Outcome 3 Flashcards
discuss the inheritance of the MHC genes
MCH class I and II molecules are co-dominantly expressed, Thus every nucleated cell expresses up to six different HLA class I and six different HLA class II molecules. One set is inherited from each parent. MHC genes are highly polymorphic, preventing two individuals from having the same MHC genes
state the other common name the MHC complex is known by
Human Leukocyte Antigen Complex (HLA)
discuss where MHC class I and class II molecules are located
MHC I: Expressed on nearly all nucleated cells (important to note RBCs do not have a nucleus and therefore do not display MHC I). Neurons and sperm cells at certain stages of differentiation appear to lack MHC I.
MHC II: APCs
explain how antigens are processed and presented with MHC class I molecules (endogenous)
Endogenous antigen processing occurs inside of the cell and happens when the endogenous antigen is bound to the class I MHC molecule on the cell’s surface. This signals that the cell has been infected and requires help.
- Digestion of the antigen into peptide fragments.
- Synthesis of MHC class I molecules.
- Binding of peptide fragments to MHC class I molecules.
- Packing of the Ag-class I MHC molecule.
- Insertion of Ag-class I MHC complex into the plasma membrane.
Cytotoxic T lymphocytes (CD8) are activated and destroy the cell.
explain how antigens are processed and presented with MHC class II molecules (exogenous)
Exogenous antigen processing occurs outside of the cell. Antigens that are present in extracellular fluid are ingested by APC by endocytosis or phagocytosis.
- Ingestion of antigen
- Digestion of Ag into fragments
- Synthesis of class II MHC molecules
- Packaging of class II MHC molecules
- Fusion of vesicles
- Binding of peptide to class II MHC molecules
- Insertion of Ag-class II MHC complex into the plasma membrane.
APC is not destroyed, the T helper cell (CD4) activates macrophages, and B cells (to produce an antibody response)
explain MHC restriction
A T cell response is only generated if a peptide created during the processing of an antigen is bound to an MHC molecule. All peptides can fail to bind to an MHC molecule, and no T-cell response will occur.
This occurs in vaccination, as some peptide fragments are too small, and therefore not recognized by the individual.
discuss the role of MHC in transplantation
MHC class I and II molecules will respond to the non-host MHC molecules on the graft, starting an immune response and graft rejection.
Define Polygenicity
MHC class I and II molecules are coded for by multiple independent genes.
Define Polymorphism
Multiple stable forms of each MHC gene exists in the population.
differentiate between humoral and cell-mediated immunity
Humoral Immunity: Immune responses that involve antibodies. Can be transferred to another individual using an antibody-containing serum. Occurs when an antigen is found within an extracellular fluid.
Cell-mediated Immunity: Immune responses mediated by T cells. Occurs when the antigen is found within body cells.
identify the effector cells of adaptive immunity
B lymphocytes
T lymphocytes
APCs
explain clonal expansion/selection
When a lymphocyte identifies an antigen, the lymphocyte with proliferating and differentiates to respond to the specific antigen. The result is thousands of lymphocytes specialized for the antigen within secondary lymphatic organs.
Two populations of cells are created - effector and memory cells. Effector cells will perform the immune response functions, and memory cells will circulate and remember the antigen for future infections.
define and state the purpose of the MHC classes
MHC I: The major function is to present peptide antigens to Tc Cells (CD8). Additionally MHC I molecules will prevent NK cells from killing normal host cells.
Helps the immune system identify host cells from antigens.
MHC II: The main function is to present peptides to T Cells (CD4).
Helps the immune system to identify antigens.
MHC III: Genes encode products that have immune functions (complement, cytokines, and TNF).
identify the MHC class present on APCs
MHC I and MHC II
describe antigen processing
Antigens must be processed with the APC and presented to specific T cell receptors (TCRs) on the T cell.
differences between MHC classes and what is the end result of antigen processing.
MHC I: Occurs inside of the cell, and ends in cell death. CD8 cells. HLA-A, HLA-B, HLA-C.
