module 02 section 01 (antigens and immunogens) Flashcards
define “communicable diseases”
infectious diseases that are contagious and which can be transmitted from one source to another by infectious bacteria or viral organisms
approximately how many of diesase related deaths world wide are associated with communicable diseases?
25%
define “immunogenicity”
the ability of a susbtance to induce a humoral and/or cell mediated immune response
define “immunogens”
a molecule that has the ability to evoke a specific immune response and can react with the resultant specific antibody (e.g. humoral immunity)
define “antigens”
a molecule (soluble or processed) that can react specifically with either a preformed antibody, immunoglobulin receptors on B-cells or T-cell receptors
can an antigen be recognized as non-self?
yes, but may or may not be immunogenic
are immunogenicity and antigenicity the same thing?
no - related but have distinct immunological properties
how do immunogens differ from antigens?
an immunogen is always an antigen and always elicts an immune response, but an antigen isn’t always an immunogen - won’t always elict an immune response
(immunogen = type of antigen)
what are the 5 properties that contribute to the magnitude of the immune resopnse elicted by an immunogen?
(1) foreignness
(2) molecular size
(3) molecular complexity
(4) degradability
(5) physical form
describe “foreignness” in terms of the immune response elicted by an immunogen
the greater the phylogenetic distance (evolutionary distinctness) between two species, the greater the structural dispairty between their molecules, and thus the greater the immune response
-i.e., the bigger the difference btwn a substance and ‘self’ cells, the greater the immune response
define “xenogenetic”
different species (e.g. duck and cow)
define “allogenetic”
different individuals of the same species (e.g. chicken and duck are both birds)
define “syngeneic”
similar genetics (e.g. twins)
define “isogeneic/autologous”
same gentics (e.g. self)
rank allogenetic, xenogenetic, isogeneic/autologous, syngeneic in order of best immune response to worst immune response
xenogenetic, allogenetic, syngeneic, isogeneic/autologous
describe “molecular size” in terms of the immune response elicted by an immunogen
- the larger the molecular size, the greater the immunogenic property
- generally molecules with a mass greater than 10,000 Da are good immunogens
isulin (5700 Da), histones (6000 Da) and oxytocin (1000 Da) are ______ immunogens
poor
ovalbumin (45,000 Da), ribonuclease (14,000 Da) and immunoglobulin (160,000 Da) are _____ immunogens
good
describe “molecular complexity” in terms of the immune response elicted by an immunogen
internal molecular complexity is essential for good immunogens
are synthetic homopolymers of single amino acids or sugars immunogenic?
the addition of aromatic amino acids changes this how?
- no - they’re structurally unstable
- addition of aromatics (tyr, phe, trp) enhances immunogenicity by stabilizing the structure
describe “degradability” in terms of the immune response elicted by an immunogen
antigens that are easily phagocytosed are generally more immunogenic
D-amino acids are _____ (good or poor) immunogens. Why?
- poor
- recall: endogenous antigens should be phagocytosed and processed first, then presented to helper T-cells by APCs
- syntehtic polymers of d-aa cannot be processed by enzymes in phagocytosis bc naturally occuring aa are in the L-configuration
describe “physical form” in terms of the immune response elicted by an immunogen
(2)
(1) particulate antigens (aggregates of protein) are more immunogenic than soluble ones
- this is bc soluble antigens will go through body fluid and can be excreted, while particulate antigens aggregate
(2) denatured antigens are more immunogenic than when they are in their native fold
- this is bc their tertiary structure is no longer intact, resulting in different portions of the peptide exposed on the outer surface
what is a hapten?
small organic molecule that is antigenic, but not immunogenic unless it is attached to a large carrier protein
what do researchers use haptens for?
researchers use them to solicit immune responses to haptens when designing vaccines
describe the results when injecting a rabbit with (1) hapten, (2) carrier and (3) the hapten-carrier conjugate
(1) no anti-DNP antibody formation (too small to elicit an immune response)
(2) development of anti-BSA antibodies
(3) development of 3 types of antibodies:
- anti-dnp antobodies (major production)
- anti-bsa antibodies (minor production)
- anti-dnp-bsa antibodies (minor production)
provide a well known example of a hapten
penicillin
what happens when penicillin enters the body?
