Autoimmunity

Question 1

Autoimmune diseases operate by what types of hypersensitivity?

Answer 1

1. Type II - cytotoxic
2. Type III - immune complex
3. Type IV - T-cell mediated/delayed

Question 2

What causes autoimmunity?

Answer 2

• Developmental regulation disfunction
• Genetics
• Environment

NO ONE FACTOR CAN CAUSE AUTOIMMUNITY

Question 3

Mutations in what gene(s) is the most common genetic determinant of autoimmunity?

Answer 3

HLA - MHCI and MHCII

Question 4

11% of caucasian people have the HLA-A1-B8-DQ2-DR3 haplotype, which is more likely to _______

Answer 4

bind self-antigen, thus predisposing them to autoimmunity

Question 5

What are the 3 “immune-privileged” sites of the human body?

Answer 5

1. Corneas
2. Brain
3. Testes

Question 6

What is the only autoimmune disease that is more common in men than women?

Answer 6

Ankylosing spondylitis

Question 7

What is the normal function of the autoimmune regulator (AIRE) gene?

Answer 7

Production of self-antigen to aide in negative selection

Question 8

What is autoimmune polyglandular disease (APD)?

Answer 8

• Autoimmune response against many endocrine glands
  
  • hypoparathyroidism
  • adrenal failure
  • ovarian failure
  • type I diabetes
  • candidiasis
  • enamel hypoplasia
  • nail dystrophy

Question 9

What are the mechanisms that contribute to central tolerance? (3)

Answer 9

1. Negative selection of B cells in the bone marrow
2. Expression of tissue-specific proteins in the thymus so that they participate in negative selection of T-cells (AIRE)
3. Negative selection of T-cells in the thymus

Question 10

What are the mechanisms that contribute to peripheral tolerance? (3)

Answer 10

1. Exclusion of lymphocytes from immune-privileged sites
2. Induction of anergy in autoreactive B and T cells that reach the peripheral circulation
3. Suppression of autoimmune responses by regulatory T-cells

Question 11

Mutation of the X-linked FoxP3 gene causes a rare immunodeficiency that principally affects boys, called _______

Answer 11

immune dysregulation, polyendocrineopathy, enteropathy, X-linked disease (IPEX)

Question 12

Children with IPEX have normal levels of _____ cells and elevated levels of ______ cells

Answer 12

• CD25 T-reg cells
• TH17 cells

Question 13

How does IPEX present clinically?

Answer 13

• Enteritis → chronic diarrhea
• Type 1 diabetes
• Eczema
• Failure to thrive
• Do not survive past 1 y/o

Question 14

_____ tolerance is negative selection during lymphocyte development, occurring in primary lymphoid organs

Answer 14

Central tolerance

Question 15

_____ tolerance refers to anergy or suppression of auto-reactive cells; occurring in secondary lymphoid organs

Answer 15

Peripheral tolerance

Question 16

True or false, peripheral tolerance only occurs after infection occurs.

Answer 16

True

Question 17

What is the consequence of a T-cell failing to receive a co-stimulatory signal from B7 on APCs?

Answer 17

Anergy

Question 18

Binding of pathogen to self-protein results in _____

Answer 18

pathogen creating a unique epitope for autoimmunity to occur

Question 19

How can disruption of cell tissue or barrier result in autoimmunity?

Answer 19

Unregulated release of cellular contents (self-antigen) can activate nontolerized lymphocytes

Question 20

What is molecular mimicry?

Answer 20

Pathogen antigen resembles host antigen, which triggers production of cross-reactive antibodies or T-cells

Question 21

How do superantigens elicit an autoimmune reaction?

Answer 21

Stabilization of the MHC-TCR complex without the need for a co-stimulatory signal, thus activating potential auto-reactive T-cells

Question 22

Describe the Bystander effect in regard to B and T cells.

Answer 22

Self-reactive B/T cells receive second signal for activation from nearby cells

Question 23

Grave’s disease is associated with mutations in what gene?

Answer 23

HLA-DR3

Question 24

Describe the mechanism of Grave’s disease

Answer 24

Auto-IgG are generated against TSH receptor, however these antibodies are agonistic so they cause activation of the receptor and cause chronic overproduction of T3 and T4

Question 25

What are the symptoms of Grave's disease?

