Term
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Definition
| The formation AND differentiation of BCs (WBC, RBC, Platelets) usually takes place in marrow of the ribs, sternum, and hips |
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Term
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Definition
-precursor to all blood cells
-Pluripotent (can differentiate into multiple types of cells)
-Once they divide the daughters can either self-renew or proceed to on eof the lineages.
-<.1% of all cells in MARROW |
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Term
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Definition
| Chemical messengers produced by BONE MARROW STROMAL CELLS and dictate which lineage the HSC differentiates into |
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Term
| Two main Blood Cell lineages, cytokines |
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Definition
Myeloid (IL-3, GM-CSF) Mono, Macro, Granulo, RBC, Platelets
Lymphoid (IL-3,7)- T,B,NK cells |
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Term
| Constitutive differentiation |
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Definition
| process that is happening all the time and continuously in the Red bone marrow to maintain basal levels |
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Term
Inducible hematopoieisis
What gives off cytokines? |
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Definition
| reaction to something, hemmorrhage, injury, etc. Need more WBC so can be induced. Activated T-Helper and macrophages produce cytokines |
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Term
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Definition
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Term
| Monocyte General characteristics |
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Definition
CD14
-Horseshoe shaped nucleus
-lots of lysosomes and phagocytic vacuoles
-LPS- component for gram negative bac.
-Cytokine producing, phagocytic, APC |
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Term
| Macrophage General Characteristics |
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Definition
Come from monocytes- have moved into the tissues and differentiated
-RES formed by Macrophages
-Phagocytosis, APC, cytokine secretion for induceable hematopoiesis |
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Term
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Definition
| Reticluo Endothelial System- network of macrophages throughout the body |
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Term
| Dendritic Cell Classes and General Characteristics |
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Definition
APC- Proffessional APC
- Capture antigen and move to lymphoid organ to present to T cell
-From the myeloid lineage w/monocyte precursor
-long filamentous projections
-Langerhans and interstitial DC
2. Follicular Dendritic cells- aid in the differentiation of B cells, only in lymphatic organs |
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Term
| Granulocyte General Characteristics |
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Definition
from the myeloid lineage,
Contain cytoplasmic granules
include Baso, Eosin, Neutrophils |
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Term
| Neutrophil General Characteristics |
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Definition
70% of nucleated BCs
-released from bone marrow- migrate to tissue- first at site of inflammation
-first line of defense in microbial infection, bacteria, fungal
-phagocytosis (O2 dep/indep)
-very segemented nucleus |
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Term
| Eiosinophil General Characteristics |
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Definition
2-5% of nucleated BCs
-biloped nucleus
-Stains red w/acidic dye
-defend against parasytic organisms via degranuliation, minor phagocytic role of particles that are broken up. |
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Term
| Eiosinophil granules contain what? |
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Definition
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Term
| Basophil General Characteristics |
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Definition
Only found in Circulating Blood
-NONphagocytic granulocyte, stains purple
-Surface receptors for IgE and C3a
-Release granules containing histamine (important role in allergic response) |
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Term
| Mast Cell General Characteristics |
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Definition
-Very similar to basophil except only found in the TISSUES
-From the myeloid lineage
-histamine granules and surface receptors for IgE and C3a
-role in allergic response |
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Term
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Definition
20-30% of peripheral leukocytes
-in blood, tissues and lymphoid organs
-Small= T,B lymphocyte (high nuclear/cyto ratio)
-Large= Activated T cells, Plasma cells (activated B cells) or NK cells (only NK is non-activated large cell) |
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Term
| Memory cell general Char. |
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Definition
| long lived lymphocyte that patrol the body in defense of the pathogen ino order to mount a quicker defense in the future |
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Term
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Definition
5-15% of lymphocytes
-differentiate and mature in Bone marrow.(Ca2+ important for maturation)
-BCR, CD19, CD20, CD21
-synthesize and secrete specifica antibodies to defened against extracellular microbes and toxins. |
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Term
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Definition
80% of lympho.
