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130 Cards in this Set
- Front
- Back
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What does the latin term "immunis" mean?
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Exempt
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What four characteristic attributes does adaptive immunity display?
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- Antigen specificity
- Diversity - Immunologic memory - Self/non-self recognition |
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Antigen specificity
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Antibodies can distinguish between two protein molecules that differ in only a single amino acid
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Diversity
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The immune system can recognize billions of unique structures on foreign antigens
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Self/non-self recognition:
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The immune system normally responds only to foreign antigens
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Immunologic memory:
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A second encounter with the same antigen induces a heightened state of immune reactivity
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What is adaptive immunity?
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Host defenses that are mediated by B and T cells following exposure to antigen and exhibit specificty, diversity, memory, self/non-self recognition
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How do plants respond to infection?
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By producing antimicrobial proteins and peptides, as well as small non-peptide organic molecules that have antibiotic activity
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What are the two major theories to account for such high specificity in humeral immunity?
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- The instructional theory - antigen served as template around which antibody would fold
- The selective theory - antigen selects appropriate receptor, they fit similar to a lock and key |
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Where do T cells mature?
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In the thymus gland
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MHC
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Major histo-compatibility complex
Antigens that are bound to cell-membrane proteins |
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How does adaptive immunity compensate for its slower onset?
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By its ability to recognize a much wider repertoire of foreign substances, and also by its ability to improve during a response, whereas innate immunity remains constant
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Compare the response time, specificity, and response to repeat infection of innate and adaptive immune systems:
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Innate:
- Response time: hours - Specificity: limited and fixed - Response to repeat infection: identical to primary response Adaptive: - Response time: days - Specificity: highly diverse, improves during course of immune response - Response to repeat infection: much more rapid than primary response |
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Altered self-cells
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Cells that display foreign antigen complexed with a class I MHC molecule. These are targets of CTL's.
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Describe CTL:
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In contrast to TC cell, it does not secrete cytokines but instead exhibits cell-killing or cytotoxic activity
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How are T helper and T cytotoxic distinguished from one another?
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By the presence of either CD4 or CD8 membrane glycoproteins on their surfaces
Cells with CD4 function as TH cells and cells with CD8 function as TC cells |
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How do T cells kill their targets?
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By physical contact. They cannot kill at a distance
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How do B cells kill their targets?
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From a distance. They secrete antibodies that can bind and kill things from a distance
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Name the two types of T cells and describe them
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- CD4 T cells (T helper cells) - regulators of the immune system
- CD8 cells (cytotoxic T cells) - kill infected cells through contact |
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How is antigen recognized differently by B and T lymphocytes?
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- B cells can recognize an epitope alone, T cells can recognize it only when it is associated with an MHC molecule on the surface
- B cells recognize an enormous variety of epitopes: on surfaces of bacteria, viruses, soluble proteins, glycoproteins, lipopolysaccharides, etc. T cells recognize protein epitopes displayed together w/ MHC molecules of self-cells |
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How do Th cells direct the activity of other cells?
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Through the combination of cytokines secreted
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Common manifestations of immune dysfunction:
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- Allergy and asthma
- Graft rejection and graft-versus-host disease - Autoimmune disease - Immunodeficiency |
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What are the two main groups of immune system organs?
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1. Primary lymphoid organs
2. Secondary lymphoid organs |
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What connects lymphatic organs, uniting them into a functional whole?
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Blood vessels and lymphatic systems
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What do primary lymphoid organs do?
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They provide appropriate microenvironments for the development and maturation of lymphocytes
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What do secondary lymphoid organs do?
