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271 Cards in this Set
- Front
- Back
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What is the function of the immune system?
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To prevent or eliminate unwanted growth of microorganisms and dysregulatoin of cells
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What are the two major types of immunity?
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Innate immunity (natural)
Acquired immunity (adaptive) |
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What are the advantages of the innate immunity?
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Components are preformed and are able to function immediately after a microorganism has entered the body
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What are the disadvantages of innate immunity?
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Component are less specific for the invading pathogen and do not develop memory for future infections
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What are the two major categories of the acquired immune system?
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Humoral (antibody-mediated) immunity
Cell-mediated immunity |
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What are the five components of acquired humoral (antibody-mediated) immunity?
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B cells
Plasma cells Helper T cells Macrophages Antibodies |
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What are the three components of acquired cell-mediated immunity?
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Antigen presenting cells
Helper T cells Cytotoxic T cells |
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What are the three main antigen-presenting cells?
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Macrophages
Dendritic cells B cells |
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What are the targets of humoral immunity?
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Free microorganisms and toxins
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What are the targets of cell-mediated immunity?
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Intracellular microorganisms, parasites, and altered host cells
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What are the advantage of the acquired immune system?
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1) Responds to millions of different antigens
2) Provides specific immunity against the invading pathogen 3) Develops long-term memory against the specific antigen in the future Accquired immunity provides diversity, specificity, and long-term memory |
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What are the disadvantages of the acquired immune system.
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Does not provide immediate immunity to novel pathogens because of the lag time for functionality and is responsible for autoimmune phenomenon
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What are two ways that immunity is acquired?
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Active
Passive |
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What is active immunity?
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Immunity that is induced upon exposure to a microorganism, either in the form of infection or with preventative vaccination.
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What is an advantage of active immunity?
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Long-term immunity
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What is a disadvantage of active immunity?
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Response is usually slow, requiring days for immunity to develop
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What is passive immunity?
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Immunity that is conferred by transferring preformed antibodies against bacteria, toxins, and/or viruses from another host
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What is an advantage of passive immunity?
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Large amounts of antibody can be administered quickly, generating a rapid response to the antigen
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What are the disadvantages of passive immunity?
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Antibodies have a short life span, may induce hypersensitivity reactions, and do not provide memory against future infections
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What are three modes of acquiring passive immunity?
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1) Transplacental transmission of IgG
2) IgA transmitted via breast milk 3) Injection of preformed antibodies |
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When is passive immunity used clinically?
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For postexposure prophylaxis of diptheria, tetanus, botulism, rabies, hepatitis A, and hepatitis B.
For preexposure prophylaxis of respiratory syncytial virus (RSV) in infants. |
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What is an antigen?
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Any molecule, or part thereof, that reacts with antibodies
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What is an immunogen?
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Any molecule, or part thereof, that induces an immune response
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Are all antigens also immunogens?
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NO
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What is a hapten?
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Molecule that is not immunogenic by itself, but elicits an immune response when bound to a specific carrier protein
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Give two examples of haptens?
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Penicillin
Catechol |
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Why are haptens unable to stimulate an immune response?
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They are unable to bind to major histocompatibility complex (MHC) proteins or activate B cells without a carrier protein.
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What is an adjuvant?
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Chemical that is unrelated to an immunogen but enhances the immune response to an antigen
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Give an example of an adjuvant
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Aluminum hydroxide
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What is the innate immune response?
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The initial response by the body to tissue damage or against or a foreign body
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What cells are involved with the innate immune response?
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Granulocytes
Agranulocytes Natural Killer cells |
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What are granulocytes?
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Cells derived from the bone marrow that contain cytoplasmic granules
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What process is ubiquitous for normally functioning granulocytes?
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Degranulation of cytoplasmic granules releasing various immune mediators
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What are four types of granulocytes?
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Neutrophils, or polymorphonuclear cells (PMNs)
Eosinophils Basophils Mast cells |
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What is the precursor cell to granulocytes?
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Myeloid progenitor
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What is the role of neutrophils in the innate immune response?
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Phagocytosis of microorganisms and cellular debris
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What is often found at the site of an infection?
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Pus, composed of dead neutrophils and organisms
Think of neutrophils as the Marines because they are the first on the scene, ingest (destroy) the bad guy, and take a lot of casualties |
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What is the morphology of neutrophils?
