Module 3.3 Altered Immunity and Infection Flashcards
Define Hypersensitivity
An inappropriate immunological reaction to an antigen that results in a pathologic immune response after re-exposure. Reactions may be immediate or delayed.
What are the four types of hypersensitivity reactions?
- Type 1 (Ig E mediated)
- Type 2 (Tissue Specific)
- Type 3 (Immune Complex)
- Type 4 (Cell-mediated)
Describe the mechanism of type 1 ( IgE mediated) reaction
- Initial exposure to the allergen: no obvious reaction, but individual “sensitized” by the production of IgE that binds to receptors on mast cells, large doses of allergen may be required.
- Subsequent exposures: antigen binds to IgE on mast cells and causes them to degranulate, releasing their contents.
- Fc receptors on mast cells bind with IgE that has not previously interacted with antigen
- If further exposure of a sensitized individual to the antigen occurs, one molecule of antigen may bind simultaneously to two molecules of IgE-Fc receptor complexes on the mast cell’s surface (cross-link) resulting in intracellular signaling pathways and mast cell degranulation
- Products of mast cell degranulation modulate almost all aspects of the acute inflammatory response.
- The most potent mediator is histamine which affects several key target cells
Describe the mechanism of type II hypersensitivity
Type II reactions are generally characterized by a specific cell or tissue being the target of an immune response.
- Antigens (tissue-specific antigens) are on the plasma membranes of only certain cells, e.g. platelets. Reactions are limited to tissues with the antigen. Environmental antigens, e.g. drugs, may bind to cell plasma membrane and function as targets for type II reactions
- Antibody binds to antigens on target cell surface.
- Lysis: example: autoimmune hemolytic anemia. The antigen-antibody reaction activates the complement cascade, ultimately lysing the plasma membrane of circulating erythrocytes.
- Phagocytosis: example: Rh incompatibility. Antibodies coat the affected RBC’s resulting in their removal by phagocytosis in the spleen.
- Cytotoxicity: antibody on the target cell is recognized by cytotoxic cells which release toxic substances that destroy the target cell
- Cell malfunction: example: Graves disease. Antibodies do not destroy affected cells, but cause them to malfunction
Describe the mechanism of Type III Hypersensitivity - Immune Complex Mediated Injury
- Formation of insoluble antibody/antigen complexes in blood. These are deposited vessel walls and other tissue, often distant from the site of the initial reaction. Alternatively, the antigen may be deposited in tissues, leading to local antigen/antibody response. In either case, the complement system is activated. Neutrophils are attracted and attempt to phagocytose the immune complexes. Local tissue damage results from the release of lysosomal enzymes.
- Very small complexes are cleared via the kidney. Larger complexes are removed by macrophages. Intermediate complexes are likely to be deposited in target tissues and cause pathologic problems. Examples of target tissues are kidneys (glomerulonephritis), joints (arthritis), and vessels (vasculitis).
- Examples of diseases produced by Type III reactions include acute glomerulonephritis and arthritis. Serum sickness is a generalized form, primarily affecting the blood vessels, joints, and kidneys.
Describe Type IV - Cell Mediated Hypersensitivity
- Does not involve antibodies, Mediated by sensitized T lymphocytes, Manifested in 24-72 hours
- Delayed - Lymphokine producing T helper (Th1, Th17) cells produce cytokines that recruit and activate phagocytic cells, especially macrophages. This causes inflammation and tissue damage.
- Cytotoxic - Cytotoxic T lymphocytes ( Tc cells) bind to target cells directly, causing lysis. Destruction of tissue is usually caused by direct killing by toxins from Tx cells
Clinical examples - contact dermatitis (poison ivy, cosmetics); graft rejections. TB skin test
What are Exotoxins?
Exotoxin are proteins released during bacterial growth. They are often enzymes that have hightly specific specific effects; they include neurotoxins, cytotoxins, pneumotoxins, enterotoxins, and hemolysis.
What do exotoxins do?
- They can damage cell membranes, activate second messengers, and inhibit protein synthesis.
- Exotoxins are immunogenic and elicit the production of antibodies (antitoxins), which aew the basis for vaccines. Vaccines are avalable for many exotoxins (i.e. tenatus, diptheria, and pertusis)
What are endotoxins?
Endotoxins are lipopolysacharides (LPS) contained in cell walls of gram-negative bacteria and released during lysis (or destruction) of bacteria.
What do endotoxins do?
- Bacteria that produce endotoxins are called pyrogenic bacteria bacause they stimulate the release of inflammatory mediators and produce fever and the local and systemic effects of inflammation including septic shock and damage to multiple organs
- Toxins released in the blood cause the release of vasoactive peptides and cytokines that produce widespread vasodilation
What is aquired immunodeficiency syndrome (AIDS)?
