6 autoimmunity Flashcards
What is autoimmunity?
Autoimmunity refers to immune responses mistakenly directed against the body’s own tissues.
What is an autoimmune disease?
Autoimmune diseases occur when autoimmunity leads to pathology despite normal immune regulatory mechanisms.
Are auto/self-reactive lymphocytes found in healthy individuals?
Yes, self-reactive T and B cells exist in people without autoimmune disease, but immune tolerance prevents them from causing pathology.
Why is autoimmune disease considered a hypersensitivity response?
Autoimmune diseases involve an excessive immune response against self-antigens, leading to tissue damage (similar to hypersensitivity reactions).
What are the two major classifications of autoimmune diseases?
Organ-specific autoimmune diseases (affecting one organ).
Systemic autoimmune diseases (affecting multiple organs).
Give an example of an organ-specific autoimmune disease and explain its mechanism.
Graves’ disease—autoantibodies against the TSH receptor lead to excessive thyroid hormone production.
Give an example of a systemic autoimmune disease and explain its mechanism.
Systemic Lupus Erythematosus (SLE)—autoantibodies to nuclear antigens form immune complexes, causing inflammation in skin, kidneys, and joints.
What causes Type 1 diabetes mellitus (T1D)?
CD8+ T cells destroy pancreatic β cells, leading to loss of insulin production.
What is Goodpasture’s syndrome?
Autoantibodies against type IV collagen in kidney and lung basement membranes lead to inflammation and damage.
How does Myasthenia Gravis impair muscle function?
Autoantibodies against acetylcholine receptors lead to their internalisation and degradation, preventing muscle contraction.
What happens in Hashimoto’s thyroiditis?
: Autoantibodies and T cells attack the thyroid, leading to hypothyroidism.
How does autoimmune pernicious anaemia develop?
Autoantibodies attack intrinsic factor, preventing vitamin B12 absorption and causing anaemia.
What is autoimmune Addison’s disease?
Autoantibodies destroy the adrenal cortex, leading to cortisol deficiency.
What causes vitiligo?
Autoimmune destruction of melanocytes leads to loss of skin pigmentation.
What is the main cause of rheumatoid arthritis (RA)?
Autoreactive CD4+ T cells activate macrophages and fibroblasts, producing inflammatory cytokines (e.g., TNF-α) that destroy joints.
How does scleroderma affect the body?
Autoimmune attack leads to excessive fibrosis and collagen deposition in skin and internal organs.
What autoantibodies are found in SLE?
Anti-nuclear antibodies (ANA), including those against DNA and histones, form immune complexes.
What is Sjögren’s syndrome?
Autoimmune attack on salivary and lacrimal glands, leading to dry eyes and dry mouth.
What is polymyositis?
T cell-mediated attack on muscle fibres, causing muscle weakness.
How do autoimmune diseases initiate?
Similar to normal immune responses—innate immune cells detect antigens, leading to T cell activation (often TH1 or TH17 responses).
What is the role of PAMPs in autoimmunity?
Some self-antigens may be presented in an inflammatory context (e.g., via TLRs) that mimics infection, leading to T cell activation.
How do autoantibodies cause disease?
Through molecular interference, cellular destruction, or immune complex formation.
What type of hypersensitivity reaction occurs in Graves’ disease?
Type II hypersensitivity—agonistic autoantibodies activate the TSH receptor, leading to hyperthyroidism.
What type of hypersensitivity occurs in autoimmune haemolytic anaemia?
Type II hypersensitivity—autoantibodies target red blood cells, leading to complement-mediated lysis.
How do autoantibodies in immune thrombocytopenic purpura (ITP) affect the body?
Autoantibodies target platelets, leading to excessive bruising and bleeding.
How does systemic lupus erythematosus (SLE) lead to tissue damage?
Autoantibodies form immune complexes (Type III hypersensitivity), leading to inflammation in skin, kidneys, and joints.
an autoimmune diseases be transferred from mother to fetus?
Yes, autoantibodies (e.g., anti-TSHR in Graves’ disease) can cross the placenta, causing temporary neonatal autoimmunity.
How can neonatal Graves’ disease be treated?
Plasmapheresis removes maternal antibodies, curing the infant.
What is Experimental Autoimmune Encephalomyelitis (EAE)?
