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Antigens, Immunogens, Superantigens TSOM Term3, Unified Exam 1

what is an immunogen?

substance capable of inducing adaptive immune response

what is an antigen?

substance capable of being recognized by the adaptive immunity.

what is the relationship between antigens and immunogens?

All immunogens are antigens, but not all antigens are immunogens

what is an epitope?

the region(s) of the antigen in direct contact with the antibody, B-Cell Receptor, or T-Cell Receptor

what is a synonym for epitope?

antigenic determinant

how many epitopes are there per antigen?

there may be one or more epitopes per antigen

what is a hapten?

a small molecule which can function as an antigen, but by itself is incapable of inducing an immune response

is a hapten an immunogen?

no

what are the 3 types of antigen/immunogen receptor molecules?

1. BCR (b cell receptor)
2. TCR (t cell receptor)
3. MHC

of the 3 types of antigen/immunogen receptor molecules, which are surface immunoglobulins?

B-Cell Receptors

how many antigen recognition sites are there on a BCR?

two identical antigen recognition sites

how many antigen recognition sites are there on a TCR?

one antigen recognition site

where are MHC-I molecules expressed?

on all nucleated cells

where are MHC-II molecules expressed?

macrophages
dendritic cells
lymphocytes

which of the 3 types of antigen/immunogen receptor molecules is expressed on antigen presenting molecules?

MHC

which various antigens or sources of antigens are immunogens?

1. parasites
2. foreign proteins
3. bacteria
4. viruses
5. fungi

draw how immunogens affect lymphocytes

antigens are big molecules- however, the area that triggers the specific immunity is a small part, known as what?

epitope

how big is an epitope?

an epitope in a protein antigen could be as few as 20 amino acids long

what is the shape of an epitope?

could be linear, conformational

what type of cells recognize a conformational epitope?

BCR only, not TCR

what is the difference between a linear and conformational epitope?

in a conformational epitope, the sequence of amino acids is discontinuous, but they are brought into proximity by the protein's 3-D structure

what is a synonym for conformational epitope?

discontinuous epitope

when is there cross-reaction between different antigens?

when a different antigen has one identical determinant or a similar determinant

when is there no reaction between different antigens?

when there is no structural similarity

what is the receptor/binding activity of a BCR?

BCR--> Ag

what is the receptor/binding activity of a TCR?

TCR --> Ag/MHC

is MHC required for BCR?

no

is MHC required for TCR?

yes

does a BCR bind soluble antigen?

yes

does a TCR bind soluble antigen?

No

what is the chemical nature of BCR antigens?

protein
polysaccharides
lipids
nucleic acids

what is the chemical nature of TCR antigens?

proteins
some lipids, glycolipids

what type of epitope is recognized by BCR?

accessible, either linear or conformational

what type of epitope is recognized by TCR?

linear peptides (short)

what makes a good antigen/immunogen?

1. physical size : > --> better
2. complexity: chemical composition and structural complexity
3. solubility or degradability by antigen processing cells, macrophages, dendritic cells and B cells
4. foreignness to the individual

what size are the best immunogens?

>=100kD

what is the minimum size for active immunogens (proteins)

>30kD

how immunogenic is an immunogen that is <5-10kD?

minimally immunogenic, usually require carrier

what is an example of a <5-50kD immunogen that is minimally active and requires a carrier?

hapten

How do the categories of chemical compounds rank in terms of their immunogenicity based on complexity in descending order?

HIGH IMMUNOGENICITY:
1. proteins and glycoproteins
2. Polysaccharides
3. nucleic acids, phospholipids
4. haptens
LOW IMMUNOGENICITY:

are proteins and glycoproteins good immunogens?

yes

how complex are proteins and glycoproteins in terms of their immunogenicity?

complex in composition and structure

can proteins and glycoproteins induce immunity?

can induce humoral and cell-mediated immunity

how complex are polysaccharides in terms of their immunogenicity?

repeating structures, generally low affinity

what type of response do polysaccharide immunogens elicit?

IgM response

do polysaccharides stimulate a cell-mediated immune response?

cannot be processed and presented as linear epitopes for T cells, thus do not induce cell-mediated response

how foreign are nucleic acids and phospholipids in terms of their immunogenicity?

evolutionarily conserved; less foreign

how do nucleic acids and phospholipids become better immunogens?

conjugation with proteins or polysaccharides

how immunogenic are haptens?

insufficient in size to be immunogenic. need carrier

what examples of natural haptens?

hormones, lipids, simple sugars

what are examples of synthetic haptens?

chemicals, drugs (penicillin)

what types of drugs can act like haptens and be associated with severe, life threatening anaphylactic reactions?

antibiotics, particularly penicillins

how do penicillins act as haptens?

they form covalent bonds with proteins to produce protein-drug adducts that elicit an immune response (hypersensitivities) in some individuals

what are the 3 types of epitopes in a hapten-conjugate complex?

