What does the thoracic duct drain into?
Positive T cell selection
- Selects for T cells that can bind MHC
- Occurs in cortex of thymus
Negative T cell selection
- Selects for autoreactive T cells
- Occurs in medulla of thymus
Where are small antigenic peptides attached to MHC I?
What is significant about CD5+ B cells?
They have not undergone class switching, and can only produce IgM
Function of perforin and granzymes
- Perforin delivers NK cell granule contents into infected cells
- Granzyme activates serine proteases, which triggers apoptosis
What activates T helper cells?
Foreign antigen presentation on MHC II, with help of B7 costimulatory molecule
Which MHC activates cytotoxic T cells?
MHC I (presents viral or self antigens)
Where is the CD40 ligand located, and what does it do?
- CD 40 ligand on T helper cell membrane
- Mediates AB class switching
Function of immunoglobulins alpha and beta on B cell membrane
Transduce AG binding signal to cytoplasm
Difference between pro-B cells and pre-B cells
- Heavy chain rearrangement occurs in pro-B cells
- Light chain rearrangement occurs in pre-B cells
- Randomly inserts nucleotides between D and J regions during DNA synthesis to increase affinity of AB for AG
- Used as a marker for ALL
Which antibody does not undergo somatic hypermutation?
What is a thymus independent antigen?
Thymus independent antigens lack a peptide component, so cannot be presented by MHC to T cells. They stimulate release of IgM only, and do not activate memory
CD21, found on B cells
C3b and IgG
- Recurrent pyogenic and respiratory infections
- Increased susceptibility to type III hypersensitivity reactions
DAF helps prevent complement activation against self-cells. Is deficient in PNH.
How do interferons kill viruses?
They induce production of a ribonuclease that degrades viral mRNA
What type hypersensitivity reaction are serum sickness and arthus reaction?
- Type III
- Present with fever, urticaria, and arthralgias, 5--10 days after antigen exposure
Hypersensitivity reactions: Grave's and Hashimoto's
- Graves--type II
- Hashimoto's--type IV
What are the type IV hypersensitivity reactions?
- Diabetes I
- Contact dermatitis
6 month old boy presents with recurrent bacterial infections, decreased B cells, and decreased immunoglobulins
- Bruton's agammaglobulinemia
- Defect in BTK tyrosine kinase gene
- B cell maturation is impaired
Baby presents with severe pyogenic infections and increased IgM with no other immunoglobulins
- Caused by defective CD40 ligand on T helper cells
Patient with a history of respiratory infections experience anaphylaxis after a blood transfusion
- Selective Ig deficiency, due to defective class switching
- Most common is IgA deficiency
- Patients often develop antibodies against the missing Ig--so don't transfuse!
Which Ig do Di George patients have?
IgM only, since T cells are needed for class switching
Patient has recurrent disseminated mycobacterial infections and low interferon gamma
- IL12 receptor deficiency
- (IL12 is secreted by macrophages and activates T helper 1 cells)
Patient presents with staphylococcal abscesses, retained primary teeth, eczema, and increased IgE
- HyperIgE/Job's syndrome
- T helper cells cannot produce interferon gamma, which inhibits neutrophil response to chemotactic stimuli
- Normally, IFN gamma inhibits T helper 2 cells--too many T helper 2 cells results in elevated IgE
Primary defense against cutaneous and hematogenous candida infection
- T cells protect against cutaneous candida
- Neutrophils protect against disseminated candida
Name 3 causes of SCID
- Defective IL2 receptor (X linked)
- Adenosine deaminase deficiency
- Missense mutation in RAG
Patient presents with TTP, recurrent infection, and truncal eczema.
- Progressive B and T cell deletion, due to an XR mutation in cytoskeleton proteins
Patient presents with cerebellar ataxia, spider angiomas, and IgA deficiency
Ataxia telangiectasia, caused by defective DNA repair enzymes
A baby presents with recurrent bacterial infections and delayed separation of umbilicus
- Defective integrin protein on phagocytes impair ability of leukocytes to adhere to endothelium
Patient presents with recurrent staph and strep infections, pale skin, and peripheral neuropathy
- An AR defect in microtubule function impairs phagocytosis
Patient presents with a history of recurrent infections by catalase positive organisms (staph, E. coli, aspergillus)
Addition of nitroblue tetrazolium to blood sample does not make sample turn blue
- Due to lack of NADPH oxidase
Mechanism and side effect of cyclosporine
- Inhibits calcineurin, which prevents release of IL2, thereby blocking T cell activation
- Major side effect is nephrotoxicity, which can be controlled with mannitol diuresis
Mechanism and side effects of tacrolimus
- Binds to FK binding protein and inhibits IL2 release
- Causes nephrotoxicity, peripheral neuropathy, and hyperglycemia
Monoclonal antibody against CD3, inhibits T cell signal transduction
- Binds to MTOR, inhibits T cell proliferation in response to IL2
- Causes hyperlipidemia
Mycophenolate mofetil (MMP)
Inhibits de novo guanine synthesis
Monoclonal antibody against IL2 receptor
What is oprelvekin used for?