Effector Responses of the Immune System Flashcards
What are effector responses?
= aim to eliminate pathogens and infected cells from the body
= also clear cells that are damaged or abnormal (e.g. tumours)
= can be humoral or cell-mediated
(can interact = when macrophages phagocytose antibody-bound pathogens)
= humoral = mediated by antibodies
(e.g. neutralisation of pathogens and toxins, agglutination of particulate antogens, opsonisation, complement activaton, cytotoxicity, degranulation)
= cell-mediated = rely on innate immune cells (e.g. NK cells, macrophages, neurophils) and cells of the adaptive immune system (cytotoxic T cells, CD4+ T helper cells)
What are antibody isotypes?
B cells can secrete different classes of antibodies (antibody isotypes)
= they differ in their Fc regions and hinge
= have different effector functions, depending on which Fc receptors they bind
= e.g. IgG = abundant in blood
= e.g. IgM = pentamer, produced first during infection
= e.g. IgA = at mucosal sites
= e.g. IgE = against worm infections and allergy
What are Fc receptors (FcR)?
FcR
= have extracellular immunoglobulin domains that recognise the Fc domains of antibodies, and intracellular signalling domains
= different FcRs recognise different antibody subtypes
(e.g. FcγRI binds IgG, FcεRI binds IgE)
= different cells express different sets of Fc receptors
(e.g. FcεRI is expressed on eosinophils, mast cells and basophils)
(e.g. FcγRI is expressed on macrophages, DCs and granulocytes)
What are the effector functions of antibodies?
- Neutralisation
- Opsonisation
- Complement Fixation
- Antibody-dependent cell-mediated cytotoxicity (ADCC)
- Activation of granulocytes
What is Neutralisation (as an effector function of antibodies)?
= antibody binding to the surface of a virus can prevent cell entry
= antibodies can bind toxins from bacteria = making them harmless
= many therapies are based on the blocking function of antibodies
(e.g. anti-venoms, cancer immunotherapy)
What is Opsonisation (as an effector function of antibodies)?
= IgG and IgA that surround pathogens can bind to Fc receptors (FcR) on macrophages
= this induces phagocytosis and the digestion of pathogens in lysosomes
What is Complement Fixation (as an effector function of antibodies)?
= IgG and IgM are recognised by the C1 complement complex
= activation of the classical complement pathway
= this induces:
= opsonisation by C3b and phagocytosis
= lysis of the pathogen or the infected cell using the membrane attack complex (MAC)
What is Antibody-dependent cell-mediated cytotoxicity (ADCC) (as an effector function of antibodies)?
= IgG on the surface of infected cells binds to the FcγRIIIa receptor on NK cells
= induces degranulation of NK cells
= NK cells granules contain perforins and granzymes which induce apoptosis in the target cells
What is activation of granulocytes (as an effector function of antibodies)?
= IgE bound to parasites or allergens causes degranulation of mast cells, eosinophils and basophils
= induces release of histamine (+ other inflammatory mediators)
= activates Th2 cells during worm infections / allergy
What are cell-mediated effector functions?
Cytotoxic effector cells include:
= natural killer cells (innate)
= CD8+ cytotoxic T lymphocytes (adaptive)
= natural killer T cells (innate and adaptive)
= cytotoxic cells induce cell death by apoptosis
= they eliminate cells that are infected with intracellular pathogens (e.g. viruses), tumour cells or cells that are damaged
What are the 2 ways of generating Cytotoxic T Lymphocytes?
Sequential activation
= licensing of an antigen presenting cell (APC)
(by interaction with a pathogen or with an activated Th1 cell)
= interaction of the licensed APC with a naive CD8+ T cell
= causes its activation and differentiation into a cytotoxic T cell
Simultaneous activation
= of an APC with an activated Th1 cell and CD8+ T cell
= causes APC licensing and CD8+ T cel activation at the same time
= particularly efficient as IL-2 from the TH1 cell promotes CTL differentiation
What is the “Kiss of Death” (as an action of Cytotoxic T lymphocytes)?
- CTL forms immunological synapse with target cell
- Secretory granules move along microtubules
- Secretory granules fuse with the pre-synaptic membrane
- Perforins assemble to make pores, granzyme causes apoptosis of the target cell
What are perforins and granzymes?
= multiple perforin monomers assemble in membrane of target cell to form pore
= granzymes can enter through the pore
(serine proteases that cleave proteins in the target cell)
= causes target cell to undergo apoptosis within a few minutes of contact
= perforins and granzymes are secreted by CTLs or NK cells
What are NKT cells?
= Natural Killer T cells
= a type of T lymphocytes that have some properties similar to NK cells
= develop in the thymus, undergo TCR gene rearrangements
= BUT express an invariant TCR: αβTCR
=αβTCR recognises certain glycolipids presented by CD1d (non-classical MHC molecule)
= NKT cells can act as both helper cells and cytotoxic cells (include CD4+ and CD4- populations)
= they lack some classical T cell markers (e.g. CD3)
= BUT express some markers characteristic of NK cells (e.g. NK1.1)
= NKT cells contribute to immunity against certain bacteria, tumours and viruses
What happens before infection (as part of the immune response)?
= APCs (e.g. DCs / macrophages) sample antigens from tissue and migrate to lymph nodes
= Naive B and T cells transit between the blood, spleen and lymph nodes to sample antigens presented by APCs
(naive lymphocytes are very motile cells)
(B lymphocytes browse for antigen along follicular DC networks in follicle)
(T lymphocytes interact with fibroblastic reticular cell networks in the paracortex)
= only ~1 in 500,000 lymphocytes can recognise any given antigen that is presented
(so they have to interact with many APCs)
= lymphocytes spend ~12-18 hrs in each lymph node then return to circulation
(called lymphocyte recirculation)
