Autoimmunity Flashcards
(14 cards)
Autoimmunity
Caused by loss of self-tolerance.
Can occur in thymus (T cells), bone marrow (B cells), or periphery (regulatory T cells).
Primarily involves adaptive immune system.
Types of Autoimmune Diseases
Based on immune cell involved:
B cell/antibody-mediated
T cell-mediated
Based on location:
Organ/tissue-specific
Systemic
Central Tolerance in T Cells
Negative selection of T cells occurs in thymic medulla.
Medullary thymic epithelial cells (mTECs) present self-antigens.
T cells that bind too strongly to peptide/MHC are eliminated to prevent autoreactivity.
Central Tolerance in B Cells
B cells undergo receptor editing in bone marrow → given multiple chances to rearrange BCR genes to eliminate self-reactivity.
Peripheral Tolerance
Regulatory T cells prevent activation of autoreactive T cells that escaped central tolerance by:
CTLA-4 expression → competes with CD28 for binding to B7 on APCs → ↓ co-stimulatory signals & T cell activation.
Cytokine secretion → release of anti-inflammatory cytokines (IL-10 & TGF-β) ↓ immune responses.
IL-2 consumption → Tregs express high levels of IL-2 receptors → deprive T cells of IL-2 needed for proliferation.
Myasthenia Gravis
Type II HS → autoantibodies target acetylcholine receptor (AChR) at neuromuscular junctions.
Autoantibody actions:
○Binding to AChRs to trigger antibody-dependent cellular cytotoxicity (ADCC).
○Blocking receptor’s binding site to prevent ACh from binding → inhibits muscle contraction.
○Modulates receptor by cross-linking AChRs → receptor internalisation & ↓ number of available ACh binding sites.
Symptoms: muscle weakness, ptosis, & difficulty breathing/swallowing.
Myasthenia Gravis Treatments
Acetylcholinesterase inhibitors provide symptomatic relief.
Immunosuppressants (e.g., corticosteroids, azathioprine) ↓ Ab synthesis.
Multiple Sclerosis (MS)
Type IV hypersensitivity, T cell-mediated chronic neurological disease.
Autoreactive T cells target myelin proteins (myelin basic protein, proteolipid protein & myelin oligodendrocyte glycoprotein) → lesions in CNS white matter.
Schwann cells normally produce myelin to insulate axons & ensure effective signal transmission → demyelination disrupts signal conduction → neurological flares.
Symptoms: fatigue, vision disturbances, & motor weakness.
MS Treatments
Corticosteroids, IFN-β, & cyclophosphamide → ↓ T cell activation & proliferation.
Rheumatoid Arthritis (RA)
Chronic autoimmune disease primarily affecting joints.
PAD (peptidylarginine deiminase) enzymes convert arginine to citrulline → alter protein folding.
Modified proteins recognized as foreign → triggers autoimmune response.
Th17 cells (promote inflammation) dominate over Tregs (promote tolerance) → chronic inflammation.
Inflammation leads to bone remodelling, tissue damage, & loss of function.
Clinical Testing in RA
Rheumatoid factor: present in most RA patients but not specific.
Anti-CCP: highly specific & detectable before symptoms.
Erythrocyte sedimentation rate (ESR) & CRP: markers of systemic inflammation.
RA Treatments
NSAIDs & steroids for symptom control.
Disease-modifying anti-rheumatic drugs (DMARDs) → ↓ inflammation, prevent joint & tissue damage, & inhibit immune cell activation.
○Ex. Methotrexate → inhibits proliferation & activation of lymphocytes & production of pro-inflammatory cytokines.
Biological agents (anti-TNF𝛂) → block specific immune pathways.
Triggers for Autoimmunity
Inflammation → may expose antigens normally hidden in sites like brain & eyes.
Molecular mimicry → pathogen antigens resemble self-antigens.
Polyclonal B cell activation → viruses can non-specifically activate B cells.
ADCC
Fc region of bound Ab recognized by Fc receptors on NK cells.
NK cells release cytotoxic molecules (perforin & granzymes) that kill AChR-expressing muscle cell → tissue damage.
