Term
| State the differences between innate and adaptive immunity. |
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Definition
Innate:
-resident and preformed
-req'd to contain infxns (w/o it, # of microorganisms go way up)
-induced (inflammation, activated macrophages)
-rapid response (hours)
-fixed
-limited # of specifities
-constant during response
Adaptive (specificity and memory):
-humoral (antibody-mediated-B cells)
-cell-mediated (effector T cells)
-w/o it, at first you can control infxn, but after awhile # of microorganisms will i/c
-slow response (days to weeks)
-variable (can recognize a lot of different things)
-numerous highly selective specificities
-improve during response
lot of interaction & overlap |
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Term
| Describe innate barriers to infection. |
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Definition
Mechanical: epithelial cells joined by tight junctions - flow of fluid!
-skin (perspiration, sloughing)
-GI tract (fluid, mucus, food, saliva)
-respiratory tract
-urogenital
-eyes
Chemical
-skin: sebum
-GI: acidity, enzymes
-respiratory: lysozyme in nasal secretion
-UG tract: acidity in vaginal secretions; spermine and zinc in semen
-eyes: lysozyme in tears
Microbiological: commensal bacteria
-normal flora in each of the barriers
-GI: colon is colonized by lots of commensal bacteria, antibiotics kill many of these, pathogenic bacteria gain foothold and produce toxins, RBC & WBC lead into gut b/t injured EC
-C. difficile can cause severe infxn after antibiotic tx |
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Term
Describe the different populations of hematopoietic cells.
where does self-tolerance and education occur? |
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Definition
Small lymphocytes (B cells and T cells)
Plasma cell: fully differentiated B cell, secretes antibodies
natural killer cells: kills cells infected with certain viruses
neutrophil: phagocytosis and killing of microorganisms
eosinophil: killing of antibody-coated parasites through release of granule contents
basophil: controlling immune responses to parasites
dendritic cell: activation of T cells and initiation of adaptive immune responses (innate and adaptive)
mast cell: expulsion of parasites from body through release of granules containing histamine, etc., found in connective tissue, allergies
monocytes: circulating precursor cell to macrophage
macrophage: phagocytosis and killing of microorganisms; activation of T cells and initiation of immune responses
megakaryocyte: platelet formation, wound repair
erythrocyte: O2 transport
-all derived from the hematopoietic stem cell-
common lymphoid prog -> B cell, NK/T cells
common myeloid prog
common erythroid, megak, monocyte prog
2 primary lymphoid organs where we have differentiation:
-bone marrow (inc B cells)
-T cells develop in thymus
other lymphoid organs:
spleen (drained by blood, not lymphatics)
intestine-assoc: Peyer's patches |
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Term
| Discuss the process of inflammation, including how it is initiated and mediators of the process. |
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Definition
Accumulation of fluids and WBC to localize and remove irritant
Initiation:
-surface wound introduces bacteria, which activate resident effector cells to secrete cytokines & hemokines (aid in recruitment of cells, make vascular wall permeable)
-vasodilation and i/c vascular permeability allow fulid, protein, and inflammatory cells to leave blood and enter tissue
-the infected tissue becomes inflamed --> redness, heat, swelling, pain
Pathogen recognition: macrophages
-toll-like receptors recognize certain components of pathogens
-scavenger recetpors
-mannose receptors
Bacteria bind to macrophage receptors, macrophage enguls and digests bound bacteria
-phagosome and lysosome fuse -> phagolysosome, toxic contents released onto bacteria
--> production of reactive oxygen species
Macrophages produce cytokines
IL-6 (fever, induces acute-phase protein production by hepatocytes)
TNF-alpha (activates vascular endothelium & i/c vascular permeability 0> i/c entry of complement and cells to tissues, i/c fluid drainage to lymph nodes; fever, mobilizatino of metabolites, shock)
IL-1beta
CXCL8
IL-12 |
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Term
Describe the function of Toll-like receptors
2 locations where they can be expressed? |
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Definition
Part of innate immunity
Recognize and trigger host responses against pathogens
Recognize patterns
TLR4 recognizes LPS (all gram-neg bacteria have LPS as part of CW)
TLR2 recognizes bacterial lipoproteins
TLR3 recognizes DSRNA
A way that the innate immune system recognizes a pathogen
Several ligands can be recognized
Can be expressed on the plasma membrane or in the endosome (phagosome)
-TLR expressed on endosomes recognize nucleotides (RNA or DNA)