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Neutrophils have large, azurophilic granules (lysosomes) at the periphery with a multilobed nuclei
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What is the role of eosinophils in the innate immune response?
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1) Phagocytosis of antibody-bound microorganisms and cellular debris
2) To release histamine |
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What infections are associated with high concentrations of eosinophils?
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Helminthic and protozoal infections
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What is the morphology of eosinophils?
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Eosinophils have large eosinophilic granules and a bilobed nucleus
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What is the role of basophils in the innate immune response?
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1) Anticoagulation (heparin release)
2) Vasodilation (histamine release) |
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What reaction is associated with basophils?
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Allergic reactions
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What is the morphology of basophils?
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Basophils have a dark-blue-staining granules with a bilobed nucleus
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What is the role of mast cells in the innate immune response?
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1) Vasodilation (histamine release)
2) Anticoagulation (heparin release) 3) Release chemotactic factors and prostaglandins |
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What reactions are associated with mast cells?
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Allergic and anaphylactic reactions
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What is the morphology of mast cells?
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Mast cells have large cytoplasmic granules and a spherical nucleus.
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What are agranulocytes?
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Cells derived form the bone marrow that lack cytoplasmic granules
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What is one type of agranulocyte?
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Macrophage
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What is the role of macrophages in the innate immune response?
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1) Phagocytosis of microorganisms and cellular debris
2) Antigen presentation to lymphocytes |
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What is the morphology of macrophages?
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Macrophages are irregularly shaped cells with projections
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What is the precursor for macrophages?
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Monocytes
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What other cells are produced form monocytes?
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1) Kupffer cells (liver)
2) Langerhans cells (skin) 3) Alveolar macrophages (lung) 4) Osteoclasts (bone) 5) Microglia (CNS) |
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What is the morphology of the monocyte nucleus?
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A kidney-shaped nucleus
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What are natural killer cells?
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Nonphagocytic killer cells related to lymphocytes
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What is the role of natural killer cells in the innate immune response?
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1) Interferon release
2) Recognition of decreased major histocompatibility complex (MHC) class I surface expression |
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What infections are associated with natural killer cells?
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Viral and intracellular bacteria
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What is the adaptive immune response?
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An immune response based on specific recognition of unique foreign antigens
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What are two types of the adaptive immune response?
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Cell-mediated response
Humoral response |
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What three cells present antigens to cells of the adaptive immune response?
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Antigen presenting cells:
Macrophages Monocytes Dendritic cells |
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What is the progenitor cell for the adaptive immune response?
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Common lymphoid progenitor
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Which cells of the innate immune response share this progenitor cells?
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Natural killer cells
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What specific types of differentiated common lymphoid progenitor cells are associated with each type of adaptive immune response?
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Cell-mediated immune response is associated with T cells and antigen-presenting cells
Humoral immune response is associated with B cells |
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What is the function of T cells?
What are two examples? |
To develop into effector T cells that either "help" or "kill"
CD4+ T cells CD8+ T cells or cytotoxic T cells |
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What is the function of B cells?
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To produce antibodies and differentiate into memory cells (plasma cells).
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What is the first line of defense against infection?
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Skin and mucous membranes
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Identify the components of the innate immune system:
Cells? |
Neutrophils
Natural killer cells Macrophages |
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Identify the components of the innate immune system:
Proteins? |
Complement cascade
Interferons Acute phase proteins |
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Identify the components of the innate immune system:
Processes? |
Phagocytosis
Inflammation (acute phase response) |
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What are three characteristics of innate immunity?
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1) Resistance is not acquired
2) Response does not inprove after exposure to antigen 3) There is no 'memory' for antigen-specific response |
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What is the initial defense of the innate immune system?
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Noninflammatory, which depends on the body's static defenses (skin, gastric pH, lysozomes)
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What is the subsequent response of the innate immune system?
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Acute-phase response produces local inflammation and promotes migration of phagocytes and plasma proteins into the infected tissues
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What are two examples of acute-phase plasma proteins?
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1) C-reactive proteins
2) Mannose-binding proteins (collectins) |
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Where are these proteins synthesized?
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In the liver
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What induces acute phase protein synthesis?
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IL-6
TNF-alpha |
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What lab test measures the amount of acute phase proteins in the blood?
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ESR
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What is the clinical significance of the ESR?
