Module 2 Flashcards
Antigen:
Substance that stimulates antibody formation
Ability to bind to an antibody
Immunogens:
Macromolecules capable of triggering an immune response
Hapten
A low molecular weight particle
Can bind to antibody but must be attached to a carrier to stimulate an immune response
Antigen: Characteristics
has a Antigenic determinant or epitope attached
Part of an antigen
Reacts specifically with an antibody or T lymphocyte receptor
Antigen: Composition & Examples
Composition: protein, polysaccharides, carbohydrate (glycoprotein)
–not lipids they are too simply structured
-not nucleic acids flexibility and rapid degradation
Found: usually on cellular membrane
Examples:
In a blood transfusion: antigen-bearing red blood cells from a donor, are transfused into a recipient:
Red cell antigens can be immunogenic
Outer surfaces of bacteria (capsule or the cell wall) can be immunogenic.
Normal immune system responds by producing antibodies
Physical Nature of Antigens
Characteristics:
Foreignness – degree of difference from self
Degradability – sufficient levels of antigen present
Molecular weight – high molecular weight = better the molecule will function as a antigen
Structural stability – stable molecule is a better antigen
Complexity – more complex molecule is a better antigen
Antigen: Major Histocompatibility Complex (MHC)
-nucleated cells (e.g. leukocytes) and tissues -have cell surface–protein antigens
MHC antigens = potent antigens provoke an immune response.
-also referred to as Human Leukocyte Antigens (HLAs)
-MHC/HLAs important in organ transplantation to determine graft survival or rejection
Characteristics of MHC classes I
Cytotoxic T cell binds to infected cell
Class 1 has A, B, and C regions
-distributed in Most nucleated cells
-presents endogenous antigen to cytotoxic T lymphocytes
-cytotoxic t cells are inhibited by CD8 cells in class 1
Characteristics of MHC classes 2
-helper T cell which binds to antigen presenting cell
MHC class II = D region
-distributed in B lymphocytes, macrophages, activated T lymphocytes
-To present endogenous antigen to helper T lymphocytes
-cytotoxic t cells against class 2 are inhibited by cd4 cells
Autoantigens
Autoantigens = “Self” antigens
Failure to recognize self as non-foreign produces autoantibodies
like hashimotos
Adjuvant
-adjuvant: enhances response to immunization
-distinct from antigen
-enhances T cell activation my promoting APC accumulation
-enhances the expression of co-stimulators and cytokines
Antibody: General Characteristics
found in plasma and other body fluids (tears, saliva, colostrum)
primary function: combine with antigen
-referred to as immunoglobulins
may require secondary interaction (e.g. with complement) to remove larger antigens (e.g. bacteria)
determining IGg concentration helps to diagnose disease
specific proteins, also called immunoglobulins (Ig)
can be isolated by electrophoresis separation
Five distinct classes of immunoglobulins:
IgM - biggest - pentamer
IgG - smallest present the most, monomers
IgA -monomer or polymer
IgD - smallest present the least, monomers
IgE monomers
Immunoglobulin Classes: Molecule Structure
12 domains arranged in two heavy (H) & two light (L) chains
-light Chains linked through cysteine residues by disulfide bonds (-s-s-)
-Remainder of chain composed of constant amino acid sequences = constant (c)
Fab region
Antigen-binding portion, hypervariable loops - complementary determining regions (CDRs)
N-terminal
Heterogeneity = variable (v)
Fc region with the heavy chains in carbs
Interacts with other phagocytic cells and complement
Hinge region
flexibility
IgG
-major immunoglobulin in serum
-diffuses readily into the extravascular spaces & neutralizes toxins, binds to microorganisms in extravascular spaces
-can cross the placenta
-In infants 3 to 4 months old: IgG levels are much lower than adult levels
-IgG in cord blood and spinal fluid
Decreased IgG: primary (genetic) or secondary (acquired) Ig deficiencies
Increased IgG: Infectious diseases- hep,rubella , collagen disorders - RA or lupus, hematologic disorders - hodgkins
IgM
-largest in size which confines it to blood
produced early in immune response
-effective in agglutination and cytolytic reactions
-4 months of age, 50% of the adult level is present; adult levels are reached by 8 to 15 years
