Diagnosis and Treatment

Chapter 8 This chapter outlines the different types of immune system alterations, specifically hypersensitivity reactions and deficiencies in immunity. Hypersensitivity reactions can be categorized by the immunologic mechanism causing the disease and the source of the antigen being attacked by the immune system. There are four main types of hypersensitivity reactions: type I (IgE-mediated reactions), type II (tissue-specific reactions), type III (immune complex-mediated reactions), and type IV (cell-mediated reactions). Diagnosis and Treatment Diagnosis of SLE is based on clinical findings and laboratory tests A positive antinuclear antibody (ANA) screening test is usually performed Further diagnostic testing may be done for specific clinical findings There is no cure for SLE or most autoimmune diseases Fatalities from SLE are usually caused by infection or organ failure Types of treatment for autoimmune diseases like systemic lupus erythematosus (SLE) Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, or naproxen are used to reduce inflammation and relieve pain Corticosteroids are often prescribed for more serious active disease Immunosuppressive drugs (e.g. methotrexate, azathioprine, or mycophenolate mofetil) are used to treat severe symptoms involving internal organs Antimalarial medications (e.g. hydroxychloroquine) are preferred treatments for individuals with stable disease Protection from sun exposure can be helpful since ultraviolet light may trigger flares Alloimmunity - immune reaction against tissues of another individual Occurs during reactions against blood transfusions, transplanted tissue, or the fetus during pregnancy Alloantigens (isoantigens) are non-self antigens from members of the same species Two types of alloantigen are blood group antigens and histocompatibility antigens (e.g. human leucocyte antigen [HLA]) Alloimmune Disease: Transfusion Reactions Red blood cells express surface antigens known as blood group antigens ABO and Rh systems are the most important blood group systems ABO blood group consists of A and B antigens expressed on erythrocytes A and B can be simultaneously expressed resulting in four different blood types (A, B, AB, O) Transfusion reactions occur when incompatible blood types are mixed Naturally occurring antibodies called iso hemagglutinins are developed early in life due to similar antigens on intestinal bacteria ABO Blood Types Individuals with blood type A have modified H antigens into A antigens and have IgM antibodies against the B antigen. Individuals with blood type B have modified H antigens into B antigens and have IgM antibodies against the A antigen. Individuals with blood type AB have modified H antigens into both A and B antigens and do not have antibodies against either A or B antigens. Individuals with blood type O lack both A and B antigens and are considered universal donors. Individuals with blood type AB can receive blood from any ABO blood type and are considered universal recipients. Rh Blood Group Rh positive individuals express the D antigen on their red blood cells, while Rh negative individuals do not. Approximately 85% of North Americans are Rh positive. Rh-negative individuals can produce an IgG antibody called anti-D if exposed to Rhpositive erythrocytes. Hemolytic disease of the newborn, caused by anti-D alloantibody, has decreased due to the use of anti-D immunoglobulin (RhoGAM). Major Histocompatibility Complex (MHC) MHC molecules are also referred to as human leukocyte antigens (HLAs). MHC genetic loci include class I (HLA-A, HLA-B, HLA-C) and class II (HLA-DR, HLADQ, HLA-DP) loci. MHC loci are highly polymorphic, with a large number of possible different alleles expressed in the population. Class III loci in the MHC region encode complement components and cytokines. HLAs (Human Leukocyte Antigens) Humans have two copies of each MHC locus inherited from each parent Molecules encoded by each parent's genes are expressed on the surface of every cell, except erythrocytes The tremendous number of possible alleles makes it highly unlikely for unrelated individuals to have the same MHC antigens Inheritance of HLA HLA alleles are inherited in a codominant fashion, with both maternal and paternal antigens expressed The diversity of MHC molecules becomes relevant in organ transplantation The recipient can mount an immune response against foreign HLA antigens, resulting in rejection To minimize rejection, the donor and recipient are tissue-typed to identify differences in HLA antigens A perfect match is unlikely, but the more similar the HLA tissue types, the more successful transplantation is likely to be Transplantation between siblings has a higher chance of success (25%) compared to the general population Transplants between identical twins are the most successful due to genetic identity Types of transplant rejection Hyperacute rejection: Immediate and rare, occurs due to preexisting antibodies to HLA antigens Acute rejection: Cell-mediated immune response that occurs within days to months after transplantation Chronic rejection: Occurs after a period of normal function, characterized by slow progressive organ failure Why do certain drugs become immunogenic to the host? Certain drugs can trigger an immune response in the host, causing them to become immunogenic Why is an individual with type O blood considered a universal blood donor? Individuals with type O blood are considered universal blood donors because their blood does not have A or B antigens on red blood cells Why is SLE considered an autoimmune disease? SLE, or systemic lupus erythematosus, is considered an autoimmune disease because the immune system mistakenly attacks healthy tissues in the body Define the different types of graft rejection There are different types of graft rejection: hyperacute rejection, acute rejection, and chronic rejection Hyperacute rejection occurs immediately after transplantation due to pre-existing antibodies attacking the graft Acute rejection is a cellular or humoral immune response against the graft that occurs within the first few weeks after transplantation Chronic rejection is a gradual and irreversible process that occurs over months or years, leading to the progressive loss of graft function