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Elevated ESR indicates an increase in acute-phase proteins in the blood, which may be a nonspecific indicator of infection, inflammation, autoimmune disease, or malignancy
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How does the innate immune system recognize foreign microorganisms?
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By detecting nonmammalian epitopes on the surface of microorganisms that differ from those on human cells
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What are four examples of foreign substances?
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Lipopolysaccharide (LPS)
Peptidoglycans Lipoteichoic acids Mannans |
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What is the first line of cellular defense against bacterial pathogens?
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Neutrophils
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What roles do neutrophils play in acute inflammation?
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Phagocytosis with oxygen-dependent or independent bacterial killing mechanisms
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What role do macrophages play in acute inflammation?
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Phagocytose and trap foreign substances, followed closely by antigen presentation
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What role do eosiophils play in acute inflammation?
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Key inflammatory cells involved in response to helminth infections and allergens
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What role do basophils and mast cells play in acute inflammation?
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Destroy abnormal host cells (virally infected or transformed) via osmotic lysis or by triggering apoptosis
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How is phagocytosis enhanced?
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Opsonization
Process by which host proteins bind to antigens to make them more easily detected by phagocytic cells. |
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What is respiratory burst?
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A transient increase in oxygen uptake by phagocytic cells during bacterial killing.
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What are the mechanisms of oxygen-dependent killing seen in neutrophils?
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1) Superoxide radical production (via NADPH oxidase)
2) Hypochlorite ion production (via MPO) 3) Hydroxyl radical production (formed spontaneously) |
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What disease is associated with NADPH oxidase deficiency?
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Chronic granulomatous disease of childhood
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What are patients with chronic granulomatous disease of childhood more susceptible to?
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Opportunistic infections including Staphylococcus aureus, gram-negative enteric rods, and Aspergillus fumigatus.
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Which disease is associated with a defect of neutrophil lysosomes?
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Chediak-Higashi syndrome
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What are patients with Chediak-Higashi syndrome more susceptible to?
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Recurrent pyogenic infections by staphylococci and streptococci
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What are three unique characteristics of macrophages?
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1) Display receptors for molecules not normally displayed on human cells (mannose, LPS, LAM)
2) Enter CT spaces forming reticuloendothelial system 3) Increased expression of class II MHC after phagocytosis |
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What is the difference between monocytes and macrophages?
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Macrophages are mature bloodstream monocytes that have migrated into tissues
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What are tissue-specific examples of macrophages?
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1) Alveolar macrophages in lung
2) Kupffer cells in liver 3) Microglial cells in CNS 4) Peritoneal macrophages in peritoneal fluid 5) Splenic macrophages 6) Macrophages in Peyer patches along the gut |
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What type of cells do natural killer cells target?
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Cells that lack MHC class I molecules
(viruses can induce the loss of MHC class I molecules in infected cells as a way to hide form the immune system) |
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What is acquired immunity?
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Immunity resulting from previous exposure to a pathogen
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What are the two types of acquired immunity?
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Humoral immunity
Cell-mediated immunity |
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What are five main processes of acquired immunity?
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1) Maturation of lymphocytes
2) Uptake and processing foreign antigens 3) Recognizing antigenic epitopes 4) Cloning effector cells 5) Removing microorganisms by reactivity with foreign antigens |
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What cells are important in the acquired immune system?
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Antigen-presenting cells
Lymphocytes - B cells and T cells |
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What are the advantages of acquired immunity over innate immunity?
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1) Targets specific pathogens
2) Provides memory, which allows for a faster immune response 3) Enhanced response wiht repeated exposure |
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What is the origin of T cells?
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Lymphoid progenitor cells
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For what two types of immunity are T cells a key component?
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Cell-mediated immunity (cytotoxic T cells)
Humoral immunity (helper T cells) |
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What are the two types of T cells?
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Helper T cells (CD4)
Killer T cells (cytotoxic, CD8) |
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What do helper T cells do?
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1) Recognized peptides presented by MHC molecules
2) Assist in activation of killer T cells by elaboration of IL-2 3) Signal B cells to secrete antibodies by secreting IL-4 and IL-5 4) Help macrophages stimulate delayed-type hypersensitivity |
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What activates helper T cells?
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Antigen-specific peptides associated with class II MHC molecules and costimulatory molecules
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What do killer T cells do?
