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72 Cards in this Set
- Front
- Back
Innate Immunity
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- receptors that recognize pathogens are germline encoded
- response to pathogens is fast and nonspecific - no memory |
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Adaptive Immunity
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- receptors that recognize pathogens undergo V(D)J recombination during lymphocyte development
- response is slow on 1st exposure, but memory response is faster and more robust - has memory |
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T cell differentiation starts in?
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- Bone marrow
- T cell precursor (bald) |
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After the bone marrow, T cells travel to?
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Cortex of Thymus:
- Positive Selection -- a T cell receptor, CD8, and CD4 are added to bald precursor - yield a CD4+CD8+ Tcell |
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After the cortex of the thymus, T cells travel to?
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Medulla of Thymus:
- Negative Selection -- either the CD8 or CD4 is removed - yields a CD8+ T cell or a CD4+ T cell |
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After the medulla of the thymus, T cells travel to?
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Lymph node
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In the lymph node, CD8+ T cell becomes:
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Cytotoxic T cell
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What do Cytotoxic T cells do?
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kill:
- virus-infected cells - neoplastic cells - donor graft cells |
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In the lymph node, CD4+ T cells becomes what via IL-12?
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Th1 cell (cell-mediated response)
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In the lymph node, CD4+ T cells becomes what via IL-4?
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Th2 cell (humoral response)
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What do Th1 cells make? (2)
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IL-2 and IFN-γ
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What cells do Th1 cells activate? (2)
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Macrophages and CD8+ cells
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Th1 cells are inhibited by?
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IL-10
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What do Th2 cells make? (4)
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- IL-4
- IL-5 - IL-10 - and helps B cells make antibody (IgE > IgG) |
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Th2 cells are inhibitied by?
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IFN-γ
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MHC
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- major histocompatibility complex
- encoded by Human Leukocyte Antigen (HLA) genes - present antigen fragments to T cells and bind TCR |
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MHC I Mneumonic
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HLA I letter:
- A, B, C |
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MHC II Mneumonic
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HLA II letters:
- DR, DP, DQ |
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MHC I
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- HLA-A, HLA-B, and HLA-C
- expressed on almost all nucleated cells - mediates viral immunity - pairs with β2-microglobulin (aids in transport to cell surface) |
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MHC II
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- HLA-DR, HLA-DP, and HLA-DQ
- expressed only on antigen-presenting cells (APCs) - antigen is loaded following release of invariant chain in an acidified endosome |
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What MHC is expressed on almost all nucleated cells?
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MHC I
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What MHC is expressed on APCs?
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MHC II
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A3 HLA subtype is associated with?
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Hemochromatosis
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B27 HLA subtype is associated with?
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PAIR:
- Psoriasis - Ankylosing spondylitis - Inflammatory bowel disease - Reiter's syndrome |
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B8 HLA subtype is associated with?
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Graves' disease
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DR2 HLA subtype is associated with?
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- Multiple sclerosis
- Hay fever - SLE (systemic lupus erythematosus) - Goodpasture's |
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DR3 HLA subtype is associated with?
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Diabetes mellitus type 1
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DR4 HLA subtype is associated with?
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- Rheumatoid arthritis
- Diabetes mellitus type 1 |
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DR5 HLA subtype is associated with?
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- Pernicious anemia → B12 deficiency
- Hashimoto's thyroiditis |
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DR7 HLA subtype is associated with?
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Steroid-responsive nephrotic syndrome
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Innate immunity consists of which cells:
(5) |
- neutrophils
- macrophages - dendritic cells - natural killer cells - complement |
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Adaptive immunity consists of which cells:
(3) |
- T cells
- B cells - circulating antibody |
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B cell functions:
(5) |
- Make antibody
- IgG antibodies opsonize bacteria and neutralize viruses - Allergy -- type 1 hypersensitivity → IgE - Cytotoxic (type 3) and Immune complex (type3) hypersensitivity → IgG - Antibodies cause organ rejection (hyperacute) |
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T cell functions:
(4) |
- CD4+ (helper) T cells help B cells make antibody and produce γ-interferon (which activates macrophages)
- Kill virus-infected cells directly (CD8+ [cytotoxic] T cells) - Delayed cell-mediated hypersensitivity (type 4) - Organ (allograft) rejection (acute and chronic) |
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Natural Killer Cells
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- use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells
- induced to kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on target cell surface |
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Natural Killer Cell activity is enhanced by:
(3) |
- IL-12
- IFN-α - IFN -β |
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The only lymphocyte member of the innate immune system?
