysis. viral infected cells or tumors are examples

Front 29

What type of hypersensitivity is myasthenia gravis or Graves disease?

Back 29

type II complement independent reaction

Front 30

Antibody (IgE) dependent cell mediated cytotoxicity which results from eosinophil destruction of helminths induces what type of hypersensitivity? Is it complement dependent or independent?

Back 30

type II hypersensivity that is complement-independent

Front 31

What are tests used for type II hypersensitivities?

Back 31

direct and indirect coombs

Front 32

What does direct Coombs test detect?

Back 32

used in type II hypersensitivity to detect IgG and C3b attached to RBCs

Front 33

What does indirect Coombs test detect?

Back 33

antibodies in serum (like anti-D)

Front 34

With a type III hypersensitivity do you have a reaction on the first exposure?

Back 34

no

Front 35

Deposition of antigen-antibody complexes in type III hypersensitivity induces what?

Back 35

complement activation in which C5a attracts neutrophils that induce damage

Front 36

What is an arthus reaction?

Back 36

type III hypersensitivity that is a localized immunecomplex reaction. It is seen in farmers lung from exposure to thermophilic actinomycetes or antigens in air

Front 37

How are type III hypersensitivities evaluated?

Back 37

immunofluorescent staining of tissue biopsies

Front 38

What are the types of type IV hypersensitivities?

Back 38

1) DRH
2) cell-mediated cytotoxicity

Front 39

What is delayed reaction hypersensitivity? What conditions is it seen in?

Back 39

1)type IV hypersensitivity where CD4 interact with APCs and release cytokines that damage tissue
2) TB granuloma, PPD reaction, MS

Front 40

Cell-mediated cytotoxicity is see in what conditions?

Back 40

1) graft rejection
2) contact dermatitis

Front 41

poison ivy and nickel induce what type of hypersensitivity?

Back 41

4

Front 42

What is the most important requirement for successful transplantation?

Back 42

ABO blood group compatibility

Front 43

When a parent is a graft donor what haplotype match are they generally?

Back 43

1-haplotype

Front 44

What graft type has the best survival rate?

Back 44

autograft

Front 45

A graft between identical twins is known as?

Back 45

syngeneic graft or isograft

Front 46

What is an allograft? What is a common allograft in women?

Back 46

1) graft between same species but genetically different individuals
2) fetus

Front 47

What is a hyperacute graft rejection? What type of hypersensitivity is it?

Back 47

1) irreversible rejection that occurs within minutes
2) type II because there are preformed HLA antibodies or ABO incompatibility

Front 48

What is a pathologic finding in hyperacute graft rejection?

Back 48

vessel thrombosis

Front 49

What is the most common transplant rejection type?

Back 49

acute

Front 50

A reversible rejection that occurs within days to weeks is?

Back 50

acute rejection

Front 51

What types of hypersensitivities are associated with acute rejection?

Back 51

Type IV and II

Front 52

What are the pathological findings of acute rejection with a Type IV hypersensitivity?

Back 52

extensive interstial round cell lymphocytic infiltrate in graft, with edema and endothelial injury

Front 53

What is the lymphocyte imbalance that occurs in autoimmunity?

Back 53

CD4+ out number CD8+

Front 54

How does methyldopa contribute to autoimmunity?

Back 54

methyldopa alters Rh antigens on the surface of RBCs

Front 55

What virus contributes to diabetes?

Back 55

coxsackievirus alters β-islet cells

Front 56

What chromosome are the immune response genes on?

Back 56

6

Front 57

What viruses and toxins cause polyclonal activation of B cells?

Back 57

◦Polyclonal activators include Epstein-Barr virus, cytomegalovirus, endotoxins

Front 58

What are 3 examples of systemic autoimmune diseases?

Back 58

SLE, rheumatoid arthritis, systemic sclerosis

Front 59

What are targets of ANA?

Back 59

antibodies against DNA, histones, acidic proteins, nucleoli

Front 60

Anti-double-stranded DNA antibodies present in SLE patients also have what condition?

Back 60

glomerulonephritis

Front 61

Antihistone antibodies are present in what?