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ID and kill cells harboring viruses and other intracellular micoorganisms, cancerous cells, and allografts
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What activates killer T cells?
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Antigen-specific peptides associated with class I MHC molecules along with costimulatory molecules.
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What percentages of peripheral T cells are helper T cells?
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67%
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What percentage of peripheral T cells are killer T cells?
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33%
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What infection causes marked lymphopenia with a reduction in the ratio of helper T cells to killer T cells?
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HIV decreases the normal CD4:CD8 ratio from 2:1 to 1:10
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Where do T cells originate?
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Bone marrow
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Where do T cells mature?
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Thymus
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What do T cells acquire when they develop in the thymus?
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T-cell receptors (TCRs)
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What is the TCR?
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A 5-chain complex of proteins forming a unique receptor for each antigen
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What process occurs in the thymus after cells develop T-cell receptors?
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Selection for T cells that recognize self-MHC complexes, but do not recognize self antigens
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What happens to immature T cells that fail to recognize self-MHC complexes?
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Cell death by apoptosis
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What happens to immature T cells that recognize self antigens?
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Cell death by apoptosis
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How many antigens does a specific T cell recognize after maturation?
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Only 1 antigen bound to 1 specific MHC molecule.
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When does the conversion of thymocytes into mature lymphocytes predominantly occur?
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From the fetal period through adolescence
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How many T cells survive thymic selection?
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2%
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Where do T cells go after the thymus?
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Into the circulation and secondary lymphoid organs
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What comprises the TCR complex?
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Heteromeric polypeptide chains
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What types of polypeptide chains form a TCR complex?
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Either alpha/beta or gamma/delta along with three proteins form CD3
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How are the two chains of polypeptides that form a TCR complex connected?
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Disulfide bonds
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What percentage of T cells express the alpha/beta TCR?
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95%
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Why are TCRs referred to as members of the immunoglobulin supergene family?
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The TCR protein structure is similar to that of antibodies
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What complex transfers the signal across the cell membrane that the TCR has engaged its specific peptide?
What is the result of this signal? |
CD3 complex
Activation of intracellular kinases, resulting in signal cascade and T-cell activation |
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What is the role of the MHC?
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To present antigenic peptide fragments to T cells
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What is the specific name for the MHC in humans?
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Human leukocyte antigen (HLA)
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What is the structure of an MHC molecule?
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Two-chained cell-surface complex with a variable extracellular peptide binding site.
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What is a unique characteristic of the MHC gene that allows for variability in the binding site?
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Genetic polymorphism
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What is genetic polymorphism?
How does this affect MHC molecules? |
The presence of many different rearrangements in the coding sequences for the MHC peptide binding site
Allows for great variability of peptide binding sites for many diverse antigens |
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Where are the peptides presented on class I MHC complexes derived from?
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Proteins endogenously made inside the cell, such as viral proteins, intracellular pathogens, cross-presented tumor antigens, and normal cellular proteins.
T cells that react too strongly with the normal cellular proteins that are a part of the class I MHC complex must be deselected during maturation in the thymus to prevent autoimmune disease |
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What are four genes that encode different types of class I MHC molecules?
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HLA-A
HLA-B HLA-C HLA-D |
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What is the second chain of the class I MHC complex?
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Beta2-Microglobulin, a member of the immunoglobulin supergene family
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What chromosome codes for the HLA gene?
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Chromosome 6
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What cells express class I MHC molecules?
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All nucleated cells
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What type of T-cell recognizes class I MHC molecules?
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CD8 T cells
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What occurs when the activated CD8 T cell binds to the class I MHC?
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Clonal expansion of the T cell
Killing of infected cell |
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Where are the peptides presented on class II MHC complexes derived from?
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Extracellular or phagocytosed proteins
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What are three gene pairs that encode different types of class II MHC?
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HLA-DP
HLA-DQ HLA-DR |
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What do
HLA-DP HLA-DQ HLA-DR encode? |
Cell-surface glycoproteins made of two polypeptide
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What are the two polypeptide chains called encoded by
HLA-DP HLA-DQ HLA-DR called? |
alpha and beta
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What cells express class II MHC molecules?
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Mainly antigen-presenting cells
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What are three antigen-presenting cells?
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Macrophages
Dendritic cells B cells |
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What type of T cell binds to class II MHCs?
