Immunity: The Humoral response Flashcards
Describe B cells
B cells secrete antibodies which bind to foreign antigens, allowing phagocytes to recognise and destroy them.
Each B-cell expresses 1 type of epitope antibody specific to 1 antigen. B cell receptors can also directly bind to a comp antigen. Microbes can have diff surface antigens, so each antigen type activates and binds diff B cells.
B cells can do phagocytosis, antigen presentation, and load antigens on MHCs to display to T cells
Describe T cells
T cells produced in the bone marrow mature in the thymus. The thymus controls central tolerance- T cells differentiate into CD8+ or CD4+, and any T cells w self antigens are destroyed to avoid AI disease.
CD8+ =cytotoxic T killer cells. When activated, they destroy cells w nonself antigens on an MHC protein.
CD4+ are helper T cells (Th). They release cytokines that induce Bcells to differentiate into plasma cells which secrete antibodies.
Treg is a type of Th cell. It inhibits other T cell function, controlling immune response and tolerance
T cells each have 1 specific antigen receptor on its surface to bind to a comp antigen and get activated.
How are T cells divided and differentiated?
ProT (immature T precursors) undergo selection in the thymus
As the T-cell matures, it will acquire the Alpha beta or the Gamma Delta type T-cell receptor.
Only the αβ cell makes a CD4 & CD8 co receptor, so they are CD4+ and CD8+. γδ cells are CD4- and CD8-.
αβ cells differentiate into either CD4+ or CD8+
After a pathogen invades, CD4+ T cells differentiate into either Th1, Th2, Th17 and Treg cells
What is the endogenous pathway of T cell priming?
Endogenous antigen pathway leads to CTL priming
Cells are infected by a pathogen/virus.
Viral antigens are presented with MHC Class I molecule on cell surface.
CD8+ T cell recognises the antigen via TCReceptors, becomes cytotoxic and starts making cytokines.
CTL proliferates to make memory cells y mas CTL cells looking for comp APCs. CTLs destroy infected cells.
Describe the exogenous pathway of T cell priming
Exogenous antigen pathway leads to Th cell priming.
Macrophage engulfs a pathogen into a vesicle. The pathogenic antigen is processed into small peptides
Antigen is presented with MHC Class II on cell surface. T helper cell (Th) recognises the APC.
CD4+ T cell becomes primed. Now it either activates B cells by releasing cytokines (Th2) or macrophages (Th1)
Describe T cell INdependent B cell activation
A pathogen containing multiple identical antigen epitopes can STRONGLY activate B-cells (rare).
Activation initiates proliferation of B cells and B memory cells. B cells are converted to plasma cells which make pentameric IgM
This pathway is restricted to specific antigens and isn’t checked for tolerance- can lead to problems eg TSS
Describe T cell dependent B cell activation
B cells bind to a comp antigen on an APC to become APCs themselves. Chemokines are released which attract Th cells and activate B cells. B cells bind w a comp CD4+ cell.
The B cell becomes activated and proliferates into: B effector cells which produce plasma cells⇢release IgM. B memory cells
Ab production needs co-stimulation with a Th cell that was already screened against self, so auto-immunity is avoided
Draw, label and describe an antibody structure
4 pp chains in a Y shape, held by non-covalent interactions and disulphide crosslinks between cysteine residues.
Fab binds the antigen. Fc binds to receptors on phagocytes, activates complement. Fc gene section determines which Ig isotype is produced.
Hay 2 identical light chains, kappa (κ) or lambda (λ), never both. Also hay 2 identical heavy chains.
Carbs help assembly and binding to cells.
What are the different types of IgM antibody structures?
IgM monomer has a long heavy chain which binds to the B cell and stick out of it.
This monomer can form a pentameter structure which is secreted & highly antigenic. It contains a J chain- a polypep involved in pentamer polymerisation
Describe IgG antibodies
IgG is the major class overall. Only IgG can cross the placenta to protect the fetus. V good at activating complement via classical pathway (removing the pathogen)
The Fc fragment at the bottom is an opsonin, which means it can induce phagocytosis: it can bring in infected organisms to immune cells like neutrophils /macrophages to be destroyed. This is bc the Fc region is recognised by Fc-receptors on immune cells
IgG can be present for long periods in the serum so may indicate past exposure and not current infection.
