Autoimmunity and Autoimmune Diseases Flashcards by Bryan Edwards

Q

Genetic factors associated with autoimmune disease?

A

Familial Incidence

Association with Specific HLA/MHC Haplotypes

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Origins of autoimmune disease?

A

Genetics
Failure to maintain self-tolerance
Loss of Treg
Expression of cryptic self epitopes
Inappropriate MHC II molecules
Antigen mimicry
Polyclonal B activation
Infectious Diseases
Hormonal influences

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Autoimmune hemolytic anemia.

Rxn Type, Autoantigen and Consequence?

A

Type II
Rh blood group antigens
RBC destruction, Anemia

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Autoimmune thrombocytopenia purpura.

Rxn Type, Autoantigen and Consequence?

A

Type II
Platelet Integrin (gpIIb:IIIa)
Abnormal Bleeding

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Goodpasture’s Syndrome.

Rxn Type, Autoantigen and Consequence?

A

Type II
Non-collagenous basement membrane, Type 4 collagen
Glomerulonephritis, Pulmonary Hemorrhage

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Pemphigus Vulgaris.

Rxn Type, Autoantigen and Consequence?

A

Type II
Epidermal Cadherin
Blistering

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Pemphigus foliaceus.

Rxn Type, Autoantigen and Consequence?

A

Type II
Desmoglein
Mild Blistering

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Acute rheumatic fever.

Rxn Type, Autoantigen and Consequence?

A

Type II
Strep Wall antigens, cross react w/ cardiac
Arthritis, Myocarditis, Late Scarring of Heart

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Grave’s Disease.

Rxn Type, Autoantigen and Consequence?

A

Type II
TSH receptor
Hyperthyroidism

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Myasthenia Gravis.

Rxn Type, Autoantigen and Consequence?

A

Type II
Acetylcholine Receptor
Progressive weakness

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Type II Diabetes.

Rxn Type, Autoantigen and Consequence?

A

Type II
Insulin Receptor
Hyperglycemia, Ketoacidosis

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Subacute bacterial endocarditis.

Rxn Type, Autoantigen, and Consequence?

A

Type III
Bacterial Antigen
Glomerulonephritis

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Mixed essential cryoglobulinemia.

Rxn Type, Autoantigen, and Consequence?

A

Type III
Rheumatoid Factor IgG complexes
Systemic Vasculitis

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Systemic Lupus Erythematosus.

Rxn Type, Autoantigen, and Consequence?

A

Type III
DNA, Histones, Ribosomes, snRNPs
Glomerulonephritis, Vasculitis, Arthritis

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Type I Diabetes.

Rxn Type, Autoantigen, and Consequence?

A

Type IV
Pancreatic beta cell antigen
beta cell destruction

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Rheumatoid arthritis

Rxn Type, Autoantigen, and Consequence?

A

Type 4
Unknown synovial joint antigen
Joint inflammation, destruction

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

MS

Rxn Type, Autoantigen, and Consequence?

A

Type 4
Myelin basic protein, proteolipid protein
Brain degeneration, Paralysis

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

How do we normally prevent autoimmunity?

A

Positive/Negative Selection of B and T cells
Regulatory CD4CD25 T Cells
Physical Separation
Limited expression of MHC II and B7

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Examples of physically separated from lymphocytes?

A

Brain, Eye, Testis

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

How are autoimmune cells repressed by Tregs?

A

IL10, TGFbeta

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Five Major Susceptibility Factors in Autoimmune Disease?

A

HLA Genotype/Genetic Background
Microbial Infection
Injury
Environmental Factors/Behavior
Gender and Sex hormones

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

How might microbial infection promote autoimmunity

A

Adjuvant effect
Induction of higher MHC and B7
Molecular Mimicry

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

How might injury lead to an autoimmune response?

A

Reveals antigens from a previously immune priveledged organ

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

Environmental factors that affect autoimmune disease?

A

Smoking and hygiene

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Which gender is more prone to autoimmune concerns?

Women

Describe the pathogenesis of Sympathetic Opthalmia

Injury in one eye releases eye antigen into local lymph nodes Immune responses to antigen affect both eyes Blindness in both damaged and undamaged eye

What does AIRE do?

Allows expression of peripheral antigen in the thymus

Mutation of AIRE leads to....

Wide range of autoimmune diseases

Mutations in AIRE are characterized by....

Autoimmune PolyEndocrynology Candidiasis Ectodermal Dystrophy

What is IPEX?

Mutation of FOXP3 Loss of generation of Tregs Tregs can't suppress activation of other immune cells

Describe the relationship of HLA allotypes with aytoimmune disease

Some unique HLA allotypes are very heavily assoicated with specific disease states compared to their prevalence in the control population Ex. B27 HLA is present in 9% of people, but more than 95% of patients with ankylosing spondylitis have it

What is Celiac disease?