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CD4 T cells
The MHC class number x T cell CD number equals 8 Class I MHC x CD8 = 8 Class II MHC x CD4= 8 |
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What occurs when activated CD4 T cells bind to class II MHCs?
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1) Clonal expansion of the T cell
2) Secretion of cytokines to stimulate either a humor or cell-mediated response |
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What is the hallmark of MHC?
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Diversity at the antigen-binding site
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Why is diversity necessary?
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To allow the immune system to identify and eliminate a wide range of pathogens
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How is a CD4 T-cell activated?
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Antigen-presenting cell (APC) presents a peptide associated with a class II MHC to a naive T cell
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What costimulatory signal is required for activation of a CD4 T cell?
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B7 on antigen-presenting cells interacts with CD28 on CD4 T cell
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Where does antigen-presentation to CD4 T cells occur?
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Secondary lymph tissues (spleen, lymph nodes)
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What are two types of CD4 cells?
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Type 1 (Th-1)
Type 2 (Th-2) |
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What determines if a CD4 cell becomes a type 1 or a type 2?
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Cytokines present in the paracortical space of lymph nodes.
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What cytokines lead to the development of type I cells?
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IFN-gamma from natural killer cells and IL-12 from macrophages
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What are the actions of type 1 (Th-1) cells?
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1) Produces IL-2, which stimulates CD4 T cells to divide, and activates CD8 T cells
2) Produces interferon-gamma, which increases expression of class II MHC and B7 proteins on APC, enhancing the delayed-type hypersensitivity response 3) Creates a memory cell population |
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What type of reaction involves Th-1 cells?
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Delayed-type hypersensitivity
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What type of immunity do Th-1 cells primarily activate?
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Cell-mediated immunity
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What cytokine leads to the development of type-2 cells?
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IL-4 produced by CD4 T cells
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What are the actions of Type 2 (Th2) cells?
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1) Expresses CD40 ligand
2) Secretes IL-4, IL-5, and IL-6, which activate B cells and facilitate antibody production. |
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Th-2 cells primarily activate which type of immunity?
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Humoral immunity
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How are CD8 T cells activated?
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Nucleated cells present a peptide associated with a class I MHC to a naive T cell
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What are the actions of activated CD8 T cells?
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1) Stimulates CD8 T cell to divide
2) Produces and secretes interferons, tumor necrosis factor, and other cytokines 3) Kills infected cells 4) Creates a memory cell population |
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How does a CD8 T-cell kill its target?
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Osmotic lysis
Inducing apoptosis |
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How does a CD8 T-cell kill target cells via osmotic lysis?
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By formation and exocytosis of perforins, cytotoxic substances that form channels through the target cell's plasma membrane
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How do CD8 T-cells induce apoptosis?
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1) Release limited number of perforins that form pores
2) Release proteases from granules that pass through pores and degrade target cell DNA. 3) Degraded DNA stimulates apoptosis of target cell |
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Why don't killed viral vaccines stimulate a CD8 T-cell response?
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CD8 T cells only attack cells that contain antigens displayed on class I MHC molecules; killed pathogens are not processed and displayed with class I MHC molecules
Killed viral vaccines stimulate a CD4 T-cell and antibody response, but not a CD8 T-cell response |
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What are superantigens?
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Molecules that are not processed by antigen-presenting cells, but bind class II MHC molecules and TCR-beta chains outside the antigen-binding site of the MHC receptor
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What is the result of this interaction of superantigens?
What can this cause clinically? How? |
Nonspecific activation of T cells with various antigen-binding sites and massive cytokine release
DIC Hypotension Shock Cytokines activate platelets and cause vasodilation |
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What are four examples of superantigens?
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1) Staphylococcal toxic shock syndrome toxin-1 (TSST-1)
2) Streptococcal pyrogenic exotoxin (Spe) 3) Staphylococcal enterotoxins (SE) 4) Exofoliative dermatitis toxin |
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What are three disorders characterized by immunodeficiency of T cells?
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1) DiGeorge syndrome
2) Chronic mucocutaneous candidiasis 3) HIV |
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What is DiGeorge syndrome?
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Congenital thymic aplasia or hypoplasia resulting from a defect in the embryonic development of the third and fourth pharyngeal pouches.
