15 - Hypersensitivity and Auto Immunity 2

Question 1

An immune reaction against self antigen is the definition of _. When is this not a bad thing?

Answer 1

Autoimmunity Tumors

Question 2

What are the 3 criteria for diagnosing autoimmunity?

Answer 2

-presence of autoimmune rxn-evidence that rxn is not secondary to tissue damage-absence of well defined cause of disease

Question 3

A break down of what process leads to pathologic autoimmunity?

Answer 3

Self tolerance

Question 4

A state where the individual is incapable of developing an immune response to a specific antigen is _. What are the 2 types?

Answer 4

• Immunological tolerance

- Central and peripheral tolerance

Question 5

One mechanism of central tolerance is clonal deletion. What happens during clonal deletion?

Answer 5

Deletion of self reactive clones of cytolytic and helper T-lymphocytes

Question 6

Why is it thought that clonal deletion of B cells is of minor importance?

Answer 6

Because there is a relatively high rate of auto-antibodies documented

Question 7

Within the thymus, where are each of the following cells found? Lymphoid cells,epithelial cells, dendritic cells, macrophages? Which express MHC1? Which express MHC 2?

Answer 7

Lymphoid cell - Thymus - MHC1
Epithelial cells - Cortex - MHC1
Dendritic cells - Corticomedullary junction - MHC1 and 2 Macrophages - medulla - MHC1 and 2

Question 8

Regarding central tolerance, the process where thymocytes are selected for their ability to bind self MHC molecules is _

Answer 8

Positive selection

Question 9

Regarding central tolerance, the process of elimination of clones of thymocytes that bind self antigens is _. This also known as _

Answer 9

Negative selection Clonal deletion

Question 10

Clonal anergy is a tolerance mechanism important is central or peripheral tolerance?

Answer 10

Peripheral tolerance

Question 11

What are 2 signals required for maximal stimulation of a T cell?

Answer 11

Recognition of MHC2 on antigen presenting cell (APC)

Costimulators presented by APC

Question 12

What happens when T cells are presented with antigen in the absence of costimulators?

Answer 12

No activation / immune response, anergy of the T cell, essentially its elimination

Question 13

Another mechanism for peripheral tolerance is suppression. What cells are characteristically involved with this process? What are the 2 major cytokines involved?

Answer 13

• CD4+/CD25+ cells

- IL-10 and TGF-beta

Question 14

Another mechanism of peripheral tolerance is activation induced cell death. How does this happen? What receptor / ligand pair is associated with this process?

Answer 14

• High antigen dose + chronic stimulation leads to elimination of T-cells- Fas receptor and fas ligand (FasL)

Question 15

Which is more highly expressed in the human body, self antigens or foreign antigens? What does this mean for self reactive lymphocytes?

Answer 15

Self antigens Self reactive lymphocytes will be maximally and continually stimulated, leading to their apoptosis and elimination (activation induced cell death)

Question 16

What is the number 1 cause of acquired immune deficiency globally?

Answer 16

Malnutrition

Question 17

Another mechanism of peripheral tolerance is sequestration. What does this mean? What are the 3 examples provided in the lecture?

Answer 17

Antigens are kept in immuno-priviledged areas Eye, testis, brain

Question 18

What disease is associated with defect in Fas/FasL?

Answer 18

ALPS - Autoimmune lymphoproliferative syndrome

Question 19

What are 2 ways infection can cause breakdown of self tolerance?

Answer 19

• Alteration in levels of co-stimulators (e.g. on fibroblasts and epithelial cells)
• Molecular mimicry

Question 20

What are the 2 broad categories of autoimmune disease?

Answer 20

• Systemic multi organ disease

- Organ systemm of cell type specific

Question 21

Regarding lupus, is it more common in men that women? What is thought to underlie this difference in gender prevalence?

Answer 21

• More common in women

- Estrogen - make more tolerant

Question 22

In what stage of life are people more likely to be affected by lupus?

Answer 22

Child bearing years, mainly women

Question 23

What are the HLA types associated with lupus? A congenital deficiency in what 2 complement proteins may promote lupus development?

Answer 23

• HLA types DR2 and DR3

- Deficiency of C2 and C4 complement components

Question 24

A hallmark of SLE is B lymphocyte hyperactivity. What are 3 antibodies that are diagnostic for lupus?

Answer 24

• Anti-nuclear ab
• Anti-native DNA
• Anti-Sm

Question 25

A hallmark of SLE is B lymphocyte hyperactivity. What are 3 antibodies that are mentioned in our notes that alter the symptomatology of SLE disease?

Answer 25

- Anti-RBC - anti- lymphocyte - Anti-phospholipid (e.g. anti cardiolipin)

Question 26

What is the characteristic skin finding on SLE patients, especially on sun exposed areas? (2)

Answer 26

- Butterfly (malar) rash on face | - erythematous patches

Question 27

What is a kidney finding on SLE patients?

Answer 27

Destruction of glomeruli (glomerulonephritis)

Question 28

What is the major determinant of the different manifestation of SLE in different patients?

Answer 28

The variety of auto antibody produced

Question 29

A SLE subtypes that is associated with skin manifestations only in the skin, especially the face and scalp with rare incidence of systemic manifestation is _. What type of antibody would you NOT see in this case?

Answer 29

- Chronic discoid lupus | - Won't see DS/native DNA antibodies

Question 30

A SLE subtype associated with skin localized and mild systemic symptoms is _. What antibody and HLA genotype is associated with this SLE subtype?

Answer 30

- Subacute cutaneous lupus | - Anti-SSA-HLA-DR3

Question 31

An SLE subtype associated with drugs that induce antinuclear antibody formation is _. What symptoms, compared to normal lupus, is usually not present in these patients?

