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Immunology
First Aid - Biochem - Immunology
Question | Answer |
---|---|
spleen sinusoids | long, vascular channels in red pulp with fenestrated barrel hoop basement membrane, macrophages found nearby |
T cells - location (thymus / spleen) | found in periarterial lymphatic sheath (PALS) and in the white pulp of the spleen |
B cells - location (bone marrow / spleen) | found in the follicles within the white pulp of the spleen |
Macrophages in the spleen | remove encapsulated bacteria (S. pneumoniae, H. flu, Salmonella, N.menigitidis) |
Splenic dysfunction | decreased IgM leads to decreased complement activation and decreased C3b opsonization that leads to increased susceptibility to encapsulated organisms |
Post-splenectomy changes in cells | Howell-jolly bodies (nuclear remnants), target cells, and thrombocytosis |
Thymus | site of T cell differentiation and maturation |
Thymus - cortex | dense with immature T cells |
Thymus - medulla | pale with mature T cells and epithelial reticular cells and contains Hassall's corpuscles |
Thymus - corticomedullary junction | positive (MHC restriction) and negative selection (nonreactive to self) occur at this junction |
Innate immunity | receptors that recognize pathogens are germline encoded, response to pathogens is fast and nonspecific, no memory, neutrophils, macrophages, dendritic cells, natural killer cells, and complement |
Adaptive immunity | receptors that recognize pathogens undergo recombination during lymphocyte development, response is slow on first exposure, but memory response is faster and more robust, T cells, B cells, and circulating antibody |
T cell differentiation > CD8+ T cell or CD4+ T cell | T cell precursor (Bone Marrow) -- CD4+CD8+ T cell differentiates to the CD4+ or CD8+ T cell in the (Thymus) --- and then the cytotoxic (8) and the helper T cell travel to (Lymph node) >> helper becomes Th1 (cell-mediated) or Th2 (humoral) |
CD8+ T cell (cytotoxic) | kills virus infected cells, neoplastic, and donor graft cells |
CD4+ T cell (helper T cell) -- **Th1 | Helper T cell > (IL-12) Th1 cell mediated response, functions: make IL-2, IFN-y and activate macrophages and CD8+ T cells, inhibited by IL-10 |
CD4+ T cell (helper T cell) -- **Th2 | Helper T cell > (IL-4) Th2 humoral response, functions: make IL-4, 5, 10 and help B cells make antibody (IgE, IgG), inhibited by IFN-y |
MHC | encoded by HLA genes, MHC present antigen fragments to T cells and bind TCR. MHC I = A, B, C and MHC II = DR, DO, DP |
MHC I | expressed on almost all nucleated cells, antigen is loaded in RER of mostly intracellular peptides - mediates viral immunity - pairs with B2-microglobulin (aids in transport to cell surface) |
MHC II | expressed only on antigen presenting cells (APC's), antigen is loaded following release of invariant chain in an acidified endosome |
APC's | professional APC's = dendritic cells, macrophages, and B cells |
B cell functions | make antibodies, IgG antibodies opsonize bacteria and neutralize bacteria, allergy (IgE), cytotoxic and immune complex hypersensitivity (IgG), antibodies cause organ rejection (hyperacute) |
T cell functions | CD4+ T cells help B cells make antibody ad produce IFN-y (Th1) that activates macrophages, Kill viruses directly with CD8+ T cells, and organ (allograft) rejection (acute or chronic) |
Natural Killer Cells (*innate immune system*) | perforin and granzymes to induce apoptosis of virally infected cells and tumor cells, activity enhanced by IL-12, IFN-B, IFN-alpha, kill when exposed to a nonspecific activation signal on target cell and/or to an absence of class I MHC on surface |
T cell and MHC binding | Helper T cells have CD4 which binds to MHC II On APC's Cytotoxic T cells have CD8 which binds to MHC I on the virus infected cell |
IL-1 and TNF-alpha release | macrophages and T cells stimulate each other - T cells activate macrophage (APC) with IFN-y and macrophages activate CD4 T cells with IL-1 and TNF-alpha |
HOT T-Bone stEAk | IL-1: fever (hot), IL-2: T cells, IL-3: Bone marrow, IL-4 IgE production, IL-5 IgA production |
CD4 Th cell activation | foreign body phagocytosed by APC, foreign antigen presented on MHC II and recognized by TCR on Th cell, co-stimulatory signal of B7(APC) and CD28(Th) > Th cell activated to produce cytokines |
CD8 cytotoxic T cell activation | endogenously made (viral or self) proteins (antigen) are presented on MHC I and recognized by TCR on Tc cell, IL-2 from Th cell activates Tc cell to kill virus infected cell |
B cell class switching | Il-4, 5, or 6 from Th2 cell, and CD40 receptor activation by binding CD40 ligand on Th2 cell |
Antibody structure and function | variable part of L and H chains recognizes antigens, Fc portion of IgM and IgG fixes complement. Heavy chain contributes to Fc and Fab fractions. Light chain contributes only to Fab function. |