-TLR on plasma membrane recognize things expressed on bacteria surface
Signaling through TLR result in activation of NF-kappaB --> inflammatory cytokines |
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Term
| Discuss the differences and similarities between the three pathways of complement activation, and the function of complement activation |
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Definition
Alternative pathway: first to act
-pathogen surface creates local environment conducive to complement activation, quick
Lectin pathway: second
-mannose-binding lectin binds to pathogen surface, induces lectin pathway
Classical pathway: third
-C-reactive pr or antibody binds to specific antigen on pathogen surface
==> complement activation, cleavage of C3 to C3a and C3b
C3b covalanelty bound to surface of pathogen
-recruitment of inflammatory cells
-opsonization (binding) of pathogens, facilitating uptake and killing by phagocytes
-perforation of pathogen cell membranes
==> death of pathogen
Induce localized vasodilation and attract phagocytic cells (anaphylatoxins)
-small soluble fragments: C5a, C3a, C4a
-cause vasodilation and edema
-recruit phagocytes to sites of antigen deposition
-participants in inflammation
Enhance phagocytosis (opsonization)
-enhances phagocytosis
-C3b and C4b
-IgG is also an opsonin
Lysis of cells, bacteria, viruses (membrane attack complex or MAC)
-MAC results in pores in the membrane
-attacks cells, extracellular pathogens and virions
-C5b, C6, C7, C8, C9 are sequentially assembled into MAC
Clearance of soluble immune complexes
-soluble immune complexes (At-Ab) in circulation need to be cleared
-RBC bind to C3b on immune complexes
-RBC carry complexes to spleen and liver for disposal by macrophages |
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Term
| Describe the acute phase response |
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Definition
Induced by a set of cytokines (IL-1, IL-6, TNF-alpha)
Cytokines induce acute phase proteins
-mannose-binding lectine, C-reactive protein, fibrinogen, etc. |
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Term
| Describe the actions of innate pro-inflammatory cytokines |
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Definition
Small secreted proteins that affect other cells by binding to a specific receptor (neutrophils, monocytes/macrophages)
Produced by phagocytes and NK cells |
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Term
| Describe the process of immunological memory |
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Definition
B cells and T cells are the two cell types that "remember" an infxn
-secondary response to a vaccine is quicker and more robust than the first time the vaccine was given - you already have B cells "ready to go," make a lot of antibody |
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Term
| Describe clonal selection and expansion |
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Definition
During development, progenitor cells give rise to large numbers of circulating lymphocytes, each having a diff form of cell surface receptor
The receptors of only a few circulating lymphocytes interact with any given pathogen
Pathogen-reactive lymphocytes are triggered to divide and proliferate
-maintain their specificity
Pathogen-activated lymphocytes differentiate into effector cells that eliminate the pathogen
(some are retained with memory, can respond quicker next time the infxn occurs) |
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Term
| Describe the basic functions of CD4 T cells, CD8 T cells, and B cells |
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Definition
CD8: can kill virally infected cells
-virus infects cells
-viral proteins synthesized in cyhtoplasm
-peptide fragments of viral pr bound by MHC class I in ER
-bound peptides transported by MHC class I to the cell surface
-cytotoxic T cell *recognizes complex of viral peptide with MHC class I* and *kills infected cell*
CD4 can activate macrophages and B cells
-macropahge engulfs and degrades bacterium, producing peptides
-bacterial peptides bound by MHC class II in vesciles
-bound peptides transported by MHC class II to cell surface
-helper T cell recognizes complex of peptide antigen with MHC II and activates macrophage (best for salmonella, etc)
-cell-surface immunoglobulin of B cell binds bacteria; the cell engulfs and degrades them, producing peptides
-bacterial peptides bounds by MHC II in endocytic vesicles
-bound peptides transported by MHC II to cell surface
-helper T cell recognizes complex of peptide antigen with MHC II and activates B cell |
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Term
| Describe the differences between active and passive immunity |
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Definition
Active: generated by individual upon exposure to pathogen or antigen
-long-term, but takes time to generate
