Chapter 6: Lecture 2

Question 1

What is central tolerance?

Answer 1

Negative selection: process of eliminating any developing T or B lymphocytes that are reactive to self in the thymus or bone marrow

Question 2

What is peripheral tolerance?

Answer 2

Ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease

Question 3

How is central tolerance mediated?

Answer 3

Thymus: Apoptosis of T cells that react w/ self antigens

Bone Marrow: Receptor editing and apoptosis

Question 4

How is peripheral tolerance mediated?

Answer 4

Anergy

Suppression by T reg Cells

Question 5

What is anergy?

Answer 5

Lack of reaction by the body’s defense mechanisms to foreign substances and consists of a direct induction of peripheral lymphocyte tolerance

Question 6

What are T cell inhibitory receptors?

Answer 6

CTLA-4

PD-1

Question 7

How can cancer cells utilize the T cell inhibitory receptors?

Answer 7

Downregulate them to avoid detection and killing

Question 8

What induces the production of T reg cells?

Answer 8

TGF-beta

Question 9

What do T reg cells express?

Answer 9

CD-25

FOXP3

Question 10

What is the purpose of AIRE and where is it found?

Answer 10

Transcription factor expressed in the thymus to eliminate self-reactive T cells
-Exposes T cells self proteins from body and T cells that react to those proteins are destroyed

Question 11

What is IPEX?

Answer 11

Defect in FOXP3 that can lead to an absence of Treg cells

Question 12

What is an autoimmune disease?

Answer 12

1. Immune reaction against self-antigen
2. Immune reaction responsible for pathologic condition
3. No other pathophysiology responsible

Question 13

What contributes to an autoimmune disease?

Answer 13

1. Genes
2. Immune Regulation
3. Environment

Question 14

What is ankylosing spondylitis?

Answer 14

Hereditary inflammatory condition of the joints, especially in the spine
-can lead to degeneration and then fusion of vertebrae

Question 15

What MHC/HLA allele is ankylosing spondylitis associated with?

Answer 15

B27

Question 16

What is Crohn’s disease?

Answer 16

Inflammatory disease of GI tract, especially in the ileum and cecum

Question 17

What causes Crohn’s disease?

Answer 17

Paneth cells in intestinal lining cannot effectively kill microbes, causing an accumulation of bacteria
-this causes an exaggerated immune response

Question 18

Crohn’s disease has polymorphisms in what gene?

Answer 18

NOD-2

Question 19

What is oral lichen planus?

Answer 19

Chronic inflammatory condition that affects mucous membranes inside mouth

1) T cell response against lesions in mucosa
2) Basement membrane is damaged and exposes brand new antigen proteins
3) Secondary B cell response occurs

Question 20

Most people test positive for _____ if they have an autoimmune disease.

Answer 20

ANA

-exception: IgG4 related disease

Question 21

People with lupus test positive for what tests?

Answer 21

Anti DS DNA (homogenous)

Anti Smith

Question 22

People with Sjogren syndrome test positive for what tests?

Answer 22

Anti Ro/SS-A (speckled)

Anti La/SS-B (speckled)

Question 23

People with systemic sclerosis test positive for what tests?

Answer 23

Anti DNA topoisomerase/SCL-70 (speckled)

Question 24

What HLA is systemic lupus erythematosus associated with?

Answer 24

HLA-DQ

Question 25

What are some symptoms of systemic lupus erythematosus?

Answer 25

- Malar rash (butterfly rash) - Discoid rash: severe rash worse with sun exposure - Photosensitivity - Oral ulcers - Arthritis - Serositis - Renal disorder - Neurologic disorders - Hematologic disorders

Question 26

When do you start to suspect systemic lupus erythematosus?

Answer 26

- Arthritis - Skin rashes - Fever - Fatigue - Hematologic disorders

Question 27

What symptoms are seen in Diffuse Lupus Nephritis?

Answer 27

- Proteinuria - Hematuria - Endothelium shows immune deposits

Question 28

What type of immunoglobulins are found in Diffuse Lupus Nephritis?

Answer 28

IgG

Question 29

How does skin change in systemic lupus erythematosus?

Answer 29

Basal layer degenerates leaving spaces

Question 30

What are some cardiovascular complications of systemic lupus erythematosus?

Answer 30

Libman-Sacks Endocarditis - warty valve deposits of fibrin - rarely can embolize - coronary artery disease

Question 31

What symptoms in systemic lupus erythematosus are seen in discoid lupus erythematosus?

Answer 31

- Discoid Rash: face and scalp - Positive ANA - Positive immunofluorescence

Question 32

What symptoms in systemic lupus erythematosus are seen in drug induced lupus erythematosus?

Answer 32

- Arthralgias - Discoid rash - Hematologic disorders - Positive ANA - Positive immunofluorescence

Question 33

What medications can cause drug induced lupus erythematosus?

Answer 33

- Procainamide: higher risk in HLA-DR6 | - Hydralazine: higher risk in HLA-DR4

Question 34

What test is drug induced lupus erythematosus positive for?

Answer 34

Anti-Histone Ab

Question 35

What is Sjogren syndrome?

Answer 35

Autoimmune disease that can destroy lacrimal and salivary gland tissue - B and T cell mediated destruction - Fibrotic destruction

Question 36

What are symptoms of Sjogren syndrome?

Answer 36

- Dry eyes - Dry mouth (xerostomia) - Difficulty swallowing - Smooth tongue with predisposition to candida yeast infection

Question 37

What are complications of Sjogren syndrome?

Answer 37

- Pulmonary Fibrosis | - Lymphoma

Question 38

What is systemic sclerosis (scleroderma)?

Answer 38

Fibrosis throughout body: collagenous deposition with subcutaneous fibrosis - Skin - GI tract - Kidneys - Heart - Lungs

Question 39

How do ANA patterns differ between systemic sclerosis and CREST syndrome?

Answer 39

Systemic sclerosis: speckled | CREST: centromere

Question 40

What test is CREST syndrome positive for?

Answer 40

Anticentromere antibodies

Question 41

What is CREST syndrome?

Answer 41

Unique form of limited sclerosis - Calcinosis: calcium deposits in skin - Raynaud's Phenomenon - Esophageal dysfunction - Sclerodactyly - Telengiectasias: dilation of capillaries causing red marks on skin surface

Question 42

What is IgG4-related disease?

Answer 42

Chronic inflammatory condition characterized by: - tissue infiltration with lymphocytes and IgG4-secreting plasma cells and T lymphocytes - Various degrees of fibrosis

Question 43

What is allorecgonition?

Answer 43

Ability of an individual organism to distinguish its own tissues from those of another

Question 44

What causes hyperacute rejection?

Answer 44

Preformed ABO antibodies | -marked inflammation followed by thrombotic microvasculopathy

Question 45

What causes acute and chronic antibody rejection?

Answer 45

Inflammation with complement C4d breakdown product | -chronic: fibrosis on vessels

Question 46

What causes acute cellular rejection?

Answer 46

T cell mediated | -endotheliitis

Question 47

What are some treatments for transplant patietns?

Answer 47

- Corticosteroids: immunosuppressive - T lymphocyte-mediated cellular rejection: Tacrolimus - Ab mediated rejection: Rituximab

Question 48

What issues can arise with graft vs host disease?

Answer 48

- Skin: rash --> desquamation - Liver: jaundice --> cholestasis - Intestines: Bloody diarrhea --> strictures