Ch 16 Disorders of the Immune Response Flashcards
What is hypersensitivity disorders? Type 1 is? the two reactions?
The immune system normally protects the body against attack but it is also capable of causing tissue injury and disease.
1. Type 1 Immediate hypersensitivity disorder - are IgE mediated reaction that begin rapidly, often within minutes of an antigen challenge. Are allergic reactions usually to proteins in plant pollens, house dust mites, animal dander, foods and chemical like the antibiotic penicillin. Can be through inhalation, ingestion, injection, or skin contact. Can be from annoying (rhinitis) to severe (asthma) to life threatening (anaphylaxis). TH2 cells and mast cells or basophils. two well defined phases 1. primary or immediate phase response by vasodilation, vascular leakage and smooth muscle contraction 5 -30 min. 2 a secondary by more intense infiltration of tissues with eosinophils and other acute and chronic inflammatory cells as well as tissue destruction. 2-8 hrs.
Systemic (anaphylactic) reactions - characterized by widespread edema, difficulty breathing, and vascular shock secondary to vasodilation. Within minutes of exposure itching, hives, and skin erythema develop, followed shortly by bronchospasm and respiratory distress. Vomiting, abd cramps, diarrhea and laryngeal edema and obstruction follow, may go into shock and die.
Treatment - establishment of a stable airway and intravenous access and the administration of epinephrine
Local (atopic) reactions - usually occur when the antigen is confined to a particular site by virtue of exposure. To common environmental allergens mediated by an IgE mast cell reaction. Most hives, allergic rhinitis, atopic dermatitis, food allergies, and some forms of asthma.
Treatment - avoidance of the offending allergen but if not use of oral antihistamines and oral or topical decongestants.
What is type II antibody mediated disorders? What is the cell destruction, inflammation and dysfunction?
Mediated by IgG or IgM antibodies directed against target antigens on cell surfaces or in connective tissues. Three different mechanisms
- Complement and antibody mediated cell destruction - deletion of antibody targeted cells can occur by way of the complement system or by antibody dependent cell mediated cytotoxicity, which doesnt require complement. It can occur because the cells are coated with molecules opsonized that make them attractive to phagocytes or because of the formation of membrane attack proteins that disrupt the integrity of the cell membrane and cause cell lysis. Mismatched blood transfusion or Rh factor birth.
- Complement and antibody mediated inflammation - When antibodies are deposited in extracellular tissue components such as basement membranes and matrix, injury results from inflammation rather than phagocytosis or cell lysis. Grafts rejection
- Antibody mediated cellular dysfunction - antibody binding to specific target cell receptors doesn’t lead to cell death, but to a change in cell function Hyperthyroidism
What is type III immune complex mediated disorders? What is systemic immune complex disorders? What is local immune complex reactions?
Are mediated by the formation of insoluble antigen antibody complexes, complement fixation, and localized inflammation. They are responsible for the vasculitis seen in certain autoimmune disorders like Lupus or kidney damage seen with acute glomerulonephritis.
Systemic Immune complex disorders - Serum sickness is a type III that is triggered by the deposition of insoluble antigen antibody IgM IgG and occasionally IgA complexes in blood vessels, joints, and heart and kidney tissue. Signs include urticaria, patchy rash, extensive edema, and fever. Most cases damage is temporary and resolve within a few days but if prolonged exposure can lead to irreversible damage.
Treatment is usually directed toward removal of the sensitizing antigen and providing symptomatic relief. May include aspirin for pain and antihistamines for pruritus. Epinephrine or systemic corticosteroids for severe.
Local Immune complex reactions - Arthurs reaction is used by pathologists and immunologist to describe localized tissue necrosis caused by type III
What is type IV cell mediated hypersensitivity disorders? What is direct cell mediated cytotoxicity? What is delayed type hypersensitivity disorders?
