1.1 Pre Course Tutorisls Part 2 Flashcards
What are antibodies (immunoglobulins)
Proteins produced by plasma cells. Used by the immune system to neutralise pathogens
Can be found in two forms: a soluble form secreted by plasma cells or in a fixed membrane bound form attached to the surface of a B cell.
How to antibodies fight antigens?
They recognise a key fragment of a pathogen and bind to it via the fragment antigen binding variable region (FAB)
What are the 5 different antibodies that exist in humans?
IgA- present within secretions such as tears and breast milk
IgD-
IgE- form part of the response to parasites and allergic reactions
IgG- form secondary antibody response, cross placenta
IgM- largest antibodies, form primary antibody response. Due to their size they are much more effective at activating compliment
What are the four ways antibodies are involved in antigen neutralisation?
Bind to antigens directly to form immune complexes which are cleared through the liver and spleen
Act as poisonings for phagocytoisss
Activate the complement cascade through the classical pathway
Bind to their cells and initiate a non-phagocytic cell mediated destruction of the cells called antibody dependent cellular cytotoxicity.
What is antibody mediated cellular toxicity?
A way that specific antibodies can initiate the killing of pathogens or target cells via immune cells from the innate immune system.
Circulating antibodies bind to complementary antigen receptors on the target cell via the fab region. The FC (bottom) end of the antibody can bind to a number of immune cells
What immune cells can the FC bind to?
NK cells
Macrophages
Neutrophils
Eosinophils
What is antibody dependent cellular toxicity.
It’s activates several phagocytic cells. However the destruction of the problematic cell does not involve phagocytosis.
How does antibody dependent cellular cytotoxicity work?
Activates NK cells and destroys problematic cells through the release of perforin and granzyme
What else can be activated when bringing to the FC portion of an antibody?
Macrophages neutrophils and eosinophils which cause the release of granules and toxic enzymes to facilitate extracellular destruction of the target cell
What is the purpose of B lymphocyte production?
Production and release of antibodies
Occurs mainly in the spleen and lymph nodes.
What cell surface receptor is found on all B cells
a B cell receptor, essentially an antibody
What ensures a great complexity in binding of antigens?
VDJ recombination allows for a great diversity in the number of the potential of antigen binding sites
What are the three mechanisms that B cells are activated in secondary lymph organs?
T cell dependant activation- B cells are activated by T cells
T cell independent activation- B cells are activated by antigens typically lipids or polysaccharides
Specific to memory B cells, when it encounters a specific antigen it differentiates into plasma cells which results in a release of antigen specific antibodies
What happens after a B cell is activated?
If bound to an antigen can turn into a short lived plasma cell releasing IgG and IgM
Can enter the germinal centre or a lymph node in order to proliferate, develop an ability to bind to the antigen or undergo immunoglobulin class switching
What is immunological class switching
Refers to the process by which B cells become able to produce a different class of immunoglobulin that can respond to the same antigen. Once these events have occurred the B cell can travel out the lymph node back to the bone marrow where it can become a memory B cell or a long lived a B cell.
What happens the first time a foreign antigen is encountered?
A lag phase occurs while B cells differentiate into plasma cells. During the lag phase no antibodies are produced. Once plasma cells have formed a low volume of IgM antibodies are released to neutralise this initial infection. IgG are memory B cells are a,so released.
What happens if a foreign antigen is encountered again?
There is an accelerated reaction initiated by memory B cells which immediate,y recognise this antigen. Once activated memory B cells quickly proliferate and create plasma cells causing a quick release of high volume IgG antibodies
What is the innate immune system?
A fats non specific initial response to pathogens. If the pathogens are able to overcome the natural barriers that keep infection at bay, these are the next step in dealing with them
What cells are involved in the innate immune system?
Mast cells Basophils Neutrophils Eosinophils Monocytes (macrophages and dendritic cells) Natural killer cells
What are the functions of the innate immune system?
Antigen recognition Inflammation Recruitment of immune cells NK cytotoxicity Phagocytosis and endocytosis Opsonisation Activation of complement cascade
What are pattern recognition receptors?
Receptors that are located on the cell surface membrane. They distinguish certain cellular motifs that are common amongst most groups of different pathogens. Often these molecular motifs are essential to the pathogens survival
What happens after pathogens are recognised the skin?
Macrophages release pro inflammatory cytokines including interleukin 1, tumour necrosing factor alpha are released by these macrophages.