MHC II: Occurs outside of the cell, and ends in an antibody response. CD4 cells. HLA-DP, HLA-DQ, HLA-DR.
define and differentiate between antigens and immunogens
Antigens: Any agent capable of binding specifically to components of the immune system. Can be complete (immunogen) or incomplete (hapten).
Immunogen: Any agent capable of inducing an immune response (Production of antibodies)
All immunogens are antigens, but not all antigens are immunogens.
the requirements for immunogenicity
Foreignness, size, complexity, degradability
a. Foreignness
The molecule must be recognized as nonself, the more foreign the more immunogenic.
b. size (mw)
The larger the molecule the more immunogenic. Carrier molecules can be added to increase molecular weight.
c. complexity
The more complex the molecule the more immunogenic. Large simple molecules will be less immunogenic than small complex molecules. Proteins elicit the best response, followed by carbohydrates. Lipids/nucleic acids elicit a poor response. particulate/aggregated antigens yield better responses than soluble antigens.
d. degradability (APC uptake and processing)
The antigen must be susceptible to enzymatic degradation. Molecules that cannot be phagocytosed or processed by APCs cannot stimulate an immune response.
Two factors must generally exist for an antigen to be degradable.
1. The antigen must be stable so that it can exist long enough to interact with a B or T cell to initiate an immune response.
2. The antigen must be susceptible to enzymatic degradation so that the antigen can be processed by APCs.
list host factors that may influence immune response to an antigen
Host factors can prevent an immune response even if all the properties of immunogenicity are present in an antigen.
The genotype of the host affects the type and degree of the immune response. MHC gene products play a role in determining the degree to which the host will respond to an antigen.
Age - very young and elderly individuals have decreased immune system function due to immaturity or degeneration.
Health- illness can contribute to weaker immune responses.
Stress
Nutrition
define epitope/antigenic determinants
They are the only immunologically active portions of antigens. Meaning they are where receptors on lymphocytes or antibodies bind, and they stimulate the activation and clonal expansion of antigen-specific T cells. Antigens can have multiple epitopes, and B and T cell receptors may recognize different epitopes on the same immunogen. As both B and T cells can recognize epitopes both humoral and cell-mediated responses can be mounted.
Epitopes recognized by B cell
Membrane-bound antibodies on B cells recognize and bind to free antigens in solutions. These antigens generally have epitopes on the outside of their cell, making the epitopes accessible for interactions with the BCR on b-cell antibodies.
Define conformational or Discontinuous epitopes
Epitopes that are non-contiguous residues along a polypeptide chain are brought together by the folded conformation of the protein.
B cell recognized epitopes.
Epitopes recognized by T cells
T cells are unable to bind to soluble antigens. For TCRs to interact with epitopes the antigen first go through antigen processing by an APC to degrade the polypeptide chain into smaller peptide chains.
Define continuous or linear epitopes
Epitopes are small peptide chains created during antigen processing.
T cell TCRs recognized epitopes.
define hapten
A substance that is capable of reacting with an antibody but cannot induce antibody formation unless it is bound to a carrier molecule. Haptens that are not bound to carrier molecules have too low of a molecule weight and are too chemically simple to induce an immune response.
identify the major classes of antigen composition
Protein, carbohydrates, lipids/nucleic acids.
Particulate/aggregate and soluble
discuss cross-reactivity
Cells/Antibodies may be able to react with two different molecules (two different antigens) that share epitopes.
When antibodies/cells with specificity to one epitope bind to another epitope that is not identical. (antibody/cell binds to an antigen it is not specific to). The epitopes must be structurally similar. The “wrong” epitope will elicit a weaker bond than the “correct” epitope.
Heterophilic Antigens - When cross-reacting substances are unrelated to each other. ABO blood group system is an example.
toxoid
An inactivated toxin whose toxicity has been suppressed by chemical or heat treatment while immunogenicity is maintained. - Altered form of toxins secreted by bacteria.
heterophile antigen
A cross-reacting antigen expressed by widely different species including humans and bacteria.
define adjuvants
Substances that enhance the immunogenicity of an antigen and are used in vaccine preparations.
