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131 Cards in this Set
- Front
- Back
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Major contribution of E. Metchnikoff?
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won Nobel prize for discovering human cells capable of "eating" other cells, aka phagocytosis.
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Major contribution of L. Pasteur?
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created vaccines for rabies and anthrax; proved germ theory of disease; invented pasteurization of milk/wine.
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Major contribution of E. Jenner?
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Created the smallpox vaccine from cowpox
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Major contribution of P. Ehrlich?
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Staining animal tissues; Won nobel prize for discovering cell-free components of blood (now called serum or anciently, humors)
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I/s
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Immune system
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I/r
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Immune response
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I/c
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Immunocompromised
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Ax
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antibiotic
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Ag
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Antigen
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Rx
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drug
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Dx
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Diagnosis
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CA
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Cancer
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Mo/
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Macrophage
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LN
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lymph node
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MHC
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Major Histocompatibility Complex
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C
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Complement
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CD
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Clusters of differentiation or cellular differentiation
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What are the 5 components of innate immunity?
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epithelial barriers, Phagocytes (neutrophils, monocyte, macrophages), Dendritic Cells (also Phagocyte), Complement, NK Cells
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Three APCs?
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- Dendritic Cells
- Macrophages - B Cells |
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Unique characteristics of Dendritic cells?
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- act as messenger between innate and adaptive I/s; can activate T helper cells - naive AND memory; most potent)
- express co-stimulatory B7 - often captures antigens of microbes that enter epithelia - lose ability to engulf cells as age but increases commun with T Cells |
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7 Properties of adaptive Immune response?
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Specificity
Diversity Memory Clonal Expansion Contraction and homeostasis Nonreactivity to Self |
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Describe Specificity as it relates to adaptive immunity
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Ensures that distinct antigens elicit specific responses
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Describe Diversity as it relates to adaptive immunity
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enables immune system to respond to a large variety of antigens
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Unique characteristics of macrophages?
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most phagocytosis done by macrophage is removal of host cellular debris
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Unique characteristics of B-Cells (as APCs)?
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B Cells recognize both protein and non-protein antigens
B Cells present to CD4+ T helper which activate antibody product FDCs present antigens to high-affinity B cells effector cells are plasma cells |
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7 Properties of adaptive Immune response?
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Specificity
Diversity Memory Clonal Expansion Contraction and homeostasis Nonreactivity to Self |
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Describe Specificity as it relates to adaptive immunity
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Ensures that distinct antigens elicit specific responses
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Describe Diversity as it relates to adaptive immunity
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enables immune system to respond to a large variety of antigens
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Describe Memory as it relates to adaptive immunity
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Leads to enhanced responses to repeated exposures to the same antigens
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Describe Clonal Expansion as it relates to adaptive immunity
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Increases number of antigen-specific lymphocytes to keep pace with microbes
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Describe Specialization as it relates to adaptive immunity
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generates responses that are optimal for defense against different types of microbes
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Describe Contraction and homeostasis as it relates to adaptive immunity
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allows immune system to respond to newly encountered antigens
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Describe Nonreactivity to self as it relates to adaptive immunity
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prevents injury to host during responses to foreign antigens
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How many days does it take for a primary response to an antigen to reach a peak?
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7-10 days
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How many days does it take for a secondary response to an antigen to reach a peak?
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approx 2 days
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Which is a bigger response, the primary or secondary response?
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Secondary
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B lymphocyte - describe antigen recognition and effector functions
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B lymphocytes recognize a microbe from soluble or cell surface antigens
differentiate into antibody secreting effector cells |
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Helper T lymphocyte - describe antigen recognition and effector functions
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recognize antigens on the surfaces of APCs and secrete cytokines, which stimulate macrophages, inflammation and activation of T and B lymphocytes; no cytotoxic or phagocytic activity
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What are CD4+ cells?
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Helper T cells
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Cytotoxic T lymphocyte - describe antigen recognition and effector functions
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recognize antigen on infected cell's MHC I and kills infected cell
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Natural Killer Cell - describe antigen recognition and effector functions
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recognize lack of MHC I on infected cell and kills infected cell
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What are the phases of the adaptive immune response?
