Immune System Disorders (Lec. 26) Flashcards
Compare and contrast primary and secondary immunodeficiencies
Primary: congenital defect, caused by a defect in immune cells or immune responses, relatively rare, therapy includes bone marrow transplants, IV Ig, or cytokine therapies.
Secondary: acquired defect, caused by medications, systemic disorders, and infections, more common than primary immunodeficiencies. Examples include natural aging, chronic alcoholism, malnutrition, cancer treatments, corticosteroid treatments, anticonvulsants, and infections (HIV, Epstein-Barr virus). Therapies include management and treating the underlying condition.
Discuss the general approaches to diagnosing and managing autoimmune disorders
General signs and symptoms: joint and muscle pain, fatigue, rash, organ dysfunction, low-grade fever. Diagnostic tests: serology (auto-antibodies) and erythrocyte sedimentation rate (ESR). Management: Immunosuppressive drugs.
Describe the erythrocyte sedimentation rate (ESR), its interpretation, when it is useful, and its limitations
ESR: blood sample is taken and put in a tube. The speed with which the red blood cells fall to the bottom of the tube in an hour. Inflammation causes red blood cells to stick together and sink faster. Simple, inexpensive, nonspecific test.
Describe Type 1 hypersensitivity reactions
Reaction mediated by IgE antibodies. Diagnostic tests: patient history, skin prick test (SPT, skin exposure to allergen, measure wheal and flare lesion), intradermal skin test, specific IgE test or Radioallergosorbent test (RAST, which measures IgE to specific allergen present in blood). Management: anti-histamine drugs (block histamine from interacting with histamine receptors), inhaled steroid drugs (for atopic asthma), epi-pen (epinephrine temporarily counteracts allergic response), desensitization immunotherapy (allergy shots switch response from IgE to IgG production).
Describe Type 2 hypersensitivity reactions
Cytotoxic or cytolytic reaction mediated by IgG or IgM antibodies. Three mechanisms: complement-dependent cytolysis (blood transfusion and HDN), complement-independent cytolysis, and receptor inactivation/over-activation.
Describe Type 3 hypersensitivity reactions
Reaction mediated by immune complexes. IgG or IgM bind soluble targets, creating excessive antibody-antigen complexes, which are deposited in tissues and trigger massive inflammation and activate complement cascades. Ex: lupus, rheumatoid arthritis
Describe Type 4 hypersensitivity reactions
Delayed reaction mediated by T cell cellular response; manifests slowly over 12-72hrs after antigen exposure. Ex: contact dermatitis, latex sensitivity, tuberculin skin test (PPD test), Graft-versus-host disease, Guillain-Barre syndrome, Type I diabetes, multiple sclerosis, celiac disease.
Describe the hygiene hypothesis and its relevance to type I hypersensitivities
The theory that a decrease in diversity of microbiota in developed countries leads to an increased risk for developing autoimmune disorders and allergies (which are type 1 hypersensitivities)
Describe allergies and classify by hypersensitivity class
Type 1 hypersensitivity: Mediated by IgE and mast cells. Ex: atopic asthma, atopic dermatitis, localized anaphylaxis (inflammation, mucus secretion, and urticaria aka hives), and systemic anaphylaxis (massive release of mast cell mediators like histamine; potentially life-threatening system-wide response).
Describe blood transfusion reactions and classify by hypersensitivity class
Type 2 hypersensitivity: complement-dependent cytolysis. Occur when the recipient’s immune system reacts to the transferred blood. Symptoms include nausea, fever, chills, chest and lower back pain, and dark urine.
Describe Hemolytic Disease of the Newborn (HDN) and classify by hypersensitivity class
Type 2 hypersensitivity. Also known as Erythroblastosis fetalis. An Rh- mother is exposed to the Rh+ blood of the fetus during pregnancy or birth. After exposure and between pregnancies, the mother develops IgG antibodies against the Rh factor. In a later pregnancy with another Rh+ fetus, maternal IgG antibodies cross the placenta and target fetal Rh+ red blood cells, leading to red blood cell lysis and severe anemia in the fetus.
Describe Acute glomerulonephritis (AGN) and classify by hypersensitivity class
Type 3 hypersensitivity: often in pediatric patients post-strep throat, deposition of antibody-antigen complexes in the kidney, causes inflammation of the kidneys (decreased urine output, increased blood pressure, and edema).
Describe contact dermatitis and classify by hypersensitivity class
Type 4 hypersensitivity: caused by antigens like drugs, nickel, chromate, poison ivy toxin. First exposure: T cells are activated and memory T cells are created. Second exposure: memory T cells respond and cause inflammation and an extremely pruritic (itchy) rash.
Describe PPD and classify by hypersensitivity class
Type 4 hypersensitivity: detects exposure to Mycobacterium tuberculosis (TB). A tuberculin purified protein derivative (PPD) is injected into the skin. Memory T cells recognize the antigen and release cytokines that promote inflammation. The injection site is observed within 48-72hours, and if an induration (hardened inflammation) develops on the skin, and if the lesion meets a certain size criterion, then the result is considered positive.
Describe GVHD and classify by hypersensitivity class
Type 4 hypersensitivity reaction. A typical transplant rejection is when the host cytotoxic T cells detect donor tissue as foreign (can be minimized by matching donor and recipient MHC genes). Graft-versus-host disease occurs in a bone marrow transplant when the donor T cytotoxic cells detect the recipient tissue as foreign (graft attacks host).
Define desensitization
Desensitization is a high-risk intervention that involves gradually reintroducing a drug that a patient is allergic to in small doses over time. It essentially tricks the immune system into adapting to the drug and developing a temporary tolerance.
Define a blocking antibody
A blocking antibody does not have a reaction when combined with a specific antigen, but prevents other antibodies from binding to that antigen.
Explain the relationships among blood groups, blood transfusions, and hemolytic disease of the newborn.
Different types of blood groups have different types of antigens and antibodies. If mixed incorrectly, antigens and antibodies from the different blood types can react together and cause an immune response. This can happen if there are mistakes in blood transfusions, or if an Rh- mother has two Rh+ babies.