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They trap antigen from defined tissues or vascular spaces and are sites where mature lymphocytes can interact effectively with antigen
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Multipotent stem cell:
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In hematopoiesis, it differentiates along one of two pathways, giving rise to either a common lymphoid progenitor cell or a common myeloid progenitor cell
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Common lymphoid progenitor (CLP) cells:
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Give rise to B, T, and NK (natural killer) cells and some dendritic cells
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Common myeloid progenitor cells:
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Give rise to neutrophils, eosinophils, basophils, monocytes, mast cells, dendritic cells, platelets, as well as RBC's
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How do we differentiate between the similar T/B cells or CD4/CD8 cells?
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By the proteins on their surface. There are straight-forward assays to detect all surface proteins on these cells. These markers also give us clues as to what function the cells may serve in the body.
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Stromal cells:
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- In bone marrow, hematopoietic cells grow on these. They include fat cells, endothelial cells, fibroblasts, and macrophages
- They influence the differentiation of hematopoietic stem cells |
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Erythropoietin (EPO)
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A cytokine produced in the kidney
It induces the terminal development of erythrocytes and regulates the production of RBC's |
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How is hematopoiesis regulated or controlled?
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1. Control by presence of specific cytokines
2. Regulation of cytokine receptor expression 3. Control by regulated cell death |
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Apoptosis:
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Distinctive morphologic changes often exhibited by cells undergoing programmed cell death
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Where are B lymphocytes made?
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In the spleen and bone marrow
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Describe B lymphocytes:
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- display antibody on their cell surface
- capable of binding soluble antigen - express a variety of CD markers on cell surface (so we can identify the cell) |
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Describe T lymphocytes:
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- Mature in the thymus
- all express the T-cell receptor, a complex of polypeptides that includes CD3 - Most mature T-cells express CD28 and CD4 or CD8 |
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Describe natural killer cells:
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- Constitute 5-10% of lymphocytes in blood
- Sometimes employs NK cell receptors to distinguish abnormalities |
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Monocytes vs. Macrophages:
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- monocytes circulate through blood stream and differentiate into specific tissue microphages when migrating into the tissues
- macrophages are dispersed throughout the body, location depending on specific type of macrophage |
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Three types of granulocytes and how are they classified:
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- Neutrophils
- Eosinophils - Basophils Classified on the basis of cellular morphology and cytoplasmic staining characteristics |
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Which cells are the first to arrive at the sight of inflammation?
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Neutrophils
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Do T cells originate from the thymus?
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NO, but they do develop there
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Organs of the immune system:
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- Thymus/Bone marrow: where maturation of lymphocytes takes place
- Lymph nodes/spleen/MALT/GALT: secondary lymphoid organs which trap antigen and provide sites for mature lymphocytes to interact with that antigen |
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Four types of dendritic cells:
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- Langerhans cells
- Interstitial dendritic cells - Myeloid cells - Lymphoid dendritic cells |
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How are basophils similar to basophils?
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They have large numbers of cytoplasmic granules that contain histamine and other pharmacologically active substances (which play a major role in allergic responses)
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How do basophils function?
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By releasing pharmacologically active substances from their cytoplasmic granules
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What do neutrophils contain within the granules?
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- Lytic enzymes
- Bactericidal substances |
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Things organisms growing inside of us must overcome:
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- Skin
- Mucous membranes of the tracts - Ciliary escalator in respiratory tract |
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What is the role of phagocytes in an immune response?
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Upon activation by microbial surfaces, they produce cytokines and chemokines that amplify immune responses (inflammation)
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From what do all cells of the immune system derive?
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- From a common hematopoietic stem cell (HSC) in the bone marrow
- They are then differentiated into the two different lineages and specific cells. This differentiation is controlled by hematopoietins |
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What are the two main lineages of immune cells?