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Antigen recognition
Lymphocyte activation Antigen elimination (effector phase) Contraction (homeostasis) Memory (applies to humoral and cell-mediated) |
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Define AIDS
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Acquired Immunodeficiency Syndrome, caused by Human Immunodeficiency Virus
-inactivates T Helper cells, which prevents adaptive I/s from turing on - begins in dendritic cells, which deliver virion - sufferers are more likely to die from opportunistic infections |
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Compare and contrast humoral vs. cell-mediated immunity
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humoral immunity is the result of HUMORAL: B lymphocytes, which produce antibodies that bind to invaders; result is infections can be blocked and extracellular microbes can be eliminated
CELL-MEDIATED: T lymphocytes either activate macrophages to destroy phagocytised microbes or kill infected cells figure 1-4 |
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define innate i/s
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aka non-specific immune system
recognizes and responds to pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. Innate immune systems provide immediate defense against infection, Thought to constitute an evolutionarily older defense strategy Recruiting immune cells to sites of infection with cytokines. Activation of the complement cascade. id and removal of foreign substances present in organs, tissues, the blood and lymph, by specialized white blood cells. Activation of the adaptive immune system through a process known as antigen presentation. Acting as a physical and chemical barrier to infectious agents |
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define adaptive i/s
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composed of highly specialized cells that eliminate or prevent pathogenic growth. activated by the innate i/s. has ability to recognize and remember specific pathogens (to generate immunity), and to mount stronger attacks each time the pathogen is encountered.
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What is an APC?
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Antigen Presenting Cell a cell that displays foreign antigen complexes with major histocompatibility complex (MHC) on their surfaces
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What is a lymph node?
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A lymph node is a small oval-shaped organ of the i/s, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. act as filters or traps for foreign particles. They are important in the proper functioning of the immune system. They are packed tightly with the white blood cells called lymphocytes and macrophages.
Lymph nodes also have clinical significance. They become inflamed or enlarged in various conditions, which may range from trivial, such as a throat infection, to life-threatening such as cancers. |
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Define antibody
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An antibody, also known as an immunoglobulin, is a large Y-shaped protein produced by B-cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen. Antibodies are produced by a type of white blood cell called a plasma cell. Antibodies can occur in two physical forms, a soluble form that is secreted from the cell, and a membrane-bound form that is attached to the surface of a B cell and is referred to as the B cell receptor
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Define active vs. passive immunity
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immunity may be induced in an individual by infection or vaccination (active) or conferred on an individual from actively immunized individual (passive); passive is not generally long-lived. Example of passive = immunity passed onto newborns from mother.
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Define clonal expansion
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when lymphocytes are activated by antigens they undergo proliferation generating thousands of progeny cells all with the same antigen specificity
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Define homeostasis
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The cycle of cell loss and replacement maintains a stable number of lymphocytes
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Define effector cells.
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The differentiation of naive lymphocytes into effector cells and memory cells is initiated by antigen recognition, thus ensuring that the immune response that develops is specific for the antigen. Effector cells are the differentiated progeny of naive cells that have the ability to produce molecules that function to eliminate antigens.
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Define plasma cells
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The effector cells in the B lymphocyte lineage are antibody-secreting cells, called plasma cells.
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Define memory cells.
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Memory cells, which also are generated from the progeny of antigen-stimulated lymphocytes, do survive for long periods of time in the absence of antigen. Therefore, the frequency of memory cells increases with age, presumably because of exposure to environmental microbes. In fact, memory cells make up less than 5% of peripheral blood T cells in a newborn, but 50% or more in an adult. Memory cells are functionally inactive-they do not perform effector functions unless stimulated by antigen. When memory cells encounter the same antigen that induced their development, the cells rapidly respond to give rise to secondary immune responses.
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Define affinity maturation
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the process by which B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response can elicit antibodies with several logfold greater affinity than in a primary response
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What is the function of macrophages?
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cells produced by the differentiation of monocytes in tissues.Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity. Their role is to phagocytose (engulf and then digest) cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens.
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What is the location of generation and maturation of macrophages?
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mononuclear phagocytes are produced in the bone marrow. After a few days they migrate to tissues as monocytes. They then migrate to tissues and become tissue macrophages. If they encounter an antigen they may differentiate into tissue-specific macrophages
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What is the function of macrophages?
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cells produced by the differentiation of monocytes in tissues.Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity. Their role is to phagocytose (engulf and then digest) cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens.
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What is the location of generation and maturation of macrophages?
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mononuclear phagocytes are produced in the bone marrow. After a few days they migrate to tissues as monocytes. They then migrate to tissues and become tissue macrophages. If they encounter an antigen they may differentiate into tissue-specific macrophages
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Is there an activation signal for macrophages?
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Discovery of PAMPs by the TLRs
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What is integrin?
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an adhesion molecule that "integrates" extrinsic signals into cytoskelatal alterations. Cause firm adhesion of as blood leukocytes migrate to an extravascular site of infection. part of "rolling" process
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what is selectin?
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a carbohydrate binding or lectin. Once a macrophage detects an infection it releases cytokines (IL-1 and TNF) to attract leukocytes. The cytokines stimulate the endothelium to produce selectin and integrin, which cause the leukocytes to "roll" along the endothelium until they reach an opening and head to site of infection.
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what is opsonization?
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process of coating microbes for efficient recognition by phagocytes.
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What cytokine do NK cells secrete to activate macrophages?
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IFN-gamma
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What do NK cells target?
