Term
| What do the extracellular "antimicrobial" peptides/proteins target? What are their functions? |
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Definition
Targets: extracellular bacteria (about 1 um), viruses, fungi, protozoa
function:
1. cytotoxic
2. promote delivery to killer cells (opsonic)
3. block uptake of bacteria and/or viruses that require host cells for intracellular multiplication |
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Term
| What do professional phagocytes target? How do they function? |
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Definition
Targets: extracellular bacteria, viruses, and certain fungi
function:
1. actin-dependent ingestion of particles or cells that are from 0.5-5 um in diameters
2. internalized into phagocytic vesicle where microbial killing and/or digestion takes place |
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Term
| What do secretory cytotoxic cells target? WHat is their function? |
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Definition
targets: certain extraceullar fungi and protozoa greater than 0.5 um
function:
1. binds the extracellular microbe and the specific cell-cell contact induces vetorial release of cytotoxins from the secretory cytotoxic cell |
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Term
| what results in an activated phagocyte? |
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Definition
| infected host cells in a phagocytic vesicle with bacteria, fungi |
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Term
| what results in programmed cell death or apoptosis? |
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Definition
| infected host cells in the host cytosol containing viruses and certain bacteria |
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Term
| What are the main targets of innate immune defenses? (2) |
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Definition
1. non-self (intra/extracellular microbes)
2. altered self (infected host, transformed host, apoptotic host) |
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Term
| How is the necessary breadth of the innate immune recognition achieved? |
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Definition
Diverse innate immune recognition molecules have diverse recognition properties, diverse subcellular localization, and linkage to different immune effector functions
*Innate immune recognition molecules are:
1. found in extracellular fluid and are directly cytotoxic and opsonic
2. found in the plasma membrane as receptor binding sites and promoting uptake by professional phagocytes allowing adherence by secretory cytotoxic cells and immune signalling
3. found in endosomes for immune signaling of virus infected cells
4. found in the cytosol for immune signaling and the induction of apoptosis |
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Term
| How is necessary selectivity achieved in host defense? |
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Definition
1. endogenous antibiotics - intrinsically selective antibacterial peptides/proteins
2. guided weapons that are non-specific and broad spectrum - mobilization/activation is physically coupled to the identification of a target |
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Term
| how do guided weapons lead to immunopathology? |
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Definition
| inappropriate recognition may lead to inappropriate targeting |
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Term
| What are the three major classes of innate immune cytotoxic effectors? |
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Definition
1. soluble cytotoxic and digestive peptides or proteins
2. reactive oxygen and nitorgen intermediates/species (ROS > RNI)
3. inducers of apopotosis |
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Term
| Describe the secretion of cytotoxic and digestive proteins and peptides. where are they stored? |
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Definition
secreted:
- constitutively or induced from epithelia, liver, etc
- secreted from stored intracellular compartments by secretory cytotoxic cells (NK cells, eosinophils) at points of attachment of cytotoxic cell to immune target
stored:
- intracellular compartments like granules, lysosomes of professional phagocytes and act during phagoyctosis by fusion with the vacuole |
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Term
| Describe the role of ROS and RNI at low concentrations, high concentrations |
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Definition
low - cell signaling
high - cytotoxic |
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Term
| What are the 4 main roles of professional phagocytes? |
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Definition
1. clearance/uptake of invading cells, apoptotic cells, cell debris
2. cytotoxicity (killing, digestion)
3. signalling to amplify mobilization of immune effectors
4. Ag uptake, processing and presentation to induce the activation leading to proliferation, differentiation of AG specific T cells |
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Term
| What is the order of professional phagocytes to the scene of an infection? |
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Definition
1. neutrophil(PMN)
2. monocyte(blood)
3. macrophage(tissue)
4. dendritic cells (Langerhans_ |
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Term
Blood monocytes
- form ____
- constitutive, inducible or both
- functional properties vary by site |
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Definition
1. tissue macrophages
2. both |
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Term
tissue macrophages
- found where? |
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Definition
| connective tissue, liver, kidneys, CNS< secondary lymphoid sites (mucosa associated lymphoid), GI tissue, respiratory tissue, regional lymph nodes, spleen |
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Term
| What are the main three functions of resident macrophages? |
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Definition
1. 1st line of phagocytic defense against invading cells, clears apopototic cells and debris
2. major signalling cell for the acute inflammatory response
3. within the secondary lymphoid tissue - ag presentation to T cells and phagocytic defense in the regional lymph nodes and spleen |
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Term
| What is the most abundant leukocyte in the blood? |
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Definition