CATCH 22 Congenital heart disease Abnormal facies Thymic aplasia Cleft palate Hypocalcemia 22q gene deletion |
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What is the result of DiGeorge syndrome?
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Increased rate of infection because of a lack of T-cell maturation
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What is chronic mucocutaneous candidiasis?
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Infection of skin and mucous membrane with Candida albicans because of a defect in T-cell response to Candida
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What is the T-cell response to other organisms?
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Normal
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What molecule does HIV bind to?
Which cells does this affect? |
CD4
CD4 T cells and CD4 monocytes/macrophages including CNS microglia |
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What type of cells are B cells?
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Lymphocytes
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What type of cells are B cells?
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Humoral immunity
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What type of pathogens do B cells mainly target with this type of immunity?
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Extracellular pathogens
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What are three roles of B cells?
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1) Antigen-presenting cells
2) Differentiation into plasma cells that produce antibodies 3) Forming memory cells for future infections |
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What transmembrane proteins function as antigen receptors on B cells?
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IgM and IgD antibodies expressed on the cell surface.
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What distinguishes the binding of B cells to antigens from the binding of T cells to antigens?
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B cells bind protein, carbohydrate, lipid, or nucleic acid (not just peptides)
T cells only bind to peptides presented by MHC complexes |
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What is the difference between a "traditional" antigen-presenting cell and a B cell?
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In B-cell antigen presentation, repeated epitopes present in bacteria and fungi cross-link many B-cell receptors (IgM and IgD on the surface of B cells) to form aggregates, promoting endocytosis; the antigens are processed and presented in the context of class II MHC molecules to activate helper T cells
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Is the process of processed antigens being presented to helper T cells efficient for activating T cells?
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Not for naive T cells because B cells do not synthesis IL-1, but it is efficient for activating memory T cells because IL-1 is unnecessary
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What is a plasma cell?
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A terminally differentiated B cell that produces antibodies with the same specificity as the B-cell receptor.
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What stimulates B cells to become plasma cells?
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Activation of B cells with antigens and helper T cells
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What are three phases of B cell maturation?
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1) Gene rearrangement in the bone marrow
2) Antigen-independent phase in the bone marrow 3) Antigen-dependent phase in the lymph node |
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What are three steps of gene rearrangement?
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Heavy (H)-chain rearrangement
Kappa (k) light-chain rearrangement Lambda light-chain rearrangement |
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What do heavy chain, and light chains correspond to?
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The chains that make up an antibody
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What occurs during heavy chain rearrangement?
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1) A diversity segment and a joining segment rearrange to form productive DJ segment; the remaining J segment is still present
2) The DJ segment joins with a variable gene segment (Vh) to form a VDJ segment 3) Transcription of DNA with subsequent splicing of RNA to remove the remaining J segment and intervening sequences and join the VDJ segment to the constant gene 4) Translation to form a heavy chain polypeptide |
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What occurs during Kappa light-chain rearrangement?
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A Vk segment is joined with a Jk segment to form a continuous domain that can be transcribed, with the resultant RNA translated to form a kappa light chain
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What occurs during Lambda light-chain rearrangement?
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A Vlambda segment is joined with a Jlambda segment to form a contiguous domain that can be transcribed, with the resultant RNA translated to form a lambda light chain
H-chain rearrangement occurs in every B cell, however, only one type of light chain undergoes gene rearrangement in that cell |
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What two enzymes are involved in gene rearrangement?
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1) Recombinase
2) Exonucleases Rearrangement is an error-prone process that is imprecise and yields unproductive products in addition to successful, highly variable gene products |
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What is antigen-independent maturation of B cells?
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Maturation of stem cells into naive, mature B cells without exposure to antigens
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What are the different stages of B cells in antigen-independent maturation?
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1) Stem cell
2) Pro-B cell 3) Pre-B cell 4) Naive, immature B cell 5) Naive, mature B cell |
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Define Pro-B cells.
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Cell that expresses B220 and is actively rearranging immunoglobulin genes
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Define Pre-B cells.
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Cell that synthesizes cytoplasmic mu heavy chains
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Define Naive, immature B cells.
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Cell that expresses surface IgM after successfully synthesizing mu heavy chains and either kappa or lambda light chains.
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Define Naive, mature B cells.
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Cell that expresses both surface IgM and IgD after successfully synthesizing light chains, mu heavy chains, and delta heavy chains
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What is antigen-dependent maturation?