Back 61

drug-induced lupus

Front 62

What are Anti-Smith antibodies found in?

Back 62

SLE

Front 63

What are Anti-ribonucleoprotein antibodies found in?

Back 63

SLE

Front 64

What are examples of acidic proteins that antibodies target in autoimmune diseases?

Back 64

Anti-ribonucleoprotein and anti-smith proteins

Front 65

What are Anti-nucleolar antibodies present in?

Back 65

systemic sclerosis

Front 66

What are the ANA patterns of immunofluorescence

Back 66

speckled, homogeneous, nucleolar, and rim

Front 67

If a rim pattern is seen on ANA immunoflouresence what is the antibody, what organ is effected and what disease is it?

Back 67

anti-dsDNA antibodies and the presence of renal disease in SLE

Front 68

Anti-acetylcholine receptor is found in what disease? How sensitive is it?

Back 68

Anti-acetylcholine recepto

>85

Front 69

Anti-basement membrane is found in what? How sensitive is it?

Back 69

Goodpasture's syndrome

>90%

Front 70

Anticentromere is found in what? How sensitive is it?

Back 70

CREST syndrome (The limited cutaneous form of systemic sclerosis scleroderma)

50-90%

Front 71

Antiendomysial IgA is found in what condition? What is the other antibody in this condition? Which is more sensitive?

Back 71

Celiacs 95%

Antigliadin IgA 80%

Front 72

Is Anti-insulin or Anti-islet cell more sensitive for diabetes?

Back 72

Anti-islet cell

Front 73

Is Anti-intrinsic factor or Anti-parietal cell more sensitive for pernicious anemia?

Back 73

Anti-parietal cell

Front 74

Antimicrosomal antibody is found in what condition?

Back 74

Hashimotos 97% (note same as antithyroid peroxidase antibody

Front 75

Anti-SS-A is found in what conditions? Which one is more sensitive for?

Back 75

Sjögren's syndrome more sensitive than SLE

Front 76

Anti-SS-B is found in what condition? Does it have a higher or lower sensitivity than anti-SS-A?

Back 76

Sjögren's syndrome

SS-A (Ro) 70-95%
SS-B (La) 50-90%

Front 77

Antithyroglobulin is found in Graves or Hashimotos?

Back 77

hashimotos

Front 78

Anti-tissue transglutaminase IgA is found in what condition? What other antibodies can be found with it? Which is the most sensitive?

Back 78

1) Celiac disease
2) Anti-tissue transglutaminase IgA>Antiendomysial IgA>Antigliadin IgA

Front 79

Anti-topoisomerase is found in what condition? How sensitive is it?

Back 79

Systemic sclerosis

only 30%

Front 80

Antimitochondrial is found in what?

Back 80

Primary biliary cirrhosis

90% sensitive

Front 81

Antimyeloperoxidase is found in what condition?

Back 81

Microscopic polyangiitis (pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of necrotizing granulomatous inflammation.)

Front 82

Antinuclear antibody is found in what 3 conditions?

Back 82

SLE
Systemic sclerosis
Dermatomyositis

Front 83

Antiproteinase 3 is found in what condition?

Back 83

Wegener's granulomatosis (vasculitis that affects the lungs, kidneys and other organs)

90% sensitive

Front 84

Anti-ribonucleoprotein is found in what conditions?

Back 84

mixed connective tissue disease (MCTD) nearly 100% sensitive

Also in SLE

Front 85

Anti-TSH receptor is found in what condition?

Back 85

graves

Front 86

What can produce a false RPR syphillis test?

Back 86

Anticardiolipin antibodies (SLE) react with cardiolipin in the test

Front 87

What can produce a false venereal disease research laboratory (VDRL)?

Back 87

Anticardiolipin antibodies react with cardiolipin in the test

Front 88

What does SLE primarily affect in the body?

Back 88

Connective tissue disease that mainly affects the blood, joints, skin, and kidneys

Front 89

Who does SLE predominately occur in?

Back 89

women of childbearing age

Front 90

Where genetic alterations been mapped to in SLE? Is the pathogenesis all genetic?

