Lec 4: Antibodies Flashcards
Describe the push for an adaptive immune system.
- pathogens have devised a number of clever mechanisms to evade the innate immune response
- the body needed to devise defence mechanisms that could adapt to each of these organisms no matter how diverse they were
Describe the adaptive mechanisms of immunity.
- necessary if pathogenic organisms breach innate defences and spread through host
- specificity
- adaptable
- systemic
- includes antibodies, antigen presentation, recognition of self/nonself
- forms basis of memory
What are the 2 main regions of an antibody?
- recognition function
- biological function
What is the recognition function?
- specifically binds to individual microorganisms (variable, complementary in shape to specific microorganisms)
What is the biological function?
- communicate with complement and phagocytes
- constant
What is an antigen?
a macromolecule that induced specific antibody formation
What is an antibody?
a protein or glycoprotein that binds antigen
Describe the molecular structure of antibodies.
- composed of 2 identical heavy chains and 2 identical light chains
- generates 2 discrete regions for binding antigen
- held together by disulphide bonds
- certain segments of the variable region are hyper variable providing a mechanism for increased affinity
What is the role of the hinge region?
- increases the efficiency of binding
- neutralization reactions in viruses (agglutinating the virus particles to form a clump of viruses to make it difficult to enter host cells)
What region of the antibody is the major determinant of antibody functional properties?
- the Fc region
What is ADCC?
- antibody dependent cellular cytotoxicity
- FcR mediated
- mast cells, basophils and eosinophils degranulate, NK cells secrete perforin and granzymes which induce apoptosis of target cells
- macrophages can also do it through other mechanisms
Is there antibody diversity across species?
- yes
- different species have different antibodies differentiated by Fc region
- cannot expect them to respond same way to pathogenic challenge; depends on what kind of antibodies they can produce
What are the 2 ways that phagocytosis can occur?
- conventional direct recognition: phagocyte recognizes conserved surface components on bacterium
- antibodies recognize variable component on bacterium. Constant region of Ab then detected by FcRs on phagocyte linking innate and adaptive responses
What is the complement system?
- made up of 25 plasma proteins that react with one another to opsonize pathogens and induce a series of inflammatory responses to help fight infection
What are the functional outcomes of the complement system?
- trigger inflammatory responses
- attract phagocytes
- promote phagocytosis by opsonization
- directly attack membrane of microbe
- stimulation of Ab production
Describe the activation of complement by IgG and IgM.
- both can do it but with different efficiencies
- IgM greater efficiency because more binding sites
- It takes two units of IgG or one unit of IgM to trigger complement activation
Describe the cellular basis of antibody production.
- antibodies are produced by B cells
- B cell mediated responses through antibodies are systemic (T cell response is local because cell-cell interaction)
- Abs carried rapidly through blood or lymph or secreted through epithelial layers to protect interface between animal and environment
- Abs are the secreted form of B cell antigen receptor (immunoglobulins)
Describe the clonal selection theory.
- antibodies are formed before antigens are ever seen by the body and they are selected by the antigen
- selection: antigen binds lymphocyte bearing a complementary receptor
- activation: activated B cell then forms an expanded clonal pool
- provides a cellular basis for the generation of effector and memory cells
Describe a primary response.
- occurs when a B cell is first activated by an antigen
- B cell proliferates and differentiates to form plasma cells and memory B cells
- plasma cells produce antibodies
- memory cells: differentiated B cells capable of rapid conversion to plasma cell upon subsequent stimulation with same antigen
Describe a secondary response
- another exposure to the same antigen
- memory B cells rapidly form plasma cells and additional memory cells
- faster and produces more antibodies than the primary response
What is affinity maturation?
- mutations of B cell immunoglobulin genes which affect the antigen binding regions and result in higher affinity for antigen
What is isotype switch?
- mutations of B cell immunoglobulin genes which results in changes in the effector functions of antibodies secreted from germinal centre B cells
- changes in antibody class/ isotope
Describe how affinity maturation provides specificity upon reimmunization
- initial exposure to an antigen results in low affinity antibodies (IgM) but continued exposure leads to high affinity antibodies
- peak of IgM is reached in 10-14 days
- antibodies then fall to pre immunization levels
- upon reimmunization, many undergo isotope switch to produce IgG
- as a result, following reimmunization, serum antibodies are primarily IgG and have a greater affinity for antigens; also antibody titres are higher and persist for longer
Describe a primary response.
- occurs when a B cell is first activated by an antigen
- B cell proliferates and differentiates to form plasma cells and memory B cells
- plasma cells produce antibodies
- memory cells: differentiated B cells capable of rapid conversion to plasma cell upon subsequent stimulation with same antigen