A mouse model of multiple sclerosis (MS) where myelin-reactive CD4+ T cells induce paralysis.
What happens in multiple sclerosis (MS)?
T cells attack the myelin sheath, leading to demyelination and neurological symptoms.
How does type 1 diabetes develop?
CD8+ T cells destroy pancreatic β cells, preventing insulin production.
How is EAE induced in mice?
Injection of myelin proteins with adjuvant induces an autoimmune attack against the CNS.
What is the role of TNF-α in rheumatoid arthritis?
TNF-α promotes inflammation, leading to cartilage and bone destruction.
What are NOD mice used for?
Studying type 1 diabetes, as they spontaneously develop β cell autoimmunity.
What is rheumatoid factor (RF)?
An IgM autoantibody against IgG, found in rheumatoid arthritis patients.
What are ACPA (anti-citrullinated protein antibodies)?
Autoantibodies specific for citrullinated proteins, useful in diagnosing RA.
What is the difference between autoimmunity and autoimmune disease?
Autoimmunity is an immune response to self; autoimmune disease is pathogenic autoimmunity.
How can disease be transferred in EAE?
CD4+ T cells from sick mice can induce disease in healthy mice.
Why do some individuals with self-reactive B cells not develop disease?
Regulatory mechanisms (e.g., Tregs) suppress their activation.
How do researchers induce T1D in NOD mice?
By transferring CD4+ T cells from diabetic mice into healthy mice.
What are the steps leading to hyperthyroidism in Graves’ disease?
- Autoimmune B cells produce antibodies against the TSH receptor (TSH-R).
- These autoantibodies mimic TSH, binding to the receptor and stimulating excessive thyroid hormone production.
- Thyroid hormones suppress TSH production from the pituitary gland via negative feedback.
- However, autoantibody production continues unchecked, leading to persistent hyperthyroidism.
How do autoantibodies lead to muscle weakness in Myasthenia Gravis?
Autoimmune B cells produce antibodies against acetylcholine receptors (AChR) on muscle cells.
The autoantibodies block receptor function and lead to internalisation and degradation of AChRs.
Fewer AChRs remain on the muscle surface, reducing sensitivity to acetylcholine.
No Na+ influx occurs, preventing muscle contraction and leading to muscle weakness.
How do autoantibodies cause red blood cell destruction in AIHA?
- Autoantibodies bind to erythrocyte (red blood cell) surfaces.
- These antibody-coated erythrocytes activate the complement system.
- Complement activation marks RBCs for destruction by macrophages in the spleen.
- Phagocytosis and intravascular haemolysis result in RBC destruction and anaemia.
What are the key steps in the development of Rheumatoid Arthritis?
- Unknown trigger causes initial inflammation in the synovial membrane.
- Leukocytes infiltrate the synovial tissue, activating CD4+ T cells.
- CD4+ T cells activate macrophages, leading to the release of TNF-α and pro-inflammatory cytokines.
- Fibroblasts produce MMPs, which degrade tissue, and RANK ligand, which activates osteoclasts.
- Bone and cartilage destruction occurs, leading to joint deformities.
How do autoreactive T cells cause β-cell destruction in Type 1 Diabetes?
Autoreactive CD4+ T cells recognise peptides from pancreatic β-cell proteins.
These CD4+ T cells activate CD8+ T cells, converting them into cytotoxic T lymphocytes (CTLs).
CTLs attack and destroy β-cells in the pancreas.
Insulin production stops, leading to high blood glucose levels.
How do immune cells damage the CNS in Multiple Sclerosis?
Unknown trigger causes initial inflammation in the CNS, increasing blood-brain barrier permeability.
CD4+ T cells are activated by dendritic cells presenting CNS antigens (e.g., myelin proteins).
These T cells re-enter the CNS, where they trigger inflammation.
Mast cells, complement, and antibodies contribute to tissue damage.
Demyelination of neurons occurs, impairing nerve function.
How do researchers induce Multiple Sclerosis in the EAE model?
Mice are injected with myelin proteins (e.g., MBP) and Freund’s adjuvant.
CD4+ T cells specific to myelin proteins are activated.
These T cells are transferred into healthy mice, inducing disease.
Mice develop paralysis, similar to MS symptoms in humans.
How does a mother with Graves’ disease transfer the condition to her baby, and how is it treated?
A pregnant woman with Graves’ disease produces anti-TSHR antibodies.
