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74 Cards in this Set
- Front
- Back
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Innate immunity (major defenses)
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Present in all individuals at all times
Recognizes groups of similar pathogens Not increased with repeat exposure Major defenses: 1. Phagocytosis (neutrophils and macrophages) 2. Cellular cytotoxicity (NK cells) via recognition of membrane features 3. Inflammation via basophils and mast cells releasing histamine et al mediators |
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Macrophages
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Lineage: myeloid
Derived from monocytes Found in tissues Phagocytosis |
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Neutrophils (3)
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Lineage: myeloid
Multi-lobed nucleus Phagocytosis |
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Eosinophils
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Lineage: myeloid
Kill pathogens too large to be phagocytosed by releasing substance |
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Basophils/Mast cells
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Lineage: myeloid
Mast - Found in tissues, release granules (histamine) Basophils - Similar to mast cells but in blood |
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Natural killer cells
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Lineage: lymphoid
Destroy virus-infected and tumor cells |
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Pattern recognition receptors (PRR) and pathogen associated molecular patterns (PAMP)
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PRRs recognize PAMPs in innate immunity for groups of pathogens
Eg: TLR4 recognizes gram negative LPS |
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Adaptive/Acquired immunity (2 types)
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Antigen specific lymphocytes
Clonal expansion - selection - differentiation Humoral - B cell immunity in blood Cell-mediated - T cells, immunity cannot be transferred via serum |
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Primary and secondary lymphoid organs
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Primary: where lymphocyte development occurs, B cells in bone marrow and T cells in thymus
Secondar: antigen-specific immune response generation, contain B and T cells, spleen, lymph nodes, mucosal associated lymphoid tissues: peyer's patches, appendix, tonsils |
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Multiple myeloma and immunology
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Plasma cell tumor derived from a single cell, so tumor only produces one antibody
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Basic antibody structure
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2 heavy and two light chains
Fab fragments contain binding site (2 per Ab) Fc is the heavy chain base |
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Complementarity determining regions (CDRs)
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Three regions of greatest variability in variable domains in both light and heavy chains.
Antigens make contact here |
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IgM
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Pentameric
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IgA
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Dimeric (or monomeric)
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What Ig classes are on naive B cells vs memory B cells?
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Naive: IgM and IgD
Memory: either IgG, IgA, or IgE |
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Neutralization
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IgG and IgA
Ab blocks ability of pathogen to bind host cell |
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Opsonization
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IgG
Ab binds pathogen Neutrophils have Fc receptors to bind Ab on pathogen and activate phagocytosis |
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Antibody-dependent cell-mediated cytotoxicity
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IgG
Ab binds pathogen and promotes NK cells binding via Fc receptor and triggering of apoptosis |
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Mast cell activation/degranulation
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IgE
Mast cells are in all mucosal surfaces Express Fc receptors that bind IgE Presence of Ag cross-links 2 IgE and causes degranulation |
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Locations of Ig classes
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IgG - diffuses in all tissues and can cross placenta (3 wk half life)
IgM - mostly in circulation as a 5-mer IgE - mucosal surfaces mast cels IgA - monomeric in serum, dimeric in secretions, in milk |
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IgA transport (secretory component)
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Transport from secretion from plasma cell through epithelial cells
Dimeric IgA binds polymeric Ig receptor on basolateral membrane. Transported across cell w/ receptor. Released from apical surface w/ a portion of pIgR attached (secretory component) which stabilizes IgA. |
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Light chain gene rearrangement (2)
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Each kappa and lambda region contains a variable and a constant region.
Variable region is coded for by V and J segments that come together in differentiating lymphocyte then joined to the C segment |
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RAG-1 and -2
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Required enzyme for cutting and pasting DNA
Expressed exclusively in developing lymphocytes |
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Heavy chain gene rearrangement (process and classes)
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One D and one J segment come together
Then one V segment joins D-J Multiple constant region genes correspond to different isotypes Closest regions are for Cmu and Cdelta for IgM and IgD VDJ is transcribed along with Cmu and Cdelta, then alternatively spliced to give either IgM or IgD So a lymphocyte can express both IgM and IgD antibodies with identical specificity |
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4 mechanisms of antibody diversity (where?)
