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exam 4

cytokines regulate intensity and duration of innate and adaptive immune response. receptor mediated. recognize foreign pathogens
monokines those proteins from monocytes
lymphokines those proteins from lymphocytes
interleukin between leukocytes
interferons interfere with viral replication
chemokines chemotactic cytokines that attract specific cells to their location
colony stimulating factors stimulate colony formation in bone marrow, stimulate stem cell differentiation
antigen receptor to trigger cytokine release TCR
PAMPs receptor to trigger cytokine release TLR
AB receptor to trigger cytokine release FcR
IL-12 produced by APCs in response to bacteria/viruses. Activate NK cells to be more efficient killers. induce IFNg production. stim diff of Th1 cells
Type I interferons have what activity antiviral. make other cells resistant to viral infection. Alpha and beta. innate immunity.
Type II interferons innate and adaptive. antiviral. activates macrophages, neutrophils, NK cells. promote Th1 dev. Promote B cell to produce IgG. upregulate MHC expression on APCs. gamma.
cytokines are produced primarily by T lymphocytes.
what do cytokines regulate lymphocyte activation, growth and differentiation
IL-2 lymphocyte prolif
IL-4 stim Th2, B cell diff (IgE)
IL-13 B cell diff (IgE)
IL-10 inhibit Th1
TGFbeta Treg cytokine, B cell diff (IgA)
IFN gamma B cell diff (IgG). activate macrophages, neutrophils, and NK cells.
TNF activate endothelial cells, neutrophils
IL-5 Eosinophil activate and generation
erythropoietin stim prod and diff of RBC
Thrompoietin and IL-11 stim platelet prod
IL-3 Stim bond marrow prod of WBC
IL-5 eosinophil stim eosinophil diff during parasite infection/ allergic response. antagonists used in eosinophilia and asthma
GM-CSG stim diff of neutrophil and monocyte
G-CSF Stim diff of neutrophil
M-CSF Stim diff of monocytes
cytokine regulation 1. receptor antagonists 2. release of soluble receptors to soak up or neutralize cytokine 3. cytokines of opposite effect to counter act the response 4. a deceptor receptor
what makes a good antigen large, complex, foreign. proteins!
ability of an antigen to elicit immune response depends on route of administration. amount of antigen administered. genetic makeup of the immunized animal.
factors influencing antigenicity of a molecule 1. size 2. stability 3. complexity 4. foreigness
what must happen in order for an antigen to elicit an immune response a molecule must be degradable w/in APCs
glycoproteins immune response AB are directed sp against the polysaccharide moiety of the molecule
lipid and Nucleic acids antigens poor antigens b/c they are readily degradable. NA linked to a carrier protein
epitopes large molecule with specific regions against which immune responses are directed.
haptens the small molecules that can function as epitopes only when bound to other large molecules
what APCs can trigger a primary immune response the first time presented to a pathogen DCs. activate naive T cells
Major functions of DCs serve as sentinel cells. process exogenous antigens. reg adaptive immunity.
follicular DCs do not migrate, located in lymphoid follicles, lack MHC II molecules on their surface, carry many complement and Fc receptors. retain antigen for many wks. Do not process antigens.
first signal of antigen presenting T cell antigen receptors bind antigen fragments attached to MHC molecules
second signal of antigen presenting Co stim molecules like CD40 and CD80/86
third signal of antigen presenting provided by cytokine secreted by DCs in response to microbial stimulus
why are macrophages not good APCs in resting stage they do not express adequate levels of MHCII and/or co-stim molecules
how do macrophages become good APCs when activated by cytokines expression of MHC II and co-stim molecules are up-reg. function as APCs
why are naive B cells not good antigen presenters they do not express B7 needed for T cell activation. express low levels of MHC II molecules.
MHC class I endogenous, innate immune. binding peptides are anchored at both ends and fit completely within binding groove
MHC class II exogenous, adaptive immune. binding peptides extend outside the binding groove
what controls antigen presentation and therefore determine an animals susceptibility MHC. antigen fragment triggers immune rxn
MHC class I distribution most nucleated cells
MHC class I function present antigen to cytotoxic T cells.
