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Immunology - CORE > T Cell Activation > Flashcards

T Cell Activation Flashcards

1
Q

What are the functions of Th and Tc cells?

A
  • Th coordinate immune response
  • Tc identifies and kills infected cells
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2
Q

How do Th and Tc cells function via TCR?

A
  • resembles a membrane bound antibody Fab fragment
  • 2 transmembrane glycoprotein chains - alpha & beta
  • form in a similar way to the B cell receptor
  • diversity: multiple copies of variable gene segments rearranged in different combinations
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3
Q

Describe the 3 signals involved with T cells

A
  • Signal 1: TCR interaction with specific antigen on MHC
  • Signal 2: co-stimulatory signals
  • Signal 3: not required but commonly delivered, cytokines that effect T cell differentiation
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4
Q

Describe antigen presenting cells in the naive immune response

A
  • dendritic cells critical in activation of T cells - both CD4 and CD8
  • dendritic cells differentiate from circulating monocytes
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5
Q

Describe APCs in active immune response

A
  • macrophages and B cells also important APCs presenting to Th cells via MHC class II
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6
Q

Describe dendritic cells in APC

A
  • Immature DCs present in epithelial surfaces - engulf antigen
  • migrate via afferent lymphatics to lymph node
  • reside in paracortex where they present antigen to naive T cells via MHC
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7
Q

Describe how dendritic cells present to CD8+ cells

A

via antigen cross presentation - presentation of exogenous antigens on MHC class I

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8
Q

Describe why there is diversity in MHC genes

A
  • T cells can only recognise antigen in context of self (MHC)
  • binding of antigen to MHC molecules critical in T cell activation
  • therefore diversity in MHC genes
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9
Q

Describe the 3 types of diversity in MHC genes

A
  • polygenic
  • polymorphic
  • combination of polygenic and polymorphic
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10
Q

Describe polygenic diversity in MHC genes

A
  • several different genes for class I and II
  • each individual will present 3 sets of class I molecules and 4 sets of class II
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11
Q

Describe polymorphic diversity in MHC genes

A
  • many alleles for each gene
  • MHC one of the most polymorphic gene known
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12
Q

Describe the variation between MHC allotypes

A

concentrated in:
- peptide binding groove affecting peptide recognition
- alpha helices forming walls affecting TCR recognition

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13
Q

Describe how polymorphism is created

A
  • point mutations
  • gene conservation - chunks of one gene copied into structure of another
  • pseudogenes can be a source of genetic material bringing about gene conservation
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14
Q

Describe Class Ia and Class II MHC

A
  • each MHC molecule binds a limited repertoire of peptides influencing adaptive immune responses
  • heterozygotes express more alleles and a wider range of peptide binding
  • overdominant selection - heterozygous advantage
  • evidence for influence on sexual selection
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15
Q

Describe how MHC can influence sexual selection

A
  • detection of MHC via olfaction due to MHC pheromones
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16
Q

Describe MHC Signal I in dogs

A
  • due to small gene pools - some pedigree breeds have limited intra-breed variability in MHC genes - increased levels of MHC homozygosity
  • DLA alleles associated with resistance/susceptibility to poor response to rabies vaccine in Rottweilers
17
Q

Describe MHC in cattle

A

BoLA alleles associated with resistance/susceptibility to:
- ticks
- mastitis
- foot and mouth disease

18
Q

Describe MHC in horses

A

ELA alleles associated with resistance/susceptibility to:
- allergic response to Culicoides bites
- sarcoid tumours

19
Q

Describe Signal I

A
  • TCR interacts with MHC
  • MHC class II interacts with CD4+/Th
  • MHC class I interacts with CD8/Tc
  • specificity dependant on CD8 and CD4
20
Q

Describe the Signal I function on CD4 and CD8 molecules

A
  • stabilise/strengthen TCR/MHC interaction
  • transduce signal to T cell
  • affinity of MHC-peptide complexes and TCRs is weak
  • needs CD4/CD8 to reinforce binding
21
Q

Describe co-stimulation of Signal II

A
  • CD40 receptor on APC
  • CD154 receptor on T cell
  • activatory signal for both APC and T cell
  • CD28 on T cell surface
22
Q

Describe CD28 on T cell surface

A
  • interacts with CD80 or CD86 on APC
  • activates T cell
  • without CD80/CD86 interaction - no activation
  • important in preventing immune responses
  • turns T cell into an anergic T cell - unable to create a response
23
Q

Describe CD8+ T cell activation

A
  • tend to require higher levels of co-stimulation
  • role of activated CD4+ also in activation of CD8+
  • release of IL-2 from CD4+ T cell one way
24
Q

Describe the ways T cells can respond to antigen after activation

A
  • effector T cells
  • no/far lower requirement for co-stimulation
  • change adhesion receptors to change circulation
25
Q

Describe what proliferating T cells express more and its effects

A
  • express more CTLA-4 (CD152)
  • CD80-86 interaction with CTLA-4 leads to inhibitory signals
26
Q

Describe the PD-1 receptor and its role in inhibiting T cell activation

A
  • present on T cells after activation
  • binding of PD-1 to either PD-L1 or PD-L2
  • PD-L upreg on macrophages/NK/B cells after IFNү stimulation
  • critical in cancer
  • cancer cells manipulate PD-1/PD-L1 downreg inflammation
  • antibodies created against PD-L1 block interaction
27
Q

Describe the antibodies created against the PD-L1 block interaction

A
  • increase stimulation
  • more pro-inflammatory cytokines (IL-2 and IFNү)
28
Q

In which species is PD-1 conserved?

A
  • cats
  • dogs
  • cattle
  • horses

Immunology - CORE (18 decks)

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