Back 90

chromosome 6

NO, it is environment and genetic

Front 91

What are examples of environmental agents that can cuase SLE?

Back 91

a) Infectious agents (viruses, bacteria)
(b) Ultraviolet light
(c) Estrogen
(d) Medications
(e) Extreme stress

Front 92

What allele is found in both SLE and RA?

Back 92

STAT4

Front 93

What is the function of STAT4? What is it mutated in?

Back 93

Protein products of STAT4 are essential for mediating responses to IL-12 and in regulating the differentiation of T helper cells

SLE and RA

IL-12 (produced by dendritic cells and macrophages that helps naive T cells differentiate in lymphocytes)

Front 94

What are hematologic findings in SLE? Lymph? Musculoskeletal? Skin? Renal? Cardiac? Respiratory?

Back 94

a.Hematologic
■Autoimmune hemolytic anemia, thrombocytopenia, leukopenia
b.Lymphatic
(1) Generalized painful lymphadenopathy
(2) Splenomegaly
c.Musculoskeletal
■Small-joint inflammation (e.g., hands) with absence of joint deformity
d.Skin
(1) Immunocomplex deposition along basement membrane
■Produces liquefactive degeneration
(2) Malar butterfly rash
e.Renal
■Diffuse proliferative glomerulonephritis (most common glomerulonephritis)
f.Cardiovascular
■(1) Fibrinous pericarditis with or without effusion
■(2) Libman-Sacks endocarditis (sterile vegetations on both sides of mitral valve; 18% of cases)
g.Respiratory
(1) Interstitial fibrosis of lungs
(2) Pleural effusion with friction rub

Front 95

What kind of skin degeneration occurs in SLE? Most common cardiac finding in SLE?

Back 95

liquifactive

fibrinous pericarditis with effusion

Front 96

What are pregnancy concerns in someone with SLE?

Back 96

(1) Complete heart block in newborns
■Caused by IgG anti-SS-A (Ro) antibodies crossing the placenta
(2) Recurrent spontaneous abortions
■Caused by antiphospholipid antibodies

Front 97

most common drug associated with drug-induced lupus erythematosus? What are other drug?

Back 97

procainamide

hydralazine

Front 98

What are features that distinguish drug-induced lupus from SLE?

Back 98

(1) Antihistone antibodies
(2) Low incidence of renal and CNS involvement
(3) Disappearance of symptoms when the drug is discontinued

Front 99

Does ANA have a higher sensitivity or specificity for SLE?

Back 99

sensitivity is nearly 100%, but specificity is lower because ANA is also present in systemic sclerosis and other diseases

Front 100

What are Anti-dsDNA antibodies and anti-Sm antibodies used for in SLE?

Back 100

confirm diagnosis

■They have high specificity for diagnosing SLE (i.e., few false positive results)
(2) Specificity for anti-dsDNA is 99% and 100% for anti-Sm.

Front 101

What do Antiphospholipid antibodies do in SLE? What are the antibodies specifically? What can it predispose someone to?

Back 101

■(1) Lupus anticoagulant and anticardiolipin antibodies
(2) Damage vessel endothelium, producing vessel thrombosis
(3) Increased incidence of strokes and recurrent spontaneous abortions

Front 102

What cell do you look for in the blood of someone with lupus erythmatous? Is it more sensitive or specific

Back 102

(1) Neutrophil containing phagocytosed altered DNA
(2) Sensitivity 76% and specificity 97%

Front 103

the band test is used for what?

Back 103

Immunofluorescent studies identify complexes in a band-like distribution along the dermal-epidermal junction in SLE

Front 104

What is the prognosis of SLE?

Back 104

■Over 90% now survive for 10 years or more

Front 105

How is the joint pain managed in SLE? Cutaneous disease? Renal disease? hemolytic anemia and thrombocytopenia?

Back 105

1) NSAIDs
2) topical corticosteroids, antimalarial agents, sunscreen, and methotrexate or azathioprine
3) cyclophosphamide
4) corticosteroids and/or splenectomy

Front 106

What is the risk of giving an SLE patient TNF-alpha inhibitors?