Answer 25

* **Hyperthyroid** * heat intolerance * nervousness * irritability * weight loss * bulging eyes * enlarged thyroid

Question 26

Grave's disease can be treated with drugs that inhibit uptake of \_\_\_\_\_

Answer 26

Iodine

Question 27

True or false. If someone with Grave's disease was pregnant, they cannot transfer the disease to their child.

Answer 27

False. IgG cross the placenta so the newborn will suffer the disease until the IgG is cleared

Question 28

Describe the mechanism of myasthenia gravis

Answer 28

Auto-IgG against acetylcholine receptors are antagonistic and marks them for endocytosis and degradation

Question 29

Describe the clinical presentation of myasthenia gravis in its early and late stages

Answer 29

* Early - drooping eyelids (ptosis); double vision (diplopia) * Late - weakening of chest muscles; impaired breathing

Question 30

How do pyridostigmine and azathioprine work to treat myasthenia gravis?

Answer 30

Inhibits the breakdown of acetylcholine

Question 31

What are the differences between warm antibody types and cold antibody types in autoimmune hemolytic anemia?

Answer 31

* Warm - IgG against RhD * Cold - IgM against glycophorin (I antigen) * only produced in individuals that live in cold climates (advised to move)

Question 32

Infection by _______ produces a mimicry response by cross-reacting with the I antigen on hemoglobin.

Answer 32

*Mycoplasma pneumonia*

Question 33

Describe the mechanism by which Rheumatic fever is triggered.

Answer 33

* IgG against *Streptococcus pyogenes* cross-reacts with heart myosin, joints, and kidneys * Occurs weeks after infection

Question 34

Describe the mechanism by which Goodpasture's syndrome develops

Answer 34

* Auto-IgG against Type IV collagen against the glomerulus basement membrane * Triggers complement cascade leading to inflammatory damage

Question 35

How does Goodpasture's syndrome present clinically?

Answer 35

* Glomerulonephritis * Pneumonitis (in smokers) * Pulmonary hemorrhage (in smokers)

Question 36

How is Goodpasture's syndrome treated?

Answer 36

Plasma exchange

Question 37

Rheumatoid arthritis is associated with mutations in what gene?

Answer 37

HLA-DR4

Question 38

Describe the two possible mechanisms by which Rheumatoid arthritis develops.

Answer 38

1. Deposition of immune complexes in the joints (rheumatoid factor) 2. Abs directed against citrullinated epitopes of self-proteins (peptidyl arginine deaminases); citrulline is a non-human amino acid

Question 39

What exactly is rheumatoid factor?

Answer 39

Auto-IgG directed against the Fc region of other IgG

Question 40

How do adalimumab and rituximab treat rheumatoid arthritis?

Answer 40

* Adalimumab - antibodies against TNF-α * Rituximab - antibodies against CD20

Question 41

In Systemic Lupus Erythematosus (SLE), how are antinuclear antibodies generated?

Answer 41

* UV radiation induces apoptosis and alteration of DNA structure * CD4 T-cells specific for self nucleosomal antigens produced

Question 42

In SLE, where do immune complexes deposit? (4) Consequences?

Answer 42

1. Kidneys → glomerulonephritis 2. Joints → arthritis 3. Blood vessels → vasculitis 4. Skin → rash

Question 43

How is SLE treated?

Answer 43

* NSAIDs * Immunosuppressants * Biologics

Question 44

\_\_\_\_\_\_ is caused by a CD4 TH1 response against a variety of thyroid antigens, leading to an infiltration of lymphocytes that destroy normal architecture and impairs thyroid function

Answer 44

Hashimoto's thyroiditis

Question 45

How does cell architecture change in Hashimoto's thyroiditis?

Answer 45

Thyroid becomes organized like lymphatic tissue

Question 46

How is Hashimoto's thyroiditis treated?

Answer 46

Replacement thyroid hormone therapy

Question 47

Mutations in ______ confer susceptibility to type I diabetes, whereas ____ confers resistance and overrides the former.

Answer 47

* DR4 * DQ6

Question 48

Infections by _____ can induce type I diabetes by cross-reacting with insulin, glutamate decarboxylase, or protein components of β-islet cells, mediated by CD8+ T-cells

Answer 48

* Coxsackie (A&B) virus * Echovirus

Question 49

Describe the mechanism by which celiac disease develops

Answer 49

* TH1 cells release inflammatory cytokines * Macrophages activated * More cytokines and ROS * Destruction of intestinal epithelial cells