Humoral Effector Flashcards
What is an antigenic shift
Mutation in the antigen so that the antibody can no longer bind - bugs do it all the time to evade the immune system
What is the difference between antibodies, immunoglobulins and gammaglobulins
Immunoglobulins is a family of antibodies whereas an antibody is specific for a given antigen or maybe a group of similar antigens. Gammaglobulin refers to the gamma peak that is seen in the electrophoresis peak. Most of our antibodies are found here in this peak
Functions of different antibodies
- Protect the neonates - IgG (even though we talked about in the last hour it was IgM) 2. Complement system - IgM, IgG 3. Mast cell mediated immune response against helminths - IgE 4. Opsonization - IgG, IgM 5. Antibody mediated cellular toxicity - IgG 6. Neutralize microbes toxins - IgG, IgM, IgA 7. Protect mucosal surface - IgA, IgM
What antibodies neutralize toxins
IgA, IgM and IgG, binds to the toxins disabling their effect and binds to the viruses and prevents them from entering cells
What antibodies promotes opsonophagocytosis
IgG and IgM, also induced more release of ROS and iNOS and proteases into the phagosome
What is a major site for phagocytosis
Spleen
What is the receptor involved in opsonophagocytosis
FCgamma receptor
How does antibodies cause cell level toxicity
Antibodies binds to the Fcgamma receptors on the target cells and on the other side they bind to the NK cells FCgamma receptors. Granzyme and perforin are released by the NK cells. It is important to know that for NK cells there has to be a lack of MHC complex. However antibodies can over ride this mechanism by activating cytotoxicity promoting signals
What mediates the hypersensitivity response and what receptor does it bind to
IgE, it bind to FCepsilon receptor
What is so unqiue about this receptor involved in hypersensitivity response
Vast majority of the receptors that regulate immune response binds to antibody-antigen complex. However FCepsilon is a high affinity receptor as it can only bind to the antibody IgE, thats why we dont have alot of IgE in our sera since all of it is stuck to the mast cells
Explain the role of eosinophils in immune regulation
- They are recruited and activated by IL-5
- Important in fighting helminths and contributing to asthma
- Granules contain large variety of cytokines and chemokines
What helps us develop muscosal immunity
Multimer antibodies IgA and IgM. IgA production is induced by TGFbeta and it is released in Muscosal Associated Lymph Tissues (MALT)
How do we pump IgA and IgG into the mucosal layer
Poly-Ig receptor is used which binds to IgA or IgM and takes it across the cell surface membrane of the mucosal cell. Then this poly-Ig receptor once it gets to the other side of the cell surface membrane is cleaved releasing the antibody into the muscosal layer
Explain the dilemma of the intestine and how does it go about in generating a fine tailored immune response
The dilemma of the intestine is that there are bacteria that are desired to be present in the intestine and then there are foreign pathogens that shouldnt be present so the job of immune system is to differentiate between essential bacteria and potentially harmful pathogens. This is achieved in several ways
- Right underneath the villi are lymphatics which drain their fluid into a special lymph node called the mesentric lymph node which has specially been tailored for the small intestine
- There are specialized epithelial cells for immune reponse in the GI tract called the M cells. He said “that is the immune system’s way of seeing into the GI tract as what is going on”
- There are Payer’s patches right underneath the epithelial lining that have dendritic cells taking out their projections all the way to the lumen. They are continuously trapping antigens and presenting to the B and T cells that lie in the germinal centers of the Payer’s patches. Memory cells and plasma cells can be generated when a foreign pathogen is detected and antibodies can be pumped into the lumen
Compare parenteral vaccine vs the oral vaccine
- One is administered intramuscularly whereas the other one is adminsitered orally
- IgG antibodies are made in the blood vs IgA antibodies made that are pumped to the lumen of GI tract
- In parenteral a person is a carrier whereas in the other one the person is not a carrier and that person has immunity towards the pathogen entering the body via GI tract
What is another exception to the antibody-antigen complex binding receptor
Neonatal FC receptor called the FcRn receptors. Mom’s IgG antibodies are transported through the placenta by this receptor
What is transient hypoglobulinemia
After 2 months of birth the infant has low levels of antibodies, especially IgG antibodies since the antibodes received from mom have surpassed their half life and the infant is still developing their immune system. This condition can stay for as long as 9 months of age.
When are B and T cell deficiences diagnosed
T cells can be diagnosed day 1 with the help of TRECs whereas B cells deficiences are diagnosed around the age of 2 when hypoglobulinemia is persistent
What is the complement proteins
It is a system of proteins, part of the INNATE immunuity, effect is mediated by complement receptors
Effects of complement system in immune response when it is activated
- Opsonization
- Cell lysis and cytotoxicity
- Development of inflammation by releasing cytokines, chemokines, recruiting macrophages and neutrophils and increasing vasodilation and vasopermeability
- Clearing of immune complexes
- B lymphocytes coactivation
Describe the complement pathway
Involved a series of steps, most of the proteins invovled are serine proteases and they are also zymogens so they have to be cleaved to be activated, cleaving is done by enzymes called “convertases”. Formation of C3 convertase is a key step
3 pathways of complement
What are the 3 pathways
It is important to know that the classical pathway and in the MBL pathway C4 and C2 are cleaved to form C4b and C2a which forms the key enzyme called the C3 Convertase.
In alternative pathway, microbial antigens are obserevd so a C3 is added which then forms a dimer with beta factor to form a C3b and Beta factor which together form the C3 Convertase
Describe the classical pathway
- Antibody must be bound to the microbe, free antibodies will not intitate complement classical pathway
- IgG or IgM are involved
- They recruit C1 complex that starts with C1q
- C1q binds to the Fc region of the antibody, which then recruits C1r and C1s to form the enzyme that cleaves the C4 and C2