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Maturation of B cells that is dependent on exposure to antigen resulting in B cell proliferation and differentiation into antibody-producing plasma cells
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What are two ways that B cells become activated to differentiate into plasma cells?
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T-helper cell activation
T-cell independent activation |
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What is T-helper cell activation?
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Th-2 (and Th-1) helper T cells bind to the antigen/class II MHC complex on the surface of B cells and activate proliferation and differentiation of B cells into plasma cells by 3 methods:
1) Costimulation between CD28 on T cells and B7 on B cells induces IL-2 production by T cells 2) Costimulation between CD40L on T cells and CD40 on B cells induces class switching 3) Secretion of IL-4 and IL-5 |
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What is T-cell independent activation?
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Activation by a large, repeating epitope that cross-links many B-cell receptors, resulting in activation of the cell without a helper T-cell signal
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What is an example of a T-independent antigen?
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LPS found in G- bacterial cell walls
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What are antibodies?
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Soluble, globular proteins that are important components of the acquired immune response
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What is another name for antibodies?
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Immunoglobulins
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How many epitopes can an antibody recognize?
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Only 1
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Which cells produce antibodies?
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Plasma cells
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What are five functions of antibodies?
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1) Opsonize bacteria
2) Neutralize toxins 3) Activate complement 4) Prevent microorganism adherence 5) Mediate lysis of microorganisms by binding |
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What type of antibody is made during a human response to antigen?
What does this mean? |
Polyclonal
Antibody response to antigen is heterogeneous because many different plasma cells are producing antibodies |
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What type of antibody can be made in the lab?
What does this mean? |
Monoclonal
The antibodies produced are identical |
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What are the components of an antibody?
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2 heavy chains and 2 light chains
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What links antibody chains together?
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Disulfide bonds
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What are two types of light chains?
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Kappa and lambda, corresponding to the gene used during rearrangement
Every person has both kappa and lambda light chains, however each antibody contains only one type |
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What regions are found in both heavy and light chains?
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Variable and constant
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What fragments are created in the lab by digestion of an antibody with papain?
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Two identical Fab fragments and an Fc fragment
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What is the role of the Fab fragment?
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Bind to antigen
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What is the role of the Fc fragment?
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Binds complement and Fc receptors on cells
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What are isotypes?
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Different antibody classes based on the heavy-chain gene used during class switching
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What are five examples of isotypes?
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IgM
IgD IgG IgA IgE |
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What is immunoglobulin class switching?
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Isotype switching from IgM initially to IgD, IgG, IgA, or IgE
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How does immunoglobulin class switching occur?
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IgM switches to IgD by alternate RNA splicing that incorporates messenger RNA from a different constant gene
IgM switches to IgG, IgA, and IgE by a second DNA rearrangement involving the constant region |
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What triggers class switching?
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Cytokines released by helper (CD4) T cells
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Which isotype is produced first in a primary immune response?
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IgM
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Which isotype is predominant in the secondary immune response?
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IgG
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Which isotype is predominant in the blood?
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IgG
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What are allotypes?
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Allelic polymorphisms with portions of the antibody genes that vary among individuals
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What are idiotypes?
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Differing amino acid sequences in the hypervariable region that are unique for the immunoglobulin produced by a specific clone of antibody-producing cells
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What is somatic hypermutation?
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Process causing mutations in the hypervariable region of antibodies, resulting in generation of greater diversity, allowing selection for increased affinity for the antigen in future
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What are two forms of IgM?
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Pentameric IgM, which is found in the circulation
Monomeric IgM, which is found on the surface of B cells IgM forms Macromolecules |
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What links the pentameric IgM molecules together?
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Polypeptide J chain and disulfide bonds.
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What other isotype is found on the surface of B cells?
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IgD
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What is the main action of pentameric IgM
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Activation of complement
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Can IgM cross the placenta?
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NO
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What are natural isohemagglutinins?
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A subset of IgM antibodies that react against antigens resembling the ABO blood group types
Natural isohemagglutinins are the reason why people with type A blood produce antibodies against type B blood and visa-versa. |
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What is the clinical significance of natural isohemagglutinins?
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They can cause hemolytic transfusion reactions if people receive blood with an A or B type that they do not have.
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What type of antibodies against ABO blood types do people with AB blood make?
