Exam 4 Lecture (Autoimmune Diseases)

Immune system related diseases

-autoimmune diseases

-hypersensitivity disorders (allergies)

-Immunodeficiencies

-neoplasia (leukemias, lymphomas, others)

Autoimmune diseases are caused by ______

erroneous attack of the immune system on self tissues

What causes/contributes to immune damage?

pathogenic antibodies or immune cells (T cells)

Facts about autoimmune diseases:

-common & arise spontaneously

-young individuals & women

-high socio economic burden

-sometimes induced

-no cure

-treatments come w/side effects

Glucocorticoids (e.g. Prednisolone)

Immunosuppression, hyperglycemia, skin atrophy, bruising,muscle atrophy, osteoporosis, weight gain, glaucoma, cataracts,euphoria/psychosis

TNF inhibitors

cell lymphomas, opportunistic infections, Tb

Interferon beta

flu like symptoms

Anti-B cell antibodies

Cardiac arrest, acute renal failure, infections, progressive multifocal leukoencephalopathy (PML), pulmonary problems

Anti-VLA-4 antibodies

Progressive multifocal leukoencephalopathy (PML)

Fingolimod

skin cancer, hemorrhagic encephalitis

Autoreactive __ or __ cells exist in _____ humans

B, T, healthy

Some __ and __ cells can recognize ___ and potentially attack ____

T, B, autoantigens, self tissues

Autoimmunity

an immune response against self tissues

Autoimmune disease

autoimmune response that results in tissue damage

___ and ___ factors increases the risk for autoimmune diseases

genetic and environmental

Notable genes linked w autoimmune diseases:

HLA, Foxp3

Notable infections linked with specific autoimmune diseases:

Campylobacter jejuni - Guillain-Barre syndrome- Group A Streptococcus pyogenes - Rheumatic fever/heartdisease- EBV - Multiple sclerosis- Coxsackie B virus - Autoimmune myocarditis

environmental risk factors:

-Gut microbiome

• Smoking

• High salt diet

• Obesity

What is molecular mimicry and how does it cause autoimmune disease?

When microbes have proteins that look similar to self-proteins, the immune system attacks the microbe and accidentally cross-reacts with the body.Examples: Rheumatic fever, Guillain-Barré syndrome (GBS).

How does failure of immune regulation lead to autoimmunity?

Loss of tolerance or defective regulatory cells (T and B cells) removes the "brakes" on the immune system, allowing it to attack self.Example: Foxp3 mutation → IPEX syndrome.

What does "access to forbidden sites" mean in autoimmunity?

Some tissues (brain, testes, eye) are normally hidden from the immune system. Injury or inflammation exposes these antigens, leading to an autoimmune attack.

What genetic and environmental factors contribute to autoimmune disease?

Genes (e.g., HLA, TNF) increase susceptibility. Environmental triggers—smoking, infections, microbiome changes—can initiate or worsen autoimmunity.

The strongest genetic base for autoimmune diseases is ________

HLA (MHC)

___ % of multiple sclerosis patients are ___

___% of Rheumatoid arthritis are __ or ___

___% of celiac patients are ___

60, DR2

80-90, DR1 or DR4

98, DQ2

MHC and T cell relationship

MHC (HLA) molecules present fragment of CNS proteins to T lymphocytes and they decide whether or not to attack

What are the two main classifications of autoimmune diseases?

Organ-specific and Systemic autoimmune diseases

What are the different types of Organ-specific autoimmune diseases?

Antibody-mediated and Cell-mediated

Antibody-mediated autoimmune diseases

Grave's disease, Myasthenia gravis, Goodpasture'ssyndrome

Cell-mediated autoimmune diseases

-Multiple sclerosis

• Type 1 diabetes

Systemic autoimmune diseases

-systemic lupus erythematosus

-rheumatoid arthritis

Key symptoms of Graves disease:

• Tremor, nervousness, restlessness

• Weight loss despite increased appetite

• Intolerance to heat

• Profuse sweating

• Tachycardia &Cardiac arrhythmia (fast heart)

• Exophthalmus* (inflammation behind the eyes) & Diffuse goiter (enlarged thyroid)

3 Main examples of antibody mediated organ-specific autoimmune diseases

- Grave's disease -> stimulating autoantibodies

- Myasthenia gravis -> blocking autoantibodies

- Goodpasture's syndrome -> destructive autoantibodies

Graves' Disease is also known as

Toxic goiter or Basedow disease

T3 and T4

-thyroid releases more T4 than T3 (20X)

-T3 is 3-4X stronger than T4

-free T4/T3 are the active forms

-body converts T4 into T3

What does the hypothalamus detect in the Hypothalamic-Pituitary-Thyroid Axis?