-e.g. vaccination
Passive: transferred to individual
-rapid, but transient
-e.g. anti-venom, maternal Ab |
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Term
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Definition
pathogens from site of infxn reach lymph nodes via lymphatics
-infected tissue -> lymphatics
Lymphocytes and lymph return to the blood via lymphatics
venous blood returns to the heart
naive lymphocytes arrive at lymph nodes in arterial blood, get activated |
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Term
| "Players" in innate immunity |
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Definition
Inflammation
Phagocytes
NK cells
Complement
Coag system
Defensins (anti-microbial peptides that can directly kill pathogens)
Toll-like receptors
Acute phase response |
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Term
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Definition
Macrophages activated to secrete TNF-alpha into tissue
I/c release of plasma pr into tissue, i/c phagocyte and lymphocyte migration into tissue, i/c platelet adhesion
Phagocytosis, local vessel occlusion, infxn containment, antigens drain or are carried to local lymph node
stimulation of adaptive immune response
"The bad" - the primary cytokine that causes septic shock
-macrophages activated in the liver and spleen secrete TNF-alpha into the blood (systemically)
-systemic edema causes d/c BV, hypoproteinemia, neutropenia, followed by neutrophili. D/c BV causes collapse of vessels
-DIC leads to wasting and multiple organ failure: septic shock |
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Term
More on alternative pathway... proteins
"don't need to know nitty gritty" |
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Definition
C3 (circulating complement protein) begins to undergo a series of rxns
-via H2O, exposure of H and OH, allows the binding of factor "B"
-B binds what's now iC3
-D (protease) cleaves factor B into 2 molecules - Bb and Ba (now iC3Bb)
-iC3Bb can now function as a *C3 convertase* - they convert C3 into C3b and C3a
Formation and action of the C3 convertase C3bBb of the alternative pathway at a pathogen surface
-C3b deposited on pathogen surface
-B binds
-D cleaves
-C3b bound to Bb
--> amplify deposition of C3b on surface
----> put C3b on surface and release C3a |
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Term
| Complement control proteins |
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Definition
Stabilize C3 convertase
-properdin
Inactive C3b
-factor H and factor I give fragment iC3b (inactive)
-limit deposition of C3b - controls immune response
**On human cell surfaces: two proteins disrupt/degrade C3 convertase. Limit complement deposition
-DAF
-MCP
-prevent phagocytosis of human cells |
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Term
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Definition
Complement activation leads to deposition of C3b on the bacterial cell surface (C3b-CR1)
C21 on macrophage binds C3b on bacterium
Endocytosis of the bacterium by macrophage
Macrophage membranes funse, creating vesicle (phagosome)
Lysosomes fuse with phagosomes -> phagolysosome
Cr3 and Cr4 bind iC3b fragments on microbial surfaces |
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Term
| Alternative C5 convertase |
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Definition
leads to production of C5b
C3b2Bb - binds another C3b - becomes C5 convertase
Is cleaved -> C5b and C5a
-C5b binds C6 and C7, initiates MAC formation (binding to pathogen surface recruits C8 and C9)
proteins like CD59 protect human cells from MAC |
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Term
| C5a and C3a as anaphylatoxins |
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Definition
Anaphylatoxins act on BV to i/c vascular permeability
-i/c permeability allows i/c fluid leakage from BV and extravasation of complement and other plasma proteins at site of infxn
-migration of monocyte and neutrophils from blood into tissue is i/c. Microbicidal acivity of macrophages and neutrophils is increased |
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Term
| More on leptin pathway... |
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Definition
Activated MASP-2 cleaves C4 -> C4a and C4b. some C4b binds covalently to microbial surface
Activated MASP-2 also cleaves C2 -> C2a, C2b
C2a binds C4b -> *classical C3 convertase, C4b2a*
C4b2a binds C3 and cleaves it to C3a and C3b. C3b binds covanlently to microbial surface |
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Term
| C-reactive protein initiates classical pathway |
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Definition
C1 binding to C-reactive protein on the pathogen surface activates the classical pathway of complement fixation
C4b binding to C2a resutls in "classical" C3 convertase
C1 can also bind IgG and IgM on the surface of pathogens, thus activating the classical pathway of complement activation |
