Autoimmune Disease - Basic Science Core

Immuno 1 Exam

What is Autoimmune Disease?

• Autoimmune disease is chronic and often requires life-long therapy

• Currently, there is no cure for most autoimmune diseases, though treatments can manage symptoms and potentially induce remission

• The immune system mistakenly attacks and damages normal body tissue, which can weaken bodily function and even be life-threatening

How Many Autoimmune Diseases are There?

• There are over 80 different types of autoimmune diseases

What explicitly causes Autoimmune Diseases ?

• We Still do not 100% know

What Factors are Thought to Cause Autoimmune Diseases (3)

1) Genetic Factors

2) Environmental Factors

3) Other Factors

Genetic Factors (Autoimmune Diseases)

• Inherited genes: Certain genes may increase a person’s susceptibility to developing an autoimmune disease

• Family history: Having a family history of autoimmune diseases increases the likelihood of developing one

• Multiple Autoimmune Syndrome: Having one autoimmune disease can increase the risk of developing another

Environmental Factors (Autoimmune Diseases)

• Infections: Epstein-Barr virus (EBV) has been associated with lupus, Sjogren’s syndrome and multiple sclerosis

• Smoking: Has been linked to risk of developing rheumatoid arthritis

• Environmental toxins: Exposure to certain chemicals, pollutants and toxins (e.g., mercury, pesticides, etc.)

• Diet: Certain nutritional deficiencies may affect the risk of developing autoimmune disease

Other Factors (Autoimmune Diseases)

• Sex: Women are more likely to develop autoimmune diseases than men

• Age: The risk of autoimmune diseases tends to increase with age, especially after 30 years old

• Vaccines: There is some evidence to suggest that some vaccines may trigger certain autoimmune disorders in very rare cases

Sjögren’s Syndrome

Autoimmune disease that attacks the SALIVARY GLANDS leading to XEROSTOMIA

Patients who cannot produce saliva (or produce very little) suffer from dental caries (cavities), dry mouth and infection & inflammation of the buccal mucosa

Sjögren’s Syndrome Risk Factors: (3)

Risk factors:

• Age > 40 years

• Female > male

• Having rheumatoid arthritis or lupus

Multiple Sclerosis

• Autoimmune disorder leading to DEMYELINATION of CNS neurons,

• Cause is unknown
  

• Two Types

  • relapsing-remitting (RRMS)

  • primary progressive

Type 1 Diabetes Mellitus

• Accounts for 5-10% of all diagnosed cases of DM

Prior Known as → insulin- dependent diabetes mellitus (IDDM)

• Two Forms of it

Two Forms of Type 1 Diabetes Mellitus

1) Immune mediated

2) Idiopathic

Immune Mediated Type 1 DM

Results from a cellular- mediated autoimmune destruction of the β-cells of the pancreas

Markers include:

• islet cell autoantibodies (ICAs),

• autoantibodies to insulin (IAAs)

• glutamic acid decarboxylase autoantibodies (GADA)

• MANY More

Rate of β-cell destruction is quite variable

• Kids is faster then adults which is slower

Result:

• INABILITY TO SYNTHESIZE & SECRETE INSULIN

• SUBSEQUENT HYPERGLYCEMIA

Hashimoto’s Thyroiditis Function

• Autoimmune disease that attacks and destroys the THYROID GLAND

• End result: PRIMARY HYPOTHYROIDISM

PRIMARY HYPOTHYROIDISM

• Inability to make thyroid Hormones

  • Levothyroxine (T 4)

  • Liothyronine (T3)

Liothyronine (T3) Synthetic Drug

Cytomel

Levothyroxine (T4)

• Levothroid

• Synthroid

• Unithroid

• Levoxyl

Rheumatoid Arthritis (RA)

RA is a chronic systemic inflammatory disease of unknown cause.

• The autoimmune reaction attacks SYNOVIAL JOINTS around the body.

• Abnormal production of numerous cytokines, chemokines, and other inflammatory mediators are seen in RA Paients

Ultimately, inflammation and proliferation of the synovium leads to destruction of various tissues, including cartilage, bone, tendons, ligaments, and blood vessels.

AUTOIMMUNE REACTION to Joint Pain

1) Release of inflammatory mediators (cytokines,

interleukins, TNF-α, etc.) & rheumatoid factors

2) Chronic inflammation of the synovial tissue lining

the joint capsule & free radical production

3) Proliferation of that tissue forming what is called

“PANNUS”

4) Pannus invades cartilage & bone surface, producing

cartilage and bone erosion

5) JOINT Destruction

Plaque Psoriasis

• Psoriasis is a common chronic skin disorder most commonly characterized by well-demarcated erythematous plaques with silver scale (“Plaque Psoriasis”) although other presentations can occur.

• The immune system attacks healthy epidermal cells.

• This misdirected attack leads to an overproduction of epidermal skin cells, causing them to build up on the skin’s surface and form the characteristic plaques and scales associated with psoriasis

Inflammatory Bowel Disease (IBD) (2)

Two Types:

• Crohn Disease

• Ulcerative Colitis

Graves’ Disease

• Graves’ disease occurs when autoantibodies known as TSIs (thyroid stimulating immunoglobulins) BIND TO

  TSH RECEPTORS

• CONSTANTLY STIMULATE THE THYROID

• Causes → HYPERTHYROIDISM

HYPERTHYROIDISM

• Overproduction of the thyroid gland

• too much of T3 & T4

Treatment of Graves’ Disease

• 1) anti-thyroid drugs (i.e.,thionamides)

• 2) radioactive iodine (RAI) therapy

• 3) Surgery (thyroidectomy)

Immunomodulating Drugs

These drugs attempt to prevent the immune system from attacking self

Side effects (Of Suppressing your Immune System)

• Infections (sometimes serious or fatal ones)

• Cancer

• Other autoimmune disorders

Two Types of these Drugs:

• 1) Monoclonal antibodies

• 2) JAK inhibitors

Two Types of Immunomodulating Drugs

1) Monoclonal antibodies

2) JAK inhibitors

Monoclonal Antibodies of Plaque Psoriasis

• Infliximab (Remicade, Inflectra) TNF-α Blocker

• Adalimumab (Humira, Cyltezo) TNF-α Blocker

• Certolizumab (Cimzia) TNF-α Blocker

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• Ustekinumab (Stelera) Interleukin IL-12 & IL-23 Blocker

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• Secukinmab (Cosentyx) Interleukin IL-17A Blocker

• Brodalumab (Siliq) Interleukin IL-17A Blocker

• Ixekizumab (Taltz) Interleukin IL-17A Blocker

• Bimekizumab (Bimzelx) Interleukin IL-17A Blocker

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• Guselkumab (Tremfya) Interleukin IL-23 Blocker

• Risankizumab (Skyrizi) Interleukin IL-23 Blocker

• Tildrakizumab (Ilumya) Interleukin IL-23 Blocker

JAK Inhibitors for Rheumatoid Arthritis

• Tofacitinib (Xeljanz)

• Upadacitinib (Rinvoq)

• Baricitinib (Olumiant)

JAK = Janus Kinase

Janus kinases participate in intracellular signaling resulting from cytokines interacting with their receptors → by inhibiting this signaling, tofacitinib suppresses immune cell function

Vaccines and Immunomodulating Drugs

However, patients receiving immunomodulating drugs should not be administered live vaccines

• Dead Ones or Inactive Vacceen is ok