Effector mechanisms of adaptive immunity Flashcards
What are the five basic functions of an antibody?
- Antibody neutralisation
- Complement activation
- Opsonisation
- Antibody- dependent cell cytotoxicity
- Mobilisation of inflammatory mediators
What happens in antibody neutralisation?
Neutralising antibody blocks binding toxin to cell-surface receptor- binds to antigens so they cant bind to receptor
Vaccination to tetanus, diphtheria, cholera
Seasonal flu vaccine to Haemagglutinin, neuraminidase
What is complement activation?
IgM and IgG can activate classical complement pathway
-Directly lyses bacteria, activates immune response, opsonises cells for uptake by phagocytosis
Bind to antigen-staple form, C1q binds
What is opsonisation?
Phagocytes have Fc receptors for antibodies and complement- opsonised if either deposited on surface
Tells phagocyte something to be eaten
What is antibody-dependent cell cytotoxicity?
Antibodies bind to pathogenic antigens to mark for killing, NK cells and neutrophils recognise antibodies- signal apoptosis via release of cytotoxic granules
(perforin/ granzyme/ cytokine TNFa)
Antigen-antibody complex needed to bind to multiple Fc receptors
What is mobilisation of inflammatory mediators?
Mast cells and basophils active in anti-worm/allergy responses
High affinity for Fc epsilon Receptor 1- binds free IgE
When receptors are cross-linked, cells degranulate, release histamine
Systemic mast cell degranulation= anaphylactic shock
How does B cell activation lead to class switching?
Antibody function determined by Fc region- isotypes Naïve B cells express IgM (and IgD)- early response dominated by IgM Activated B cells can class switch to make IgG,A,E
What are the differences in Fc receptors?
Distinct for each isotype- G gamma, A alpha, E epsilon, M mu
Several isotypes have both high and low affinity receptors
Restricted distribution of receptors, expression pattern (different functions)- Fc epsilon receptor 1 only on mast cell and basophil
Describe IgM
Multimer, first to be produced
Good at neutralising and trapping lots of antigen, activating complement
Poor at opsonisation and ADCC
Describe IgG
Monomeric Action depends on subclass but can opsonise, activate complement, neutralise and ADCC
Describe IgA
Dimeric
Found in mucosa- gut and lung
Neutralising intestinal pathogen, ensure flushed out
Poor at opsonisation, activating complement, ADCC
Describe IgE
Monomeric
Best for activating mast cells, basophils and eosinophils
Allergy and parasite infection
What is somatic hypermutation?
Point mutations in variable regions of receptor and antibody
How does B cell activation lead to somatic hypermutation?
Leads to generation of antibodies with stringer/ weaker binding to antigen- stronger binding selected by affinity maturation- important for monomeric IgG, bind strongly to monovalent antigens
What does Signal 3 for CD4+ T helper cells do?
Determines quality of T cell response- PRR
Cytokines from dendritic and other cells
Differentiation
What are the different types of T helper cell?
Th1- IFNy, intracellular bacteria and viruses, autoimmunity and IBD
Th2- IL-4, parasitic worms, allergy
Th17, IL-17, extracellular bacteria and fungi, autoimmunity and IBD
Tregs- IL-10, suppress immune responses
How do CD4+ T helper cells help B cells?
Provide signal 2 only when B cell presents with peptide/ MHC2 that they recognise
B cells only present MHC2-peptide complexes when antigen is taken up via B cell receptor
Linked recognition- only provide help to B cells that recognise the same antigen they do
How does requirement for help by T helper cells drive affinity maturation of B cells?
Linked recognition allows selection of those B cells expressing receptors/ antibodies that bind antigen most strongly- competition for uptake of antigen
How do T helper cells select appropriate class of antibody during class-switching?
Class-switching requires Costimulation, cytokines from CD4+ T helper cells select class of antibody
How do NK cells work?
- CD8+ CDLs recognise antigen presented on MHC1
- Many pathogens downregulate expression of MHC1
- NK cells recognise downregulation of MHC1 and kill cell (missing self)
How do CD8+ Cytotoxic T Lymphocytes work?
- Recognise foreign proteins on MHC1
- All nucleated cells express MHC 1 except neurons
- Presents endogenous antigens (inside cell)
- Kill cell
How are CTLs activated?
Initial- MHC1/peptide on dendritic cellscross-presentation
Subsequent- MHC1/peptide on infected cell
How do CTLs kill?
FAS ligation- directly signals to induce apoptosis
Perforin forms pore allowing granzymes to enter
Granzymes activates caspases, DNase activation and mitochondrial breakdown