What is the function of IgM antibodies?
IgM is better at activating compliment via classical pathway bc its pentameric structure means it has more antigen binding sites. IgM binds higher number of epitopes, enhancing phagocytosis
Presence of specific IgM antibodies to an antigen indicates a recent primary response to that antigen- current infection
Draw a graph to describe the primary response to infection
The “switch” on the graph represents the isotype switching- this is the switch from making IgM to IgG antibodies.
The adaptive response to new infections is SLOW and SPECIFIC w long lasting memory.EMORY
How does isotope switching work?
Ig heavy chain genes are in a specific order.
T cells produce cytokines, which will interact w the B cells. The interaction will cause chem reactions w in the cell that synthesise specific DNA cutting enzymes. This rearranges the Fc region, so the class of antibodies produced changes. The Fab region holding antigen specificity does not change
What is the secondary response?
The i.response is faster bc memory cells recognise the antigen and differentiate straight away to produce antibodies. ⇡ IgG is produced for a longer time period.
The organism is destroyed so rapidly the person is unaware of any symptoms and is now immune to the disease.
How does antibody-antigen interaction work?
Hay non-covalent interactions entre antibodies and ag: Electrostatic, hydrophobic, vdw forces, H bonds
The antibody b.site must being sterically and chemically comp w a site on the surface of the antigen.
A single antigen can have many possible binding sites (epitopes)
How are natural immune responses polyclonal?
More than one clone of B-cells is generated and more than one Ig is synthesised
This is bc hay multiple antigens on organism, multiple epitopes on each antigen. Therefore more than 1 Ig may recognise the same epitope
How does antibody fight infection?
By coating and neutralising a pathogen, eg if a virus is coated with Ab it can’t bind to its receptors on the cell surface
By activating complement, which can then form holes in a bacterial cell membrane
By opsonisation: phagocytes bind to pathogens coated with Ab and phagocytose them due to Fc receptors
Describe IgA antibodies
Secretory IgA -most abundant in external bodily secretions (milk, sweat, tears etc)
1st line of protection at external surfaces. It binds Fc receptor on immune cells which initiates inflammatory reactions. Circulatory IgA can’t activate complement.
Secretory component protects IgA from degradation, so it can work in harsh environments (eg, GI tract)
Describe IgE antibodies
IgE binds to specific Fc-receptor on mast cells/basophils, releasing histamine during allergic reactions. Over response can cause anaphylactic shock
Activates eosinophils via Fc receptor binding in response to parasitic worms
Low conc in circulation but raised in allergic patients and large parasitic infections
Describe IgD antibodies
extremely low conc in circulation
Mainly found on surface of B cells as antigen-binding B cell receptor
Does not bind complement. Probably helps B cell activation
What is the difference between BCRs and TCRs?
B cell receptors can recognise and bond to an antigen directly.
T cell receptors need cells to process and present antigens on their surface in the form of MHCs
What is MHC class I?
MHC class I: present in all nucleated cells, inc APCs. The cells continuously break down intracellular peptides from the cytosol and present it on MHC I.
This means infected or cancerous cells display mutated peptides. These r recognised by CD8+ CTLs
Exception: Some APCs like dendritic cells present engulfed peptides normally in MHC class II, or MHC class I. This is cross presentation
What is MHC class II?
Present on professional APCs only (mononuclear phagocytes, dendritic cells). APCs have class I and II MHCs.
APCs engulf extracellular pathogens. Pathogenic peptides are processed in vesicles. Peptides bind w MHC class II sent from the ER. This is presented on the APC to be recognised by CD4+ Th cells.
Exception: autophagy, where the cell degrades part of itself to remove misfolded/damaged protein. Although the peptides come from within the cell, they’re displayed on MHC class II instead of I.
Describe the structure of MHC class I
MHC class I consists of 2 protein subunits, the alpha and the beta-2-microglobulin chains. A transmembrane region anchors the molecule on the cell membrane.
The alpha chain is larger and consists of alpha 1, 2 and 3 subunits. Alpha 1 and 2 form the peptide-binding cleft which presents the antigen. Disulphide bonds in alpha-2, alpha-3 and B-2 domains stabilises the protein.
The b-2-microglobulin interacts w alpha chain via other forces too
