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502
👑 AUTOIMMUNITY — 1 MINUTE BEFORE EXAM REVISION
🔹📌 Definition
🔹Autoimmunity = immune response against self-antigens causing tissue damage and disturbed function.
🔹🔥 3 THINGS MUST BE PRESENT FOR AUTOIMMUNITY
🔹1. Genetic susceptibility
🔹2. Environmental trigger
🔹3. Loss of self-tolerance
🔹⚠️ Female > Male
🔹⚠️ Usually starts at 20–40 years
🔹⚠️ Chronic and usually irreversible
⸻
🔹👑 MOST IMPORTANT CAUSES OF LOSS OF SELF-TOLERANCE
🔹1️⃣ Sequestered antigens released
🔹Eye, Brain, Testis, Thyroid, Sperm
🔹2️⃣ Molecular mimicry ⭐⭐⭐
🔹Microbe resembles self-antigen
🔹🔥 Streptococcus M protein → Rheumatic fever
🔹🔥 Coxsackie B4 → IDDM
🔹🔥 Campylobacter jejuni → Guillain-Barré syndrome
🔹3️⃣ Polyclonal lymphocyte activation
🔹LPS → B-cell activator
🔹Superantigen → T-cell activator
🔹4️⃣ Altered self-proteins
🔹Procainamide → SLE + Autoimmune hemolytic anemia
🔹5️⃣ Abnormal Class II MHC expression ⭐⭐⭐
🔹Normally only on APCs
🔹IFN-γ causes expression on:
🔹Pancreatic β-cells → IDDM
🔹Thyroid cells → Autoimmune thyroid disease
🔹6️⃣ HLA associations ⭐⭐⭐
🔹HLA-B27 → Ankylosing spondylitis
🔹HLA-DR2, DR3 → SLE
🔹HLA-DR3, DR4 → IDDM
🔹7️⃣ Cytokine dysregulation / Treg failure
🔹8️⃣ Thymic defects
🔹9️⃣ Hormonal factors
🔹🔟 Complement deficiency
⸻
🔹👑 AUTOIMMUNE DISEASES & HYPERSENSITIVITY TYPES
🔹🔥 Type II
🔹Autoimmune hemolytic anemia
🔹Graves disease
🔹Myasthenia gravis
🔹ITP
🔹🔥 Type III
🔹SLE
🔹🔥 Type IV
🔹IDDM
🔹Hashimoto thyroiditis
🔹Rheumatoid arthritis
🔹Multiple sclerosis
🔹Guillain-Barré syndrome
⸻
🔹👑 GRAVES DISEASE ⭐⭐⭐
🔹Type II hypersensitivity
🔹Stimulating antibody against TSH receptor
🔹Goiter
🔹Exophthalmos (bulging eyes)
🔹Hyperthyroidism
⸻
🔹👑 MYASTHENIA GRAVIS ⭐⭐⭐
🔹Type II hypersensitivity
🔹Blocking antibody against ACh receptor
🔹Muscle weakness
⸻
🔹👑 SLE ⭐⭐⭐⭐⭐
🔹Type III hypersensitivity
🔹ANA positive
🔹Anti-DNA
🔹Anti-histone
🔹Immune complex deposition
🔹Complement activation
🔹Skin + Kidney + Joints involvement
🔹Female : Male = 10 : 1
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🔹🧨 EXAM TRAPS
🔹Molecular mimicry → Rheumatic fever
🔹IFN-γ → Class II MHC expression on non-APCs
🔹Graves = Stimulating antibody
🔹Myasthenia = Blocking antibody
🔹SLE = Type III, not Type II
🔹IDDM = Type IV, not Type II
🔹Females have stronger immune responses due to estrogen
🔹Complement deficiency predisposes to autoimmunity
⸻
🔹🔪 KILLER MEMORY
🔹**“Mimic → Rheumatic fever, Stimulate → Graves, Block → Myasthenia, Complexes → SLE, T-cells → IDDM.”**
502
👑 Q6 (Very Sneaky)
Which finding most strongly suggests regulatory T cells are functioning normally?
502
👑 Q5
A self-reactive T cell escapes thymic deletion and enters peripheral tissues. Which mechanism can still prevent autoimmunity?
502
👑 Q3
A mutation causes loss of CTLA-4 function.
What is the most likely consequence?