Answer 31

- Drug induced lupus | - No CNS or renal manifestations

Question 32

In patients with drug induced lupus, would you expect to find anti-DS-DNA antibodies? What about anti-histone antibodies? What HLA subtype is associated with this type of lupus?

Answer 32

- Anti- DS-DNA antibody negative - Anti-histone antibody positive - HLA-DR4

Question 33

How do you treat patients with drug induced lupus?

Answer 33

Remove the drug

Question 34

What are behavior modifications that can be suggested to treat lupus?

Answer 34

- Reduce stress | - avoid sun

Question 35

What are the 3 drugs that were presented as immunosuppresives used to treat the systemic manifestations of lupus?

Answer 35

- Corticosteroids - Cytoxan - 6-mercaptopurine

Question 36

Why is therapy for SLE using rituximab considered "hit or miss"?

Answer 36

Rituximab targets CD20. Plasma cells producing antibodies associated with lupus don't have CD20 on their surfaces

Question 37

The 10 year survival for SLE patients is at about 80%. What are the 2 main causes of death in these patients?

Answer 37

- Immunosuppressive toxicity (BM aplasia,secondary neoplasms, infectious diseases) - Renal failure

Question 38

Rheumatoid arthritis affect more males or females? What is the age range of most patients?

Answer 38

- More females than males | - 35-50 yrs old

Question 39

Symmetric symptoms including pain affecting 2-3 joints, stiffness that improves as the day goes along, swelling and inflammation in joints are all characteristic of _.

Answer 39

Rheumatoid arthritis

Question 40

True or false. RA may be associated with malaise, fever, fatigue, loss of appetite, weight loss, myalgias,weakness

Answer 40

True - In serious cases only

Question 41

What are joints that are most affected by RA?

Answer 41

Hands and wrists

Question 42

Is juvenile RA more or less common that adult RA? Is it more or less severe?

Answer 42

Less common, more severe

Question 43

What happens to the normal cartilage within the joints of patients with RA?

Answer 43

It is destroyed by inflammatory cells and replaced by fibrous tissue

Question 44

What is the cytokine that is secreted by infiltrating leukocytes and inflamed synovial cells that is thought to underlie the positive feedback loop associated with RA pathogenesis?

Answer 44

TNF-alpha

Question 45

What are the 3 types of hypersensitivity associated with RA? Which is particularly associated with extrarticular manifestations of RA?

Answer 45

- Types 2, 3 and 4 | - Type 3 assoc. with extra-articular manifestations of RA

Question 46

What is the autoantibody that is detected in serum of 80% of RA patients? Is it specific for RA?

Answer 46

Rheumatoid factor | Not specific

Question 47

How would the clinical course of RA be described?

Answer 47

Relapsing and remitting

Question 48

True or false: joint deformities associated with RA are progressive in only 50% of patients

Answer 48

True

Question 49

What is the classic treatment for RA?

Answer 49

Rest and aspirin

Question 50

Beyond aspirin, what are 3 types of drugs used to treat RA?

Answer 50

- Corticosteroids - Cytotoxic drugs - Biological response modifiers

Question 51

What are the 3 examples of biological response modifiers used to treat RA?

Answer 51

- TNF-alpha blockers - Anti-TNF-alpha antibodies - Rituximab

Question 52

What is another name for systemic sclerosis? Are males or females more likely to be affected? What are 2 genes associated with this disease?

Answer 52

- Scleroderma - More females than males - HLA class 2 and Fibrillin

Question 53

Majority of the clinical findings associated with systemic sclerosis are because of _

Answer 53

Increased deposition of connective tissue in skin, intestines and blood vessels

Question 54

What are 2 antibodies used to diagnose systemic sclerosis? Which is specific for the CREST variant of systemic sclerosis?

Answer 54

- Anti Scl-70 antibody | - Anti-centromere antibody (specific of CREST variant)

Question 55

What lyphocyte type is thought to mediate increased release of cytokines associated with the manifestations of systemic sclerosis? What cells are thought to be hyperreactive to these released cytokines?

Answer 55

- CD4+ cells cause cytokine release | - Fibroblast hyperreactive to the cytokine release

Question 56

The variant of scleroderma that has widespread skin andvisceral involvement with rapid progression is _

Answer 56

Diffuse scleroderma

Question 57

The variant of scleroderma that mainly has skin involvement primarily in the face, hands and forearms is called _.

Answer 57

- CREST syndrome - C alcinosis - R aynaud Phenomenon, - E sophageal dysmotility, - S clerodactyly, - T elangectasia

Question 58

What is the result of vascular thickening as seen in systemic sclerosis?

Answer 58

Reduced blood flow

Question 59

What is the major cause of death in patients with systemic sclerosis?

Answer 59

Malnutrition - Because of replacement of GI submucosa with fibrosis

Question 60

What is the patient demographic of Sjogren's syndrome?

Answer 60

50-60 y.o. females

Question 61

What are the 5 proteins (non-antibody) associated with Sjogrens?

Answer 61

- HLA-B8, - HLA-DR3, - HLA-DQA1, - HLA-DQB1, - DRW52

Question 62

What are the 2 auto antibodies associated with Sjogrens?

Answer 62

- Anti - SS-A (ro) | - Anti - SS-B (La)

Question 63

What are the 2 glands destroyed in patients with Sjogren's syndrome? What are the 2 likely mediators?

Answer 63

- Lacrimal and salivary glands - CD4+ cells - Viruses (EBV, HCV, HTLV-1)

Question 64

Why do many patients with Sjogren's go blind?

Answer 64

Loss of lacrimation leads to drying of the cornea