Effects:
Prolong antigen persistence (increases half-life of antigens)
Enhance costimulatory signals
Increase local inflammation by converting soluble proteins into particulate forms - enhance phagocytosis.
Improve antigen delivery and processing.
increases the production of local inflammatory cytokines
describe the factors that affect immunogenicity: Route of administration.
Various routes of administration will influence which immune organs and cell populations will be involved with the response.
Subcutaneous/Intramuscular - high immune response due to dendritic cells processing and transporting antigens to lymph nodes.
Intravenous - Moderate/low immune response. Antigens are carried to the spleen.
Intragastric - Low, mainly a local response is elicited. Often induces tolerance.
Intranasal - Low immune response. Mainly allergic reactions.
describe the factors that affect immunogenicity: Dosage
Too little or too much of the antigen may induce tolerance in the host, preventing an immune response. Various routes of administration will influence which immune organs and cell populations will be involved with the response.
Define Immunogenicity
The ability to produce a cell-mediated or humoral response.
Define Antigenicity
The ability to combine specifically with the final products of the immune response.
Define Tolerance
The ability to distinguish between self and non-self
Freund’s complete adjuvant
The most common adjuvant - consists of mineral oil, lanolin, and heat-killed Mycobacterium tuberculosis (TB). Allows the antigen to be released slowly and continuously, prolonging antigen exposure.
Freund’s incomplete adjuvant
Consists of mineral oil and lanolin.
Antigen Recognition
The more epitopes that are processed the more diverse the immune response will be.
B cells bind to soluble antigens, these tend to have accessible epitopes and consist of proteins, polysaccharides and lipids.
T cell epitopes are derived from internal amino acid sequences that have been enzymatically digested during antigen processing and then bound to MHC molecules allowing them to be recognized by T cell receptors. Can only recognize proteins.
Binding of antigens
Binding occurs through electrostatic interactions (hydrogen bonding), hydrophobic interactions, and Van Der Waals forces. Binding does not involve covalent bonds.
Define Signal Transduction
Lymphocyte receptors with other molecules deliver intracellular signals that activate the cell to respond.
Define Carrier
A high molecular weight compound to which a hapten combines. Makes the hapten immunogenic.
List the major classes of antigens.
- Carbohydrates (polysaccharides): Only immunogenic when associated with protein carriers. ABO blood group is an example.
- Lipids: Rarely immunogenic unless bound to protein carriers. Cab be regarded as a hapten.
- Nucleic acids: Poor immunogens, become immunogenic when they are bound to protein carriers.
- Proteins: Virtually all proteins are immunogenic. The greater the degree of complexity of the protein the greater the immune response. Proteins contain multiple epitopes.
Define Homologous
Denotes that the antigen and the immunogen are the same.
Define Heterologous
Denotes that the substance used to induce the immune response is different from the substance that is used to react with the products of the induced response.
Define exogenous antigens
Antigens that come from outside a host cell and are taken inside, normally by endocytosis or phagocytosis. Interacts with MCH class II/CD4 cells.
Define endogenous antigens
Proteins are synthesized inside a cell and are generally derived from pathogens that have infected a host cell. Interacts with MHC class I/CD8 cells.
Define superantigen
Exotoxins produced by pathogenic bacteria that bind ti MHC class II. Activating huge numbers of CD4 T cells which secrete high levels of cytokines into circulation. This exaggerated release of cytokines ca cause fever, shock, or death.
Discuss the general characteristics of an immunoglobulin.
Immunoglobulins are produced by plasma cells and can be either membrane-bound (B-cells), or soluble molecules that are secreted into plasma and body fluids.
They will have two major functions:
1. Binding of foreign antigens.
2. Mediating effector functions to neutralize or eliminate foreign invaders.
Fab
Binds to antigens and marks it for the immunological attack. Additionally activates nonspecific defence mechanisms that can destroy the antigen. Each antigen has two fab fragments.
Fc
Crystallizable portion. Does not bind antigens, but mediates binding to host cell receptors, and additionally contains the biological functional portion of the antibody. The first component of the complement system. Allows different antibodies to carry out the same functions even with different epitope binding specificities.
