Overview of immune responses Flashcards
What are the properties and actions of NK cells?
Lymphoid cells with innate immune functions -> early response to infection with viruses + intercellular bacteria.
Upon activation:
Directly lyse target cells by exocytosis of perforin + granzymes.
Secrete cytokines e.g. IFNgamma, TNFalpha -> pro-inflammatory.
How is NK cell activity regulated?
Activating receptors -> initiate killing of cells recognised as aberrant.
Inhibitory -> abort killer function when host-cell surface markers are recognised.
NK cells distinguish healthy cells from infected / cancerous cells through balance between activating + inhibitory signals -> activated to kill when there’s either upregulation of activating signals or downregulation of inhibitory signal.
Outline antibody dependent cellular cytotoxicity (ADCC)
Antibody binds antigens on surface of target cells.
Fc receptors on NK cells recognise bound antibody.
Cross-linking of Fc receptors signals NK cells to kill target cell.
Target cell dies by apoptosis.
What are the first responses when a pathogen enters the body via a wound in the skin?
Antimicrobial peptides at epithelial surfaces
Recognition + phagocytosis (macrophages, neutrophils)
Killing of virus-infected cells by NK cells
Complement activation
Inflammation
What is inflammation initiated by?
Macrophages + DCs:
Call neutrophils + monocytes -> (more macrophages) for help and leukocytes.
Prevent spread of infection (coagulation of blood vessels).
Repair wounded tissue.
Achieved via production + secretion of cytokines + chemokines by macrophages.
What is inflammation mediated by?
TLR ligation and signalling.
Expressed in macrophages, DCs, B + specific T lymphocytes, fibroblasts + epithelial cells for recognition of PAMPs -> induction of signalling events -> transcriptional activation of pro-inflammatory cytokine + chemokine genes e.g. TNF, IL-1, IL-6, IL-8, IL-12.
What are the functions of complement?
Covalent binding to pathogens (opsonisation), marking for phagocytosis.
Products of enzymatic reactions act as chemoattractants (like chemokines) to recruit and activate (like cytokines) phagocytes.
Formation of MAC that directly kills bacteria by lysis.
How is adaptive immunity initiated?
Adaptive immune responses aren’t initiated at sites of infection.
Some pathogen is transported by lymph to peripheral lymphoid tissues where naïve T cells are continually migrating.
Pathogens infecting:
mucosal surfaces -> accumulate in Peyer’s patches
blood -> spleen
other sites -> lymph nodes downstream of site of infection.
How do dendritic cells initiate adaptive immunity?
DCs in peripheral tissues ingest microbes + are activated -> become APCs -> migrate to lymph nodes + present antigens to naïve lymphocytes -> lymphocytes with appropriate receptors undergo clonal selection + expansion.
DCs in tissue -> phagocytic but can’t activate T cells.
DCs in lymph nodes -> can’t phagocytose but can activate T cells.
What are the antigen presenting cells?
Activation of DCs + macrophages:
recognition of PAMPs by innate immune receptors,
production of cytokines,
expression of co-stimulatory molecules (e.g. CD80 / CD86).
DCs most relevant for antigen presentation to naïve T cells.
Macrophages aren’t migratory so don’t meet naïve T cells in lymph nodes where most are activated.
B cells present antigen to receive T cell help from activated effector T cells.
Which signals are involved in activating naïve T cells by APCs?
3 kinds of signals are involved.
Binding of foreign-peptide, self MHC complex by T-cell receptor -> e.g. CD4 co-receptor transmits signal to T cell that antigen has been encountered.
2nd signal requires co-stimulatory signal to be delivered by same APC -> e.g. CD28 on T cell encountering B7 on APC -> increased survival + proliferation of T cell that has received signal 1.
Cytokines direct differentiation.
What drives the proliferation and differentiation of T cells upon activation?
IL-2 produced by activated T cell.
Resting T cells express only beta + gamma chains –> allows binding of IL-2 with low affinity.
Activation induces synthesis of IL-2 + alpha chain
IL-2, proliferation of B + NK cells.
What is the effect of IL-2?
Resting T cells express only moderate-affinity IL-2 receptor.
Activated T cells express high affinity IL-2 receptor + secrete IL-2 -> binding IL-2 to its receptor signals T cell to enter cell cycle -> induces T-cell proliferation.
CD4 T cells can develop into different effector T helper cells under direction of different cytokines.
How are B cells activated by T cells?
Linked recognition:
B cells activated by T cells that recognise antigen from same pathogen.
CD4 T cell specific for peptides from pathogen must first be activated to produce armed effector T cells.
Epitopes recognised by B cell + T cell must be linked.
Antigen recognition by Tfh cells induces signals that activate B cells -> B cell proliferation generates plasmoblasts -> further differentiation -> germinal centre B cell / plasma cell / memory B cell.
What is the humoral immune response?
Mediated by antibodies secreted by plasma cells -> neutralisation / opsonisation / complement activation.
Antibodies produced by B cells cause destruction of extracellular microorganisms + prevent spread of intracellular infections.