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What type of antibodies against ABO blood types do people with O blood make?
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Type A
Type B |
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Where is IgG found?
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Predominant isotype found in blood, lymph, cerebrospinal fluid (CSF), and peritoneal fluid
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How many subclasses of IgG exist?
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Five
IgG1 IgG2 IgG2b IgG3 IgG4 |
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What is the half life of IgG?
What is the clinical significance of this? |
Roughly 20 days, which is the longest of all isotypes
Because of its long half-life, IgG is used for passive immunization |
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What is unique about the transmission of IgG?
What disease can this cause? |
It is the only immunoglobulin that can cross the placenta
Erythroblastosis fetalis |
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What is erythroblastosis fetalis?
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Disease that occurs when IgG from a Rh- mother crosses the placenta and is directed against Rh+ fetal red blood cell antigens, causing hemolysis in the fetus
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When can erythroblastosis fetalis occur?
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Only with the second or subsequent pregnancy because the first child generates the first Rh exposure to the Rh- mother
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How is Erythroblastosis fetalis prevented?
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By administering RhoGAM, an Rh immune globulin that binds to and covers the Rh antigen, to prevent a maternal antibody response
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How does IgG aid in cell-mediated immunity?
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IgG binds to antigens and enhances uptake by phagocytes through opsonization
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What is ADCC?
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Antibody-dependent, cell-mediated cytotoxicity, a process that ocurs when IgG binds to antigen and stimulates natural killer cells to destroy the invading pathogen
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Can IgG activate complement?
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YES
but not as efficiently as IgM because it is not pentavalent |
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Where is IgA found?
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In secretions including mucus, tears, saliva, gastric fluid, sweat, and breast milk
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How does IgA exist in secretions?
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As dimers
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What links IgA molecules together?
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Polypeptide J chain
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Where is IgA formed?
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In plasma cells within the blood
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How does IgA get into secretions?
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It must cross epithelial cells
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How does IgA achieve this?
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Dimeric IgA binds to poly-Ig receptors on the basal membrane of epithelial cells and is taken into the cell by endocytosis.
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How is IgA released from cells?
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Endocytic vesicles fuses with the luminal membrane of the epithelial cell and the poly-Ig receptor is cleaved
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What does secretory IgA consist of?
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IgA dimer
Polypeptide J chain Portion of the poly-Ig receptor called the secretory component |
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What is the main role of IgA?
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Prevent adherence and penetration of microorganisms
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Can IgA activate complement?
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NO
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Where is IgE found?
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At low concentrations in the serum
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What is the main role of IgE?
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Triggers degranulation of mast cells and basophils
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How does IgE trigger degranulation of mast cells and basophils?
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1) First exposure to an antigen causes 'sensitization' whereby plasma cells synthesize IgE
2) The Fc portion of IgE binds to mast cells and basophils 3) In subsequent exposures, antigen binds to the Fab portion of IgE, causing the IgE to cross-link and stimulate degranulation of previously bound mast cells/basophils. |
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What compounds are released by degranulation?
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Histamine
Leukotrienes Prostaglandins Heparin and other chemicals |
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What do Histamine, leukotrienes, prostaglandins, and heparin cause?
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Vascular permeability and increased blood flow
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What type of allergic reaction does IgE mediate?
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Type I hypersensitivity response
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How does Type I hypersensitivity present clinically?
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Anaphylaxis, asthma, or local wheal
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What type of infection results in elevated IgE levels?
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Helminth infections
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What are three disorders characterized by immunodeficiency of B cells or antibodies?
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1) Bruton's agammaglobulinemia
2) Selective IgA deficiency 3) Common variable immunodeficiency (CVID) |
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What are patients with bruton's agammaglobulinemia, selective IgA deficiency, or CVID at higher risk for?
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Recurrent infections with encapsulated bacteria, including Streptococcus pneumoniae and Haemophilus influenzae
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What is Bruton's agammaglobulinemia?
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X-linked recessive disorder characterized by a defective gene for tyrosine kinase resulting in low levels of B cells and immunoglobulins.
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What is IgA deficiency?
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The most common immune deficiency resulting in a lack of IgA; most patients, however, are asymptomatic
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What is common variable immunodeficiency?
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An acquired immunodeficiency characterized by normal levels of B cells, but low levels of IgG and other immunoglobulins
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