MHC class I result T cell mediated toxicity
MHC class II distribution B cells, macrophages, and DCs
MHC class II function Present antigen to T helper cells
MHC class II result T cell mediated help
MHC class Ia is adaptive or innate adaptive
MHC class Ib, Ic, Id is adaptive or innate innate
structure of MHC class Ia molecule antigen binding site is formed by what units a1, a2 domains. Heavy a chain is polymorphic to increase variety.
steps of endogenous pathway of MHC I 1. ubiquitin binds to cytoplasmic protein and targets proteasome 2.proteasome degrades protein in peptides 3.TAP bind cytosolic pep from proteasome. transported to lumen of ER 4. Peptides trimmed to ERAP 5. Bind MHC I in ER 6. move to golgi. suface.
structure of MHC class II molecule antigen binding site is formed by what units a1 and B1 chains. polymorphic
steps of exogenous pathway of MHCII 1. APC internalize antigen 2.lysosomal enzymes digest antigen into peptides 3.MHC syn in RER 4.a and B chains form binding groove 5.Invariant chain inserted as transport to golgi 6.form endosome/phagolysosome 7.digest invariant chain, leave CLIP
what removes CLIP from MHC II removed by DM, antigen pep binds to MHC II groove
MHC restriction only antigen fragments that can bind in the groove of MHC can trigger an immune response
why are MHC heterozygotes adventageous they can respond to a greater range of antigens. optimal number is 6
BoLA-Aw7 resistance to what bovine leukosis. bovine leukemia virus
BoLA-A*16 resistance to what mastitis
BoLA DR resistance to what Dermatophilus sp
ELA-A9 susceptibility to what equine recurrent uveitis
ELA-A3, ELA-A15, ELA,Dw13 and dev of what sarcoid tumors
B cells general job responsible for AB production
T cells general job reg adaptive immunity. cell mediated immune reponses
NK cells general job innate immunity
B cell distribution lymph node cortex. splenic follicles
B cell antigen receptors BCR immunoglobulin
B cell surface antigen immunoglobulin
B cell antigen recognize Free foreign proteins
B cell progeny cells Plasma cells, memory cells
B cell secreted products Immunoglobulins
T cell distribution lymph node paracortex. splenic periarteriolar sheath
T cell antigen receptor TCR- protein heterodimer associated with CD3, CD4, or CD8
T cell important surface antigens CD2, CD3, CD4, CD8
T cell antigen recognized processed foreign proteins in MHC
T cell progeny cells effector T-cells, memory T cells
T cell secreted products cytokines
CD4 is marker for T helper cells. MHC II
CD8 is marker for cytotoxic T cell. MHC I
what marker is always present on T cells CD3
T helper cells recognize what antigen on MHC II
T helper cells differentiate into what TH1, TH2, TH17, Treg. depends on signals from APC and env
Th 1 cells secrete IFNgamma. activate macrophages, neutrophils, NK, CTLs. B cells to make opsonizing and complement fixing AB
Th2 cells secrete IL-4,5,10,13
Th2 cells activate mast cells, eosinophils. B cells to make IgE
Th2 cells provide defense against some parasites and some mucosal pathogens.
Th17 cells secrete IL-17A, IL-17F, IL-22
Th17 cells attract and activate neutrophils and monocyte. leading to acute inflammation.
Th17 cells are important when responding to what EC bacteria and fungi
Treg cells secrete TFGB
Treg cells suppress T cells response by secreting suppressive cytokines
Treg cells help prevent what reactions to self peptides
cytotoxic T lyphocytes or CTLs or CD8 T cells recognize what antigen on MHC 1
what happens once CDB T cells encounter antigen clonally expand, diff and dev killing machinery in cytoplasm
CD8 T cells are important in responding to what protection from intracellular microbes that cause the syn of foreign proteins in cytoplasm (viruses)
first step of T cell activation binding of antigen on MHC to APC
second step of T cell activation need co stimulation. 1. stim of CD154 to CD40 2.stim of CD28 and CD80/86
T cell deactivation step stim of CD152 and stim of CD80/86
what cell expresses CD80 DCs
what cell expresses CD86 B cells
superantigens directly link binding region of TCR and MGH. binding is very strong therefore response is strong. dont need co stim
generation of Th substypes is regulated by what stimuli that naive CD4T cells receive when they encounter microbial antigens
What is the most important signal for differentiation of naive CD4 T cells into distinct subtypes is what cytokines produced by APCs that are determined by the type of infection
Major function of Th1 cells that produce IL2 Activate T cells, B cells, NK cells, macrophages
Major function of Th1 cells that produce IFN-gamma Inhibit Th2 cells, stimulate Th1 cells, activate NK cells, activate macrophages
Major function of Th2 cells that produce IL-4 stimulate B cell growth and differentiation. activate mast cells
Major function of Th2 cells that produce IL-13 stimulate B cell growth. suppresses macrophage function
Major function of Th2 cells that produce IL-5 stimulate B cell growth. mobilizes and activates eosinophils
Major function of Th2 cells that produce IL-9 T cell growth factor
Major function of Th2 cells that produce IL-10 Inhibit Th1 cell function. suppresses macrophage function.