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Cells that are not displaying MHC I flag. Stressed cells, infected with virus or intracellular bacteris, irreparably damaged or tumor cells. Also ADCC antibody-dependent cellular cytotoxicity.
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Contrast balance between CTL and NK cells
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viruses can block MHC I in infected cells, which allows virus to evade killing by CTL. But NK cells kill any cell not displaying MHC I
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What are the three pathways of activation for the complement system?
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Alternative (microbe - innate), Classical (antibody - adaptive/humoral), and Lectin (mannose-binding lectin - innate).
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What is C3?
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The central component of the complement system; a plasma protein; Activating it generates the complement cascade
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How is C3 activated?
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Enzymes generated by one of the activation pathways cleave C3, creating C3b, which becomes covalently attached to microbes and activates downstream complement proteins on the microbial surface.
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What does C3b do?
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coats microbes and promotes binding of the microbe to phagocytes (opsonized); also a chemoattractant for phagocytes and promotes leukocyte recruitment (inflammation)
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How does the innate I/s respond to both extracellular vs. intracellular microbes?
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Extracellular bacteria and fungi - phagocytes, complement proteins
Intracellular bacteria and viruses - phagocytes, dendritic cells, NK cells cytokines communicate b/w leukocytes |
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Define TCR
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T Cell receptor found on surface of T lymphocytes responsible for recognizing antigens on surface of MHC
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Define Ig
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Ig stands for immunoglobulin also known as an antibody; Y-shaped protein created by plasma cells (B) to identify and neutralize microbes and viruses
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Define TLR
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Toll Like Receptor; exist on/in leukocytes to recognize microbes (PAMPs); some exist on surface of cell; some are endosomal, into which microbes are digested. create cascade ending in gene trascription of cytokines
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Define PAMPs
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Pathogen Associated Molecular Patterns - microbial molecules that are the target of innate immunity
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Define neutrophils
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Leukocyte that is typically first to respond to infections, particularly bacterial and fungal. Phagocytic. Short life - a few hours after ingestion; aka PMN (polymorphonuclear leukocyte. Most plentiful WBC
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define inflammation
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the accumulation of leukocytes at sites of infection, with concomitant vascular dilation and increased leakage of fluid and proteins in the tissue
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Define ADCC
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Antibody-dependent cellular cytotoxicity. NK cells are principal mediators of ADCC. Cell coated in Ig's results in NK cell killing coated cell.
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Define septic shock
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caused by gram negative bacterial infection. Presence of gram- bact, which has LPS in cell wall, caused by very high levels of TNF and IL-1 produced in response to the bacteria.
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Define DIC
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Disseminated Intravascular Coagulation. response to high levels of LPS
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What is the principal source of TNF?
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macrophages, T cells
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What are the cellular targets and biological effects of TNF?
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Endothelial - activation, inflammation, coagulation
Neutrophils - activation Hypothalamus - fever Liver: synthesis of acute phase proteins (C5?) Muscle, fat - catabolism many cell types - apoptosis |
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What is the principal source of IL-1?
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macrophages, endothelial cells, some epithelial cells
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What are the cellular targets and biological effects of IL-1?
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Endothelial cells - activation (inflammation, coagulation)
Hypothalamus - fever Liver - synthesis of acute phase proteins T cells - TH17 differentiation |
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What is the principal source of IFN-gamma?
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NK cells, T lymphocytes
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What are the cellular targets and biological effects of IFN-gamma?
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activation of macrophages
stimulation of some antibody responses |
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What is the principal source of the cytokine, Type I IFN (alpha, beta)?
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alpha - macrophages, dendritic cells
beta - fibroblasts |
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What are the cellular targets and biological effects of type I IFN?
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All cells - anti-viral state, increased MHC I expression
NK cells - activation |
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Define chemokine
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produced by macrophages; type of cytokine that is chemoattractant of lymphocytes making them increase affinity for the integrins on the endothelium; regulate movement of lymphocytes from blood to tissues
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define interleukin
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a cytokine that works on leukocytes
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Define cytokine
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secreted proteins that function as mediators of immune and inflammatory reactions.
Innate I/r - macrophages and NK adaptive i/r - T lymps |
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Define C-reative protein
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a protein in the blood from inflammation; binds to phoshocholine on dead or dying cells, microbes to activate complement; also enhances phagocytosis
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Define the acute phase response.
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elevated circulating level of plasma proteins, such as CRP, in response to inflammation
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define adjuvant
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substance administered with antigens in vaccine to increase immune response; enhances T Cell activation by promoting accumulation of APCs at site of exposure and by enhancing expression of costimulators and cytokines by APCs
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What is the maturation process for Dendritic cells?
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Immature - sample blood, tissue for PAMPs via TLRs; once they contact an antigen, they activate and head to the LN; once in LN act as APC to activate Th, Tc and B cells. can activate naive and memory T cells
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What is the maturation process for NK cells?