Back 106

disseminated infection

Front 107

What sights are effected in systemic sclerosis?

Back 107

skin (scleroderma), gastrointestinal tract, lungs, and kidneys

Front 108

Who does systemic sclerosis predominately occur in?

Back 108

women of childbearing age

Front 109

What is the pathogenesis of systemic sclerosis?

Back 109

a.Small-vessel endothelial cell damage produces blood vessel fibrosis and ischemic injury.
b.T-cell release of cytokines results in excessive collagen synthesis.
c.Stimulatory autoantibodies against platelet-derived growth factor

Front 110

What is the initial sign of systemic sclerosis? How is this sign characterized?

Back 110

1) Raynaud's phenomenon
2) Sequential color changes (white to blue to red) caused by digital vessel vasculitis and fibrosis

Front 111

What are the skin and facial feature changes in systemic scleroderma?

Back 111

(1) Skin atrophy and tissue swelling beginning in the fingers and extending proximally
(2) Parchment-like appearance
(3) Extensive dystrophic calcification in subcutaneous tissue
(4) Tightened facial features (e.g., radial furrowing around the lips, thin lips)

Front 112

What types of GI changes occur in systemic sclerosis?

Back 112

1) Dysphagia for solids and liquids
(a) No peristalsis in the lower two thirds of the esophagus (smooth muscle replaced by collagen)
(b) Lower esophageal sphincter relaxation with reflux
(2) Small bowel
(a) Loss of villi (malabsorption)
(b) Wide-mouthed diverticula (bacterial overgrowth)
(c) Dysmotility (cramps and diarrhea)

Front 113

What is the most common cause of death in systemic sclerosis? why?

Back 113

respiratory failure from interstitial fibrosis

Front 114

What are renal changes in systemic sclerosis?

Back 114

(1) Vasculitis involving arterioles (i.e., hyperplastic arteriolosclerosis) and glomeruli
(2) Infarctions, malignant hypertension

Front 115

What is CREST? What are clinical features?

Back 115

■Limited sclerosis
a.Clinical findings
(1) C-calcification, centromere antibody
(2) R-Raynaud's phenomenon (see Fig. 3-2B)
(3) E-Esophageal dysmotility
(4) S-sclerodactyly (i.e., tapered, claw-like fingers)
(5) T-telangiectasias (i.e., multiple punctate blood vessel dilations)

Front 116

How is CREST treated?

Back 116

d-Penicillamine; recombinant human relaxin

Front 117

Who does Dermatomyositis occur in?

Back 117

women 40 to 60 years of age

Front 118

Who does poliomyositis occur in? Does it have skin involvement?

Back 118

women 40 to 60 years of age

no

Front 119

What are dermatomyositis and poliomyositis associated with?

Back 119

malignant neoplasms (15-20% of cases), particularly lung cancer

Front 120

Is dermatomyositis or poliomyositis associated with antibody destruction? Which is associated with T cell destruction?

Back 120

a.DM is associated with antibody-mediated damage.
b.PM is associated with T cell-mediated damage.

Front 121

What are clinical findings in DM/PM?

Back 121

a.Muscle pain and atrophy
■Shoulders are commonly involved.
DM/PM: heliotrope eyes; Gottron's patches
b.Heliotrope eyelids or "raccoon eyes" (purple-red eyelid discoloration)
c.Purple papules over the knuckles and proximal interphalangeal joints
■Called Gottron's patches

Front 122

What are lab findings in PM/DM?

Back 122

a.Serum ANA is positive in <30% of cases.
b.Increased serum creatine kinase
c.Muscle biopsy shows a lymphocytic infiltrate.

Front 123

How can acute rejection be reversed?

Back 123

potentially reversible with immunosuppressive agents, such as cyclosporine (blocks CD4 T-cell release of IL-2), OKT3 (monoclonal antibody against T-cell antigen recognition site drug is muromonab), and corticosteroids (lymphotoxic).

Front 124

Immunosuppressive therapy is associated with an increased risk of what cancers? Which is most common?

