Week 3 Lec: Antigens and MHC Flashcards
The immune response of lymphocytes is triggered by materials called?
immunogens
This term refers to a substance that reacts with antibody or sensitized T cells but may not be able to evoke an immune response in the first place.
antigen
It is a foreign substance that can initiate an immune reponse.
antigen
These are macromolecules that trigger adaptive immune response.
antigen
Factors influencing the immune response?
- Age
- Overall Health
- Dose
- Route of Inoculation
Relationship between immunogens and the antigens?
All immunogens are antigens but not all antigens are immunogens.
Most common portal of entry?
mucous membrane
The ability of an immunogen to stimulate a host response depends on the following characteristics?
- Macromolecular size
- Chemical composition
- Molecular complexity
- The ability to be processed and presented with MHC molecules
Macromolecular size of immunogen?
10,000 daltons
Chemical composition of immunogen?
composed of protein and polysaccharides; proteins are more immunogenic than polysaccharides
Why do humans accept modifications within their body systems (hip replacement, knee replacement, elbow replacement, artificial heart valve, etc.)?
because the materials used for the procedure are made of teflon or nylon, which are non-immunogenic
True or false: pure lipids and pure carbohydrates are never immunogenic.
True
How do pure lipids and pure carbohydrates become immunogenic?
when they attach and combine with other molecules such as proteins and carbohydrates (ex: lipids + proteins = lipoproteins, nucleic acids + proteins = nucleoproteins, glycogen + lipids = glycolipids)
True or false: Although an immunogen must have a molecular weight of at least 10,000 Dalton, only a small part of the immunogen is actually recognized in the immune response.
True
These are molecular shapes or configurations that are recognized by B or T cells.
Epitopes
For proteins, epitopes recognized by B cells may consist of ______ amino acids.
6 to 15
This key portion of the immunogen is known as the determinant site or?
Epitope
Epitope where amino acids follows one another on a single chain.
Linear Epitope
Linear Epitope is also called?
Sequential
Type of epitope that results from the folding of one chain or multiple chains, bringing certain amino acids from different segments of a linear sequence or sequences into close proximity with each other so they can be recognized together.
Conformational Epitope
T-cell epitopes are?
linear
They are non-immunogenic materials that, when combined with a carrier, create new antigenic determinants.
Haptens
Examples of Haptens?
- Poison Ivy
- Drug related
Poison ivy (Rhus radicans) contains chemical substances called __________, which are haptens. Once in contact with the skin, these can couple with tissue proteins to form the immunogens that give rise to _______________.
catechols; contact dermatitis
Example of drug-related hapten?
The best known example of this occurs with penicillin, which can result in a life-threatening allergic response (thrombocytopenia).
Book written by Karl Landsteiner?
The Specificity of Serological Reactions
When was the book “The Specificity of Serological Reactions” published?
1917
Who was the author of the book “The Specificity of Serological Reactions”?
Karl Landsteiner
Karl Landsteiner discovered which concepts?
- Haptens
- ABO blood group
True or false: Hapten alone cannot stimulate antibody formation.
True
True or false: Haptens can still react with antibodies but no complexes form since it is monovalent.
True
True or false: When complexed to a carrier, the hapten can stimulate antibody formation.
True
If hapten is complexed to a carrier at multiple sites, _________ can take place.
agglutination
__________ are those antigens that belong to the host.
Autoantigens
True or false: Autoantigens are capable of antibody production.
False
__________ are from other members of the host’s species, and these are capable of eliciting an immune response.
Alloantigens
They are important to consider in tissue transplantation and in blood transfusions.
Alloantigens
Alloantigens are important to consider in?
tissue transplantation and in blood transfusions
True or false: Alloantigens are capable of antibody production.
True
Tissue transplantation from the host itself. Used for severe/3rd-degree burns (skin from leg/thigh part) and rhinoplasty (skin from earlobe).
Autograft
Tissue transplantation wherein the organ or tissues came from a different person. Example: kidney transplant. Tissue match is one criteria before transplantation is approved.
Allograft
Tissue transplantation from identical individuals (twins).
Isograft/Syngraft
Tissue transplantation from different specie. Example: pig heart to human.
Heterograft/Xenograft
Antigens from other species, such as other animals, plants, or microorganisms.
Heteroantigens
Those that exist in unrelated plants or animals but which are either identical or closely related in structure so that that antibody to one will cross-react with antigen of the other.
