L25 Autoimmune Diseases

Question 1

What is the definition of autoimmune disease?

Answer 1

An immune process characterised by the activation of adaptive immune cells that respond to self- antigens and cause immune pathology.

Question 2

How many different human autoimmune diseases are recognised?

Answer 2

The lecture said 80, but possibly over 100.

Question 3

What percentage of the population is affected by autoimmune disease?

Answer 3

5-8%

Question 4

What are the two main classifications of autoimmune diseases based on target type?

Answer 4

Systematic and organ specific.

Question 5

What type of immune response is characteristic of T-Cell mediated autoimmune disease?

Answer 5

Cell mediated immune response.

Question 6

Name two-organ specific autoimmune disease that are T-cell mediated.

Answer 6

Diabetes and MS.

Question 7

What autoimmune disease is associated with stimulating antibodies against Thyroid Stimulating Hormone receptors?

Answer 7

Graves Disease (Hyperthyroidism)

Question 8

What immune response is primarily involved in systemic autoimmune diseases?

Answer 8

Antibody-mediated immune response.

Question 9

Give an example of an autoimmune disease that produces autoantibodies?

Answer 9

SLE (Systematic Lupus Erythemotosus.

Question 10

What is the significance of environmental factors in the development of autoimmune disease?

Answer 10

They play a larger role in AD that genetics. Environmental triggers, such as infections, can influence the onset of AD.

Question 11

What genetic factor is strongly associated with susceptibility to autoimmune diseases?

Answer 11

HLA (MHC) genes.

Question 12

What term describes the process by which an immune response is directed against self-proteins that resemble foreign antigens

Answer 12

Molecular Mimicry

Question 13

In which autoimmune disease do autoantibodies target DNA and neucleoproteins?

Answer 13

SLE

Question 14

Which syndrome is caused by mutations in the gene FOXP3 leading to autoimmune dysregulation?

Answer 14

IPEX (Immune Dysregulation Polyendocrinopathy Eteropathy-Xlined syndrome)

Question 15

How to infectious agents relate to autoimmune diseases?

Answer 15

Certain infections may trigger AD through mechanisms like molecular mimicry.

Question 16

What kind of therapy is often used to manage autoimmune diseases?

Answer 16

Immunosuppressive therapy/Immunosuppressants.

Question 17

What are the mechanisms through which autoimmune diseases can be triggered?

Answer 17

Bystander activation, molecular mimicry, and abnormal immune regulation.

Question 18

What defines organ-specific autoimmune diseases?

Answer 18

They affect a specific organ. The immune response is directed against specific organ antigens leading to localised pathology.

Question 19

What role does education play in the immune system regarding autoimmune diseases?

Answer 19

An individuals immune system is shaped by lifelong education through tolerance mechanisms, which can impact susceptibility to autoimmune conditions.

Question 20

Describe the mechanisms involved in abnormal immune regulation that may lead to autoimmunity.

Answer 20

1. Treg Dysfunction: Regulatory T cells (Tregs) normally function to suppress auto-reactive T cells, but if they are dysfunctional or insufficient, auto-reactive responses can become dominant.
2. Loss of Central Tolerance: During development in the thymus, some auto-reactive T cells may escape negative selection, leading to autoimmunity.
3. Bystander Activation: Non-specific signals from tissue damage can activate auto-reactive T cells that may not have been primed directly by self-antigens. These mechanisms can create a breach in self-tolerance and lead to the activation of immune cells against host tissues.

Question 21

How would you diagnose a specific autoimmune disease like rheumatoid arthritis?

Answer 21

1. Clinical Evaluation: Assess patient symptoms, including joint pain, swelling, and morning stiffness lasting more than 30 minutes.
2. Laboratory Tests: Use serological tests for specific autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). 3. Imaging Studies: Perform X-rays or ultrasound to detect joint erosion and inflammation.
3. Classification Criteria: Apply the ACR/EULAR classification criteria to support the diagnosis. A combination of symptoms, serological tests, and imaging findings will guide the final diagnosis.

Question 22

What steps would you take to ensure the proper management of a patient diagnosed with multiple sclerosis?

Answer 22

1. Neurological Assessment: Regular follow-ups to monitor disease progression and treatment efficacy.
2. Disease-Modifying Therapies (DMT): Prescribe medications such as interferons or glatiramer acetate to reduce relapse frequency and slow progression.
3. Symptomatic Treatment: Address specific symptoms such as muscle spasticity, fatigue, and pain with appropriate therapies.
4. Lifestyle Modifications: Encourage a healthy lifestyle, including balanced nutrition, regular exercise, and smoking cessation.
5. Support Services: Provide access to support groups, physical therapy, and occupational therapy to enhance quality of life.

Question 23

Describe the role of environmental factors, including infections, in the pathogenesis of autoimmune diseases.