AIDS is a viral disease cause by human immunodificiency virus (HIV). AIDS is the most notable form of secondary or acquired immune difficiency.
What is HIV and its structure?
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HIV is a retrovirus and carries genetic information in the form of two copies of RNA
- Contains reverse transcriptase that can copy RNA to DNA
- Normally DNA is copied by mRNA and is a one-way process, i.e. DNA is not made from RNA.
- Contains 2 strands of RNA (no DNA) and enzymes packaged in a protein cell or capsid
- Capsid surrounded by a lipid envelope with 2 protruding proteins. One is called gp120.
- Contains reverse transcriptase that can copy RNA to DNA
How does HiV use intergrase?
Intergrase is a viral enzyme and it inserts new DNA into infectected cells genetic material, where it may remain dormant.
If the cell is actived, translation of the viral information may be intiated, resulting in the formation of new virions, lysis, and death of infected cell.
What is the HIV life cycle?
- Gp120 forms a firm bond to CD4 receptor molecule on t-helper lymphocytes and monocytes
- RNA & enzymes from the virus are inserted into the cell cytoplasm
- Reverse transcriptase copies HIV RNA into DNA
- HIV DNA enters the cell nucleus and is incorporated into host DNA
- When the cell reproduces, the HIV is also duplicated
- HIV DNA uses the cell’s genetic machinery to make viral components and enzymes that bring about their assembly.
- The new HIV viral particles move to the periphery of the cell, emerge by budding and enter the blood stream to infect new cells.
- This process eventually results in the destruction of affected t-helper cells (also called CD4 cells.
How does HIV weaken the immune response?
It decreases the amont of CD4+ Th cells.
- Antibodies are of limited effectiveness because they only work on antigens on the outside of the cells. HIV is “hidden” inside the cells where it reproduces. Antibodies may signal cytotoxic immune cells to destroy cells with HIV antigen on their surface. But they need t-helper cells to direct them to those cells. The level of t-helper cells is reduced by HIV infection, limiting the effectiveness of the cytotoxic cells.
How is the Zika Virus transmitted?
ZKV It is transmitted by anarthropod (the Aedes mosquito) as well as sexual transmission among humans. Incubation period is likely 3-12 days. Once infected, the person is likely to be protected from future infections.
What is Middle Eastern Respiratory Syndrome (MERS) and how is it transmitted?
MERS-CoV is a coronavirus that produces a respiratory illness that was first reported in Saudi Arabia in 2012. The source is unknown, but likely zoonotic (animal source)bats and camels. Produces severe acute respiratory symptoms and 30% of confirmed case have died. Close person to person contact, not generally transmitted in public places
Where was Ebola originated? What are the symptoms?
Ebola is a filo virus that has mainly had outbreaks in Africa that was first noted in the 1970s and subsequent outbreaks in the 2000, 2004, 2011, and most recently in 2014. Prognosis is poor, 89% mortality, those who survive the first weeks usually make a slow recovery. High fever, maculopapular rash, pharyngitis, abdominal pain, headaches, myalgias, bleeding from eyes, nose, and rectum. Terminal patients exhibit bleeding from body orifices, hypotension, anuria, and coma.
How is Ebola transmitted?
Person to person transmission, primate to person transmission-direct contact with infected body fluids. It is not transmitted by respiratory.
You look in a patient’s chart and find she has a history of seasonal allergic rhinitis. Your clinical instructor is visiting you and asks you to identify which type of hypersensitivity response this is and explain the underlying pathophysiology.
This is a type 1 Hypersensitivity reaction. In some individuals exposure to an environmental intigen causes IgE production. Type 1 Reactions are mediated through the binding of IgE to Fc receptors on mast cells and cross linking of IgE by antigens that bind to the Fab portions of IgE. Cross linking causes mast cell degranulation and the release of histamine and other inflammatory substances.
Dr. aughsteen response:
Seasonal allergic rhinitis is a type I IgE mediated response. IgE binding to the surface of mast cells causes the release of histamine and other cytokines, which induces the inflammatory response, i.e. inflammation of the nasal mucosa causing congestion and serous otitis media. Eosinophils are particularly active. It is the action of histamine binding to H1 that causes allergic responses. H1 receptors are found in abundance in smooth muscle and endothelial cells, i.e. bronchial tube lining, nasal and oral mucosa. The H2 receptors act to prevent over reactions in the smooth muscle contractions brought on by histamine binding to H1 receptors. So histamine binding to H1 causes smooth muscle contraction, histamine binding to H2 causes smooth muscle relaxation.