Back 124

cervical squamous cell cancer, malignant lymphoma, and squamous cell carcinoma of the skin (most common cancer).

Front 125

What type of hypersensitivities occur in acute rejection? What is the pathogenesis of each?

Back 125

1) Type IV cell-mediated hypersensitivity
a) Host CD4 T cells release cytokines, resulting in activation of host macrophages, proliferation of CD8 T cells, and destruction of donor graft cells.
b) Extensive interstitial round cell lymphocytic infiltrate in the graft, edema, and endothelial cell injury
2) Antibody-mediated type II hypersensitivity reaction
a) Cytokines from CD4 T cells promote B-cell differentiation into plasma cells, producing anti-HLA antibodies that attack vessels in the donor graft.
b) Vasculitis with intravascular thrombosis in recent grafts
c) Intimal thickening with obliteration of vessel lumens in older grafts

Front 126

Is chronic rejection reversible or permanent? What is the danger of giving immunosuppressive therapy?

Back 126

1) Irreversible reaction that occurs over months to years
2) Involves continued vascular injury with ischemia to tissue
3) Blood vessel damage with intimal thickening and fibrosis

Immunosuppressive therapy: danger of squamous cell carcinoma

Front 127

What conditions commonly cause graft vs host disease? What is the major condition?

Back 127

1. Potential complication in bone marrow (85% of cases) and liver transplants
2. Potential complication in blood transfusions given to patients with a T-cell immunodeficiency and newborns

Front 128

What is the pathogenesis of graft vs host disease?

Back 128

1. Donor cytotoxic T cells recognize host tissue as foreign
2. Proliferate in host tissue and produce severe organ damage

Front 129

What are common graft vs host symptoms?

Back 129

1. Bile duct necrosis (jaundice)
2. Gastrointestinal mucosa ulceration (bloody diarrhea)
3. Dermatitis

Front 130

How can graft vs host be prevented?

Back 130

1. Treat with anti-thymocyte globulin or monoclonal antibodies before grafting
2. Cyclosporine reduces the severity of the reaction.

Front 131

What allograft has the best survival rate? What is the danger associated with the transplant?

Back 131

cornea

transmission of Creutzfeldt-Jakob disease

Front 132

what occurs in a bone marrow transplant with donor cells? What is the risk of bone marrow transplant?

Back 132

1) Graft contains pluripotential cells that repopulate host stem cells
2) Host assumes donor ABO group
3) Danger of graft-versus-host reaction and cytomegalovirus infection

Front 133

What are reactions that occur in type I hypersensitivity?

Back 133

Atopic disorders: hay fever, eczema, hives, asthma, reaction to bee sting

Drug hypersensitivity: penicillin rash or anaphylaxis

Front 134

What are reactions that occur in type II hypersensitivity? give examples of IgM, IgG mediated, etc....

Back 134

Complement-dependent reactions

Lysis (IgM mediated): ABO mismatch, cold immune hemolytic anemia

Lysis (IgG mediated): Goodpasture's syndrome, PA
Phagocytosis: warm (IgG) autoimmune hemolytic anemia, ABO and Rh hemolytic disease of newborn, Idiopathic thrombocytic purpura

Complement-independent reactions

Antibody (IgG)-dependent cell-mediated cytotoxicity: natural killer cell destruction of neoplastic and virus-infected cells

Antibody (IgE)-dependent cell-mediated cytotoxicity: eosinophil destruction of helminths

Antibodies directed against cell surface receptors: myasthenia gravis, Graves' disease

Front 135

What are reactions that occur in type III hypersensitivity?

Back 135

Systemic lupus erythematosus (DNA-anti-DNA)

Serum sickness (horse antithymocyte globulin-antibody)

Poststreptococcal glomerulonephritis

Front 136

What are the 2 types of reactions that occur in type IV hypersensitivity?

Back 136

Delayed type: tuberculous granuloma; PPD reaction, MS
Cell-mediated cytotoxicity: killing of tumor cells and virus-infected cells; contact dermatitis (e.g., poison ivy, nickel)