Involved cell mediated rather than antibody mediated immune responses. Is the principal mechanism of response to a variety of microorganisms, including intracellular pathogens tuberculosis and viruses, as well as extracellular agents such as fungi, protozoa and parasites. By specifically sensitized t cells. Direct cell mediated cytotoxicity - CD8t cells directly kill target cells that express peptides derived from cytosolic antigens that are presented in association with class I major histocompatibility complex molecules. CTLs cant distinguish between cytopathic and non cytopathic viruses, they kill virtually all infected cells regardless of whether the infection is harmful. Delayed type hypersensitivity disorders - they occur in response to soluble protein antigens and primarily involve antigen presenting cells such as macrophages and CD4 helper t cells of the TH1 type. Take up to 24-72 hours to develop, best known is the tuberculin test. Allergic contact dermatitis and hypersensitivity pneumonitis.
What is transplantation immunopathology? Immune recognition of allografts, patterns and mechanisms of solid organ graft rejection? Transplantation of hematopoietic cells? Graft versus host disease?
Transplantation is the process of taking cells, tissues, or organs, called a graft, from one individual and placing them into another individual.
Rejections of allografts is a complex process that involves cell mediated immunity and circulating antibodies Two pathways - t cells directly recognize donor MHC molecules of the surface of antigen presenting cells in the graft The indirect pathway, recipient CD4 t cells recognize donor MHC molecules after they have been picked up, processed, and presented by the recipients own antigen presenting cells.
Patterns and mechanisms -
Hyperacute rejection - occurs almost immediately after transplantation - kidney transplants it can often be seen at the time of surgery, as soon as the blood flows from the recipient to the donor it takes on a cyanotic, mottled appearance.
Acute rejection - may occur within the first few days to weeks after transplantation or it may occur suddenly months or even years later, after the discontinuation of immunosuppressants in the post transplant period.
Chronic rejection - develops insidiously over months and years may or may not be preceded by episodes of acute rejection.
Stem cell or bone marrow transplantation as therapy for hematopoietic and some nonhematopoietic malignancies, aplastic anemia, and immunodeficiency disorders.
Graft versus host disease - occurs when immunologically competent cells or precursors are transplanted into recipients who are immunologically compromised. 3 requirements - 1. the transplant must have a functional cellular immune component, 2 the recipient tissue must bear antigens foreign to the donor tissue, 3. recipient immunity must be compromised to the point that if cant destroy the transplanted cells. Causes pruritic, maculopapular rash, begins on the palms or soles, subsequent desquamation GI include nausea, bloody diarrhea, and abd pain. Liver painless jaundice, hyperbilirubinemia, and abnormal liver function test results.
What are autoimmune disease? Immunologic tolerance? What is b and t cell tolerance?
Autoimmune diseases represent a group of disorders that are caused by a breakdown in the ability of the immune system to differentiate between self and non self antigens.
Self tolerance - several mechanisms have been thought to explain the tolerant state, Central tolerance refers to the elimination of self reactive t cell and b cells in the thymus and bone marrow. Peripheral tolerance derives from the deletion or inactivation of autoreactive lymphoid organs Anergy represents the state of immunologic tolerance to specific antigens.
B cell tolerance - to filter autoreactive b cells out of the population - clonal deletion of immature b cells in the bone marrow; deletion of autoreactive b cells in the spleen or lymph nodes; functional inactivation or anergy; and receptor editing. This is done with help from t cells.
T cell tolerance - involve the deletion of self reactive t cells in the thymus. they develop from bone marrow derived progenitor cells that migrate to the thymus, or outside the thymus, apoptotic death or autoreactive t cells.
What are mechanisms of autoimmune disease? Genetic susceptibility and role of infections? and release of Sequestered antigens? Diagnosis and treatement of auWhat toimmune?
It not known what triggers, could be many things but is more prevalent in women more then men so estrogen could play a role.
Genetic susceptibility - can inc the incidence and severity of autoimmune diseases as shown by familial clustering or several autoimmune diseases and the observation of certain inherited HLA types and with a variety of immunologic disorders
Role of infections - Viral and bacterial infections may contribute to the development and exacerbations of autoimmunity. 3 possible mechanisms
Breakdown of t cell anergy, molecular mimicry, and superantigens.
Release of sequestered antigens - any self antigen that was completely sequestered during development and then reintroduced to the immune system is likely to be regarded as foreign.
Criteria for diagnosis - evidence of an autoimmune reaction, determination that the immunologic findings are not secondary to another condition and no other identifiable causes for the disorder. It is based primarily on clinical findings and serologic testing. Detection of antibodies in the laboratory three methods: indirect fluorescent antibody assay IFA, enzyme linked immunosorbent assay ELISA, or particle agglutination of some kind.