T4

What hormone does the hypothalamus release in response to T4?

TRH (Thyrotropin-Releasing Hormone)

What does the anterior pituitary release in response to TRH?

TSH (Thyroid-Stimulating Hormone)

What gland is stimulated by TSH?

Thyroid gland

What hormones are produced by the thyroid gland?

T3 and T4

What causes Graves' disease?

-body produces antibodies that mimic TSH

-stimulates the thyroid gland to produce high levels of T3/4

thyroid storm and be caused by

-high fever

-severe tachycardia

-extreme restlessness

CAUSED --> stress or infection

-death from heart or organ failure

How is Graves' diagnosed?

-T3/4 levels are high

-TSH is low

-TSH antibodies are present

How is graves' treated?

-antithyroid drugs (block iodine and decrease hormones)

-surgery

-radioactive iodine

Myasthenia gravis (MG)

-blocking antibodies that prevent acetylcholine from binding

-receptor turnover may also be accelerated

-progressive weakening of muscles

Clinical symptoms of MG

-difficulty chewing, swalling, talking (slurred speech)

-weakening of eye muscles = double vision

-drooping eyelids

-difficulty breathing

-remitting relapsing

What is a dangerous complication of Myasthenia gravis (MG)

Myasthenic crisis

-respiratory failure due to MG

-pneumonia

What are the ways to diagnose MG?

-nerve stimulation test

-anticholinesterase (edrophonium) test = injection

-thymoma (tumor in thymus) on chest CT (15% of patients)

What are the treatments to MG?

-Pyridostigmine --> helps acetylcholine stay longer so muscles can work better

-Plasmapheresis --> filters out the harmful antibodies from the blood

-Thymectomy --> removal of the thymus

-Immunosuppressants --> lower the immune attack

What type of disease is Goodpasture's syndrome?

An autoimmune disease where antibodies attack the basement membranes of the lungs and kidneys. ("destructive" autoantibodies)

What organs are primarily affected in Goodpasture's syndrome?

Lungs and kidneys.

What lung symptoms occur in Goodpasture's?

Hemoptysis (coughing up blood) and shortness of breath.

What kidney condition develops in Goodpasture's syndrome?

-Hematuria (blood in urine)

-Edema

-High BP

-Proteinuria

True or false: Goodpasture's disease can be silent for years before symptoms appear.

T

Someone diagnosed with Goodpasture's syndrome would present what on their immunofluorescence test?

-bright green on the basement membranes

-antiGBM antibodies are stuck

Diagnosis for Goodpasture's syndrome?

-Kidney biopsy

-anti-GMB antibodies

-anti-alveolar antibodies

Treatment for Goodpasture's' syndrome?

immunosuppressive drugs (ex. glucocorticoids, cyclosporine)

How does Goodpasture's Syndrome occur (steps)?

1) auto antibodies stick to the basement membrane of the basement membrane of kidney and lung

2) activates C3b

3) C3b triggers inflammation

4) inflammation --> bleeding in lungs/kidneys --> destruction

___ and ___ found in the basement membrane confirm immune attack

IgG and C3b

Suspected Diagnosis? You are at a UTSA football game. All of a sudden there is a lot of commotion around a young boy who seemingly is disoriented, has slurred speech, and shows noticeably deep but regular breaths. You notice that the boy smells funny (you cannot really place the smell, but it is a bit fruity, like an old apple). • It turns out that this child had been extremely thirsty for weeks, urinated frequently, was tired, and did not feel well for the last day or two. • The child is dehydrated by the "back of the hand" test.

Insulin-dependent diabetes mellitus (IDDM, type I diabetes)

What are some examples of Cell-mediated organ specific autoimmune diseases?

-Insulin-dependent diabetes mellitus (IDDM, Type 1 diabetes)

-Hashimoto's thyroiditis

-Multiple sclerosis

How did old doctors diagnose diabetes with urine?

-Used the "urine wheel"

-tested color, smell, sweetness, and foaminess

-diabetic urine tasted sweet like honey

What does Diabetes Mellitus mean?

diabeinein = "syphon, passing through", excessive urine

mellitus = honey, urine tastes sweet

T/F: Type 1 diabetes usually starts in kids or teenagers, not adults.

T

What are T cells role in Type I diabetes?

T cells destroys pancreatic Langerhans islet cells (beta) that produce insulin

___ is required to regulate glucose uptake into cells

Insulin

What happens if there is no insulin present in the cell?

-hyperglycemia in the blood

-decreased protein synthesis

-acidosis

when was the first insulin treatment?

1922

In the absence of _____, the body will act as it if is starving and make ___ in the liver from ___ ____

insulin, ketones, fatty acids

Are ketones basic or acidic?

acidic

Untreated T1D leads to...