Answer 23

1. Infection Triggers: Certain infections can initiate autoimmune responses via molecular mimicry, where microbial antigens resemble self-antigens, leading to cross-reactivity.
2. Hygiene Hypothesis: Increased sanitation in developed countries may reduce exposure to infectious agents in early life, impairing immune system development and promoting autoimmunity.
3. Geographical and Migratory Studies: Observing incidence differences in various populations indicates that environmental factors (like infections, diet, and sunlight exposure) influence susceptibility to autoimmune diseases.

Question 24

How would you approach the treatment of autoimmune diseases exhibiting both antibody and T cell-mediated mechanisms?

Answer 24

1. Immunosuppressive Therapy: Utilise medications such as corticosteroids for rapid control of inflammation and longer-term agents (e.g., methotrexate, azathioprine) to modify the disease course.
2. Biologics: Implement targeted therapies that either inhibit specific cytokines (e.g., TNF inhibitors for rheumatoid arthritis) or B-cell depletion therapies (e.g., rituximab).
3. Symptomatic Treatment: Manage symptoms with analgesics, anti-inflammatory drugs, or physical therapy as necessary.
4. Regular Monitoring: Conduct close follow-ups to assess the effectiveness of the therapy and adjust dosages as needed to prevent adverse effects.

Question 25

What diagnostic tests would you use to confirm a diagnosis of Graves' disease?

Answer 25

1. Serum Thyroid Hormones: Measure elevated levels of T3 and T4 alongside suppressed TSH levels, indicating hyperthyroidism. 2. Thyroid Autoantibody Tests: Assess for the presence of stimulating antibodies against the TSH receptor (TRAb). 3. Radioactive Iodine Uptake Test: Evaluate the thyroid's uptake of iodine; a high uptake indicates hyperactivity consistent with Graves' disease. 4. Thyroid Ultrasound: Perform imaging to assess thyroid structure and detect any nodularity.

Question 26

Describe the pathophysiological mechanisms involved in systemic lupus erythematosus (SLE).

Answer 26

1. Autoantibody Production: Patients produce a wide range of autoantibodies, including anti-nuclear antibodies (ANA), which lead to the formation of immune complexes. 2. Immune Complex Deposition: These complexes deposit in various tissues, causing inflammation and damage, particularly in the kidneys (lupus nephritis), skin, and joints 3. T-cell Dysregulation: An imbalance in T helper (Th) cell populations, mainly an increase in Th2 cells, contributes to the autoantibody response and diminished clearance of apoptotic cells, perpetuating the autoimmune process.

Question 27

What lifestyle changes would you recommend to a patient with an autoimmune disease?

Answer 27

1. Nutrition: Emphasise an anti-inflammatory diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats while minimising processed foods. 2. Exercise: Encourage regular low-impact exercise, such as walking, swimming, or yoga, to maintain physical fitness and reduce fatigue. 3. Stress Management: Promote stress reduction techniques, such as mindfulness, meditation, or counselling, which can help manage symptoms. 4. Adequate Sleep: Advise establishing a regular sleep schedule and practicing good sleep hygiene to enhance overall wellbeing and manage fatigue.

Question 28

How would you differentiate between organ-specific and systemic autoimmune diseases in a clinical setting?

Answer 28

1. Symptoms: Organ-specific diseases typically present with symptoms localised to affected organs (e.g., hyperthyroidism in Graves' disease), while systemic diseases involve multiple systems, presenting with generalised symptoms (e.g., fatigue, fever in SLE). 2. Laboratory Findings: Assess the presence of specific autoantibodies – organ-specific diseases often produce specific antibodies against organ antigens, while systemic diseases present multiple autoantibodies (e.g., anti-nuclear antibodies in SLE). 3. Imaging or Biopsies: Utilise specific imaging techniques or biopsies to confirm localised damage in organ-specific diseases compared to diffuse, systemic involvement in systemic diseases.

Question 29

What role does genetic susceptibility play in autoimmune diseases?

Answer 29

1. Polymorphisms in Immune Genes: Variations in genes such as those encoding major histocompatibility complex (MHC) molecules or cytokine receptors can predispose individuals to autoimmunity. 2. Family History: Having a family member with an autoimmune disease increases the risk due to shared genetic and environmental factors. 3. Single Point Mutations: Mutations in genes responsible for immune regulation (e.g., CTLA4, AIRE) can disrupt tolerance checkpoints and promote autoimmunity. This complex interplay of genetics highlights the need for personalised approaches in treatment and risk assessment.

Question 30

Describe the concept of "molecular mimicry" and its relevance to the development of autoimmune diseases.

Answer 30

Molecular mimicry refers to a situation where a pathogen's antigens closely resemble certain self-antigens, leading to confusion in the immune system. When the immune system mounts a response against the infectious agent, it may inadvertently target and attack the host's own tissues due to this structural similarity. This phenomenon is particularly relevant in autoimmune diseases, as seen in cases such as rheumatic fever, where antibodies against Streptococcus pyogenes can also react with cardiac tissue due to similarities in the antigenic structure. Understanding molecular mimicry is crucial for elucidating the triggers of various autoimmune diseases and guiding preventative and therapeutic strategies.