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Germline
Combinatorial Junctional Somatic hypermutation First three in bone marrow, SHM in secondary lymphoid organs |
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Junctional diversity
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Imprecise joining of V, D, and J segments
After excision exonuclease randomly chews back NTPs and terminal deoxynucleotidyl transferase (TdT) randomly adds Responsible for majority of antibody diversity |
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Somatic hypermutation
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High mutation rate in V regions
During clonal expansion, B cells w/ highest affinity are selected |
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Class (isotype) switching (exclusive to what?)
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Subsequent to antigen expsoure
Involves rearrangement of same heavy chain VDJ with a different constant region segment Exclusive to B cell and Ab heavy chains |
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Outline of B cell class switching from mature to plasma/memory cell
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Mature B cell (pre exposure) - IgM and IgD
EXPOSURE Plasma cells - IgM pentamer at 1 wk and IgG or IgA or IgE at 2 wk Memory cells: IgG, E, or A After secondary exposure plasma cells secrete G, E, or A |
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Steps in B cell development (6 cell types)
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1. Pluripotent stem cell in bone marrow
2. Pre-B Cell - undergone VDJ heavy chain rearrangement w/ Cmu, produces heavy chain peptide but no light chain 3. Immature - Complete VDJ rearrangement, expresses IgM, negative selection via exposure to self-antigens 4. Mature - express IgM and IgD, migrate from marrow to secondary lymphoid organs and circulation, capable of activation 5. Plasma - Mature B cell activated by antigen, expresses IgM then class switches 6. Memory - Class switching to IgG, E, or A, do not secrete until secondary response -> differentiate to plasma cells |
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Serum Ig during development
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IgG high at birth, half-life on order of months
Slow IgG development by newborn results in recurrent infections IgA and IgM not really present until well after birth |
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Serum antibodies
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Immunization of animals generates antiserum polyclonal antibodies used for passive immunity
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Intravenous immunoglobulin
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Serum antibodies produced from very large pools of donors given to individuals deficient in humoral immunity
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Monoclonal antibodies (hybridomas)
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Produced by a single clone of B cells
Hybridomas - Ab-producing B cells fused to immortal cancer cells |
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Enzyme-linked immunosorbent assay (ELISA)
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Bind enzyme labeled antibody to antigen
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Antigen presenting cells (3 common cells)
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Dendritic, B cells, macrophages/monocytes
PRRs recognize PAMPs |
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Cytokines (two examples in innate immunity)
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Released after APC binds antigen
Interleukin-1 and TNFα |
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IL-1 and TNFα function in innate immunity (3)
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1. Make endothelial cells in vessels sticky so WBC stick and migrate to antigen site
2. Activate liver to release C-reactive protein 3. Act on hypothalamus to produce fever, depression, anorexia |
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MHC structure (I vs II)
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Class I: HLA-A,B,C
Each gene encodes one transmembrane glycoprotein Non covalently associated to β2-microglobulin Class II: HLA-DP,Q,R Each gene encodes two membrane proteins (α+β chains) |
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Narcolepsy (summary of disease, HLA type)
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Excessive/involuntary sleeping
Strongly associated with HLA-DR2 |
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How many different class I or II MHC molecules can a single gene express?
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6 for each class
(eg: 2 for HLA-A because we have two haplotypes, one from mom, one from dad) |
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Ankylosing spondylitis (summary of disease, HLA type)
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Inflammatory disease of joints of the spine
90% have HLA B27 |
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TCR structure (differentiate from B cells in two main ways)
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T cells express one α and one β chain
Outer portions of chains are V regions Portions closer to cell surface are C regions Only one antigen binding site No SHM |
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CD3 and ζ
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Part of TCR complex
TCR always expressed in association with Function as signal transduction molecules |
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TCR genetics (α+β chains)
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α constructed from V-J segments
β constructed from V-D-J |
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T cell coreceptors
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A T cell expresses either CD4 or CD8 but not both
Do not bind antigen Enhance activation |
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CD4+ T cells (which MHC?)
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Bind MHC II (APC) to stimulate release of cytokines
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CD8+ T cells (which MHC?)
