Antibodies Flashcards
What are the defining characteristics of the adaptive immune system?
- Adaptive immune system-
o Defining characteristics
Specificity for millions of different molecules
Specialization of the immune response to different types of microbes
Ability to remember and respond more vigorously to repeated exposures to the same microbe (immunological memory)
What are antigens?
o Antigens- substances that are recognized as foreign by the immune system
What 2 connected systems is adaptive immunity composed of?
-Humoral immunity
-Cell-mediated immunity
What is humoral immunity and how does it work?
Humoral immunity
* Mediated by proteins called antibodies produced by B cells
o Antigen receptor of a B cell is a B cell receptor (BCR)-> includes a membrane bound form of antibody and associated signalling proteins
o B cells secrete antibodies of the same specificity as their BCRs
* Principle defence mechanism against microbes (and their toxins) outside of the host cell
* Secreted antibodies bind to microbes and toxins: the bound antibodies trigger an immune response to neutralize or eliminate the threat
What is cell-mediated immunity and how does it work?
- Primary effects of adaptive cell-mediated immunity are T lymphocytes
o T cells have their own antigen receptor called a T cell receptor (TCR)
o T cells only recognize one form of antigen, which is a peptide bound to a particular kind of protein on the surface of self cells
Describe the major functions of antibodies
- Neutralization
o Antibody binds to virus/toxin, preventing it from engaging its receptor and infecting the cell
o Antibodies neutralize viruses and toxins by directly blocking their functions - Opsonization
o Antibodies coat pathogen so that it is recognised through the tail of the antibody by phagocytes which eat the microbe
o Antibodies opsonize pathogens, which leads to phagocytosis and destruction of pathogens - Complement fixation
o Antibody coats microbe-> antibody recognised by complement proteins-> complement proteins make microbe porous-> microbe dies
o Antibodies activate the complement system - Antibody dependent cellular cytotoxicity (ADCC)
o Virally infected cell produces spike protein-> antibodies bind to the spike protein-> natural killer cell comes by and binds to the antibodies-> cells are activated and release perforin and granzymes-> infected cell dies by apoptosis
o Antibodies bind to infected cells and activate ADCC
What is the basic shape of an antibody?
- Antibodies are Y shaped protein
- Antibodies are tetramers
What is the basic structure of an antibody?
- Arms of antibodies are called Fab, tail is Fc
o Fc-> bound to complement, or is recognised by phagocytes or killer cells - There are 4 distinct peptide chains found in a single molecule of IgG (2 heavy chains and 2 light chains)
How many distinct binding sites in a single molecule of IgG?
- There are 2 distinct binding sites in a single molecule of IgG
o One binding site= 1 heavy chain and 1 light chain
What are the two domains of the heavy or light chains?
o Each of the chains have a portion at the N terminus called a variable domain and a portion at the C terminus called a constant domain
What is the purpose of the variable domain in an antibody and how does it achieve this purpose?
Variable domain binds to the antigen
* Each variable domain (one in heavy chain, one in light chain) has 3 loops-> correspond to those 3 CDRs
o Form antigen binding site of antibody
o Loops are spread out to accommodate antigen/protein
o When they’re brought close together, they form a cleft-> can happen when bound to small molecules
What are complementarity determining regions/Hypervariable regions (CDR/HV)
- 3 regions where sequence varies a lot from one antibody to the next in the variable domain
What are the major Ig heavy chain isotypes and what are their general functions?
- IgG
o Provides protection against many microbes - IgD
o Useful in the lung - IgE
o Part of responses to worms and in allergies - IgA (dimer)
o Two tetramers bound by a J chain
o Protected against proteases and is part of protection against microbes in the gut (mucosal immunity) - IgM (pentamer)
o Bound by J chain
o Low affinity but high avidity because it has multiple binding sites
What are the 2 situations in which antibodies can cause disease?
o Antibodies cause disease when they recognise self-antigens
o When antibodies form complexes with antigens in the circulation
Immune complexes (antibody-antigen complexes)
* Can deposit on vessel walls/other places-> binding to basement membrane on which endothelial cells sit
Through what processes do antibodies cause disease
- Cause tissue damage by complement fixation of self, opsonization of self, inflammation and neutralisation