-some IgM in cord blood; not detectable cerebrospinal fluid
Decreased : primary (genetically determined) Ig disorders, secondary Ig deficiencies
Increased: Infectious diseases, collagen disorders, hematologic disorders, monoclonal gammopathies
IgA
-predominant Ig in secretions: tears, saliva, colostrum, milk, intestinal fluids
-synthesized by plasma cells on body surfaces and intestinal wall
-binds to secretory component in intestine to protect IgA from proteolytic digestive enzymes (secretory IgA)
-Decreased: primary or secondary Ig deficiencies
-Increased: infectious diseases - tb, collagen disorders-RA, hematologic disorders, monoclonal gammopathy, liver disease
IgD
very low concentrations in plasma; less than 1%
extremely susceptible to proteolysis
cell membrane Ig found on the surface of B lymphocytes in association with IgM
IgE
-trace plasma protein - THE LEAST IF YOU DONT HAVE PARASITES
- invading parasites
-mediates hypersensitivity (allergic) reactions, allergies, anaphylaxis
-binds strongly mast cells and basophils; mediates release of histamines, and heparin
Antibody Response: Antibody Synthesis
Antibody response: antigen encountered
cells of the immune system recognize the antigen as nonself
-elicit an immune response or become tolerant of it
Immune response: cell-mediated immunity: T cells and macrophages or production of antibodies by B lymphocytes and plasma cells
IgM antibody response follows four phases
primary phase
Lag phase: no antibody detectable
Log phase: antibody titer increases IGM and IGG increase
Plateau phase: antibody titer stabilizes plateau
Decline phase: antibody catabolized both decline
Secondary Response/Anamnestic Response
same four phases of antibody response as primary response.
clones of memory cells proliferate
Anamnestic response differs from a primary response:
Time: shorter lag phase, longer plateau, more gradual decline
Type of antibody: IgG class more (some IgM)
Antibody titer: antibody levels attain higher titer
Examples:
hemolytic disease of the fetus and newborn, booster vaccination
Functions of Antibodies
Principal function: to bind antigen
Secondary effector functions:
1. Complement fixation: mainly IgG1, IgG3
- Placental transfer: most IgG
Passive immunity for the newborn
antibody ability to combine with a particular antigen, determined by Fab isotope side site
binding by non covalent forces (e.g. hydrophobic or electrostatic bonds )
depends on three-dimensional fit
Heterophile antibodies
Cross-reactivity occurs between bacteria that possess the same cell wall polysaccharides as human red blood cells
(e.g. blood group A-like and B-like antigens)
Antibody affinity:
Binding strength at a single binding site
-between a Fab site on anitbody and an epitope
Antibody avidity:
Measure of total binding strength of an antibody and antigen
Immune complex:
non covalent combination of antigen with its specific antibody (small/soluble or large/precipitating)
-soluble ones dominate
Antigen + Antibody:
bond
multiple, reversible, intermolecular attractions
bonds weak and across short distances
4 Types of bonding:
Hydrophobic Bonds: major bonds; exclude water molecules to strengthen bond
Hydrogen Bonds: hydrogen bridges
Van der Waals Forces: electron clouds and hydrophobic bonds
Electrostatic Forces: Goodness of Fit (the strongest bond includes lock and key), zeta potential
Monoclonal Antibodies: Application
-identifying and quantifying hormones
-typing tissue and blood
-identifying infectious agents
epitope as part of an antigen
reacts specifically with an antibody or T lymph receptor
hapten
small molecule but binds to large molecule and behave an antigens
SPECIFICITY
ability of a particular antibody to combine with a particular antigen
cross reactivity
when antibodies directed at one type of antigen will also react with another type of antigen
monoclonal antibodies how are they produced
-purified antibodies cloned from a single cell
-mice are immunized with antigen
-after 2-4 days spleen cells are mixed with mouse myeloma cells
-cell membrane fusion is promoted
-
zeta potential
electrostatic potential:
-net charge between cell membrane and the surface of shear
-larger antibodies (e.g. IgM) bridge the zeta potential
-large cells like red blood cells able to bind and agglutinate
