Adaptive immune system I Flashcards
What are the 2 types of adaptive immune response?
- Cell mediated
- Humoral
Briefly describe the innate response to new infection and why it’s important
- Response to new infection fast
- Acts on pre-determined non-self signals
- Sometimes can be primed/trained for intense reactivation (innate memory)
What are the components of the cell mediated innate response?
- Phagocytes
- Natural killer cells (NK cells)
What are the components of the humoral response?
- Complement and pentraxins (CRP)
- Pattern receptors (soluble TLR- toll-like receptors, makes response quick)
- Enzymes (lysozyme)
- Cytokines releasing antimicrobials
- Binding proteins (Lactoferrin)
Briefly describe the adaptive response to new infections
- Slow
- Selects for specific signals and generates memory
Where are T and B cells made?
- Bone marrow with a randomly assigned antigen-binding specificity
- T and B cells can have the same specificity
What cells and molecules are involved in the innate immune response?
- Dendritic cell
- Mast cell
- Macrophage
- NK cell
- Complement protein (mark pathogens to be destroyed)
- Neutrophil - granulocyte
- Eosinophil - granulocyte
- Basophil - granulocyte
What cells and molecules are involved in the adaptive response?
- B cell
- Antibodies
- CD4+ T cell (T helper cell)
- CD8+ T cell (T cytotoxic cell)
Where are T lymphocytes developed?
What happens to them there?
Migrate to Thymus gland, become CD8+, CD4+ or are destroyed if strongly recognise self antigens (central tolerance)
Where are B lymphocytes developed?
- Bone marrow
- Developed and matured in bone marrow to express a single epitope antibody used as a receptor to bind to an antigen
What is T cell priming?
The activation and clonal expansion of a naive T cell on initial encounter with antigen on the surface of an antigen-presenting cell
Describe the endogenous pathway of T cell priming
- Endogenous antigen pathway leads to cytotoxic (CD8) T cell priming
- Antigen binds to APCs
- These cells are infected by the virus
- Viral proteins in the cytoplasm are detected and processed
- Viral antigens presented with MHC class I molecule on cell surface
- CD8+ cell recognises antigen, becomes cytotoxic, begins to make cytokines
- Cytotoxic T cell (CTL) proliferates making memory cells, and CTL cells looking for cells with presented antigen
- Infected cell destroyed by cytotoxic cell
Describe the exogenous pathway of T cell priming
- Exogenous pathway leads to T helper cell priming
- Antigen (pathogen) engulfed by dendritic cell or macrophage via phagocytosis
- Antigen processed into small peptides
- Antigen presented with MHC class II molecule on cell surface
- CD4 T helper cell recognises presented antigen
- CD4 Th cell becomes primed and can help with either B cell activation or macrophage activation
Describe antibody-antigen interaction
- Non covalent interactions
- Electrostatic, hydrophobic, van der Waals, Hydrogen bonds
- Depends on antibody binding site being exactly complementary sterically and chemically, with a site on the surface of the antigen
- A single antigen can have many possible binding sites (epitopes)
Describe the structure of antibodies
- Immunoglobulin + glycoprotein
- 2 identical antigen binding sites
- A hinge ‘H” region - flexible space between binding sites
- Protease cleavage generates large fragments called Fab (variable region, antigen binding) and Fc (constant region, crystallisable)
- 4 polypeptide chains held together by non-covalent interactions by disulphide crosslinks between cysteine
- 2 identical Heavy chains
- 2 light chains
- Carbohydrates help assembly and binding to cells
What is the function of constant regions?
- Fc constant region allows binding of phagocytes to receptors of the antibody, activates complement
What is complement?
System of plasma proteins activated directly by pathogens or indirectly by pathogen-bound antibody
They interact with pathogens and mark them so that phagocytes are able to detect and destroy them
What is the function of the variable region?