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- Myeloid (inflammatory cells)
- Lymphoid (lymphocytes) |
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Describe neutrophils
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- Granulocytes
- Most abundant leukocyte - Short-lived (2-3 days) - Major function = destroy things as they phagocytose - Cells of acute inflammation - release inflam cytokines |
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Steps of phagocytosis:
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1. Bacteria attaches to membrane envaginations (pseudopodia)
2. Bacteria is ingested, forming phagosome 3. Phagosome fuses with lysosome 4. Digestion products are released form cell |
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Describe macrophages:
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- Mononuclear cells derived from blood monocytes
- Found in various tissues; important in tissue maintenance and repair - Relatively long-lived - Are involved in both destruction and repair - Cells of chronic inflammation - release cytokines - Activated by T cells and antibodies |
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Types of phagocytic cells:
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- Neutrophils
- Macrophages |
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Primary lymphoid organs:
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1. Thymus
2. Bone marrow |
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Secondary lymphoid organs:
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1. Lymph nodes
2. Spleen 3. MALT (tonsils, adenoids) 4. GALT (Peyer's patches) |
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How do innate immune mechanisms function?
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They focus on highly conserved features of microbes that are very difficult for the organisms to change
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How do defensins kill microbes?
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They bind to acidic phospholipids then enter their membranes and generate pores
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Reasons MHC is important:
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- It is important in discrimination between self and non-self
- Your susceptibility to many diseases is associated with what MHC genes you express |
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Class I MHC genes:
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Code for glycoproteins expressed on nearly all cells in the body. They are important in presenting peptide antigens to Tc (CD8) cells
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Class II MHC genes:
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Code for glycoproteins expressed primarily on antigen presenting cells. They present this antigen to Th (CD4) cells
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Describe ubiquitin:
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It can attach to proteins and label them for destruction.
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What is TAP?
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Transporter associated with antigen processing.
If this molecule is missing, the peptide is not loaded correctly into the MHC I molecule |
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CD3 Complex
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A signaling complex with which T cell receptors are always associated
The role is to transmit a signal to the nucleus after TCR has detected antigen |
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What is ITAM?
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Sites important in signal transduction. It's essential for the signaling capacity of TCR
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Allogenic recognition:
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Genetically different individuals of the same species
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What do interferons do?
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Interfere by increasing the ability of uninfected host cells to resist new infection by virus
Activate immune cells, such as NK cells and macrophages Increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes |
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How do virus-infected cells warn their neighbors of viral presence?
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- By releasing interferon
- In response to the interferon, the cells produce large amounts of protein kinase R. |
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How does a cell recognize that it is infected with a virus?
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Toll Like REceptor 3 (TLR3)
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What determines the type of TH cell an antigen primed CD4 T cell will become?
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The cytokine environment
Once a TH1 or TH2 response has started, it is hard to change |
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What happens when you have uncontrolled cytokine production?
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The massive numbers of T cells would result in mortality
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What happens when there is an excessive uncoordinated release of cytokines?
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The body is overloaded which results in rash, fever, shock, multi-organ failure, coma, and death
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What do B cells do?
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They make antibody
There are different classes but all start out as IgM |
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What is Ig (as in IgM or IgG)?
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Immunoglobulin
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Describe B2 B cells:
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- thymus-dependent
- considered "normal" |
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Positive selection
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- Selecting thymocytes with receptors capable of binding to self-MHC
- Immature thymocytes interact w/ epithelial cells - Successful interaction = protective signal and no death - To survive positive selection, the young thermocyte must have a TCR that recognizes self-MHC |
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Negative selection:
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- Kills cells that may be self-reactive
- Cells that bind to self too tightly are eliminated |
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What happens when a T cell binds antigen?
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The cell becomes activated and starts to proliferate
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What do T cells need to really get turned on?
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Costimulation: two independent stimuli
- TCR/CD3 signal - CD28 interacting w/ B7 signal |
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Superantigens
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Viral or bacterial proteins that bind simultaneously to the V-beta domain of a T cell receptor and to the alpha chain of class II MHC
This results in the Th cell becoming activated |
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Effector cells
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Carry out specialized functions such as providing cytokines for proper B cell function
They are short-lived: survive from days to weeks |
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Memory T cells
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- Long-lived
- In G0 phase of cell cycle (doing nothing) |
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Regulatory T cells
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- CD4 T cells that work to down regulate (suppress) immune function
- Loss of these leads to autoimmune disease |
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In what two ways can a CTL kill targets?