- it forms a covalent bond with proteins, forming a penicilloyl-protein derivative
- this conjugate derviative can mount an immune response in some individuals - which is why doctors ask if youre allergic to penicillin before prescribing it
what are adjuvants?
substances that enhance the immunogenicity of an antigen when injected into a human, without resulting in the mouting of an immune response against it
what exactly is the need for adjuvants? what does this phenomenon contribute to?
most antigens are soluble so they dont elict a strong immune response
- adjuvants keep the antigen localized to tissue, preventing it from being dispersed in the body
- this approach is the basic principle behind developing vaccines
what are the mechanisms by which adjuvants work? (3)
(1) keep the soluble immunogen localized to a tissue, acting as a depot and preventing the antigen from dispersing in the body
(2) enhancing the inflammation and developing immune response
(3) activating macrophages to digest and present the processed antigen on MHCII molecules to the helper T-cells, to develop an immune response
how can you increase the immunogenicity of a weak immunogen? (3)
- add an adjuvant
- attach a carrier protein if the antigen is too small
- complex it with other molecules to increase the molecular complexity
what are epitopes?
the immunologically active regions of an antigen that bind to:
-antigen specific T- or B-cell receptors on lymphocytes
OR
-secreted preformed antibodies
describe the relationship between epitopes and the production of vaccines
- the production of vaccines is contingent on the epitope binding to the antigen-specific receptor (t- or b-cell receptor) to elicit the specific immune response
- thus, an effective vaccine leads to the generation of antibodies and t-cells that are specific to a particular epitope of the infectious agent
how do soluble antibodies bind to epitopes of exogenous antigens?
via weak non-covalent interactions that only operate over short distances
what are 2 characteristics of the interactions btwn soluble antibodies and the epitopes of exogenous antigens?
(1) complementary shape (lock and key) of the binding site of the antibody and the epitope
(2) flat or undulating interacting surface
can antibodies recognize epitopes consisting of amino acids that are sequential (linear) and/or non-sequential (discontinous)?
yes to both - but in adjacent regions due to their secondary or tertiary structure
what are BCRs?
B-cell receptors: membrane bound immunoglobulin/antibodies on the b-cell surface
what do BCRs recognize?
exogenous antigens
can BCRs recognize epitopes consisting of amino acids that are sequential (linear) and/or non-sequential (discontinous)?
yes
list 4 characteristics displayed by epitopes that are recognized by both secreted and membrane-bound antibodies
(1) multivalency
(2) immunodominance
(3) specificity
(4) accessability
multivalency and immunodominance describe the interactions between what?
the epitope and the antibody
specificity and accesability describe characteristics of what?
the epitopes that influence their interaction with their receptor
describe “multivalent antigens”
multivalent antigens are those with multiple epitopes that can be recognized by antibodies
what are homologous multivalent epitopes?
describe the resulting immune response.
these contain the same epitope repeated multiple times, resulting in a single type of immune response
what are heterogenous multivalent antigens?
describe the resulting immune response.
these express different epitopes, which would result in variation in the immune response depending on the epitope recognized by the antibody
define “immunodominant”
when does this occur?
- with multivalent antigens, some epitopes will be immunodominant:
- antigen that produces a more pronounced immune response
what is immunodominance determined by? (3)
- accessibility of the epitope
- specificity of the binding site
- affinity of the epitope binding to the BCR
immunodominance is an important concept in vaccine design, true or false?
why?
- true
- there will be more antibodies produced specific to the immunodominant epitope than any of the other epitopes
accessibility of the epitope is a contributing factor to immunodominance, true or false?
why?
