Autoimmune diseases
HYPERSENSITIVITY REACTIONS
Definition of Hypersensitivity
Hypersensitivity: Excessive stimulation of the normal effector mechanisms of the immune system can lead to tissue damage.
Characterized by aberrant, excessive uncontrolled immune reactions.
Types of Hypersensitivity Reactions
Type Other Names Reaction Mediating Antibodies Antigen Type Cells Involved Complement Involved | |||||
Anaphylactic (I) | Immediate | IgE | Allergen, External Particles | Mast cells, basophils (IgE on the surface) | NO |
Cytotoxic (II) | Antibody Mediated | IgG or IgM | Ag on Surface of Host Cells | Host tissue cells including RBC, WBC, platelets | YES |
Immune Complex (III) | Complex Mediated | IgG or IgM | Soluble Ag | Neutrophils, monocytes | YES |
Delayed Type (IV) | T cell Mediated | None (T cell mediated) | Cells involved | CD4 cells & activated macrophages | NO |
Response Characteristics of Hypersensitivity Types
Type Maximum Reaction Time Histology Examples | |||
Anaphylactic (I) | 30 min | Degranulated mast cells, edema | Allergy: Hay fever, asthma, urticaria, angioedema |
Cytotoxic (II) | Minutes to hours | Antibody and complement detected in the lesion by IF | Goodpasture’s syndrome, Autoimmune Hemolytic Anemia (AIHA), Grave’s disease |
Immune Complex (III) | 3-8 hours | Acute inflammatory reaction; predominant neutrophils | Farmer’s lung, Serum sickness, Arthus reactions |
Delayed Type (IV) | 24-48 hours | Perivascular inflammation: Monocytes and lymphocytes | Poison Ivy contact dermatitis, Crohn's disease, Leprosy |
AUTOIMMUNE DISEASES
Defined as conditions in which damage to organs or tissues arises from autoantibodies or autoreactive cells.
Etiology: Unknown. Theories include:
Loss or breakdown of self-tolerance
Sequestered antigens
Loss of suppressor cells (immunoregulators)
Cross-reactive antigens including exogenous antigens
Altered self-antigens due to chemical/viral infections or molecular mimicry.
Spectrum of Autoimmune Diseases
Specificity Disease Target Tissue | ||
Organ-Specific | Hashimoto's thyroiditis | Thyroid |
Graves' disease | Thyroid | |
Pernicious anemia | Gastric parietal | |
Addison's disease | Adrenal glands | |
Type I diabetes mellitus | Pancreas | |
Myasthenia Gravis (MG) | Nerve-muscle synapses | |
Multiple Sclerosis (MS) | Myelin sheath of nerves | |
Autoimmune hemolytic anemia | Red blood cells | |
Idiopathic thrombocytopenic purpura (ITP) | Platelets | |
Goodpasture's syndrome | Kidney, lungs | |
Rheumatoid Arthritis (RA) | Joints, lungs, skin | |
Scleroderma | Skin, gut, lungs, kidney | |
Systemic Lupus Erythematosus (SLE) | Skin, joints, kidney, brain, heart, lungs |
Rheumatoid Factor Characteristics
IgM Ab directed against Fc portion of IgG.
Classes of rheumatoid factors: IgM, IgG, and IgA.
Clinical Significance: Found in rheumatoid arthritis, but not in all cases. Not found in osteoarthritis, gouty arthritis.
Serological Testing: Rapid Latex Agglutination Test; Positive results >1:80 titer, <1:20 is negative.
Systemic Lupus Erythematosus (SLE)
An autoimmune disorder characterized by auto-antibody production and inflammation across multiple organs.
Primarily affects females.
Notable symptoms: Erythematous/malar/butterfly rash across the nose and cheeks.
Immunologic features include:
LE cell formation
25 different autoantibodies
Dysregulated autoreactive T and B cells.
Serological Factors: Antinuclear Antibodies (ANA)
Significant but not specific to SLE; presence is not diagnostic, but absence may rule it out.
Present in conditions like RA, chronic HBV, and others.
Indirect Immunofluorescence Test
Utilizes fluorescein-conjugated antiglobulin; highly sensitive.
Positive results exhibit apple green/green gold fluorescence with characteristic patterns.
Common Antinuclear Antibodies
Autoantibody Characteristics of Antigen Immunofluorescent Pattern Disease Association | |||
Anti-ds-DNA | ds-DNA | Homogeneous | SLE |
Anti-histone | Different classes of histones | Homogeneous | Drug-induced SLE |
Anti-Sm | Extractable nuclear antigen | Speckled | Diagnostic for SLE |
Anti-SS-A (Ro) | Proteins complexed to RNA | Finely speckled | SLE, Sjögren's syndrome |
Anti-Scl-70 | DNA topoisomerase I | Atypical speckled | Systemic sclerosis |
Transplantation Immunology
Type Source Example | ||
Autograft | Tissue from the recipient | Autologous skin grafting |
Syngraft/Isograft | Tissue from a genetically identical individual | Kidney transplant, Bone marrow transplant |
Allograft | Tissue from genetically distinct individuals of the same species | Most organ transplants (kidney, heart, lungs) |
Xenograft | Material from an animal of a different species | Baboon heart transplanted into human |
Graft Rejection Types
Type Time of Tissue Damage Predominant Mechanism Cause | |||
Hyper-Acute | Within minutes to hours | Humoral (Ab mediated) | Preformed cytotoxic Ab to donor Ag |
Acute | Weeks | Cell mediated | Cytotoxic T cell activation recognizing foreign MHC |
Chronic | Weeks, months, or years post transplant | Cell mediated | Non-T cell derived growth factors |
Graft Versus Host Disease (GVHD)
Occurs in immunocompromised hosts where donor cells attack recipient tissue.
Key Players: T cells.
Prevention: Immunosuppressive treatment, most commonly Cyclosporine A to block T cell growth factor.