Immunopathology II

Question 1

describe the direct pathway of transplant rejection

Answer 1

in the direct pathway, donor class I and class II MHC antigens on antigen-presenting cells in the graft are recognized by host CD8+ cytotoxic T cells and CD4+ helper T cells.

• CD4+ cells proliferate and produce cytokines (IFN-gamma) which induce tissue damage by a local inflammatory reaction
• CD8+ T cells responding to graft antigens differentiate into CTLs that kill graft cells

Question 2

describe the indirect pathway of transplant rejection

Answer 2

in the indirect pathway, graft antigens are picked up, processed, and displayed by host APCs and activate CD4+ T cells which damage the graft by an inflammatory reaction and stimulate B lymphocytes to produce antibodies

Question 3

describe the time of onset, the mechanism and morphology of hyperacute rejection

Answer 3

• time of onset: minutes to few hours
• mechanism: preformed antibodies bind to graft endothelium
• morphology: vascular thrombosis +/- necrosis

Question 4

describe the time of onset, the mechanism and morphology of acute cellular rejection

Answer 4

acute cellular rejection

• time of onset: days to weeks, months to years
• mechanism: T cells injure graft by direct cytotoxicity and type IV HS
• morphology: interstitial infiltrate of lymphocytes with tubulitis +/- arteritis

Question 5

describe the time of onset, the mechanism and morphology of acute humoral rejection

Answer 5

acute humoral

• time of onset: days to weeks, months to years
• mechanism: antidonor antibodies against graft antigens
• morphology: microcirculatory inflammation +/- arteritis/thrombosis

Question 6

describe the time of onset, the mechanism and morphology of chronic rejection

Answer 6

chronic rejection

• time of onset: months to years (irreversible)
• mechanism: T cell cytokines stimulate vascular smooth muscle proliferation
• morphology: arteriosclerosis; ischemic injury; interstitial fibrosis

Question 7

describe what is seen in the image

Answer 7

Question 8

describe what is seen in the image

Answer 8

Question 9

describe what is seen in the image

Answer 9

Question 10

describe what is seen in the image

Answer 10

Question 11

describe graft versus host disease

Answer 11

• donor tissue is immunocompetent
• donor T cells react to “foreign” antigens of host tissues
• recipient is immuno-depleted (whole body irradiation or chemotherapy)
• most commonly occurs following allogeneic bone marrow transplantation
• activation of donor CD4 and CD8 T cells
  
  • type IV HS rxn

Question 12

describe the acute vs. chronic form of graft versus host disease

Answer 12

Question 13

describe central tolerance

Answer 13

• apoptosis of self-reactive lymphocyte clones during maturation
  
  • T cells in thymus
  • B cells in bone marrow
• some survive to become regulatory T cells

Question 14

describe peripheral tolerance

Answer 14

• back-up mechanisms to neutralize self-reactive T cells that escape central neutralization
  
  • anergy
  • suppression by regulatory T cells
  • activation-induced cell death
  • antigen segregation

Question 15

in SLE, there are antibodies against ___ components and ____

Answer 15

in SLE, there are antibodies against nuclear components and phospholipids

Question 16

the basic mechanism of SLE is the loss of _____

Answer 16

the basic mechanism of SLE is the loss of self-tolerance

Question 17

describe how SLE affects the skin

Answer 17

Question 18

describe what is seen in the image

Answer 18

Question 19

describe what is seen in the image

Answer 19

Question 20

describe how SLE affects the kidney

Answer 20

Question 21

describe what is seen in the image

Answer 21

SLE

focal proliferative glomerulonephritis with 2 focal necrotizing lesions at the 11 o clock and 2 o clock positions

Question 22

describe what is seen in the image

Answer 22

SLE

diffuse proliferative glomerulonephritis; note the marked increase in cellularity throughout the glomerulus

Question 23

describe the image

Answer 23

SLE

lupus nephritis showing a glomerulus with several “wire loop” lesions representing extensive subendothelial deposits of immune complexes (PAS stain)

