NEMO Deficiency SSPE SCID Omenn Syndrome Bare Lymphocyte Syndrome Burkitt s Lymphoma DiGeorge s Syndrome ALPS Hyper IgM syndrome Diseases sub acute sclerosing panencephalitis brain disease that is a late consequence of measles X linked hypohydrotic ectodermal dysplasia and immunodeficiency lack one subunit of IKK impaired activation of NF B inefficient macrophage activation through TLR4 signaling on x chromosome more common in boys severe combined immunodeficiency disease one of the RAG genes doesn t work both B and T cells are absent children die in early infancy from common infections unless they have bone marrow transplants RAG proteins have partial enzymatic activity differs from SCID in symptoms red rash on face and shoulders TAP is non functional no peptides in ER MHC I doesn t reach surface patients have less than 1 of normal MHC class I lack of MHC II expression CD4 T cells fail to develop lack of MHC I loss of CD8 T cells patients have poor CD8 T cell responses and suffer from chronic respiratory infections parts of chromosome 8 and 14 have been exchanged MYC proto oncogene on chromosome 8 and heavy 14 light 2 or 22 chain genes switch abnormal expression as a result of translocation causes increased growth deletion in chromosome 22 thymus fails to develop T cells are absent susceptibility to wide range of opportunistic infections resembles SCID Lymphadenopathy in autoimmune lymphoproliferation syndrome patients lack functional Fas molecules cannot control size of lymphocyte population nor remove autoimmune cells secondary lymphoid organs become swollen in absence of infection patients that lack CD40 ligand on T cell abnormally high levels of IgM in blood serum almost no IgG and IgA B cells are unable to switch isotype cannot make Ab responses to TD antigens no germinal centers X linked prominent in males Hemolytic Disease of the Newborn Mom is Rh negative but dad isn t 1st child is fine but when first baby is born fetal RBCs bleed into mom adaptive immune response second pregnancy if fetus is also Rh positive mom can make IgG antibodies that can cross the placenta and tag RBCs for destruction Anti Rh IgG RhoGAM is given to mom at 28 weeks and within 72 hrs after birth coats baby s RBCs that enter mom tricks immune system into thinking it s a secondary immune response RNA virus Pattern of infection epidemics Virus spreads fast and subsides quickly genome 8 RNA molecules RNA replication is error prone generates many point mutations new viral strains lack hemagglutinin or neuraminidase epitopes that induced protective immunity in previous epidemis new generation of virus evades protective immunity ensures long term survival of virus antigenic drift changes are small point mutation so some cross reaction occurs epidemics occur every other winter pandemics are caused by recombinant viruses part avian and part human so hemagglutinin neuraminidase epitopes are very different from humans Antigenic shift pandemic severe avian origin creates very different strain every 10 50 years most often occurs in farmers near to livestock viruses arise from pigs that become infected with both avian and human simultaneously caused by trypanosomes a protozoan trypanosomes live in mammals and insects cyclic trypanosomes use gene rearrangement to change surface antigens they usually express one dominant type of VSG antibodies produced against it but not against those that have switched VSG genome contains more than 1000 genes encoding VSGs this mechanism produces a dramatic cycling in of parasites chronic cycling of Ab production and antigen clearance heavy deposition of immune complexes and inflammation inflammation causes neurological damage and coma persists in host by hiding from immune response in sensory neurons Influenza Herpes African sleeping sickness Herpes Epstein Barr Herpes Varicella Zosters Tuberculosis Syphillis Toxic shock syndrome infects epithelial cells spreads to sensory neurons serving infected area Latency dormant state no replication nor generation of enough peptides to signal presence virus is unrecognized stress reactivates the virus reinfects epithelial tissues causes sores nerve cells have little MHC reduced CD8 T cell participation childhood infection mild cold like diseases infects B cells by binding to CR 2 component of B cell receptor complex infected B cells proliferate and produce virus stimulates EBV specific T cells to react small number of B cells become latently infected but replication is controlled by CD8 cells chicken pox dormancy in dorsal root ganglia reactivation causes shingles caused by mycobacterium tuberculosis prevents fusion of phagosome with lysosome caused by treponema pallidum coats itself with human protein toxins bind to sites shared by many different TCRs stimulate excessive polyclonal response involved 2 20 of total of CD4 T cells after proliferation T cells with bound antigen die by apoptosis and remove memory T cells massive cytokine release IL 1 IL 2 TNF alpha antigen bridges MHC class II and TCRs X linked Agammaglobulinemia Antibody deficiency X linked hyper IgM C3 complement deficiencies B cell growth and differentiation blocked at pre B cell stage due to defect in gene coding for tyrosine kinase Btk intracellular signaling is lost increase in bacterial infections that require antibodies for clearance capsulated complement activation increase in viral infections that enter in gut normally neautralized by antibodies diminished antibody production see Hyper IgM syndrome above defects in complement components C3 deficiencies increased bacterial infections phagocytosis is decreased Leukocyte adhesion deficiency immune complex clearance is impaired increased inflammation and tissue damage C5 C9 deficiencies lysis of bacteria is decreased Neisseria defect in phagocytes inability of white cells to migrate caused by mutations in the gene coding for CD18 necessary for leukocyte integrins on phagocytes to leave blood and enter site of infection recurrent pyogenic infections and wound healing problems Chronic granulatomatous disease Chediak Higashi syndrome Wiscott Aldrich syndrome ADA or PNP deficiency AIDS inability to produce superoxide radical 02 compromised antibacterial activity Defect in ability to fuse phagosome with lysosome cytoskeletal arrangement of T cell lost no cytokine released impairment of platelets and lymphocytes x linked accumulation of nucleotide metabolites affect B and T cell development accumulation is toxic to