Lymphocytes cells of our immune system that produce receptors specific for diverse antigen
Lymphocytes are distinguished by surface proteins
B lymphocytes subclass of lymphocytes capable of producing antibodies.
B lymphocytes express what membrane forms of antibodies that serve as antigen receptors and initiate B cell activation
B lymphocytes are activated by what binding of antigen to antibodies.
Activation of B lymphocytes lead to what secretion of soluble forms of membrane bound antibodies
interactions needed to form an early pro-B cell binding of VLA-4 integrin to VCAM-1 and SCF ligand to KIT
Pro B cells expressing IL-7 causes what stimulates survival and proliferation of pro-B cells. activation of RAG. becomes Pre-B cell
DNA rearrangement of Pre-B cells is due to the activation of what RAG1/2 genes
What is the first immunoglobulin expressed first on pre-B cells mu. VDJ spliced to Cu exon, Transcript forms heavy chain
heavy chain locus contains coding sequences called what VDJC
V chain locus variable
D chain locus diversity
J chain locus jointing
C chain locus constant
light chain locus contains coding sequences called what VJC
in B lymphocyte maturation what is the first check point assembly of pre-B receptor leading to survival signal.
Pre-B cell receptor expression causes what 1.cell survival 2.turns off recombination on second chromosome 3.turns on recombination at Ig Kappa light chain locus
when is lambda locus turned on only when kappa light chain locus fails to express functional protein
lymphocytes that successfully express surface IgM are referred to as immature B cells
last step of complete formation of IgM recepetor final light chain product associates with Ig mu chain to form complete IgM receptor
what features must a mature B cell have 1. must have rearranged Ig heavy and light chain 2.must produce function of Ig protein (IgD, IgM) 3.immunoglobulins associate with Ig alpha and Ig beta chains to form functional B cell receptor
B cell receptor is composed of what 1. Membrane bound IgM or IgD 2. associate trans membrane Ig alpha and Ig beta proteins
First step of B receptor activation antigen binding to EC variable domain (CDR region in V domain)
where does the First step of B receptor activation occur lymphoid tissue
T cell dependent antigens must contain a protein component
T independent antigens mutlivalet. ex bacterial polysaccharides or repeating determinatns on the surface of viruses.
diversity of B lymphocytes that recognize T cell dependent antigens have the most diversity. produce majority of AB with highest affinity
diversity of B lymphocytes that recognize T cell independent antigens have reduced diversity. produce low levels of IgM only. reduced antigen affinity
B lymphocytes that recognize T cell dependent antigens are found where lymphoid organs
B lymphocytes that recognize T cell independent antigens are found where mucosal tissues, peritoneum, spleen
T dependent B cell activation starts with what antigen recognition, binding, cross linking by two or more B cell receptors
what happens once T dependent B cells are activated 1. ITAMs of Ig alpha and Ig beta become phosphorylated(active) 2. recruit and activate sky tyrosine kinase 3.activate transcription factors that lead to prolif and diff
in general in T dependent B cell activation the initial signal leads to what activation, proliferation, and migration
in general in T dependent B cell activation the receptor activation leads to what Ig antigen complex is internalized and protein is processed via endosome/lysosome. peptide expressed on MHCII. Migration into paracortical region
directed migration of B and T cells toward each other is due to what changes in chemokine receptors. CCR7 (Tcells) and CXCR5 (Bcells)
In T dependent B cell activation primary signal leads to what initial antibody production IgM only. low levels with low affinity
In T dependent B cell activation secondary signal leads to what initial antibody production 1.mature B cells differentiate into plasma cell or memory cell. 2. isotype switching 3.affinity maturation
after full activation, subsets of B lymphocytes differentiate into 1.memory cells 2.plasma cells
isotype switching is prompted by what activation of CD40 co stimulation and cytokines
what happens during isotype switching intervening DNA segments are cleaved creating new VDJ C coding sequences
isotype switching uses what enzyme AID
what determines which heavy chain isotype is involved of switch recombination` of B cells is produced cytokines produced by CD4 T cells
production of IFN gamma leads to production of what antibody production IgG, major opsonin.
production of IL-4 leads to production of what antibody production IgE
Principal effector functions of IgM complement activation
Principal effector functions of IgG Fc receptor dependent phagocyte responses. complement activation neonatal immunity
Principal effector functions of IgE immunity against helminths. Mast cell degranulation (immediate hypersenitivity)
Principal effector functions of IgA Mucosal immunity (transport of IgA through epithelia)
T independent B cells react to lipids, polysaccharides, toxins. molecules with repeating subunits. molecules that can't bind to MHC molecules (aren't seen by T cells).