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1. Perforin
2. Fas |
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What is perforin?
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- It's a lot like complement
- Held in granules in the CTL - Can be pushed out to the target cell, forming pores in the target cell, which causes it to undergo apoptosis |
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How do CD4 cells affect immune response?
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They tell other cells what to do
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What do TH2 cells do?
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Promote antibody responses
Very important in some parasite infections |
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Antigens:
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Substances that can be recognized by the immunoglobulin receptor of B cells or by the T-cell receptor when complexed with MHC
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Difference b/n antigen and immunogen:
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- Immunogen induces humoral/cell mediated immune response
- Antigen is recognized but doesn't necessarily induce a response |
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What are the most potent immunogens (in order of potency):
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1. Proteins
2. Polysaccharides |
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By what is immunogenicity determined?
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By the four properties of the immunogen:
1. Foreignness 2. Molecular size 3. Chemical composition 4. Complexity |
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Five common routes of administration:
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1. Intravenous
2. Intradermal 3. Subcutaneous 4. Intramuscular 5. Intraperitoneal |
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What are adjuvants?
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Substances that when mixed with an antigen and injected with it, enhance the immunogenicity of that antigen.
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How do adjuvants work?
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- Antigen persistence is prolonged
- Co-stimulatory signals are enhanced - Local inflammation is increased - The nonspecific proliferation of lymphocytes is stimulated |
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What is an epitope?
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An immunologically active region of an immunogen that bind to antibody or T cell receptors
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What conditions must exist for an epitope to bind?
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1. Epitope cannot be larger than the size of the antibody's binding site
2. Epitope must be accessible |
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Haptens:
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Small organic molecules that are antigenic but not immunogenic
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Immunogenic hapten-carrier conjugate:
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Yielded by a chemical coupling of a hapten to a large protein, called a carrier
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What do animals immunized with an immunogenic hapten-carrier conjugate produce?
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Antibodies specific for...
- The hapten determinant - Unaltered epitopes on the carrier protein - New epitopes formed by combined parts of both the hapten and carrier |
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What four peptide make up the common antibody molecule structure?
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- two identical light (L) chains
- two identical heavy (H) chains |
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How are the light and heavy peptide chains bound together?
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By a disulfide bond and noncovalent interactions
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What determines the antibody class?
(Class = IgG, IgM, IgA, IgD, or IgE) |
The heavy chains of the antibody molecule
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Describe the IgG antibody:
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- Most abundant class in serum (80% of serum immunoglobulin
- 4 human subclasses, distinguished by differences in gamma-chain sequence - IgG1, IgG3, and IgG4 readily cross the placenta and protect the fetus - IgG3 = most effective complement activator (of the IgG antibodies) - IgG1 and IgG3 bind with high affinity to Fc receptors on phagocytic cells |
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Describe the IgM antibody:
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- First immunoglobulin class produced in primary response to antigen
- First immunoglobulin to be synthesized by neonate - Higher valency than other isotypes - Less required to neutralize viral infectivity - It's the BEST at activating complement |
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Describe the IgA antibody:
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- Predominant immunoglobulin class in external secretions such as breast milk, saliva, tears, mucus, etc.
- Daily production of secretory IgA > any other immunoglobulin class - IgA-secreting plasma cells are concentrated along mucous surfaces - IgA secreted in breast milk is vital to the health of the infant |
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Describe the IgE antibody:
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- Responsible for symptoms of hay fever, asthma, hives, & anaphylactic shock
- Cross-linkage of IgE molecules by antigen (allergen) induces degranulation of basophils |
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Degranulation:
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Granules are translocated to the plasma membrane and their contents are released into the extracellular environment
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Describe the IgD antibody:
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- One of the major membrane-bound immunoglobulins expressed by B cells
- No biological effector function has been identified for IgD |
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Which classes of antibody can activate the complement system?