- Fab variable region allows for antigen binding, contributes to antigen-binding site
Describe the B cell activation pathway that is independent of T cells
- B cell receptors bind to antigen on pathogens
- Activation initiates proliferation with some cells being memory cells and other cells being committed to antibody production
- Activated B cells convert to plasma cells and begin making antibody
- This pathway is restricted to specific antigens (will always make only 1 type of antibody)
- Can lead to problems such as toxic shock syndrome (too much antibody)
Describe the B cell activation pathway that is dependent on T cells
- B and Th cell interact, this activates the B cell
- Activation initiates B cell proliferation with some cells being memory cells, others being committed to antibody production
- Antibody production required co-stimulation with a Th cell that was already screened against self, hence avoided autoimmune response
Define epitope
- A single antigen that has multiple binding sites
Why is the immune system classed as polyclonal?
- More than 1 clone of B cells is generated
- More than one immunoglobulin is synthesised
This is because: - Multiple antigens on organism
- Multiple epitopes on each antigen
- More than one immunoglobulin may recognise the same epitope
How do antibodies fight infection?
- By coating and neutralising a pathogen- if a virus is coated with antibody, 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 have Fc receptors on their cell membrane, bind to pathogens coated with antibody and phagocytose them
Describe the 2 structures of the IgM antibody
Structure 1: Membrane bound
- Monomer of basic subunit B cell receptor
- Extra heavy chain domain that is membrane bound in the B cell
Structure 2: Secreted
- Pentamer of basic sub=unit in plasma (secreted + highly antigenic - many antigens)
- Contains a J chain - a polypeptide involved in pentamer polymerisation
What is the order of Ig production?
IgM - first antibody class made
IgG - second antibody class made
What is the function of IgG?
- Major class overall (75% of Ig)
- Major class made by secondary responses
- Only antibody class able to cross placenta and protect the developing foetus
- Good at activating complement via classical pathway (removing the pathogen)
- Acts as opsonin inducing phagocytosis - Fc region recognised by ‘Fc receptors’ on surface of immune cells, e.g. neutrophils and macrophages
- Can be present for long periods in serum, so may indicate past exposure, not current infection
What is the function of IgM?
- Presence indicates a recent primary response to that antigen
- Implies a current primary infection
- Activates complement via classical pathway (due to pentameric structure)
- Higher valency of pentameter increases overall affinity (by binding higher number of epitopes)
- Binds to immune cells via Fc receptor (ie, inducing phagocytosis)
What is the primary response?
- Body’s first response to unfamiliar infection
- Slow, specific response
- Produces lasting memory cells
What is the process of isotope switching?
- Biological mechanism that changes a B cell’s production of an immunoglobulin from one type to another
What is the secondary response?
When a pathogen that has already infected the body before reinfects the body
Much faster and stronger response due to memory cells
What is the function of IgA?
Which one is serum IgA and which is secretory IgA?
- 2 forms IgA1, IgA2 (differ in constant regions)
- IgA1 is predominant in serum
- IgA2 is predominant in secretions
- Monomer - This is Serum IgA
- Most abundant class in external secretions (milk, sweat, tears, saliva, gut fluids etc)
- Serves as opsonin (eosinophils, neutrophils, some macrophages)
- Main immunoglobulin in mucosal sites; sometimes occurs as dimer - This is secretory IgA
First line protection at external surfaces: - Initiates localised mucosal response different from more general circulating immune response
- Neutralises pathogens, prevents binding to cell surface receptors
- Secretory components protects IgA from degradation, hence it can work in harsh environments (eg. GI tract)
What is the function of the IgE antibodies?
Are they normally in high or low concentration?
Harmful function in allergies:
- Binds to specific Fc receptor on mast cells and basophils releasing histamine
Useful function is response to parasitic worms
- Release chemicals from mast cells
- Activates eosinophils (via Fc receptor binding)
Normally low concentration in circulation
- Raised in allergic patients
- Raised in infections with large parasites
- Over response can cause anaphylactic shock