Wheat flour gluten peptide-specific CD4+ T cells Later anti-transglutaminase autoantibodies Destruction of villi structure

How does Celiac Happen

``` Gluten degraded in lumen to resistant fragment Fragment enters gut tissue Deaminated by transglutaminase Native CD4 t cell responds via HLA-DQ Inflammatory T cell response ```

What happens in molecular mimicry?

Antibodies to pathogens cross-react against host antigens

Group A Strep | HLA Association? Consequence?

Not Known | Rheumatic Fever

Chlamydia trachomatis | HLA Association? Consequence?

HLA-B27 | Reiter's Syndrome (arthritis)

Campylobacter jejuni | HLA Association? Consequence?

HLA-B27 | Reactive Arthritis

Borrelia Burgdorferi | HLA Association? Consequence?

HLA-DR2, DR4 | Chronic Arthritis in Lyme Disease

Cocksackie A and B | HLA Association? Consequence?

HLA DQ2, DQ8, DR4 | Type I Diabetes

Mechanism of induced autoimmune thyroid disease?

IFNg from infection/inflammation induces MHC II Activated T cells recognize thyroid peptides Induce Autoimmune thyroid disease

How does the thyroid typically avoid immune response?

Thyroid does not normally express HLA molecules

What is autoimmune hemolytic anemia (type 2)

Erythrocytes bind anti-RBC autoantibodies | Destruction through phagocytosis or completment

How do you treat autoimmune hemolytic anemia (type 2)

Splenectomy to reduce Blood cell loss

What happens in Immune Thrombocytopenic Purpura (ITP)

Antibodies attach to blood platelets for destruction

What is Goodpasture's syndrome?

IgG agains alpha3 chain of type 4 collagen in BM | Renal Glom is most sensitive to the antibody deposits/inflam

HLA types associated with Type I diabetes?

HLA-DR3, DR4

Grave's disease is associated with what HLA type?

HLA-DR3

Difference in presentation of Hashimoto's and Grave's?

Hashi - Destroys Thyroid | Graves -- Hyperproduction of thyroid

Autoimmune disease of adrenal gland?

Addison's

Treatment for Grave's disease?

Thyroidectomy or destruction of the gland by radioactive I

Concern for pregnant women with Grave's

Antibodies to TSHR can cross placenta Newborn also suffers from Grave's Plasmaphoresis should cure the disease

What happens in Hashimoto's thyroiditis?

Antibodies against effector T cells specific for thyroid Destroy Thyroid, loss of T3/T4 production Th1 type disease

Treatment for hashimoto's

administration of thyroid hormone

List three autoimmune liver/GI diseases

IBD Pernicious Anemia Autoimmune Chronic Active Hepatitis

Autoimmune Chronic Active Hepatitis is assocaited with which HLA antigen?

HLA-B8/DR3

Three autoimmune rheumatic diseases? HLA? Sensitivity?

Rheumatoid Arthritis - DR4 -- (III and IV) Systemic Lupus Erythematosus -- DR2,3 -- II and III Polymyositis/Dermatomyositis -- DR3, DR -- IV

Immediately apparent sign of systemic lupus

``` Wolf Erythematosus (Skin Rash) Caused by antibodies to histone and DNA ```

Two big problems with Systemic Lupus Erythematosus?

IgG binding to cell surfaces --> Inflammatory responses | Immune complexes deposited in vessels, kidneys

Cause of rheumatoid arthritis?

Rheymatoid Factor = IgM/G/A against the Fc region of IgG | Leukocyte infiltration in the joint synovium

What cells make rheumatoid factor?

Plasma B cells

How is Rheumatoid arthritis treated?

Anti inflamamtory | Immunosuppressive drugs

How does smoking affect Rheumatoid arthritis?

Smoking --> Injury --> Generation of Citruline Residues | Citruline residues --> CD4 T Cell Activation -> RA

How can RA be treated with NK cells?

Add in an anti-CD20 antibody (Rituximab) to promote lysis by NK cells

Four autoimmune neurologic diseases.

MS Acute disseminated encephalomyelitis Acute Inflammatory Polyneuropathy/Guillon Barre Myasthenia Gravis

MS is what type of hypersensitivity?

2 and 4

Acute disseminated encephaloyelitis is what type of hypersensitivity?

4

Guillon barre is what type of hypersensitivity?

II and IV

Myasthenia gravis is is what type of hypersensitivity?

II

T cells implicated in MS?

Th17 or Th1

Cytokines associated with CNS inflammation and demyelination

IL-17, IFNg