Question 24

describe how SLE affects the joints

Answer 24

• non-erosive synovitis
• no deformities
• neutrophils and fibrin in synovial fluid

Question 25

describe how SLE affects the heart and blood vessels

Answer 25

* pericarditis, myocarditis * Libman Sacks endocarditis * necrotizing vasculitis of small arteries & arterioles

Question 26

a sensitive but not specific test for SLE (or any autoimmune disorder) is for \_\_\_\_

Answer 26

a sensitive but not specific test for SLE (or any autoimmune disorder) is for **antinuclear antibodies (ANA)**

Question 27

name the 2 *main* specific antibodies used for diagnosis of SLE name 3 other one

Answer 27

* specific antibodies * **anti-double stranded** **DNA (ds-DNA)** * **anti-Smith (Sm)** * other antibodies * antiphospholipid * antiplatelets * antiRBCs

Question 28

\_\_\_ levels are decreased in active SLE disease

Answer 28

**complement levels** are decreased in active SLE disease

Question 29

name the antibodies specific for SLE

Answer 29

**anti-dsDNA** **anti-Sm**

Question 30

name the antibodies specific for drug-induced SLE

Answer 30

**antihistone**

Question 31

name the antibodies specific for systemic sclerosis (scleroderma)

Answer 31

**Scl-70**

Question 32

name the antibodies specific for CREST

Answer 32

**anticentromere**

Question 33

name the antibodies specific for Sjogren syndrome

Answer 33

**SS-A** **SS-B**

Question 34

name the antibodies specific for myopathies

Answer 34

**Jo-1**

Question 35

describe the significance of antiphospholipid antibodies in SLE and name 2 major complications

Answer 35

* against proteins complexed to phospholipids * can bind to Cardiolipin Ag of Treponema (syphillis) and cause a false positive * causes procoagulant complications: * **recurrent** **thromboemboli** * **recurrent abortions, focal cerebral ischemia** * anti-phospholipid antibody syndrome = when without SLE

Question 36

describe **drug-induced SLE** (4 drugs) which antibody is present in this condition?

Answer 36

* drugs * procainamide = most common * hydralazine * isoniazid * D-penicillamine * renal and CNS involvement uncommon * remits with withdrawal of drug * high frequency of **anti-histone antibodies**

Question 37

in **systemic sclerosis**, there is excessive ___ throughout the body and ___ is almost always involved name the 2 basic forms of the systemic type

Answer 37

in **systemic sclerosis**, there is excessive **fibrosis** throughout the body and **the skin** is almost always involved * 2 basic forms of systemic type: * diffuse * limited (CREST syndrome)

Question 38

describe symptoms associated with systemic sclerosis (scleroderma)

Answer 38

* skin abnormalities distinctive * Raynaud phenomenon * difficulty swallowing

Question 39

describe how systemic sclerosis (scleroderma) affects the GI tract

Answer 39

* GI tract * muscular and mucosal atrophy and fibrosis * loss of normal motility and absorption

Question 40

\_\_\_\_ aka ____ is highly specific for systemic sclerosis (scleroderma) while \_\_\_\_ is highly specific for CREST

Answer 40

**anti-topoisomerase I** aka **anti-SCL 70** aka **anti**is highly specific for systemic sclerosis (scleroderma) while **anticentromere** is highly specific for CREST

Question 41

describe CREST syndrome and symptoms

Answer 41

* limited form of systemic sclerosis * relatively mild, indolent course * acronym: * **C**alcinosis * **R**aynaud phenomenon * **E**sophageal dysmotility * **S**clerodactyly * **T**elangiectasia

Question 42

in Graves disease, immunoglobulins mimic ___ which results in \_\_\_\_

Answer 42

in Graves disease, immunoglobulins mimic **TSH** which results in **hyperthyroidism**

Question 43

in autoimmune gastritis, there are autoantibodies against ____ which leads to a decrease in ___ and \_\_\_\_

Answer 43

in autoimmune gastritis, there are autoantibodies against **gastric parietal cells** which leads to a decrease in **acid secretion** and **intrinsic factor secretion (necessary for B12 absorption → leads to pernicious anemia)**