Autoimmunity and Immune Deficiency PDF

Immunology 6 Pt 3 – Autoimmunity & Immune Deficiency Learning Objectives 1. Describe how autoimmune disease can be organ specific or systemic. 2. Describe what an autoantibody is and how it can cause disease 3. Classify autoimmune diseases based according to the four different types of hype...

Immunology 6 Pt 3 – Autoimmunity & Immune Deficiency Learning Objectives 1. Describe how autoimmune disease can be organ specific or systemic. 2. Describe what an autoantibody is and how it can cause disease 3. Classify autoimmune diseases based according to the four different types of hypersensitivity reactions 4. Describe the difference between primary and secondary immune deficiency Autoimmunity Autoimmune diseases arise when normal ‘self-tolerance’ to a certain biomolecule, cell type, or tissue breaks down 🡪 an immunological mistake Autoimmunity Autoimmunity Autoimmune Disease Autoimmune Disease A pathogenic autoimmune process 🡪 the autoimmune reaction causes the disease Autoantibody Antibody against a self antigen, also known as “autoantigen” Autoreactive T cell T cell against a self antigen Mechanisms of Tolerance/Regulation “Central Tolerance” Negative selection of autoreactive T cells during development “Peripheral Tolerance” Activation Induce Cell Death, Anergy, Induction of Tregs Anti-idiotypic Antibodies Signaling – IL10, Fas, CTLA4, LRBA Regulatory T cells Th3 – maintain mucosal tolerance Treg – CD3+CD25+ - express CTLA4 Autoimmunity - Tissue/Organ Specific Autoimmunity - Systemic Self antigen is widely distributed in different organs/tissues Autoimmunity Case Example #1 ∙ 28 year old woman presents with a 4-month history of itchy debilitating hives on her neck and chest ∙ They are worse in the morning, and disappear by the end of each day, only to recur the next morning; a particular hive never lasts more than 24 hours ∙ Very itchy and uncomfortable ∙ Negative allergy testing Autoimmunity Case Example #1 ∙ IgE created against an autoantigen ∙ Causes mast cell degranulation and histamine release 🡪Type I HS Chronic idiopathic/spontaneous urticaria Autoimmunity Case Example #2 Graves Disease Autoimmunity Case Example #2 - In Graves disease an ‘agonistic’ autoantibody against the TSH receptor arises - Interruption of normal regulation by TSH, and puts the thyroid into overdrive - This represents a Type II hypersensitivity reaction. Autoimmunity Case Example #3 ∙ Autoantibody against the Ach Receptor ∙ Blocking rather than activating Myasthenia Gravis 🡪Type II HS  Autoimmunity Case Example #5 ∙ In autoimmune diseases like systemic lupus erythematosus (SLE) autoantibodies develop against DNA and other self antigens ∙ Immune complexes often form which damage the kidney microcirculation 🡪 glomerulonephritis ∙ Monitoring blood pressure and kidney function is essential! 🡪Type III HS Autoimmunity Case Example #6 ∙ In type 1 diabetes, a cellular autoimmune process arises that specifically targets the cells that make insulin (=pancreatic beta cells). ∙ CTLs are the main cells that kill the beta cells. ∙ Once the patient can no longer make insulin, they cannot store glucose inside their cells ∙ High glucose in blood ∙ High glucose in urine ∙ Severe dehydrations and electrolyte abnormalities (diabetic ketoacidosis) if untreated 🡪Type IV HS Autoimmunity – sometimes not so simple….. ∙ IgE created against an autoantigen 🡪Type I HS Activating autoantibody 🡪 Type II HS Immune Deficiency  Immune Deficiency Primary Secondary Immune Deficiency due to an Immune Deficiency due to an acquired or external cause error in a genes involved in Infections – HIV, Influenza Medications the immune system Chronic Disease States – “Inborn Error of Immunity” malignancy, immunometabolism BOTH Variable age of presentation –sometimes infancy/childhood, some in adulthood Can involve very specific arms, or multiple arms of the immune system  Immune Deficiency Severe, Persistent, Inflammation Unusual, Recurrent Infections (SPUR) Autoimmunity Malignancy Atypical age EBV related Learning Objectives 1. To understand that autoimmune disease can be organ specific or systemic. 2. To understand what an autoantibody is and how it can cause disease 3. To classify autoimmune diseases based according to the four different types of hypersensitivity reactions