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Bind MHC I to activate killing of infected cell
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Differential cell expression of MHC I and II
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MHC I on all nucleated cells
MHC II on APC |
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Major steps of T cell differentiation (4)
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1. Pluripotent bone marrow cell differentiates and leaves bone marrow
2. Pre-T cell - double negative (neither CD4 or 8), rearranged β and α genes (γδ lineage splits off) 3. Double positive - express both CD4 and 8, positive then negative selection 4. Single positive - downregulate either CD4 or 8 after thymic selection |
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T cell positive selection (where, how, why)
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Thymic cortex
Double positive thymocyte interacts w/ MHC class I and II on epithelial cells. Cells that cannot interact die: Selection for only cells that will only respond to antigen presented on self MHC |
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T cell negative selection (where, how, why)
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As cells move to thymic medulla
Interactions between TCR complex and MHC I and II of dendritic and epithelial cells: Too high reactivity -> apoptosis |
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How are exogenous antigens processed and presented? (4 steps, 3 cell types)
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1. Taken up by APC
2. Broken down in acid vesicles 3. Fuse w/ MHC II containing vesicles (from ER) 4. Peptides selective bind MHC groove presented w/ CD4+ Macrophages, DC, B cells |
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How are endogenous antigens processed and presented? (3 steps, what cells?)
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1. Antigens catabolized in proteasome and transported to ER
2. Peptides (8-12 aa) associate w/ MHC I 3. MHC I - peptide presented to CD8+ cells All nucleated cells |
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How are processing and presentation of antigens negatively/positively modified?
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Positively modified by interferon-γ
Negatively modified by some viruses/tumors |
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Signals necessary for CD4+ T cell activation (2)
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First signal - peptide + MHC II on APC interacts w/ TCR of CD4+ cell
Second signal - costimulator pairs on T cell and APC |
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Two pairs of costimulators
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B7 (APC) and CD28 (T cell)
CD40 (APC) and CD40 Ligand (T cell) |
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What role do dendritic cells play in T cell activation?
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DC express PRRs, MHC II and costimulators
Immature DC in tissues that have encountered/presented antigen migrate to lymph nodes Expresses cytokines to activate T cells |
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What is the link between innate and adaptive immunity?
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Dendritic cells by recognizing pathogens and activating CD4+ T cells
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Results of T cell activation (3)
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Synthesis of cytokines/cytokine receptors (IL-2 is major activator of T cell differentiation/proliferation)
Proliferation Changes in expression of adhesion molecules so T cells leave lymph nodes to combat pathogens |
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Interleukin-2
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Synthesized by T cells
T cell growth factor |
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Interleukin-4
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Synthesized by T cells and others
Growth factor for B cells and promotes IgE switch |
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Interferon-γ (in cooperation with which interleukin?)
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Synthesized by T cells
Activates APC to present lots of MHC Amplifies signal because more MHC -> more T cell activation -> more interferon In amplifaction loop with IF-12 |
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Interleukin-10 and TNF-β
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Turn down imune response
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Interleukin-1
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Promotes inflammation by making lymphocytes stick to blood vessels
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TH1 cells: synthesize? response? activated by?
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Synthesize Il-2, IFN-γ, and TNFβ
Activate effectors of cell-mediated immunity and complement to eliminate viruses and bacteria Activated by IL-12 |
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TH2 cells: synthesize? response? activated by?
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Synthesize IL-4,5,6,10,13
IL-4,13 activate B cell switch to IgE + IgG4 IL-5 activates eosinophils Response to worms and allergens Activated by IL-4 |
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TH17
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Synthesize IL-17
Activates neutrophils Proinflammatory response Feature in autoimmune disorders |
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Thymus dependent antigens (where? 2 signals)
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B cells require help from CD4+ cells to make antibody
In lymph node Requires: peptide-MHC on B cell recognized by TCR and costimulator pairs CD40 (B cell) and CD40-ligand (T cell) Stimulates both cells Necessary for B cell class swith |
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Thymus independent antigens
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Such as gram- LPS
B cells can only make IgM and thus no memory response |
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How are CD8+ cells activated (specify cytokine)?
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Requires two signals:
MHC I - peptide presentation Costimulator pairs/cytokines (IL-2) |
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What interaction between B and T cells induces class switch?
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CD40 on B cell w/ CD40L on T cell
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Mechanisms of CD8+ killing (two mechanisms)
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Release of perforin that makes pore for granzymes to enter cell and stimulate apoptosis
Fas Ligand on T cell with Fas on host cell also activates apoptosis |
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CTLA-4 (CD152)
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Expressed on T cell
Costimulator w/ B7 on APC Transmits negative signal to activated T cell to turn off response |