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Natural killer cells
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Helper T cells and T cell glycoproteins
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Have CD4, which binds to MHC II on APCs
- product of CD and MHC = 8 - CD4 x MHC II = 8 |
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Cytotoxic T cells and T cell glycoproteins
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Have CD8, which binds to MHC I on virus-infected cells
- product of CD and MHC = 8 - CD8 x MHC I = 8 |
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CD3 complex
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- cluster of polypeptides associated with a T cell receptor
- important in signal transduction |
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APCs (3)
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Antigen Presenting Cells
- macrophage - B cell - dendritic cell |
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Macrophage-Lymphocyte interaction
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- activated lymphocytes release IFN-γ
- activated macrophages release IL-1 and TNF-α - stimulate one another |
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Effects of Superantigens
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S. pyogenes and S. aureus
- cross-link the β-region of the T cell receptor to the MHC class II on APCs - results in the uncoordinated release of IFN-γ from Th1 cells and subsequent release of IL-1, IL-6, and TNF-α from macrophages |
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Effects of Endotoxins/Lipopolysaccharides
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gram-negative bacteria
- directly stimulate macrophages by binding to endotoxin receptor CD14 - Th cells are NOT involved |
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T and B cell activation
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2 signals are required for T cell activation and B cell class switching → signal 1 and signal 2
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Th activation
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1. foriegn body is phagocytosed by APC
2. foreign antigen is presented on MHC II and recognized by TCR on Th cell (signal 1) 3. "Costimulatory signal" is given by interaction of B7 and CD28 (signal 2) 4. Th cell activated to produce cytokines |
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Tc Activation
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1. endogenously synthesized (viral or self) proteins are presented on MHC I and recognized by TCR on Tc cell (signal 1)
2. IL-2 from Th cell activates Tc cell to kill virus-infected cell (signal 2) |
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B cell Class Switching
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1. IL-4, IL-5, or IL-6 from Th2 cell (signal 1)
2. CD 40 receptor activation by binding CD40 ligand on Th cell (signal 2) |
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Which part of the antibody recognizes the antigen?
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Variable part of L and H chains
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Which part of the antibody fixes complement?
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Fc portion of IgM and IgG
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Heavy chain makes up which portion of antibody?
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All of the Fc fragment and part of the Fab fragment
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Light chain makes up which portion of antibody?
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only part of the Fab fragment
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Fab portion of antibody
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- antigen-binding fragment
- determines idiotype: unique antigen-binding pocket --> only 1 antigenic specificity expressed per B cell - amino terminal - made up of all of the L chain, part of the H chain (including variable parts of both) |
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Fc portion of antibody
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- Constant
- Carboxy terminal - Conplement binding at CH2 (IgG + IgM only) - determines isotype (IgM, IgD, etc.) - Fc = lots of C's |
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Antibody diversity is generated by:
(4) |
1. Random "recombination" of VJ (light-chain) or V(D)J (heavy-chain) genes.
2. Random combination of heavy chains with light chains. 3. Somatic hypermutation (following antigen stimulation). 4. Addition of nucleotides to DNA during "recombination" (see #1) by terminal deoxynucleotidyl transferase. |
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Opsonization
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Antibodies attach to antigen, coating it and promoting phagocytosis
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Neutralization
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Free antibodies coat antigen and prevent bacterial adherence
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Complement Activation
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- Antibody activates complement, anhancing opsonization and lysis
- Membrane Attack Complex (MAC) |
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What do mature B lymphocytes express on their surface?
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IgM and IgD
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How do B cells change in to plasma cells?
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Isotype Switching
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Isotype Switching
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- how B cells differentiate into plasma cells
- alternative splicing of mRNA - mediated by cytokines and CD40 ligand |
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What do plasma cells secrete?
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IgA, IgE, or IgG
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IgG
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- main antibody in the secondary (delayed) response to an antigen
- most abundant - fixes complement - crosses the placenta -- provides infants with passive immunity - opsonizes bacteria - neutralizes bacterial toxins and viruses |
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IgA
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- prevents attachment of bacteria and viruses to mucous membranes
- does NOT fix complement - monomer (in circulation) or dimer (when secreted) - found in secretions (tears, saliva, mucus) and breast milk (known as "colostrum") - picks up secretory component from epithelial cells before secretion |
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IgM
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- produces in the primary (immediate) response to an antigen
- fixes complement - but does NOT cross the placenta - antigen receptor on the surface of B cells (along with IgD) - monomer on B cell or pentamer - shape of pentamer allows it to efficiently trap free antigens out of tissue whil humoral response evolves |
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IgD
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- unclear function
- found on the surface of many B cells and in serum |
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IgE
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- binds mast cells and basophils
- cross-links when exposed to allergen --> mediating immediate (type I) hypersensitivity --> through the release of inflammatory mediators such as histamine - mediates immunity to worms by activating eosinophils - lowest concentration in serum |
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Ig Epitopes
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- allotype (polymorphism) -- Ig epitope that differs among members of the same species
- can be on the light chain or heavy chain - "ALLotypes represent different ALLeles" |
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Isotypes
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- ie. IgG, IgA, etc.
- Ig epitope common to a single class of Ig (5 classes, determined by heavy chain) - Isotype = iso (same) --> common to the same class |
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Idiotype
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- specific for a given antigen
- Ig epitope determined by antigen-binding sites - Idiotype = idio (unique) --> hypervariable region is unique |
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Thymus-Independent Antigens
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- antigens lacking a peptide component
- cannot be presented by MHC to T cells - stimulate release of IgM antibodies only - do not result in immunologic memory - ie. lipopolysaccharide from cell envelope of gram-negative bacteria and polysaccharide capsular antigen |
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Thymus-Dependent Antigens
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- antigens containing a protein component
- class switching and immunologic memory --> occur as a result of direct contact of B cells with Th cells (CD40-CD40 ligand interaction) - causes release of IL-4, IL-5, and Il-6 - ie. conjugated H. influenzae vaccine |