TCR and CD3 on ALL T Cells
-all activated upon antigen exposure
-become effector or memory T cells
-Generated in bone marrow, migrate to Thymus (10% survive)
-Become Helper T cells, Regulatory cells, Cytotoxic T cells |
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Term
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Definition
-Helper T cells have TH or CD4+
-cytokine production to activate macrophages, induce inflammation, and induce proliferation and differentiation of T,B lymphocytes |
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Term
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Definition
Treg, CD4, CD25+
-cytokine production to controle autoimmune and turn off immune response |
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Term
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Definition
Tc, CTLs, CD8+
-direct killing of tumor cells and cells infected with intracellular microbes |
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Term
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Definition
Specific Antigens
-CD16a, CD57
-destroy tumor cells or virally-infected cells that have decreased expression of MHC class 1 proteins |
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Term
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Definition
low number, <1000 cells/ul
indicates increased risk of infection (esp from gram- bac) |
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Term
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Definition
PMN (neutrophil)count >8000/ul
clinical sign of infection
-response of the bone marrow to circulating cytokines (left shift of band cells, immiture neutrophils) |
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Term
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Definition
>600/ul
-due to parasitic infection, addison's disease, allergy, asthma |
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Term
| BLympho and Epstein Barr Virus |
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Definition
Human Herpes Virus- exploits CD21
-Heterophile antibodies produced |
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Term
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Definition
| TH cell is the target of HIV- High levels fo CD4 which HIV binds and uses to infect T helper cell |
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Term
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Definition
Bone marrow and thymus
-where lymphocytes mature |
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Term
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Definition
Lymph nodes, spleen, MALT, Tonsils
-Where actual immune response takes place and lymphocytes respond to the antigen
-environment where antigen filter and lymphocytes circle throug to increase changes of interactions |
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Term
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Definition
| Hematopoiesis, Myeloid cells mature, b-cells formed and mature, T cells formed and move on |
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Term
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Definition
location of t-cell maturation into three types that are aducated about self and non-self
-size and function decreases with age (dec in t-helper and Regulatory T cells) |
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Term
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Definition
secondary lymph organ
-B cells in cortex and T-cells in paracortex b/c activated differently
-filter antigen from local tissue via afferent lymphatic vessels or DC cells- site of lymphocyte activation.
-B and T cells circulate through and only stay if they see the antigen (takes 7-10 days to be activated) or move through to next node if don't see one. |
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Term
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Definition
network of capillaries and vessels that transports lymphocyte and antigesnf rom body tissues to lymph nodes.
-fluid moves as a result of muscle contraction |
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Term
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Definition
secondary lymph organ
-filters angigen from the blood adn site of lymphocyte activation
Red Pulp- destroy old and damaged RBCs via phagocytosis
Wite Pulp- lymph tissue- antigens enter via the splenic A and exit via the splenic A
B cells in Follicles
T cells in PALS |
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Term
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Definition
large pop of antibody producing plasma cells
-loose arrangement of cells and connective tissue that defends mucus-lined epithelial cells
-majority of antigens come from MALT due to the large size.
-BALT or GALT depending on location |
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Term
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Definition
Oral, nasal and paryngeal tissue
-Partially encapsulated MALT |
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Term
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Definition
movement through an unruptured vessell into surrounding tissues
-CAMS slow it down so it can get through the junctions |
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Term
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Definition
molecules on endothelium that slow leukocytes so they can enter tissues (extravasate)
Selectins- form a loose interaction that slows the WBC down (rolling)
Integrins- stronger bond that actually stops the cell so that it can move through. |
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Term
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Definition
Directed movemnt through tissue eliicited by chemokines and chemokine receptors on cells
-ex. IL-8 attracts Neutrophils |
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Term
| Review recirculation patterns for Naive lymphocytes |
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Definition
| Review recirculation patterns of Activated lymphocytes (really do this!) |
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Term
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Definition
| Normal body constituents or natural components of an individual |
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Term
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Definition
Cells or Molecules to which immune system has no exposure during its maturation ro does not normally encounter in the body
-Threats= antigens, viruses, bacteria, parasitic organisms, toxins, transplanted tissues, cancer (if a cell responds to self during maturation then it is selected against) |
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Term
| Characteristics of innnate immunity |
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Definition
born with all components
1. Structural- TJs Mucus Cilia Sweat Tears Saliva
2. Chemicals- Digestive enzymes acids lysosomes defensins (embed into membrane of bacteria, create pores and destroy)
3. Phagocytes- Neutrophils, macrophages, monocytes, DC
4. NKs
5. Granulocytes
6. Complement system
-These all have the same mechanism regardless of antigen and the response is in place before the threat is encountered.