1. the pure hapten
2. the pure antigen
3. the hapten-antigen complex

how can a hapten be made immunogenic?

immunizing with a hapten-carrier conjugate

do identical twins recognize each other's proteins as foreign?

no.
they have the same genetic makeup and their immune systems would recognize eachother as self

what are examples of immunologically privileged anatomical sites (sequestration)?

corneal, spermatic, CNS cell antigens

What are the types of antigens?

1. mitogens
2. superantigens
3. T cell independent
4. T cell dependent

mitogens are characterized by what?

the same epitope repeated many times

how many types of B cells can mitogens activate?

more than one B cell type/clone

are mitogens B cell monoclonal or polyclonal activators?

B cell polyclonal activators

what are superantigens?

antigens that can activate more than one type of T cell

are superantigens polyclonal/monoclonal B/T cell activators?

polyclonal T cell activators

what effect do superantigens have on the immune system?

cause hyper activation of the immune system

what is an example of excessive T cell activation having drastic effects?

toxic shock syndrome

what does an antigen being T cell independent vs. T cell dependent depend on?

whether an anigen can stimulate B lymphocytes with or without the help from T lymphocytes

How do superantigens induce activation of multiple types of T cells?

they are polyclonal stimulators of T cells, binding to the MHC-TCRβ (on the outside of the polypeptide of TCR) complex, without regard for antigen specificity

How much of CD4 T cells are activated by super antigens?

up to 20%

what is the result of a superantigen activating up to 20% of circulating CD4 T cells?

massive production of cytokines such as IL1, IL2, and TNFα which causes systemic shock

what are examples of conditions that are caused by superantigens?

food poisoning
toxic shock syndrome

what microbes cause food poisoning and/or toxic shock syndrome?

bacterial exotoxins:
staphylococcal
enterotoxins
staphylococcal toxic shock toxin
staphylococcal exfoliating toxin
streptococcal pyrogenic exotoxins

what forms a bridge between CD4 T cell's receptor and the MHC II molecule?

superantigens

what do T cells do in response to a superantigen?

divide and differentiate into effector cells

what are T-independent antigens?

antigens which can directly stimulate B cells to produce antibody without the requirement for T cell help

do T independent antigens require to be presented by APC?

no

usually, T independent antigens are what?

mitogen and are resistant to degradation by antigen presenting cell

what are examples of T independent antigens?

pneumococcal polysaccharide
lipopolysaccharide
flagellar antigen

what are T dependent antigens?

antigens that require the help of T lymphocytes to activate be cells to produce antibody

are T dependent antigens degradable by antigen presenting cell?

yes

what type of compounds are T dependent antigens?

protein

in addition to size, molecular complexity and foreignness, immunogenicity of an antigen depends on what?

1. physical form
2. degradability
3. route
4. dose
5. adjuvant

which physical form of an antigen is more immunogenic, particulate or soluble?

particulate > soluble

why are particulate antigens more immunogenic than soluble ones?

particulate form are more easily taken up by antigen presenting cells

which physical form is more immunogenic, denatured or native?

denatured > native

what speed of release is important for immune response?

slow release

what are the relative immunogenicities of routes of administration?

subcutaneous > intraperitoneal > intravenous > intragastric

what is the limitation of the oral route of administration's immunogenicity?

oral route induces local mucosal immunity but not systemic immunity

what is low zone tolerance?

low doses appear to inhibit the specific antibody production

what is high zone tolerance?

very high doses of antigen inhibit immune responsiveness to a subsequent challenge

what is the effect of an adjuvant on immunogenicity?

substances mixed together with an antigen and enhance an immune response to an antigen

what is the difference between an adjuvant and a carrier molecule?

unlike carrier molecule an adjuvant does not form stable linkage with the antigen

what is an example of an adjuvant?

1. complete Freund's adjuvant
2. aluminum hydroxide/aluminum phosphate

what is Complete Freund's Adjuvant?

water in oil emulsion containing killed mycobacteria

how does an adjuvant increase immunogenicity of an antigen?

1. insolubilize antigen for better phagocyte uptake
2. insolubilize antigen for gradual release over time in lipid emulsions called liposomes with delayed time release of antigen
3. stimulating the influx of phagocytic cells or other immune cells to the site

some adjuvants contain mycobacterial components capable of stimulating what?

the innate immunity- acitvation of macrophages

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