These IgG antibodies cross the placenta into the fetal circulation.
The newborn develops hyperthyroidism due to antibody-induced TSHR activation.
Plasmapheresis removes maternal antibodies, curing the infant.
How do autoantibodies lead to bleeding in ITP?
Autoantibodies against platelets are produced.
Platelets are marked for destruction by macrophages.
Platelet count decreases, reducing blood clotting ability.
Patients develop bruising and spontaneous bleeding.
How do immune complexes cause tissue damage in SLE?
Autoantibodies bind to nuclear antigens (e.g., DNA, histones).
This forms immune complexes, which circulate in the blood.
Complexes deposit in tissues (skin, kidneys, joints).
Complement activation and inflammation lead to tissue damage and disease symptoms.
What is the key failure in autoimmune disease?
Failure of immune tolerance mechanisms → immune system attacks self
Why do some self-reactive lymphocytes exist in healthy individuals?
Some self-reactive B and T cells escape deletion in central tolerance
Normally suppressed by peripheral tolerance mechanisms
What happens when immune tolerance fails?
Unchecked self-reactive lymphocytes cause chronic inflammation and tissue damage
How does autoimmunity develop? (Basic Process)
1️⃣ Loss of tolerance
2️⃣ Activation of self-reactive T/B cells
3️⃣ Autoantibodies and/or autoreactive T cells attack self-tissues
4️⃣ Chronic inflammation and tissue destruction
What are the two main types of autoimmune disease?
Organ-specific: Limited to a specific organ (e.g. T1D, Graves’)
Systemic: Affects multiple organs (e.g. SLE, RA)
Key Difference Between Organ-Specific and Systemic Autoimmune Diseases
Organ-specific → antigens are unique to one organ
Systemic → antigens are widespread (e.g. nuclear antigens in SLE)
Example of Autoimmune Disease with Both Organ & Systemic Features
Primary Sjögren’s syndrome → affects salivary glands (organ-specific) but also causes systemic inflammation
Two Main Types of Pathogenic Autoimmune Responses
Autoantibody-mediated (B cell-driven) → e.g. Graves’, Myasthenia gravis
T cell-mediated → e.g. Multiple sclerosis, Type 1 Diabetes
How Do Autoantibodies Cause Disease?
Type II hypersensitivity: Direct binding to self-antigens (e.g. TSH receptor in Graves’)
Type III hypersensitivity: Formation of immune complexes (e.g. SLE)
How Do T Cells Cause Autoimmune Disease?
CD8+ T cells kill self-cells directly (e.g. pancreatic β-cells in T1D)
CD4+ T cells activate macrophages, leading to inflammation and tissue destruction
Key Cytokines in Autoimmune Disease
TH1 cytokines (e.g. IFN-γ, TNF-α) → promote cell-mediated immunity (MS, T1D)
TH17 cytokines (e.g. IL-17, IL-22) → drive inflammation (RA, MS)
How do autoantibodies contribute to Graves’ Disease?
Autoantibodies act as TSH receptor agonists, leading to hyperthyroidism
Mechanism of Autoimmune Haemolytic Anaemia (AIHA)
Autoantibodies bind erythrocytes, causing complement activation and destruction
How Do Autoantibodies Cause Myasthenia Gravis?
Anti-AChR antibodies cause receptor internalisation → muscle weakness
Why is Multiple Sclerosis Considered a T Cell-Mediated Disease?
CD4+ T cells (TH1 & TH17) drive inflammation in the CNS, damaging myelin
What is the Role of CD8+ T Cells in Type 1 Diabetes?
CD8+ T cells kill pancreatic β-cells, preventing insulin production
How Does Rheumatoid Arthritis Cause Joint Damage?
CD4+ T cells activate macrophages → TNF-α and RANK-L drive bone/cartilage destruction
How Do Researchers Study T Cell-Mediated Autoimmune Diseases?
EAE (Experimental Autoimmune Encephalomyelitis) → model for MS
NOD mice → model for Type 1 Diabetes
What Are ACPA in Rheumatoid Arthritis?
Anti-citrullinated protein antibodies (ACPA) → help in RA diagnosis
How Do Researchers Confirm Autoantibody Pathogenicity?
Transfer autoantibodies from a diseased patient to an animal → if disease develops, autoantibodies are pathogenic