-no memory is generated, doesn't enhance or change w/ inc. exposure |
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Term
| Characteristics of adaptive immunity |
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Definition
T and B cells respond very specifically to a specific antigen.
1.Memory-develops after a first exposure of B and T cells to a specific antigen (activation is much quicker, repeated exposure increases response)
2.Specificity- Each T,B cell has surface receptors that are speficic for one antigen only.
3.Humoral
4.Cell Mediated |
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Term
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Definition
immunity mediated by antibodies (B cells) that are present in blood, lymph, and other body fluid
-important in the defense against extracellular microbes and microbial toxins |
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Term
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Definition
immunity mediated by T lymphocytes- effect through direct cell-to-cell contact
-important in the defense against intracellular microbes and tumor cells |
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Term
| Innnate vs adaptive receptor differences |
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Definition
Innate- non-sepcific( respond in a general fashion to foreign stimuli), Recognized different patterns on the surface of antigens, Pattern Recognition Receptors (PRRs) ex. Mannose on bacteria surface or LPS on Gram neg Bacteria
Adaptive- Each B,T Cell has surface receptor BCR, TCR, that are specific for one antigen only and recongize down to single AA differences
-Receptors created by somatic recombination of a gene which allows for great diversity to rearrange genes and give cells varying specificities |
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Term
| Importance of cooperation b/t innate and adaptive immune system |
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Definition
-innate system is typically the first to respond and then adaptice are second if necessary
-When both are active
-macrophages can also act as APC for T cells
-Antibodies optimize phagocytosis by macrophages and PMN
-Antibodies activate complement system.
-Cytokines produced by cells of the adaptive immune system enhance phagocytic and cytotoxic activity of innate immune cells |
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Term
| Pattern recognition Receptors (PRR) |
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Definition
| Molecular pattern sutilized by cells of the inate immune system to recognize self from non-self (Non-specific) |
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Term
| Receptors for Pathogen Associated Molecular Patterns (PAMPs) |
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Definition
| Mannose receptor, Scavenger receptor, LPS Receptor (gram neg bac) |
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Term
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Definition
Host derived proteins the coat pathogens,
phagocytes ahve receptors for the proteins bound to the pathogen and can recognize, bind, and phagocytose.