Treatment - is based on the tissue or organ that is involved, the effector mechanism and the magnitude and chronicity of the effector processes. Corticosteroids and immunosuppressive drugs may be used to arrest or reverse the downhill course of some autoimmune disorders. Purging autoreactive cells during plasmapheresis in severe cases.
What are immunodeficiency disorders? What are primary?
Immunodeficiency can be defined as an abnormality in one or more components of the immune system that renders a person susceptible to diseases normally prevented by an intact immune system.
Two groups
1. Primary - 180 syndromes have been identified. Most are transmitted as recessive traits, caused by mutations in genes on the X chromosome or autosomal chromosomes. Many have been traced to affecting signaling pathways that dictate immune cell development and function. Early detection is important before they become life threatening infections but also to prevent life vaccine - measles mumps, rubella and varicella. First clinical sign is a history of infections that are persistent and difficult to treat
Primary disorders - Humoral (B-cell) immunodeficiency disorders?
Defects in humoral immunity increase the risk of recurrent pyogenic infections, like S. pneumoniae, H influenza, staphylococcus aureus and pseudomonas.
They can cause transient hypogammaglobulinemia of infancy - after 6 mths the mothers IgG have left if the child has any abnormality it can interfere with the production of immunoglobulin producing plasma cells that can produce a state of immunodeficiency.
X-linked agammaglobulinemia - is a recessive trait that almost exclusively affects boys, as the name says they have essentially undetectable levels of all serum immunoglobulins and are susceptible to meningitis, recurrent otitis media. A clue to this infection is failure to respond completely and promptly to antibiotic therapy.
Common variable immunodeficiency - the terminal differentiation of mature b cells to plasma cells is blocked. 80% of persons with this disorder have a normal number of B lymphocytes, but they fail to differentiate into antibody -secreting cells when the lymphocytes are presented with antigen.
Selective immunoglobulin A deficiency - is the most common type, it is characterized by moderate to marked reduction in levels of serum and secretory IgA, probably due to a block in the pathway that promotes terminal differentiation of mature B cells to IgA secreting plasma cells. No specific treatment.
Immunoglobulin G subclass deficiency - can affect one or more of the IgG subtypes, despite normal levels or elevated serum concentrations of IgG. so at greater risk for sinusitis, otitis media and pneumonia caused by polysaccharide encapsulated microorganisms Treatment can be prophylactic antibiotics to prevent repeat infections. IV immunoglobulin can be given to children with severe manifestation of this deficiency.
X linked immunodeficiency with hyper immunoglobulinemia M - is characterized by low IgG and IgA levels with normal or more frequently, high IgM concentrations. Mostly seen in boys, Like the other one it affect individuals become symptomatic first years of life. They have recurrent pyogenic infections
What are cellular t cell immunodeficiency disorders?
T cell are unlike b cell it consists of distinct subpopulations with divers immunologic assignments they have infections of other clinical problems that are more severe than those seen with antibody disorders.
They rarely survive beyond infancy or childhood unless immunologic reconstitution is achieved.
Thymic hypoplasia DiGeorge Syndrome - is from an embryonic developmental defect. it affects males and females is more common then other t cell disorders. They have partial or complete failure in development of the thymus and parathyroid glands and have congenital defects of the head, neck and or heart. Can have a thymus transplant for t cell immunity or bone marrow transplant has worked to restore t cell populations..
What is severe combined immunodeficiency disorders?
SCID is a syndrome of diverse genetic causes characterized by profound deficiencies in t and b cell function and in some cases NK cells and function. They begin to develop frequent episodes of diarrhea, pneumonia, otitis media, sepsis, and cutaneous lesions. Is x linked,
Diagnosis and treatment - Severe is an emergency, but isn’t noticeable at birth so t cell screening has been added to birth testing, as the earlier detected the better off the child is. Bone marrow transplant is the mainstay treatment.
What is Acquired Immunodeficiency syndrome AIDS?
What is the transmission of HIV infection? Molecular and biologic features of HIV infection?