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IgM and IgG
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Precipitins:
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Antibodies that aggregate soluble antigens
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Why must an antibody be bivalent?
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Because a precipitate will not form with monovalent Fab fragments
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Hemagglutination
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A technique to test for blood types in which antigen-coated RBC's are prepared by mixing a soluble antigen with RBC's that have been treated to promote antigen adsorption. Serum-containing antibody is diluted into microtiter plate wells and antigen-coated RBC's are then added to each well. Agglutination is then assessed.
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Radioimmunoassay (RIA):
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- One of the most sensitive techniques for detecting antigen or antibody
- Involves competitive binding of radiolabeled and unlabeled antigen - Labeled antigen is mixed w/ antibody at conc that saturates antigen-binding sites |
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Compare ELISA (or EIA) to RIA:
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Similar in principle, but depends on an enzyme rather than a radioactive label
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Western Blotting
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- A technique for the identification of a specific protein in a complex mixture of proteins
- Protein mixture is eletrophoretically separated - Protein bands are transferred to a nylon membrane by electrophoresis - Individual protein bands are identified by flooding the nitrocellulose membrane w/ antibody specific for protein of interest |
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Direct vs. indirect fluorescent-antibody staining:
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- Direct: the primary antibody is directly conjugated with fluorescin
- Indirect: the primary antibody is unlabeled and is detected w/ an additional fluorochrome-labeled reagent |
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Flow cytometer:
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- Uses a laser beam and light detector to count single intact cells in suspension
- Every time a cell passes the laser beam, light is deflected and the interruption is recorded - Cells w/ fluorescently tagged antibody on their surface are excited by the laser and emit light that is recorded by a second system - Relative size and shape are determined, which give clues to the cell type |
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Two photon microscopy:
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Allows visualizing individual living cells moving and interacting in vivo. Samples can also be digitally reconstructed into 3-D images
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Atopy
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The genetic tendency to develop the classic allergic diseases. It involves the capacity to produce IgE in response to common environmental proteins. In these individuals, non-parasitic antigens stimulate an IgE response.
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IgE-Mediated (type 1) hypersensitivity:
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- Allergen refers specifically to nonparasitic antigens capable of stimulating type 1 hypersensitive responses
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Leukotrienes and prostaglandins:
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- Secondary mediators formed after degranulation
- Effects are more pronounced and last longer - Cause many of the same effects as histamine: bronchoconstriction and mucus production |
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How does epinephrine work?
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It counteracts the effects of mediators such as histamine and leukotrienes by relaxing the smooth muscles and reducing vascular permeability. It blocks
further degranulation of mast cells. |
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Describe allergic asthma:
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Occurs when mast cells degranulate in the lower respiratory tract
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What occurs during a food-allergy reaction?
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- Allergen crosslinking of IgE on mast cells along GI tract cause contractions resulting in vomiting and diarrhea
- Mast cell degranulation along the gut can increase permeability of mucous membranes and allows allergen to enter bloodstream |
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What regulates type 1 responses?
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- Genetic factors
- Dose - Adjuvant choice (influences IgE vs IgG responses) |
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How can type 1 hypersensitivity be controlled?
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- Avoid contact w/ allergens
- Immunotherapy (repeated exposure to allergen by subcutaneous injections - causes a shift from IgE to IgG response - Blocking antibody - Anti IgE antibodies |
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Two examples of type II hypersensitivity:
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- Transfusion reaction (massive hemolysis of transfused RBC's)
- Erythroblastosis fetalis |
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Type III hypersensitivity:
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- Generalized reactions when large amounts of antigen enter bloodstream
- Serum sickness - Lupus |
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Type IV Hypersensitivity:
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- Cell-mediated, NOT antigen-mediated
- Reactions to poison ivy |