-antibodies Igs, Complement C3b, C-reactive protein CRP. |
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Term
| PhagocyteSpecific Receptors |
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Definition
| can stimulate other immmune responses |
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Term
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Definition
| -On the surface of phagocytes and expressed primarily by innate cells to recongize various PAMPs that are not found in our own cells such as Flagellin and Viral DSRNA, DNA |
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Term
| Toll like receptors on cell surface look for |
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Definition
| extracellular components such as LPS, bacterial peptidoglycan, flagella |
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Term
| Toll like receptors in endosomal ompartments look for |
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Definition
| intracellular components of microbes such as SSRNA, Viral DNA, anything weird that got in. |
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Term
| What happens when pathogens bind to Toll Like Receptors (TLR) |
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Definition
stimulates two transcription factors:
NF-kB= promotes inflammation and prepares cellsf or interaction of the adaptive immune system (T-cells), upregulates cell surface expression of costimulatory molecules
IRF-3= promotes production of antiviral interferons to block viral replication and stimulates NK cells |
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Term
| What affects how the cell will respond to cytokines? |
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Definition
| Receptor affinity and/or number |
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Term
| Cytokine Receptor signals |
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Definition
released to signal cells that will thell them when to exit circulation and tell them where to go (migration)
-act as autocrine or paracrine
-NEVER stored, produced in response to microbes or other antigens |
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Term
| Oxygen dependent vs independent killing |
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Definition
independent-using various proteolytic enzymes
dependent- Respiratory burst= cellst taking up a lot of o2 to make ROS, RNS; synthesizing NO, superoxide anion and H2O2 that can be used to destroy bacteria. |
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Term
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Definition
-NKs only respond to cells not expressing Class 1 MHC molecules
-MHC inhibits killing, w/o it NK cell is activbated and releases cytotoxic substances into the infected cells which leads to apoptosis. |
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Term
| Granular enzymes and function in NK |
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Definition
Perforin- pore forming protein that inserts into membrane and forms a proe that allows granzymes to pass
Granzymes= activate the caspase pathway that results in apoptosis |
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Term
Type 1 Interferon Cytokines
give abbreviations |
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Definition
| IFN-a, IFN-b, IFN-gamma, IL-12, |
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Term
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Definition
antiviral cytokines, activate antiviral mechanisms in neighboring cells by inducing an antiviral state in that cell (the cell dies but hopefully the viral replication is stopped)
-Increase class I MCH expressions, stimulate NK activity, and present antigens to CD8 T-cells (cytotoxicT-cells) |
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Term
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Definition
Interferon, cytokine.
Naturally released by T cells and NK cells; used as a treatment for CGD patients.
-Enyhances the production of ROS
-Increases the microbial activity of macrophages |
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Term
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Definition
| Cytokine, secreted by macrophages to activate NK cells- they in turn directly kill infected cells and release IFN gamma to activate macrophages and increase ROI and lysosomal enzymes |
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Term
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Definition
| ability of a cytokine to have a variety of effects based on what it is interacting with |
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Term
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Definition
| ability of a cytokine to have a method for chekcs and balances in which multiple cytokines can produce the same effect |
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Term
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Definition
| the ability of cytokines to work to gether to produce/augment a response |
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Term
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Definition
| cytokine ability to work in opposition to eachother, allowing signals to be turned on/off |
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Term
| The four functions of the Complement System |
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Definition
1. Oposonization= C3b C4b
2. Clearance of immune complexes (C3b binds to immune complexes)
3. Membrane attack lysis (C5b)
4. Inflammation and Chemottraction (C3 and C5) |
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Term
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Definition
C3b an C4b
-proteins coat microorganisms to enhance phagocytosis
-C3b can be protolyticlaly cleaved into iC3b which is an opsonin that can't further amplify the enzyme cascade. |
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Term
| Complement Clearance of immune complexes |
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Definition
| C3b binds to immune complexes, serve as chemoattractant facotrs |
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Term
| Complement Membrane attack lysis |
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Definition
C5b is the starting point for MAC generation
C5b binds to C6,7,8, and multiple copies of 9. This forms a large pore on the surface of the pathogen allowing water to rush in and lyse the cell |
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Term
| Complement Inflammation and Chemoattraction |
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Definition
C3a and C5a are chemoattractants and anaphylatoxins
-recruit phagocytes to area of infection and cause release of inflammatory mediators
-"a" cells create concentration gradient that attracts cells to the area.
-Also bind mast cells- degranlation and release of histamine |
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Term
| Formation of C3 Classical Pathway |
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Definition
C1 binds to antibodies (IgG or IgM) that are bound to pathogen surface
-Conformation shape change activates C1- cleaves C4 into C4a,b
-C4b binds to pathogen surface and C2 binds to C4b
-C1 cleaves C2 into C2a,b (a leaves)
-C4b2b is formed= C3 convertase, cleaves C3 into C3a,b |
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Term
| Formation of C3 Lectin Binding Pathway |
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Definition
Liver stimulated by cytokines to secrete Mannose-Binding Lectin, which binds to the Mannose on pathogen surface.