502
👑 Q1
A mature T cell recognizes self-antigen in peripheral tissues but receives only Signal 1.
502
👑 IMMUNE TOLERANCE —
THE NOTE MOST LIKELY TO APPEAR IN EXAM🔹 Immune tolerance = Specific unresponsiveness to an antigen despite a normal immune system. ⚡ Central tolerance = Clonal deletion (Negative selection) 🔹Occurs during lymphocyte development. 🔹Self-reactive T cells deleted in thymus. 🔹Self-reactive B cells deleted in bone marrow. 🔹Purpose: prevent autoreactive cells from maturing. ⚡ Peripheral tolerance = Controls self-reactive cells that escape central tolerance 🔹Immunological ignorance. 🔹Anergy (lack of Signal 2). 🔹Treg suppression. 🔹Deletion by Fas-FasL apoptosis. 🔥 Signal 2 = CD28–B7 🔹Signal 1 without Signal 2 → Anergy (functional unresponsiveness). 🔹One of the highest-yield concepts in the lecture. 🔥 Treg cells 🔹CD4⁺ CD25⁺. 🔹Express FOXP3. 🔹Suppress immunity by: 🔹IL-10. 🔹TGF-β. 🔹Prevent autoimmunity. 🔥 *CTLA-4 OR CD152 🔹Inhibitory receptor. 🔹Binds B7. 🔹Turns T cells OFF. 🔹Causes peripheral tolerance/anergy. 🔹 Exam connection 🔹Failure of central or peripheral tolerance → Autoimmune disease. 🔹Killer Memory 🔹Central tolerance deletes the bad cells. 🔹Peripheral tolerance controls the bad cells that escaped. 📕 *CTLA-4 = Cytotoxic T-Lymphocyte Antigen-4 ملاحظة للفهم 🔹CTLA-4 = Cytotoxic T-Lymphocyte Antigen-4 🔹CD designation = CD152 🔹It is an inhibitory receptor on T cells. 🔹Competes with CD28 for binding to B7 (CD80/CD86). 🔹When CTLA-4 binds B7 → T-cell activation is suppressed → tolerance/anergy develops. 🔹🎯 Exam pearl: 🔹CD28 = ON signal 🔹CTLA-4 (CD152) = OFF signal 🔹 Killer memory: 🔹28 activates, 152 terminates. نزلوا شوية جوه ححط الامسكيوات
502
🔥ULTRA HIGH-YIELD (Almost every immunology exam)
B27 → Ankylosing spondylitis
DR3 + DR4 → Type 1 DM
DR4 → Rheumatoid arthritis
DR2 → SLE
DR5 → Hashimoto thyroiditis
⸻
🔹🟡 HIGH-YIELD
🔹DR3 → Celiac disease
🔹DR3 → Graves disease
🔹DR3 → Myasthenia gravis
🔹B27 → Reactive arthritis
🔹B27 → Acute anterior uveitis
🔹DR2 → Multiple sclerosis
⸻
🔹🌤 MEDIUM-YIELD
🔹DR5 → Pernicious anemia
🔹DR4 → Pemphigus vulgaris
🔹DR2 → Goodpasture syndrome
🔹DR2 → Narcolepsy
🔹Dw3 → Sjögren syndrome
⸻
🔹⚪ LOW-YIELD / Usually skipped unless mentioned by lecturer
🔹A1 → Graves disease
🔹A1 → Dermatitis herpetiformis
🔹B8 → Autoimmune hepatitis
🔹B8 → Primary sclerosing cholangitis
🔹B13 → Psoriasis
🔹B17 → Psoriasis
🔹DR7 → Steroid-responsive nephrotic syndrome
🔹DR8 → Primary biliary cirrhosis
🔹Dw4 → Rheumatoid arthritis
⸻
🔹🎯 If I only had 2 minutes before the exam:
🔹B27 → Ankylosing spondylitis
🔹DR3 + DR4 → Type 1 DM
🔹DR4 → Rheumatoid arthritis
🔹DR3 → Celiac disease
🔹DR3 → Graves disease
🔹DR3 → Myasthenia gravis
🔹DR2 → SLE
🔹DR2 → Multiple sclerosis
🔹DR5 → Hashimoto thyroiditis
🔹These alone are probably 90% of what an examiner would actually ask from this table. 👑