Light chains
There are two types of light chains. Normal antibodies will only have one type of light chain. Light chains that are produced in excess are excreted in urine (called Bence-Jones proteins).
Kappa: 60% of light chains in humans.
Lamda: 40% of light chains in humans. Four subtypes exist (λ1,λ2,λ3,λ4), with the difference being amino acid substitutions.
Heavy chains
There are five isotypes of heavy chains, and they relate to antibody specificity. IgG, and IgA have subtypes, which differ in the number and arrangement of the interchain disulphide bonds and alterations in structural features producing changes in functional properties.
variable domain
The V of the VDJ chain.
Constant domain
where isotype switching occurs, and the area on a chain that tells you if it is a light or heavy chain. Causes antigen specificity.
CDR
Complementarity-determining regions. The region that forms the antigen binding site of the antibody. There are three CDRs on both heavy and light chains (6 CDRs per antibody). CDRs are unique to each antibody and are responsible for antibody specificity. Located in loops that connect VH and VL domains. Provides diversity of the shape of the binding site to create ABs of different specificities.
hinge
The extended peptide sequence that connects the CH1 and CH2 domains. Provides flexibility between the two fab arms of the Y-shaped antibody. Allows the two Fab arms to open and close to accommodate binding to two identical antigenic epitopes.
V region
The variable region- consists of the first 110 amino acids of both the light and heavy chains. The v regions amino acid sequence determines the antigen specificity of the antibody
C region
The constant region - occurs after the v region. This region remains constant and is the site of attachment for carbohydrates. The C region on heavy chains determines the effecter function of the antibody.
J Chain
The Joining chain- a small glycoprotein that is found in IgM and IgA. It joins monomers of the basic immunoglobulin unit.
IgG
The most abundant immunoglobulin in plasma is mainly produced following secondary exposure to an antigen (typically bacterial infections).
- Consists of 2 gamma heavy chains, and two light chains (kappa or lambda).
- Contains two antigen-binding sites
- Can cross the placenta, providing passive immunity to the fetus and newborn.
Most effective in activating complement.
- Can neutralize bacterial toxins or inactivate some venoms.
-Play a role in cell-mediated cytotoxicity - The Fab portion binds with the target cell and the Fc portion binds with specific receptors that are found on NK cells
IgM
The largest immunoglobulin. It is found in intravascular space, and on the surface of B cells where it serves as a BCR. It is generally the first antibody produced following exposure to an antigen and the first one synthesized in neonates.
- A pentamer molecule (10 mu heavy chains, and 10 kappa or lambda light chains)
- Contains up to 10 antigen binding sites
- High IgM levels usually follow a recent infection or exposure to an antigen.
- Efficient in agglutination due to their pentameter form.
- Most efficient initiator of complement (because complement activation requires at least two Fc regions)
- Most common surface Ig bound on B lymphocytes.
IgA
The major immunoglobulin found in body secretions, and the most abundant immunoglobulin in the body. It is found in two forms: 1. Monomeric (plasma) 2. Dimeric (secretions)- allows it to cross-link large antigens with multiple epitopes.
- Consists of two alpha heavy chains, and two kappa or lambda chains.
- The secretory component is produced by epithelial cells of mucous membranes.
- IgA-secreting plasma cells are concentrated along mucosal membrane surfaces.
- Cannot activate complement - therefore cannot cause bacterial lysis.
- Secretory IgA can bind to bacterial and viral surfaces to prevent the attachment of pathogens to mucosal cells.
- Offers protection against infections in newborns during the first few months of life.
IgE
Found in very low concentrations in plasma. Mediates the immediate hypersensitivity reactions seen in allergies.
- Consists of two epsilon heavy chains, and two kappa or lambda light chains.
- Cross-linkage of receptor-bound IgE by an antigen induces the degranulation of basophils and mast cells.
- Protects against infection by releasing mediators that attract eosinophils to the site of infection.
- Increased levels in plasma are seen during roundworm infections.