-diabetic ketoacidosis

-coma

-death due to brain edema

normal vs. insulitis T1D histology

Normal: uniform, not crowded, islet cells

Insulitis: swarmed by immune cells (dark t cells) attacking, disorganized/crowded

What is the "Classical Triad" of T1D/IDDM

*polydipsia --> increased thirst

*polyuria --> increased urination

*polyphagia --> increased appetite (+loss of weight)

*fatigue

What are ways to diagnose T1D?

-fasting plasma glucose > 125 mg/dL (pre: 100-125 mg/dL)

-HbA1c (glycated hemoglobin): >6.5% (pre:5.7-6.4%)

-Oral glucose tolerance test: blood glucose > 200 mg/dL two hours after 75 g oral glucose

-Random glucose > 200 mg/dL

Treatment of T1DM

Insulin

Complications of T1DM

-Coma and death (ketoacidotic)

-Small vascular disease (blindness, numbness/tingling/pain)

-Large vascular disease (Coronary artery disease)

-stroke

What is "diabetic foot"?

-large vascular disease

-poor blood flow in legs --> ulcer formation --> diabetic foot

Diagnosis/Cause: A 23-year old female college student presents to family physician after Thanksgiving holidays with chronic fatigue, cold intolerance, excessive sleepiness, muscle cramps, and constipation.

Diagnosis: hypothyroidism

Cause: Hashimoto's thyroiditis

Most common cause of primary hypothyroidism in USA =

Most common cause worldwide =

Hashimoto's

iodine deficiency

Hashmito's Thyroiditis:

Inflammation and infiltration of thyroid by __ cells and ___

___ type reaction

___ may also contribute

T cells, macrophages, DTH (main cause is T cells), antibodies

What is a typical indicator physically of Hashimoto's?

-goiter

-signs of hypothyroidism

-pain can occur but not typical

Symptoms of Hashimoto's Thyroiditis

Hypothyroidism, cold intolerance, hoarse voice, decreased sweating, depression, memory loss, sleepiness, fatigue, hair loss, bradycardia,

How would you diagnose Hashimoto?

-elevated TSH, low T4

-anti-thyroid antibodies

-thyroid ultrasound

-fine needle biopsy with histology

How would you treat Hashimoto and what is it misdiagnosed commonly?

-giving thyroid hormone

-depression

Enhanced RAIU indicates

=hyperthyroiditis (Graves)

-dark intense staining --> thyroid absorbs alot of iodine

decreased RAIU indicates

= hypothyroidism

-blank/faint stains --> thyroid isn't absorbing iodine

Decreased radioactive iodine uptake is seen in...

-hashimoto thyroiditis

-de quervain's thyroiditis = subacute granulomatous thyroiditis

Thyroid glands use ____ to make ___ hormone

iodine, thyroid

What is the core pathological feature of Multiple Sclerosis?

Multiple areas (foci) of demyelination in the white matter of the CNS.

What are MS plaques and how do they appear?

Sharply defined gray areas where myelin is lost; over time they become firm, scar-like lesions ("sclerosis").

Where is inflammation commonly found in MS lesions?

Around blood vessels and along the lateral ventricles (periventricular infiltrates)

About ___ percent of MS converts from relapsing-remitting to progressive disease

60

what is the mcdonald criteria for diagnosing MS?

These are the official rules doctors use to diagnose MS.

-MRI findings

-CSF oligoclonal bands

-Abnormal evoked potentials

*you need proof that there is nerve damage in different places and at different times.

Treatment of MS

-immunosuppressive drugs (glucocorticoids)

-disease modifying therapies (DMTS)

Case diagnosis: You are seeing a young woman, mother of two children, at the office.She has been having tingling sensations in her left arm and left face over the last week or so. What brings her to the office is that she had pain in her right eye, and blurry vision since last night, and now she cannot see anymore with this eye.

Multiple Sclerosis (MS)

What are the key features of Multiple Sclerosis (MS)?

-Recurrent episodes of neurologic deficits

-Wide range of symptoms

-Most common in young adults

-Women affected more than men (2:1)

-Relapses are typical

-Disease duration often lasts 20+ years

What are the main forms of MS?

-Remitting-Relapsing MS (RRMS) - 85% of cases

-Primary Progressive MS (PPMS)

-Secondary Progressive MS (SPMS)

What does a patients MRI display with MS?

-white spots (plaques)

-myelin damage

Why is MS most frequent north of the equator?

ppl receive less sunlight --> decrease vitamin D --> increases risk of autoimmune diseases

Systemic lupus erythematosus (SLE) have autoantibodies to __, __, and ___

DNA, RBC, and histones

What is rheumatoid arthritis?

Chronic inflammatory disease of small and large joints. Often other tissues such as skin and heart are affected too.