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innate immunity
- natural immunity
- treats all foreign objects the same
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what is amensalism
one species restricts growth of the other
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what characteristics of the skin aid in innate immunity?
- dry, salty, low pH (5-6)
- continuous shedding
- covered with normal micorbiota
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what characteristics of the mucous membranes aid in innate immunity?
- protective layer of mucus traps microbes to be swept out by cilia
- bathed in antimicrobial peptides
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what characteristics of the respiratory system aid in innate immunity?
- expels microbes by coughing or sneezing
- salvation washes microbes to stomach
- alveolar macrophages
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what characteristics of the GI and GU tracts aid in innate immunity?
- low pH
- normal flora restrict the growth of pathogens
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what are the 4 chemical barriers that aid in innate immunity
- lysozyme
- gastric juices
- lactoperoxidase
- lactoferrin
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lysozyme
hydrolyzes bonds between sugars in peptidoglycan leading to bacterial lysis
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gastric juices
mix of HCL, proteolytic enzymes and mucus that has a pH of 1-3
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lactoperoxidase
produces superoxide radicals that damage microbes
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lactoferrin
sequesters iron limiting microbe replication
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how do antimicrobial peptides work?
kill microbes by interacting with their membranes
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what are the 2 major types of antimicrobial peptides?
cationic and bacteriocins
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what do most cationic peptides do to kill microbes?
most form pores of transient gaps, thereby altering membrane permeability often leading to lysis
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what are the 3 generic classes of cationic peptides?
- cathelicidin - linear alpha helical peptides
- defensins - rich in arginine and cysteine that stimulate mast cell degranulation
- histatin - larger peptides that have regular structural repeats and has anti fungal activity
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what are bacteriocins?
antimicorbial peptides that are produced by bacteria to kill other species of bacteria
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where to NK cells originate?
in the bone marrow
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what do NK cells do?
kill malignant cells and cells infected with pathogens by releasing cytotoxic granules resulting in direct lysis of the target cell
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how are NK cells activity governed?
by the integration of activating and inhibitory signals from cell surface receptors
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what is the mechanism of target cell recognition and lysis?
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1. ADCC - antibody -dependent cell mediated cytotoxicity relies on Fc receptors
- 2. loss of MHC class 1 on the target cell
- 3. presence of activating ligand
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granulocytes
circulate int he blood and migrate to sites of tissue damage because they contain substances that kill microbes and enhance inflammation
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what are the three types of granulocytes?
- neutrophils
- eosinophils
- basophils
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neutrophils
- most abundant WBC
- rapidly responds to infection
- highly phagocytic
- kill ingested microbes with lytic enzymes and reactive species
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eosinophils
- migrate to musous membranes
- control helminth infections
- role in allergy and hypersensitivities
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basophils
- release vasoactive mediators (histamine, prostaglandins,serotonin, leukotrienes
- role in allergic responses
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monocytes
circulate in the blood, then migrate to tissues where they mature into macrophages or dendritic cells
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macrophages
- reside in specific tissues
- highly phagocytic
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dendritic cells (DCs)
have long dendrites that capture foreign particles to phagocytose. The antigens are processed to display on their surface for T-cells (antigen presentation)
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phagocytosis
engulfs the microbe where it is digested by lysosomal enzymes
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what are the functions of the complement system?
- defend against infection
- provide chemotactic signals that recruit phagocytes to their site of activation
- puncture microbial cell membranes causing cell lysis
- complements the antibacterial activity of an antibody
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describe the process of opsonization
microbes are tagged with serum proteins (opsonins) that lead to their recognition and ingestion by phagocytic cells
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what are some common opsonins?
- complement proteins
- antibodies
- mannose binding protein
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what are the 3 pathways through which complement proteins are formed?
- classical pathway--> C3a + C5a
- MB-lectin pathway --> C3b
- alternative pathway --> terminal complement components C5b, C6,C7,C8,C9
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c3 convertase
cleaves C3 to make complement proteins
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where is activation confined to in complement proteins?
confined to the pathogen surface
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MAC (membrane attack complex)
a tubular structure that forms a transmembrane pore in the target cells membrane so that H2O and Na+ can enter leading to lysis
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what are cytokines?
- soluble proteins that are released by one cell and act on the same cell or on other cells
- they induce a signaling cascade
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chemokines
they are cytokines that function as chemoattractants to recruit immune cells to sites of infection
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type 1 interferons
- primarily involved in antiviral immunity
- prevents viral replication and assembly
- characterized by their autocrine and paracrine activity
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steps for IFN -alpha/beta immunity
- 1. virus infects cell
- 2. activates IFN gene
- 3. infected cell synthesizes IFN and releases it to neighboring cells
- 4. activation of antiviral proteins in uninfected cells before virus invades a new cell
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type 2 interferons
involved in immunity against many types of infections
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Endogenous pyrogens
cytokines that elicit fever in the host
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what are the steps for endogenous pyrogen induced fever?
- 1.a macrophage ingests a gram-negative bacterium
- 2. the bacterium is degraded releasing endotoxins to induce macrophage to produce interleukin -1 (IL - 1)
- 3. IL-1 is released into bloodstream to travel to hypothalamus
- 4. IL-1 induces hypothalamus to produce prostaglandins which reset the body's thermostat to a higher temperature producing fever
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pathogen associated molecular patterns
conserved microbial molecular structures that are recognized by the host's immune response called pattern recognition receptors
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what are some types of PRRs (pattern recognition receptors)
- toll like receptors
- NOD like receptors
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what is the effect of endotoxin on immunity?
- cause fever
- acitvate clotting cascade
- complement activation
- fever
- increased heart rate
- increased respiration
- induces the release of pyrogens
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what is the effects of high levels of endotoxin on the body?
- septic shock
- systemic blood clots
- multi organ failure and death
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inflammation
the immune response to tissue injury due to infection of autoimmune reaction
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what are the tissue responses to inflammation?
- vasodilation - capillary diameter increases
- vascular permeability increases
- movement of leukocytes into tissues attracted by chemokines
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functions of inflammation
- increased blood flow
- increased temperature
- chemotactic factors
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acute inflammation
release of inflammatory mediators from injured tissue cells initiates a cascade of events resulting in the signs of inflammation
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chronic inflammation
- slow process (weeks)
- usually causes permanent tissue damage
- involves formation of new connective tissue
- dense infiltration of lymphocytes and macrophages at site of inflammation
- formation on new connective tissue
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granuloma
- formed when phagocytes cannot destroy pathogen
- walled off area
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