Heterophile antigens
Example of Heterophile antigens?
Polysaccharide type XIV of pneumococcus reacting with anti-A antisera
It is a substance administered with an immunogen that increases the immune response.
Adjuvant
Adjuvant is administered?
intramuscularly
Adjuvant acts by producing a ____________ that attracts a large number of immune system cells to the injection site.
local inflammatory response
________________ are the only adjuvants approved for clinical use in the United States, and these are used to complex with the immunogen to increase its size and to prevent a rapid escape from the tissues.
Aluminum Salts
Another example of adjuvant?
Freund’s adjuvant
Freund’s adjuvant consists of?
- Mineral oil
- Emulsifier
- Mycobacterium butyricum
Freund’s adjuvant killed?
Bordetella pertussis, the causitive agent of whooping caugh
Mycobacterium in Freund’s adjuvant accounts for about?
0.5 mg/mL
True or false: Freund’s adjuvant can be used in humans.
False. Freund’s adjuvant cannot be used in humans because it could produce granulomas or large areas of scar tissue.
Different Effects of Adjuvants?
- Forms complex to antigen to increase its size
- Prevent rapid escape from the tissues
- Increase processing of antigen
- Stimulate T-cells → that enhance CMI
- Stimulate B-Cells → enhance HI
- Also stimulates phagocytic cells
Evidence now indicates that the genetic capability to mount an immune response is linked to a group of molecules originally referred to as?
Human Leukocyte Antigen
The French scientist __________ gave them the name HLA, because they were first defined by discovering an antibody response to circulating white blood cells.
Jean Dausset
The HLAs are also known as?
Major Histocompatibility Complex/MHC
Why are HLAs also called MHC?
GRAFT REJECTION - because they determine whether transplanted tissue is histocompatible and thus accepted or recognized as foreign and rejected (in short, they place a role in graft rejection)
True or false: MHC molecules are actually found on all nucleated cells in the body, and they play a pivotal role in the development of both humoral and cellular immunity.
True
Gene coding for the MHC molecules in humans are found in the?
short arm of chromosome 6
All MHC molecules are expressed in all nucleated cells in the body and in?
MHC class I
Three categories or classes of genes coding for the MHC molecules?
- Class I
- Class II
- Class III
Class ___ molecules are coded for at three different locations or loci.
I
Class I molecules are coded for at?
three different locations or loci
Class I genes are found at three different locations or loci, termed?
A, B, and C
Class I non-classical genes?
HLA - E, F, G
Class ___ genes are situated in the D region, and there are several different loci.
II
Class II genes are situated in the _____, and there are several different loci.
D region
Class II genes are situated in the D region, and there are several different loci, known as?
DR, DQ, and DP
Class II non-classical genes?
DM, DN, DO
Class ___ genes are located in between class I and Class II regions.
III
Class III genes code for the complement component proteins ________ and cytokine ________.
- C4A
- C4B
- C2
- Factor B
- tumor necrosis factor (TNF)
Class III genes are located in between?
Class I and Class II regions
Category of MHC molecule involved in antigen recognition?
Class I and Class II
At each of the loci, or locations of MHC molecules, there is the possibility of?
multiple alleles
These are alternate forms of a gene that code for slightly different varieties of the same product.
Alleles
The MHC system is described as __________, because there are so many possible alleles at each location.
polymorphic
HLA-A has at least _____ different alleles.
580
HLA-B has at least _____ different alleles.
921
HLA-C has at least _____ different alleles.
312
True or false: The probability that any two individuals will express the same MHC molecules is high.
False. The probability is very low.
There is a possibility of two different alleles for each gene on the chromosome unless that person is __________ (has the same alleles) at a given location.
homozygous
Means that all alleles that an individual inherits code for products that are expressed on cells.
Codominant
Contribution from both parental generation.
Codominance
Because the MHC genes are closely linked, they are inherited together as a package called a?
haplotype
Thus, each inherited chromosomal region of an MHC molecule consists of a package of genes for?
A, B, C, DR, DP, and DQ
The full genotype of an MHC molecule would consist of ___________ at a particular locus.
two of each gene
Class ___ MHC molecules expressed on all nucleated cells.
I
Highest concentration of Class I MHC molecules are found on?
Lymphocytes
Class I MHC molecules are low or undetected on?
liver hepatocytes, neural cells, muscle cells, and sperm
Class I MHC molecules are made up of?
