Antigen/ Ab Reactions (Bowden) Flashcards
What are circulating Abs
soluble glycoproteins that recognize and bind Ag
What is the structure of Ab
unit of 4 polypeptide chains
2 heavy and 2 light
5 classes of Ab in mammal
IgG IgM IgA IgE and IgD
term for exceptional variability in variable regions of heavy and light chains
hypervariable regions (30,50 and 95)
What do hypervariable regions have to increase Ag binding
interaction site that is complementary in shape charge and hydrophobicity to the epitope it binds
called Complementarity determining regions
How many complementarity determining regions are there
6 CDR per Ab and TCR
idiotypes
how do the isotopes of Ig differ
size charge aa sequence and carb content. Functional differences
How are isotopes determined
by C region of H chain
Allotype
allelic differences on H chain
Idiotype
Antigenic determinants on the V regions- we all see antigens just see different parts of it
What occurs after Ab bind Ag
promotion of killing or removal of immune complex through activation of effector mechanisms
Effector functions
binding Ab to R on host tissues
and start the complement cascade with C1q
Each immunogobulin isotype mediates…
..a distinct set of effector functions
What is the first Ab in the primary response
IgM, because first gene in the line, produced by neonates
What is the structure of IgM
pentamer- 10 antigen binding sites- good for binding viruses and RBCs
efficient in binding complement
Where is IgM expressed
on B cells in monomeric form
What is unique about IgM structure
J piece: Fc linked polypeptide that is disulfide bonded to 2/10 mu chains
this binds to mucosa
Primary immune response takes how long
2 weeks
What is the most abundant Ig in serum
IgG
Predominant Ab in the secondary immune response
IgG
4 classes or IgG and their structural differences
IgG1- IgG4 in order of concentration low to high. differences in structure are on the H chain
What IgG cross placenta
all four
Which IgG is an efficient activator of C’
IgG3
Which IgG is relatively restricted to carb Ags
IgG2
What IgG binds high affinity to Fc R on phagocytic cells
low affinity?
middle affinity?
IgG1 and IgG3
low= IgG2
medium= IgG4
What are the Fc R for IgG and where are they found
CD16: NK cells, monocytes/macrophages and granulocytes
CD32: B cells, monocytes/macrophages and granulocytes
CD64: monocytes/macrophages
What Ig is constituent of secondary immune response
IgA found in serum usually as monomer
Describe Secretory IgA
this is the polymer form with J chain, predominant Ig in external secretions
concentrated along jejunum of SI
What is the purpose of secretory IgA
entry port for Ag
Polymeric= efficiency
Newborn immunity
How long is IgE in serum
about 2 days longer when bound to mast cells.
Where does IgE bind
blood basophils and tissue mast cells by Fc R with High affinity. CD23a and CD23b
What physiologic response is IgE assoc with
pharmacologic reactions. asthma hay fever, peanut allergy and worm infections.
IgD function
no known function in serum. monomeric form is present as an Ag specific R on B cells.
R in Ig superfamily
Igalpha/beta heterodimer, IgM, T cell receptor and HLA molecules
Immunogens
antigens that induce immune response
Epitope
specific part of Ag that contacts site of Ab or TCR to bins. (antigenic determinant)
Pathogen
organism that causes disease
Haptens
small molecular weight molecules that can bind to an Ab but must be attached to a large carrier to stimulate immune response
vaccinations or penicllin allergy
Types of endogenous Ags
Autoantigens: self-antigen ex autoimmune diseases
Alloantigens: tissue specific ex: ABO, HLA
Intracellular Pathogens: viruses, intracell bacteria and parasites, chlamydia, Rickettsia, Plasmodia etc
Types of exogenous Ags
Allergens
Iatrogenic
Microbial
Factors that influence immunogenicity
Molecular mass: 1000-10,000kDa for response
Foreignness
Chemical composition: more complex=more immunogenic
Physical form: particulates more immunogenic
Degradability:easily phagocytose=more immunogenic
Genetic factors: immunological repertoire
Age: very young or very old have diminished ability for immune response
MEthods of Administration of Igs
Dose: specific dosages are known
Route: subcut better than intravenous because phagocytes are there
Adjuvants: substances that can enhance the immune response to immunogen
Anergy
cells become anergic when the does of Ab is above normal
types of immunogens ranked from best to worst
Proteins
Polysaccharides
Nucleic Acids
Lipids
The size of a B cell epitope is determined by what
size of the antigen binding site on the Ab. !3D conformation of globular Ag!!
composition of epitopes recognized by B cells
generally contain hydrophilic aa
If the epitope for B cell consists of non-sequential aa, what is vital
the 3D conformation of epitope
Epitopes are assoc with what types of immunogens
soluble or particulate
T cells don;t recognize what type of antigens
free peptides. polysaccharide or nucleic acid Ag
What do T cells recognize on Ag and why
primary aa sequence because in order to be seen by T cell the Ag is proteolytically degraded into smaller peptides then presented
What are the size of epitopes recognized by T cells
8-15 aa, very small and sequentially oriented.
How many cellular components are needed for interaction with Ag on T cells
3: TCR Ag and HLA molecule
T dependent Ags
requires both Thelper and B cells. these are proteins
T independent Ags
Non protein, polysaccharides and lipids that stimulate response without T help. multiple identical epitopes that can cross link B cell R
Mitogens
cause cells (lymphocytes) to undergo division
What is a mitogen that is a polyclonal activator of human B cells
Endotoxin
What substances stimulate T lymphocytes
PHA, ConA, PWM and S. aureus enterotoxinA
What substrates activate B cells
SAC and S typhimurium
Superantigens
bind directly to HLA class II and Vbeta of TCR. activates distinct set of T cells- large response
examples of superantigens
staph enterotoxins (food poisoning)
staph toxic shock toxin (toxic shock syndrome)
staph exfoliating toxins (scalded skin syndrome)
strept pyrogenic exotoxins (shock)
also virus and microorganisms superantigens
What type of bonds are between Ag and Ab
Hydrogen bonds, electrostatic bonds
van der waals forces and hyrdophobic forces
all together strong interaction but still reversible
Affinity
strength of interaction between univalent Ag (epitope) and univalent Ab(idiotype)
Avidity
Strength of interaction between multivalent Ag and multivalent Ab. depends on number of binding sites and ability of Ab to engage multiple epitopes on Ag
Are avidity and affinity related
avidity is dependent on affinities
Which Ig have 10E3 or 10E7 multivalence advantage
IgG and IgM
which Ig are defined as affinity?
avidity?
Fab, and IgG are affinity (intrinsic affinity)
IgG and IgM are avidity (functional affinity)
How do drugs create immune response
forming multivalent hapten-carrier complexes
hapten is the drug, carrier is a protein that is not immunogenic in free form.
Monoclonal antibodies
monospecific identical Ab produced from one immune cell. clones of single parent cell. mAb or moAb
Yervoy or ipulimumab
Blocks Ab for CTLA-4
reverse tumor-mediated immune suppression
What do we detect using flow cytometry
CD markers
General overview of subgroups of Ags
endogenous, exogenous, T dependent, T independent, mitogens, super Ags