Antibody - Fab | antigen binding fragment, determines idiotype: unique antigen binding pocket, only 1 antigenic specificity expressed per B cell |
Antibody - Fc | constant, carboxy terminal, complement binding at Ch2 (IgG, IgM only), carbohydrate side chains, determines isotype (IgM, IgD...) |
opsonization | antibody promotes phagocytosis |
neutralization | antibody prevents bacterial adherence |
complement activation | membrane attack complex (MAC), antibody activates complement, enhancing opsonization and lysis |
Antibody diversity | random recombination of light chain or heavy chain genes, somatic hypermutation after antigen stimulation, addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase |
Antibody Isotypes include... | IgG, IgA, IgM, IgD, and IgE - mature B cells express IgM and IgD on their surfaces, they may differentiate by isotype switching (alt. splicing of mRNA, mediated by cytokines and CD40 ligand) into plasma cells that secrete IgA, IgE, or IgG |
IgG | main antibody in secondary response to antigen, most abundant, fixes complement, crosses the placenta (provides infants with passive immunity), opsonizes bacteria, neutralizes bacterial toxins and viruses |
IgA | prevents attachment of bacteria and viruses to mucous membranes, found in secretions (tears, saliva, mucus) and breast milk, picks up secretory component from epithelial cells before secretion |
IgM | produced in the primary response to antigen, fixes complement but doesn't cross the placenta, antigen receptor on surface of B cells, traps free antigens out of tissues while humoral response evolves |
IgD | unclear function, found on surface of many B cells and in serum |
IgE | binds mast cells and basophils, cross-links when exposed to allergen, mediates inflammatory response mediators like histamine (allergy), lowest concentration in serum |
Thymus independent antigens | antigens lacking a peptide component, can't be presented by MHC to T cells, only release IgM antibodies, no memory, (ex. lipopolysaccharide from cell envelope of Gram-, and polysaccharide capsular antigen) |
Thymus dependent antigens | antigens with a protein component, class switching and memory occur as result of contact btwn B cells and Th cells (CD40-CD40 ligand interaction) and release of IL-4,5, and 6 |
Active immunity | induced after exposure to foreign antigens, slow onset, long lasting protection - memory |
Passive immunity | based on receiving preformed antibodies from another host, rapid onset, short life span (half life - 3wks) ex. IgA in breast milk |
Antigen variation examples | Viruses: influenza, major = shift or minor = drift, due to DNA rearrangement and RNA segment reassortment |
Autograft | from self |
Syngeneic graft | from identical twin or clone (isograft) |
Allograft | from non identical individual of same species |
Xenograft | from different species |
hyperacute rejection | antibody mediated due to presence of preformed antidonor antibodies in transplant recipient, minutes after transplantation |
acute rejection | cell mediated due to cytotoxic T lymphocytes reacting against foreign MHC's, happens weeks after transplantation, reversible with immunosuppressants like cyclosprine and OKT3 |
chronic rejection | T cell and antibody mediated vascular damage (vascular fibrosis) occurs months to years after transplantation. irreversible. Class-I MHC (non-self) perceived as class I MHC (self) presenting a non self antigen |
Rejection - symptoms of disease | grafted T cells proliferate in the immunocompromised host and reject cells with "foreign" proteins resulting in severe organ dysfunction, symptoms include maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea |
Cyclosporine | binds to cyclophilins, blocks differentiation and activation of T cells inhibits calcineurin, prevents production of IL-2 and receptor, suppresses organ rejection, some autoimmune disorders, viral infections and nephrotoxic |
Tacrolimus | binds to FK binding proteins, inhibits secretion of IL-2 and other cytokines, no T cell differentiation, activation. organ transplant recipients. nephrotoxic, neuropathy, HTN, hyperglycemia. |
Azathioprine | antimetabolite precursor of 6MP that interferes with metabolism and syn of nucleic acids. toxic to proliferating WBCs. kidney transplants, hemolytic anemias. bone marrow suppressed, 6MP metabolized by XO, toxic with allopurinol (gout) |
Sirolimus (rapamycin) | binds to mTOR (cell regulator), inhibits T cell proliferation in response to IL-2. kidney transplants combined with cyclosporine and corticosteroids. hyperlipidemia, leukopenia, thrombocytopenia. |
Mycophenolate mofetil | inhibits de novo guanine synthesis and blocks WBC production |
Daclizumab | monoclonal antibody with high affinity for IL-2 receptor on activated T cells |