adaptive immunity Flashcards
What is the Major Histocompatibility Complex?
genes encoding proteins that enable the host to distinguish self and non-self
What is the human MHC?
human leukocyte antigen (HLA)
What does it mean when the HLA genes are codominant?
both parental alleles of each MHC gene are expressed
What do MHC molecules bind to?
only peptides
Proteins in the cytosol of nucleated cells display what MHC class?
class I MHC molecule
Extracellular proteins, internalised by APCs and processed late endosomes and lysosomes display what MHC class?
class II MHC molecule
What are class I MHC molecules?
identify all nucleated cells of the body as “self”
e.g. leukocytes, epithelial cells, mesenchymal cells
endogenous antigen processing
What happens when class I MHC molecules bind to peptides?
signals to the immune system that it is an infected host cell
What do class II MHC molecules bind to?
antigens
What happens when class II MHC molecules bind to antigens?
degraded as a consequence of phagocytosis or receptor mediated endocytosis
What type of processing is MHC class II molecules?
exogenous (antigen processing)
What type of T cells do class II MHC molecules interact with?
CD4+ T cells
Why are CD4 and CD8 molecules useful on T cells?
stabilise interaction of TCR and MHC/peptide
What is immunologic tolerance?
lack of response to antigens that is induced by exposure of lymphocytes to these antigens
What is central tolerance?
death of immature T cells and the generation of CD4+ regulatory T cells
What is peripheral tolerance?
functional inactivation or death, or suppression of self-reactive T cells by regulatory T cells
What are the two types of TCR?
αβ
γδ
What is the antigen-recognising domains of the TCR called?
variable regions
True or false: every individual T cell has a different TCR specificity?
true
TCR diversity allows for?
identification of a plethora of antigens
How is TCR diversity generated?
by combining the distinct variable (V), diversity (D), and joining (J) gene segments
The vast amount of TCR clones can be formed due to…
recombination, random insertion, deletion and substitution
What does the variable region of each TCR contain?
complementary determining regions (CDRs)
How can T cells die or become unresponsive when exposed to antigens?
no co-stimulation
What happens in the presence of co-stimulation of T cells?
rapid secretion of IL2 = increase expression of IL-2R (increases sensitivity)
What are the main functions of IL2?
stimulate the survival and proliferation of T cells
What are the 3 signals needed to activate a T cell?
- TCR binding to peptide-MHC antigen + co-receptor (CD4/CD8)
- APC molecules (B7-1 + B7-2) bind to costimulatory receptors (CD28)
- cytokines induce the expression of transcription factors
During immune synapse DCs trigger what cell?
naive T cells (TH0)
What are the different subset of TH0 cells?
TH1, TH2, TH17, T(reg)
Cytokines released by activated T cells are used to?
communicate with other cell types
Cytokines released by activated T cells are used to?
communicate with other cell types
TH17 cells are activated due to?
response to extracellular bacterial and fungal infections
Regulatory T cells main function is to?
suppress immune response
- block immune cells
- block B7 on APCs
- consume IL-2
What is the role of TH1 cells?
increase the ability of macrophages to kill phagocytosed microbes
How are TH1 cells developed?
DCs produce INF-γ and IL-12
How does the release of IFN-γ by TH1 cells help in phagocytosis?
recruitment of monocytes and granulocytes
activates anti-microbial activity of macrophages
What does TH2 cells stimulate?
antibody responses, and defend against helminth parasites
What cytokines released by DCs produce TH2 cells?
IL-4
What cytokines do TH2 cells release?
IL-4, IL-5 and IL-13
What do TH2 cytokines inhibit?
the activation of classical macrophages
What do TH2 cytokines stimulate?
the alternative pathway (important in tissue repair and fibrosis)
What are TH2 cells involved in?
allergic reactions (trigger mast cells and eosinophil activation)
What is the role of CD8 T cells?
recognition of peptides on infected cells or tumour cells expressed by MHC-1 molecules
What are a ways CD8 T cells are activated to induce differentiation?
cross-presentation = DCs sufficiently activated
require additional help from CD4 cells
How does CD4+ cells help differentiate CD8+ T cells into cytotoxic T cells?
B7 expressed by DC activates CD4+ T cells to express IL-2 and CD40 ligand
CD40 ligand binds to CD40 on DC = increase B7 expression
increase co-stimulatory signals to CD8+ T cell
IL-2 acts to promote effector cell differentiation
What is perforin?
disruption of the integrity of target cell plasma membrane and endosomal membranes
What is granzymes?
activate enzymes called caspases which induce apoptosis