- true
- if the antibody cannot reach the epitope, no immune response can be elicted
antigens located between the polyalanine and polylysine backbones are _______ for antibody binding?
(available, unavailable)
unavailable
what would be necessary for amino acids located at the core of a protein to be exposed to an antigen?
denature the protein so the specific aa sequence is exposed to the antibody
do antibodies have a higher affinity for certain configurations of antigens over others?
yes
define specificity in terms of epitope-antibody binding
antibodies can discriminate between antigens that differ in configuration
how is specificity accquired?
by gene rearrangement
define gene rearrangement
genetic recombination in developing lymphocytes
how do acidic groups contribute to antibody specificity?
specificity varies depending on whether the acidic group is in the:
- ortho: strong immune response
- para: no response
- meta: no response
how do glycoside groups contribute to antibody specificity?
-epitopes with glycoside groups develop extreme antibody specificity due to the different alpha/beta configurations of these groups
describe specificity using the example of galactoside and glucoside
the specific configuration of the OH group in galactoside requires antibody specificity to distinguish it from glucoside
(antibodies will respond to one and not the other)
how do T-cells recgonize antigens?
via TCRs (t-cell receptors)
describe what happens to proteins following phagocytosis
they are enzymatically degraded into smaller peptides
what happens to the linear peptides generated via phagocytosis
they go through the process of binding MHC molecules
what specific molecule is recognized by TCRs?
the small peptide (from phagocytosis) and the MHC molecules together
t-cell recognition is referred to as what? describe this
MHC restriction
- t-cells interact with both the MHC molecule (self) and the peptide that is bound to it (foreign)
- it will recognize and respond to the antigen only when it is bound to the same MHC molecule
- i.e. for T-cells, the antigens are processed and presented on MHC molecules to TCR molecules by APCs
overview: compare the interaction btwn b-cells and t-cells with the antigen
b-cells: involves binary complex of membrane Ig and antigen
t-cells: involves ternary complex of T-cell receptor, antigen and MHC molecule
overview: compare the binding of a soluble antigen for b-cells vs t-cells
b-cells: yes, can bind soluble protein
t-cells: no, needs to be presented on MHC molecules by APC
overview: compare the involvment of MHC molecules for b-cells vs t-cells
b-cells: none required
t-cells: required to display processed antigen
overview: comapre the epitope properties for b-cells vs t-cells
b-cells: accessible, hydrophillic peptides containing sequential or non-sequential aas
t-cells: internal linear peptides produced by processing of antigen and bound to MHC molecules
what is antibody cross-reactivity?
- the ability of an antibody to react with two or more antigens that possess a common epitopes
- some responses may however be stronger than others
epitopes of what groups contribute to antibody cross-reactivity?
epitopes of nonionic groups
what are the antibdodies for blood type A?
anti-B
what are the antibdodies for blood type B?
anti-A
what are the antibdodies for blood type AB?
none - universal acceptor
what are the antibdodies for blood type O?
anti-A and anti-B - universal donor
ABO blood group antigens are ______ and have similarities to the _______
(1) inherited from your parents
(2) the gut microbiota
people can develop antibodies to the gut microbiota antigens which can cross react with the ABO blood group antigens, true or false? explain.
- true
- if you are type A you will have anti-B antibodies
- during B-cell development the b-cells specific for the A blood group antigens are clonally deleted, but if you are type AB you wont have any antibodies against type A or B antigens
list 3 factors that may influence whether antigens are immunogenic
(1) the host must be genetically fit to produce an immune response to an antigen
- thus immunodeficient people are not able to mount an immune response
(2) each immunogen has an optimal concentration that is required to elicit an effective immune response
(3) route of entry of the antigen can strongly influence the organ and cell populations that are involved in the immune response, for e.g.:
- ingestion, inhalation: mucosal response
- tissue (scratch, cut): strong response in draining lymph nodes
- blood (injection): general (systemic) response, especially in the spleen.