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Term
| when are neutrophils found in tissue? |
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Definition
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Term
| What are 2 things found on the surfaces of neutrophils? |
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Definition
1. chemoattractant receptors (IL-8, fMLP)
2. adherence proteins (LFA-1 interacting with endothelium) |
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Term
| what is the first cell recruited to the site of infection or injury during acute inflammation in response to invading bacteria, fungi? |
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Definition
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Term
| what is the major role of neutrophils? |
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Definition
| host defense against extracellular bacteria and some fungi |
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Term
| How long do neutrophils last? |
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Definition
hours to days and then apopototic and macrophages clean them up
- the inflammation leads to increased proliferation/differentiation of myeloid precursors in the bone marrow and increases the release of mature neutrophils from bone marrow
- dead cells are prominent in pus |
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Term
| WHere are dendritic cells found? |
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Definition
| major AG presenting cell (APC) in the connective tissue and skin |
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Term
| What are the functions of immature dendritic cells in the tissue? |
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Definition
highly phagocytic and endocytic
- uptake live microbes, remnants and activate PRR |
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Term
| what is the role of mature/activated Dendritic cells |
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Definition
migrate to draining lymph node and process and present AG
- express co-stimulatory molecules to activate T cells |
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Term
| What two cell types activate macrophages? |
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Definition
1. NK cells (innate immunity)
2. Th1 cells (adaptive) |
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Term
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Definition
from activated macrophages
- induce mobilization/activation of NK cells (innate) and induce differentiation and activation of TH1 cells (adaptive) |
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Term
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Definition
from activated NK and Th1 cells
- activate macrophage cytotoxicity
*** most important in macrophage activation |
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Term
Professional phagocytes:
1. how large of a particle can they internalize?
2. which cells take in viruses about 0.2 um or less by endocytosis?
What are the three types or receptors found on phagocytes? |
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Definition
1. greater than 0.5 um diameter
- neutrophils up to 2-3 um
- macrophages digest up to apoptotic hosts
2. ALL cells
3. PRR's, receptors for specific actiated components of complement, receptors for Ag-AB complexes |
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Term
| What are two common properties of phagoccytes that are immune effector cytotoxic cells |
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Definition
1. express components of respiratory burts (NADPH) oxidase
2. express antimicrobial peptides. proteins, enzymes
- both of these are latent in resting cells |
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Term
| Describe a latent resting cells involved in phagocyte cytotoxicity? |
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Definition
1. components of oxidase are unassembled and inactive (found in membranes and cytosol)
2. antimicrobial peptides/proteins.enzymes are confined to granules or lysosomes and are inactive |
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Term
| describe an activated phagocytic cell? |
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Definition
1. assembled and activated oxidase
2. degranulation to release granule contents |
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Term
| When the microbe attaches to phagoycte receptors what are the three things that happen in a phagocytic cell? |
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Definition
1. phagocytosis
2. assmebly of oxidase
3. degranulation
- deliver the cytotoxins to phagosome wiht the target |
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Term
| Describe innocent bystander damage? |
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Definition
| phagocyte receptor activation by cells too big to be ingested leads to extracellular release of cytotoxins that deposit on host cells and lead to damage |
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Term
| What are two aspects of innate immunity to viral infection? |
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Definition
1. induction of infected cells of type 1 interferons (IFN alpha and beta)
2. induction of cytokines inducing recruitment of NK cells |
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Term
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Definition
| locally - autocrine or paracrine |
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Term
| What are the effects of IFN type 1 |
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Definition
| induction of intracellular biochem systems that reduce transcription and translation in thea ffected cells - requiring signaling from the intracellular virus or metabolites to induce IFN-indced inhibiotors of metabolic activity |
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Term
| Describe the secretory process of NK cells? |
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Definition
vectorial
- granules secreted specifically at membrane sites of activating receptrs who engagement triggers degranulation |
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Term
helper t cells
- secrete?
- activate? |
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Definition
Ag specific contact with infected macrophages
- secrete IFN-y
- activate macrophages to become more cytotoxic toward the pathogen |
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