-MASP binds to MBL, forms MBL-MASP complex that forms just like C1
-MBL-MASP cleaves C4 to C4a,b
-C4b binds to pathogen surface, C2 binds to C4b
-MBL-MASP cleaves C2 to C2a,b forming C4b2b= Convertase enzyme |
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Term
| Formation of C3 Alternate Pathway |
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Definition
Spontaneous or pathogen initiated cleavage of C3
-C3b binds to pathogen surface and provides binding site for Factor B, C3bB formed
- Factor D cleaves B into Ba,b
-C3bBb formed= convertase enzyme (stabilized by Properdin) |
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Term
| Describe what can happen to C3 after C3 convertase is formed |
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Definition
C3 convertase is the convergence of all three pathways
-Some C3b binds to pathogen surface
-Some C3b binds to C3 convertase forming C5 convertase |
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Term
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Definition
It is C3b bound to C3 convertase
-It cleaves C5 to C5a,b, which serves to aid lysis, opsonization, activate inflammatory response, and clearance of immune complexes.
-C5b is the starting point for MAC-cell lysis |
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Term
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Definition
functions to inactivate the classical and lectin pathway by inhibinting protease activity via C1 and MASP.
-turning off C1 and MASP limits how much C3a and C5a are produced.
=Hereditary Angioedema |
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Term
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Definition
| C1 and MASP are always active, no C1inh. They continuously generate anaphylatoxins causing excessive swelling most common in the mouth. THey are not able to turn off complement. |
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Term
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Definition
| These are host regulatory proteins on the cell surface of RBCs. |
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Term
| CD59 and DAF(CD55) defects |
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Definition
Hemolytic anemia and venous thrombosis
excessive complement activation evident on RBC- generation of MAC complex formation on RBC- RBC lyse- Recurrent intravascular hemolysis. |
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Term
| Immunodeficiency associated with classical protein C1,2,4 |
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Definition
| increase the predisposition for developing immune complex diseases- persistence of immune complexes- inflammatory mechanisms continuously activated= tissue damage and dsease such as lupus and SLE |
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Term
| Immunodeficiency associated with C3 deficiencies |
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Definition
| all of the pathways will be deficient- immune complexes diseases, recurrent bacterial infections- defective opsonins and lysis |
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Term
| Immunodeficiency associated with MAC deficiency |
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Definition
| C6 or C9 issues- unable to generate MAC- increased risk of certain bacterial infections- Gonorrhea and meningitis |
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Term
| 5 points of acute inflammation |
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Definition
-Rapid and short lived (minutes to days)
-Dilation
-Inc permeability of vasculature (cells and proteins escape)
-Inc expression of CAMS on endothelium
-influx of PMNs into the tissue (halmark sign) |
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Term
| What inflammatory mediators result from tissue damage? |
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Definition
| Clotting factors and bradykinin |
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Term
| Explain the purpose and synthesis of bradykinin |
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Definition
Kallikrein converts Kininoge to bradykinin.
-inc vascular permability, vasodilate, promote pain, sm M contraction |
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Term
| Explain events in endothelial damage with the clotting cascade |
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Definition
| endo damage- clotting cascade- thrombin- fibrin degradation- inc vascular permeability, neutrophils, chemotaxis |
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Term
| Explain events in endothelial damage with the fibrinolytic system |
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Definition
| Endothelial damage- fibrinolytic system- plasmin- complement activation- increased vascular permeability, neutrophil, chemotaxis, opsonization, cell lysis. |
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Term
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Definition
C5a and C3a
-complement proteins that can serve as chemoattractant factors for neutrophils or bind to mast cells- histamine release- increased permeability and dilation |
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Term
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Definition
| released from mast cells and causes dilation and increased permeability |
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Term
| Arachadonic acid metabolites |
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Definition
Prostaglandins, leukotrienes, thrombozane,
-derived from membrane phospholipids |
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