Alpha and β2-Microglobulins polypeptide chains
Alpha polypeptide chain is folded into three domains?
α1, α2, and α3
The α chain is folded into three domains is inserted into the cell membrane via a ________________.
transmembrane segment that is hydrophobic
Alpha polypeptide chain has a molecular weight of?
44,000 daltons
The α3 region reacts with _____ on cytotoxic T cells.
CD8
Polypeptide chains that do not penetrate the cell membrane, but it is essential for proper folding of the α chain.
β2-Microglobulins
β2-Microglobulins has a molecular weight of?
12,000
True or false: The occurrence of class I MHC molecules is much more restricted than that of class II.
False. The occurrence of class II MHC molecules is much more restricted than that of class I.
The major class II molecules consist of _______________ that are both encoded by genes in the MHC complex.
two noncovalently bound polypeptide chains
Most polymorphic MHC class II molecule?
DR, which has 18 different alleles
The class II has __________ and __________ anchored on the cell membrane.
2 alpha chain and 2 beta chain
The class II has 2 alpha chain and 2 beta chain anchored on the?
cell membrane
MHC class II molecule that is expressed at the highest level, as it accounts for about one-half of all the class II molecules on a particular cell.
DR
The groove where the antigen recognition happens is called?
peptide-binding cleft
The main role of the class I and class II MHC molecules is to bind peptides within cells and transport them to the plasma membrane, where T cells can recognize them in the phenomenon known as?
Antigen Presentation
Class I molecules mainly present peptides that have been synthesized within the cell to?
CD8+ / T-Cytotoxic cell
Class II molecules mainly bind exogenous proteins and present it to?
CD4+ / T-helper cell
It is thought that the two main classes of MHC molecules have evolved to deal with two types of infectious agents?
- those that attack cells from the outside
- those that attack from the inside
Both MHC class (Class I and II) are synthesized in the?
rough ER
It keeps the α-chain in a partially folded state while it awaits binding to β2–microglobulin.
Calnexin
Other term for calnexin?
Chaperone
Three other chaperone molecules _____, _____, and _____ are associated with the complex and help to stabilize it for peptide binding.
calreticulin, tapasin, and ERp57
Characteristics of Class I in summary?
- Effective for endogeneous antigens (Tumors, Viruses, Parasites)
- Presented in CD8+ T-cytotoxic cells
- Proteasomes/proteosome
- Transporting peptides (TAP1, TAP2)
Function of proteasomes?
helps class I for antigen recognition
TAP means?
transporters associated with antigen processing
Characteristics of Class II in summary?
- Effective for exogenous antigens (Bacteria)
- Presented in CD4+ T-helper cells
- Invariant chain, Invariant chain peptide (chain that protects the binding site)
Digestion of these defective or early proteins is carried out by proteases that reside in large cylindrical cytoplasmic complexes called?
proteasomes
These are a packet of enzymes that play a major role in antigen presentation.
Proteasomes
Once cleaved, the peptides must then be pumped into the lumen of the endoplasmic reticulum by specialized transporter proteins called?
transporters associated with antigen processing (TAP1 and TAP2)
It helps TAP transporters to have close proximity to the newly formed MHC class I molecule and mediates interaction with them so that peptides can be loaded onto the class I molecules.
Tapasin
Once the alpha-chain has bound the peptide, the MHC I-peptide complex is ______________ to the cell surface.
rapidly transported
Unlike class I molecules, class II molecules must be transported from the endoplasmic reticulum (ER) to an ______________ before they can bind peptides.
endosomal compartment
_______________ are the most potent activators of T cells, and they are excellent at capturing and digesting exogenous antigens such as bacteria.
Dendritic cells
This prevents interaction of the binding site with any endogenous peptides in the endoplasmic reticulum.
Invariant chain (Ii)
The invariant chain is degraded by a protease, leaving just a small fragment called _____________________ attached to the peptide-binding cleft.
class II invariant chain peptide (CLIP)
CLIP is then exchanged for __________.
exogenous peptides
Applications of MHC Typing (HLA typing)?
- Tissue/Organ Transplantation
- Disease Association
- Paternity Testing
- Studies of Racial Ancestry and Migration
- Forensic Medicine
MHC Class II are found in what cells?
B cells, APC/Dendritic Cells, Monocytes, Macrophages