Primary signal of T independent B cells BCR activation by antigen recognition of repeating subunits.
Secondary signal of T independent B cells engagement of Toll like receptor, complement receptor
T independent B cells induce what low amounts of IgM, little class switching.
the vast majority of activated B cells differentiate into what short lived plasma cells.
engagement of Fc receptor on B cells forms antigen antibody complex.
special types of Fc receptor expressed on B cells 1. FcyRIIB binds Fc portion of complexes 2. binding sends inhibitory signals via ITIM to terminate B cell response
immunoglobulins component of B cell receptor that confers the antigenic specificity of the B cell.
Basic structure of immunoglobulins consists of 2 identical heavy chains and 2 identical light chains linked by disulfide bonds
immunoglobulins can be fragmented by enzymatic digestion into what 2 components Fc region (carboxyl end of heavy chains) Fab region (amino and of heavy and entire light chain)
what region determines the class of the immunoglobulin constant region
antibody structure and function is determined by what heavy chain sequence. the constant region
IgG is found where in serum, lymph, CSF, colostrum, placental transfer
IgG has how many binding sites 2
In IgG the hinge region and proximate residues in CH2 domain is responsible for what effector function. provide binding site for complement. bind to Fc receptor on effector cells
what is the most abundant IgG subclass in humans IgG1
what is the first Ig made after exposure to antigen IgM, important for complement activation
IgM is found where serum and lymph
IgA is found where saliva, mucus, sweat, tears, milk
Secretory IgA is produced where by plasma cells in the lamina propria
What does secretory IgA do binds to polymeric Ig receptor on basolateral surface, taken up via endocytosis, transported to luminal surface
what Ig is reponsible for hypersensitivity IgE. found bound to Fc receptors on mast cells and basophils. prim
FceRI a high affinity receptor for the Fc portion of IgE.
FceRI is found where found on mast cells, basophils, macrophages, platelets.
cross-linking of adjacent IgE attached to FceRI causes what degranulation and allergic response
IgD is found where on the surface of B cells. functions as an antigen receptor. co-expressed on IgM
IgY is found where birds, reptiles, lungfish, egg yolk
IgM has how many binding sites 10
IgA has how many binding sites 4
Fc region contains binding sites for complement, phagocytes, NK cells
Antibody Fc region function 1. feedback inhibition of antibody production 2. prolongs antibody half-life
antigen binding results in what biological properties 1.neutralizing of toxins 2. immobilization of organisms 3.aggultination and precipitation 4.opsonization 5.initiation of complement
what Ig neutralizes toxins IgG
what Ig immobilizes organisms IgG by binding flagella and cilia
what Ig is responsible for aggultination and precipitation IgM, IgG. makes soluble substances insoluble and easily phagocytosed
first step of Ig heavy recombination activation of recombinase genes
2nd step of Ig heavy recombination binding of recombinase proteins to D-J segments
3rd step of Ig heavy recombination binding of recombinase proteins to V-DJ segments
4th step of Ig heavy recombination processing of RNA transcript. results in VDJ-Cu joining and final mRNA transcript
5th step of Ig heavy recombination translation of a functional Ig heavy polypeptide. silences other alleles. activates light chain rearrangement
combinatorial diversity Ig locus arranged in many segments only one of each type used in final polypeptide
combinatorial diversity occurs via somatic recombination. happens for both heavy and light chains
allelic exclusion only one copy of each allele is expressed at both havy and light chain loci
junctional diversity mutations generated at splice junction
somatic hypermutation due to actions of AID enzyme
isotype switching due to cytokines stimulation from T cells
what mechanisms are only seen in T cell dependent B cell response somatic hypermutation and isotype switching
apoptosis programmed cell death. controlled dismantling of intracellular components while avoiding inflammation and damage to surrounding cells
morphological hallmarks of apoptosis DNA fragmentation and membrane blebbing
major pathways of apoptosis intrinsic or mitochondrial extrinsic or death receptor pathway
initiator caspases 2,8,9,10,14. activated by multimolecular death complexes
effector caspases 3,6,7. break down cellular structures
inflammatory caspases 1,4,5,11. activated by multimolecular inflammations
perforin pore-forming protein and the granzymes are serine proteases
CD95 or Fas transmembrane 'death receptor'.
engagement of Fas on target cell by FasL or CD95L expressed by an armed CTL results in death of the target cell by apoptosis
what regulates T cell survival CD95L-CD95.
Created by: ejohnson17



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