AIDS is a disease caused by infection with human immunodeficiency virus HIV and is characterized by profound immunosuppression with associated opportunistic infections, malignancies, wasting and CNS degeneration. HIV is a retrovirus that attacks the CD4 t lymphocytes, it attacks the immune response to infection. As a result a person has deteriorating immune system.
Is transmitted through conditions that facilitate the exchange of blood or body fluids that contain the virus or virus infected cells, the major routes being sexual contact; contaminated blood, either through sharing needles or syringes used for illicit drugs or passage from infected mothers to their newborns
Replication of HIV has 8 steps
- involves binding of the virus to the CD4 t cell.
- allows for internalization of the virus. which is fusion results in an uncoating of the virus, allowing the contents of the viral core to enter the host cell.
- Consists of DNA synthesis. using reverse transcriptase enzyme it changes its RNA to DNA
- intergration - the cDNA made by the virus is inserted into the cells original DNA called provirus.
- involves transcription of the double stranded DNA to form a single stranded messenger RNA with the instructions for building new viruses.
- is the translation of the viral mRNA. and create a protein and enzymes called a polyprotein.
- cleavage where the protease enzyme cuts the polyprotein chain into the individual proteins that will make up the new viruses.
- finally the core proteins migrate to the cell membrane, where they acquire a lipid envelope that buds off from the cell membrane
What the classification and stages of HIV infection?
The typical course of HIV infection has three phases, usually occur over 8-12 years. The primary infection phase, chronic asymptomatic or latency phase, and overt AIDS phase. When first infected with HIV may have acute mononucleosis like symptoms - fever, fatigue, myalgias, sore throat, night sweats, gi problems, lymphadenopathy, maculopapular rash, and headache. During primary there is a inc in viral replication, usually 1-4 weeks after exposure. And last 7-10 days. Then it stays there for the next couple of years.
Latent stage - the CD4 t cell count drops gradually to low. Lymphadenopathy for more than 3 months in at least two location develops in some persons with HIV. The lymph nodes may be sore or visible externally.
Stage 3 - low less than 200 t cells. Without antiretroviral therapy the person can be dead in 2-3 years.
What are opportunistic infections with someone with HIV? Malignancies with HIV? Wasting syndrome and metabolic disorders?
Opportunistic infections involve common organisms that don’t typically produce infection unless there is impaired immune function. As CD4 declines the risk increases. Host of many viral, fungal, protozoal and bacterial.
Respiratory tract infections - most common causes of is bacterial pneumonia, pneumocystis jiroveci pneumonia and pulmonary tuberculosis. TB is the leading causes of death for people with HIV.
GI tract - candidiasis, CMV infection, herpes simplex causing painful swallowing, diarrhea, gastroenteritis which could be from the infection or the medicine.
Nervous system - neurocognitive disorders, toxoplasmosis, and progressive multifocal leukoencephalopathy.
High incidence of certain malignancies, especially Kaposi sarcoma KS non hodgkin lymphoma, and cervical and anal carcinoma.
The wasting syndrome, which is an AIDS defining illness, is characterized by involuntary weight loss of at least 10% baseline body weight in the presence of diarrhea, more than two stools per day or chronic weakness and a fever.
Metabolic disorders - such as insulin resistance and diabetes, lipodystrophy, hyperlipidemia, and mitochondrial disorders.
What is Diagnosis and treatment of HIV? HIV in pregnancy and infants and children
Positive results on screen test, signs and symptoms or mani of immunodeficiency state. The most accurate and inexpensive method is HIV antibody test. Treatment - there is no cure but the medication that are currently available to treat HIV infection dec the amount of virus in the body, but they don't eradicate HIV. 5 different classes of antiretroviral - each class of agents attempts to interrupt the life cycle HAART which uses a combination of three antiretrovirals.
Transmission from mother to infant is the most common way. either with invitro, birth or breastfeeding.
Diagnosis and treatment - It is complicated because the HIV infected mothers share the IgG so to test they may stay positive for up to 18 months They will usually start the mother on HAART to decrease the chance of spreading to the infant.
Children may present differently then adults. Failure to thrive, CNS abnormalities, an developmental delays are the most prominent primary mani. Early pneumonia is the cause of early mortality.
