Cell Mediated Immunity Flashcards
Cell Mediated Immunity
The adaptive immune system that functions to combat intracellular pathogens
T-cell interactions during cell-mediated immunity
Interactions with:
- Phagocytes
- Infected host cells
- B lymphocytes
Epitope
That part of an antigen that is recognized by lymphocyte antigen receptors (also known as antigenic determinant)
C-region:
V-region:
Constant region: Genetically conserved receptor domain
Variable region: genetically diverse antigen recognition domain
Affinity for antigen (B-cells and T-cells)
BCR has higher initial affinity which increases during response
TCR affinity is fixed
T-cells are ________ restricted
MHC
What provides the mitogenic signal for developing lymphocytes to proliferate and where is it produced
IL7 produced by bone marrow stromal cells
Failures at each checkpoint (1 - 3)
1) Failure to express pre-antigen receptor (β chain)
2) Failure to express antigen receptor (α chain)
3) Negative selection (strong antigen recognition)
TCR (T-cell receptor) structure
αβ T-cells - Most abundant - MHC restricted γδ T-cells - Common in gut mucosa (recognize lipids) - Not MHC-restricted
The variable region of the TCRβ chain is composed of three gene segments
V - Variable
D - Diversity
J - Joining
Recombination events making up first checkpoint
- First recombination event is the heavy chain D and J exons
- Second recombination of V with DJ
- VDJ recombination with TCRβ constant region
- The heavy chain transcript (VDJ-C) is processed and expressed within the cell and then at the cell surface with a surrogate light chain
Formation of the intact TCRαβ protein (Second checkpoint)
TCRα chain V and J recombine and VJ recombine with a C segment (VJ-C) to form α chain for TCR - combines with β chain to form the intact TCRαβ protein
What are the 3 regions of hypervariability in the variable region of the TCRα and TCRβ chains
CDR1
CDR2
CDR3
What is the purpose of CDRs?
Encode specific amino acid residues in the TCR protein that contact the antigen
2 mechanisms of antigenic diversity
Combinatorial - variation amongst possible VDJ or VJ combinations
Junctional: Removal of nucleotides AND addition of nucleotides by TdT enzyme; strand repair during recombination process
Total number of possible epitopes with combinatorial and junctional diversity
TCR: 10^16
Immunoglobin: 10^11
Location of induction and effector phases of cell mediated immunity
Induction phase: lymphatic tissues; spleen
Effector phase: Peripheral tissues (site of infection)
General activation of T cells
- Microbial antigens traffic to peripheral lymphoid tissue inside activated phagocytic antigen-presenting cells (APC)
- In combination with antigen-presentation these T cells receive signals from the microbe or from the innate immune system (cytokines or pattern recognition receptors) which enhance their activation (co-stimulatory second signal)
- T cells only recognize and respond to those antigenic peptides displayed by MHC
Steps in T Cell gaining Effector functions
1) Antigen recognition
2) Activation
3) Clonal Expansion
4) Differentiation
5) Effector functions
Recognition of antigen by T cell increases _______ (integrin) affinity
LFA1 (anchor naive T cells to APC during antigen presentation)
First Signal
T cell receptor and the CD4 or CD8 co-receptor together recognize MHC: antigen peptide complexes on the APC cell surface
\_\_\_\_\_\_ recognize antigen presented by MHC class II \_\_\_\_\_\_ recognize antigen presented by MHC class I
TCR-CD4; TCR-CD8
How many TCR-co-receptors need to be engaged simultaneously to activate naive T-cells?
two or more
CD4+ T cells become:
CD8+ T cells become:
Cytokine-producing helper cells
Cytolytic T-lymphocytes (CTLs)
Second Signal
T-Cell CD28 interaction with co-stimulatory molecule on APC cell surface
Co-stimulatory molecule on APC
B7
CD3
Signaling receptor expressed on all T-cells
Marker used to find T-Cells in the body