What occurs during the inflammatory process?
Vascular permeability is increased
Other immune cells are recruited
Seals off invading pathogen
Adhesions molecules are activated to allow leukocytes to adhere to the endothelium
Chemokines are released to recruit immune cells to the point of inflammation
How do neutrophils adhere to the epithelium?
They bind onto selectin which provides friction and allows the molecules to roll to a stop
What is the job of histamine and bradykinins?
Loosen the junctions between the neighbouring cells. This allows the bound neutrophils to crawl along the endothelial surface until they can squeeze through a gap junction between two endothelial cells.
What are the principle signs of inflammation and how are they caused?
Dolor (pain) release of bradykinin and histamine stimulating nerve cells
Calor (heat)
Ru or (redness)
Tumour (swelling)
All caused by vasodilation and increased vascular permeability
What are the professional antigen presenting cells? What do they do?
Dendritic cells, macrophages and B-lymphocytes. Present antigens to t helper cells through the MHC II complex
What are the atypical antigen presenting cells? What do they do?
Mast cells, basophils and eosinophils, present antigens to T helper cells but not always through the MHR II complex
What cells do not have a nucleus but still present MHC 1 complexes?
Platelets
What is the difference between the MHC I and MHC II complexes
MHC I- present and process endogenous, intracellular antigens
MHC II- process and present exogenous or extracellular antigens
How does the antigen presenting process work?
When antigens are found within cells they are processed by proteasomes. They are transported to the ER where they bind to the MHC complex
What is the job of natural killer cells?
Target abnormal/infected cells and produce a rapid response. They do not require antigen priming and do not have immulogical memory.
They target cells that have an abnormal or reduced MHC I signal
How do NK cells determine which cells are abnormal
The signal received through the inhibitory pathway of the NK cell by the MHC I pathway is evaluated by the NK cell. If the signal does not match its programming it is killed.
If a cell is damaged or significantly altered it can release receptor that bind to the activating pathway, activating the NK cell no matter what
Red blood cells do not have a MHC I molecule. How do they not become obliterated?
They express other protective markers in their membrane
What is the capable pathway?
The pathway that immune cells use to induce apoptosis in unwanted cells
What else can activate a NK cell?
Interferon gamma, interleukin 2 and antibody opsonising agents
What happens once an NK cell is activated?
Perform and granzyme create a hole or a pore within the membrane of a target cell which allows granzymes to enter and induce the caspase pathway.
Releases interferon gamma- activates macrophages
Releases tumour necrosing factor alpha- enhances cytotoxic effects of NK cells
What is meant by phagocytes?
Immune cells that clear up cells and antigens through phagocytosis. Phagocytosis is the process of engulfing a pathogenic invader to digest and neutralise the threat they pose
What are the phagocytes of the body?
Mast cells, neutrophils, macrophages and dendritic cells
What activates phagocytes?
Cytokines such as interferon gamma or cytotoxins such as lipopolysaccharides?
What is chemotaxis?
Directional locomotion of cells towards the source of a chemical gradient
Describe the process of phagocytosis?
Phagocyte is activated and moves towards microbe through chemotaxis. It adheres to the microbe and then engulfs it into a vesicle called a phagosome. The phagaosome then funded with a lysosome containing enzymes to form a phagolysosome. This degrades the pathogen and excretes is via waste products
What is opsonisation?
“Preparing for eating”, invading cells are tagged and this enhances the likelihood that binding will occur between a phagocyte and a pathogen. This is achieved by increasing the number of binding sites available on the phagocyte and also by reducing the charge that repels phagocytes.
What are some opsonisation
Complement proteins (especially C3b)
Antibodies
Plasma proteins
What is the complement system
Another way the immune system can target a foreign pathogen for distraction. It is a biochemical cascade of palsma proteins that are activated in a sequential fashion. Complement proteins trigger the recruitment of immune cells
Give some examples of the compliment system
Classical pathway- activated by immune complexes
Lectin pathway- binding of microbial polysaccharides
Alternative pathway- activated by complement binding to pathogen surfaces
What is C3 convertase?
An enzyme that is produced once all three complement pathways are activated. It splits the complement proteins into two fragment s
What are the two fragments created by C3 and what do they do?
C3a- pro-inflammatory acts as an anaphkaxotoxin
C3b- acts as an opsonin