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Term
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Definition
Specificity & memory are major characteristics
Major cell types are the lymphocytes
-B lymphocytes: make antibody
-T lymphocytes: regulate immune responses, kill infected cells, activate macrophages, etc - the boss! |
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Term
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Definition
B-cell receptor
-2 antigen binding sites (identical, bivalent)
-light chain, heavy chain
-transmembrane region holds them to B cell
-once you activate a B cell, it can turn into a plasma cell that secretes antibody (recognizes the same thing the B cell did)
T-cell receptor
-monovalent
-variable regions & constant regions
-transmembrane region
-alpha and beta chain (alpha, beta T cells) |
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Term
| Activation of Adaptive immune responses |
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Definition
Pathogens adhere to epithelium
skin would allows pathogens to penetrate epithelium
local infection, innate immunity (cytokines, cell recruitment, etc)
*dendritic cells* take infxn (via lymphatics) to lymph node and stimulate adaptive immunity, present antigen to T cells delivered through lymphatics ro blood, activate T and B cells
-plasma cells (fully differentiated B cells) make antibody
effector cells and molecules of adaptive immunity leave lymph nodes, travel via lymphatics to the infected tissue
(can also happen in spleen if it's blood-borne) |
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Term
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Definition
present antigen, via MHC molecules, to T cells
dendritic cell takes up pathogen for degradation
pathogen is taken apart inside the dendritic cell
pathogen proteins are unfolded and cut into small pieces
peptides bind to MHC molecules and the complexes go to the cell surface
T-cell receptors bind to peptide: MHC complexes on dendritic cell surface
-T cells learn to recognize self-MHC while in the thymus - can ONLY recognize a small peptide fragment - can't just bind to bacteria or virus
MHC Class I - on surface of at presenting cell - present antigens to CD8 cells (kill)
MHC class 2 - presents CD4 T cells - dont' directly kill cells, but secrete cytokines and provide help |
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Term
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Definition
Cytotoxic (CD8+ T cells)
-kill cells infected with virus and intracellular bacteria, as well as cancerous cells (prob with cancer: not really foreign, can over/under-express proteins)
T helper cells (CD4+ T cells)
-Th1 cells - cell mediated immunity (IL-2, IFN-gamma, TNF-alpha, GM-CSF)
-Th2 cells - humoral immunity (IL-4, IL-5, IL-6, IL-13)
-Th17 cells - inflammatory responses (IL-17A, IL-17F, IL-22)
-Treg cells - anti-inflammatory (IL-10, TGF-beta) |
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Term
| Humoral (antibody-mediated) immunity |
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Definition
B cells
Antibody (immunoglobulin) specifically binds to antigen and targets its destruction
Functions:
-neutralization (binding inhibits activity)
-opsonization (enhances phagocytosis)
-complement activation (triggers complement activity)
-antibody-dependent cell-mediated cytotoxicity (cells - NKC, macropahges, neutrophils - recognize antibody bound to target cell and release substances to destroy target cell)
-multiple classes (IgM, IgG, IgA, IgE, IgD) |
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Term
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Definition
Neutralization - binds to bacterial toxin, neutralizes its ability to bind; ingestion and destruction by phagocyte
Opsomnization - Ab directly on surface of bacteria, recognized by EpC receptor, ingestion & destruction by phagocyte
-can also induce the activation of complement -> ingestion and destruction |
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Term
| What are sometimes correlated with autoimmune disease? |
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Definition
Anti-viral responses
Ex:
In childhood a viral infxn of the upper respiratory tract is terminated by adaptive immune response
By chance one clone of virus-specific T cells also reacts with MHC:peptide complexes on the surface of healthy beta cells in pancreas
Activated T cells attack and kill pancreatic beta cells -> diabetes |
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Term
| Allergic responses can be caused by: |
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Definition
Antibodies
Inhalation of pollen produces the symptoms of a respiratory infxn through IgE-mediated degranulation of mas cells
mast cell (IgE binds) -> cytokines, histamine, other active substances |
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