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lymphocyte that plays role in viral and tumor management by killing cells not displaying MHC I flag; induce apoptosis
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What are 4 types of macrophages that can differentiate from a tissue macrophage?
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Microglial (CNS)
Kupffer cells (liver) Alveolar macrophages (lungs) Osteoclasts (bone) |
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what are the four stages of mononuclear phagocytes?
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Bone marrow stem cell
blood monocyte tissue macrophage differentiation or activation |
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Why don't NK cells kill healthy host cells?
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healthy host cells display MHC I molecules that are recognized by inhibitory receptors. When MHC I is downregulated inhibitory receptors are not engaged and the NK cell induced apoptosis
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Compare and contrast the three activation pathways of the complement system.
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classical - antibodies
alternative - microbe, always active at low level; C3 reacts to microbe lectin - activated by mannose-binding lectin, uses opsonin |
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What are the early steps of the complement activation?
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C3 proteins cleave to C3b, which triggers inflamation
C3b is deposited on the microbe for opsonization and phagocytosis |
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WHat are the late steps of the complement system?
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C5 protein is generated and cleaves to C5b, which binds to C9 and forms the membrane attack complex, which results in lysis of the microbe.
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How can a cytokine storm be prevented/stopped/
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hinder CD4 binding
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What part of the I/s will attack a virus that is freely circulating in the blood?
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Antibody
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What part of the I/s will attack a virus that has infected host cells?
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Cytotoxic T Cells
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Which cell, B or T, is capable of recognizing more types of molecules?
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B
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Define MHC restriction
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characteristic of T lymphocytes that they recognize a foreign peptide antigen only when it is bound to a particular allelic form of MHC. T Cell recognizes 1) antigen 2) source of information
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Which APC can present to a naive T lymphocyte?
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Dendritic cells
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True? Activated dendritic cells lose their adhesiveness for the epithelia and begin to express a surface receptor for attracting chemokines produced in T cell zones of LNs.
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True
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Define cross-presentation
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cell infected with virus is captured by APC, antigen is broken down and presented on MHC I to CD8+ (CTL) with co-stimulator, naive CTL primed to activate and clonally expand.
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What are Human MHC proteins called?
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HLA Human Leukocyte Antigens; highly polymorphic genes
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What is a beta-2 microglobulin and what happens if it is defective?
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protein that is noncovalently bonded to alpha chain of MHC I; if defective MHC chain falls apart and cannot present
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What type of antigens can CD4 and CD8 T cells respond to?
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only peptides
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where do MHC molecules acquire peptides for display?
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MHC I - cytosol
MHC II - intracellular vesicles |
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Define CLIP
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Class II Invariant chain Protein; not an antigen protein; binds to peptide binding cleft of the MHC II; when MHC II has a CLIP it is "occupied." Binds in ER
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Define DM
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a protein that removes CLIP from the MHC II molecule so it can accept peptides
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define immunodominant epitope
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portion of an antigen that is recognized by the marjority of lymphocytes specific for that antigen
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Define TAP
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Transporter Associatd with Antigen Processing. located in ER membrane, binds peptides from the cytoplasm and actively pumps them across the ER membrane into interior; associates with MHC I
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How does the composition of the MHC I and II differ?
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II - polymorphic alpha and beta chains
I - polymorphic alpha chain and beta2-microglobulin |
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what are the responsive cells to MHC I and II?
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II - CD4+ T cells (helper)
I - CD8+ T cells (cytotoxic) |
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which enzymes are responsible for peptide generation?
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II - endosomal and lysosomal proteases
I - cytosolic proteasome |
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Where is the peptide loaded onto MHC II and I?
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II - specialized vesicular compartment
I - ER |
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What molecules are involved in the transport of peptides and loading of MHC II and I?
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II - CLIP (Class II Invariant chain Protein) and DM
I - TAP (transporter associated antigen processing) |
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Define proteasome
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protealytic organelle through which unfolded proteins are degraded for display on MHC I
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define antigen processing
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the intracellular conversion of protein antigens into peptides and loading these peptides onto MHC molecules
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Which MHC molecule can be loaded extracellularly?
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Neither. Only inside cells for both. Extracellular microbes are captured by APCs and presented after processing on MHC II
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What do CD4 T cells (helper) do after they recognize an antigen?
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alert the B cells to make antibodies and help phagocyte destroy the ingested microbe (not effective against virus bc antibodies only effective when extracellular)
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What combats an intracellular virus?
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CTL (or NK if no MHC I); before intra combated by antibodies and phagocytes.
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Define FDC
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Follicular Dendritic Cell, population of cells in LNs and spleen whose function it is to display antigens (coated with antibodies or complement by products) to activated (high affinity) B Cells.
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define MHC haplotype
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MHC alleles present on each chromosome
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