BSC: T cell interactions 9/9

Question 1

What does Class II HLA deficiency look like?

Answer 1

• decreased CD4+ cells
• problem with positive selection
• decreased T reg cells ???
• decreased Ab’s in blood - these are needed for the activation of B cells
• increased CD8+ cells

Question 2

What does HLA Class I deficiency look like?

Answer 2

• decreased CD8+ T cells
• decreased ability to fight viral infections
• decreased HLA I (thus decreased HLA-a,b,c)
• Can result in the deficiency of Positive selection (No CD8+ T cells )
• increased Ab production - overstimulation of CD4+ T cells

Question 3

Relate how B cell production of Abs protects against reinfection with EBV

Answer 3

EBV = “mono”

• infects B cells by entering through the CR2 (CD21) receptor
• heterophile Abs (nonspecific Abs against Ags other than EBV) can be used in diagnosis
• in most cases EBV is self-limiting but during acute EBV infection, adaptive immunity is suppressed, which limits the host’s ability to fight other infections

Question 4

Predict the clinical outcome of a TH2 dominant to a TH1 dominant response in Mcyobacterium leprae infection

Answer 4

• Mycobacterium leprae infection s a TH2 dominant response: thus IFNgamma would be a treatment in order to increase the TH1 response
• TH2 dominant response would show increased IL-4, IL-5, and IL-13, which would upregulate IgE and would not have a large amount of IgG
• a IFNgamma deficiency would lead to a similar susceptibility to mycobacterial infections

Mycrobacterium leprae:

• • M. leprae lives in macrophages
• • M. leprae grows best at 30°C so lesions tend to show up on the extremities
• • Neurologic damage becomes apparent in the cases of uncontrolled infection
• • bacterial proliferation in Schwann cells
• • formation of granulomas and inflammation of the tissue around the nerve
• • The balance between TH1 and TH2 responses will determine the outcome of M. leprae infection

Question 5

Evidence that T cells are necessary to control EBV infection

Answer 5

1. Deficiencies in T cell-mediated immunity can lead to disseminated and lethal acute EBV infections.
2. EBV-infected B cells can survive in vitro indefinitely only if T cells are depleted or suppressed.
3. CTLs for EBV antigens can be isolated from patients with acute infectious mononucleosis.
4. B cell lymphomas occur with an increased frequency in individuals with T cell deficiencies.

Question 6

Compare how T cell activation by superantigens is different than conventional Ags

Answer 6

• Toxic Shock syndrome: common Vbeta chains due to superantigen binding
• superAgs activate without antigen presentation and without costimulation from CD7/CD28 - this will result in a much quicker response
• Super Ags can activate a whole bunch of T cells at the same time –> response of greater magnitutde
• rapid release of cytokines due to Super Ags results in suppression of adaptive immune responses: too many inflammatory signals results in T cell responses being suppressed during infection
• which cytokine would be responsible for vascular depletion observed after infection with superantigen? TNFalpha
• • Superantigens do not rely on MHC specificity for T cell activation.
• • Superantigens directly activate T cells by linking the Vβ chain of the TCR to MHC class II molecules (outside of the binding groove)
• • Since superantigens depend on Vβ chain specificity, anywhere from 2-20% of T cells can be activated at one time
• • The response observed after superantigen activation is not antigen-specific and leads to excessive production of cytokines by CD4+ T cells
• • Symptoms include:
• o Fever, rash
• o Edema, hypotension and shock with multiple organ failure due to intravascular volume depletion
• o Reversible suppression of adaptive immune responses

Question 7

Correlate the clinical presentation in the IFNgamma deficiency case to the mechanism of myobacteria clearance

Answer 7

• no IFNgamma = no stimulation of macrophages = no clearance of myobacteria