unit 7 (specific adaptive immunity) Flashcards
adaptive immunity defined by two characteristics
specificity and memory
specificity definition
refers to the adaptive immune system’s ability to target specific pathogens
memory definition
refers to adaptive immune system’s ability to quickly respond to pathogens to which it has been previously exposed
primary response definition
immune system’s first exposure to a pathogen or vaccine
secondary response definition
subsequent exposure to pathogen that is faster and stronger as a result of the body’s memory of the first exposure
adaptive specific immunity involves two distinct cell types:
B lymphocytes (B cells) and T lymphocytes (T cells)
B cells mature in ___ and are responsible for ___
mature in bone marrow and are responsible for production of glycoproteins called antibodies or immunoglobulins
humoral immunity definition
mechanisms of the adaptive specific immunity that involve B cells and antibody production
T cells mature in ___ and are responsible for ___
mature in the thymus and are responsible for destruction of cells with intracellular pathogens and orchestration of both innate and adaptive immune responses
cellular immunity (cell-mediated) definition
immunity involving the targeting and destruction of intracellular pathogens by T cells
antigen definition
pathogen-specific molecular structures that trigger activation of adaptive immune defenses
antigenic definition
a molecule that stimulates antibody production
antigen belong to what macromolecule
carbs, proteins, lipids, nucleic acids, and combinations of these molecules
most effective and potent antigen
proteins are capable of stimulating both humoral and cellular immunity
epitopes definition
very specific smaller exposed regions on the surface of antigens where antibodies bind
haptens
molecules that are too small to be antigens themselves, essentially free epitopes
antibodies are __ and present in __
glycoproteins and present in blood and tissues fluids
antibody structure
four chains held together by disulfide bonds, two identical heavy chains and two identical light chains formed into Y shape
Fab region (of antigen)
two arms of Y shaped antibody molecule
Fab stands for
fragment of antigen binding
variable region
far end of the Fab region which serves as the site of antigen binding
binding to the Fab region is necessary for
neutralization of pathogens, agglutination or aggregation of pathogens, and antibody-dependent cell-mediated cytotoxicity
constant region
includes trunk of Y and lower portion of each arm of the Y
Fc region
trunk of the Y, site of complement factor binding and binding to phagocytic cells during antibody-mediated opsonization
classes of antibodies
IgG, IgM, IgA, IgD, and IgE
IgG antibody characteristics
monomer that is most abundant antibody. penetrates tissues effectively, only antibody that can cross placental barrier. most versatile antibody class in terms of role in body’s defense against pathogens. able to activate complement
IgM antibody characteristics
monomeric membrane bound form that serves as an antigen-binding receptor on B cells. secreted IgM has pentameric form that is the first antibody produced and secreted by B cells during primary and secondary immune response. able to activate complement and secreted IgM is able to neutralize a lot of antigens due to its form
IgA antibody characteristics
secretory IgA is most abundant antibody class in mucus secretions, assembled into a dimeric form making it resistant to degradation by proteases, able to trap pathogens in mucus
IgD antibody characteristics
membrane-bound monomer found on surface of B cells, serving as an antigen binding receptor. not secreted by B cells, may be important in the lung and in inhibiting self-reactive B cells in other peripheral tissues
IgE antibody characteristics
secreted as a monomer, role in adaptive immunity limited to anti-parasitic defenses. Fc region binds to basophils and mast cells, Fab region interacts w/ antigen specific epitopes, causing the cells to release pro-inflammatory mediators. this reaction aids in defense against parasites, but also central to allergic reactions
antibody functions
neutralization of pathogens, opsonization for phagocytosis, agglutination, complement activation, and antibody-dependent cell-mediated cytotoxicity
Neutralization
involves the binding of certain antibodies to epitopes on surface of pathogens or toxins, preventing their attachment to cells
opsonization with antibodies
IgG serves as opsonin that bind to specific epitopes on surface of pathogen and macrophages, dendritic cells, and neutrophils have receptors that bind to the IgG
agglutination or aggregation
involves the cross-linking of pathogens by antibodies to create large aggregates making it easier to filter out from blood and easier for phagocytes to ingest for destruction
complement cascade activation by antibodies
initial binding of IgG or IgM to the surface of a pathogen cell, allowing for recruitment and activation of the C1 complex
antibody-dependent cell-mediated cytotoxicity (ADCC)
occurs when Fab region of an IgG antibody binds to a large pathogen; Fc receptors on effector cells (NK cells) then bind to Fc region of antibody, effector cell release cytokines perforin and granzyme that kill the pathogen
MHC molecules function
expressed on surface of healthy cells, identifying them as “self” to NK cells, play important role in presentation of foreign antigens
cells that express MHC molecules
MHC found on surface of all nucleated cells of the body, RBCs are only cell that do not express MHC molecules
MHC I molecules
found on all nucleated cells; they present normal self-antigens as well as abnormal or nonself pathogens to the effector T cells
MHC II molecules
only found on macrophages, dendritic cells, and B cells (APCs); they present abnormal or non-self pathogen antigens for initial activation of T cells
dendritic cell and macrophage antigen presentation
pathogen phagocytized, protease degrades pathogen, most antigenic epitope associate w/ antigen binding cleft of MHC II molecule in the phagolysosome, antigen-MHC II complex translocated to cell surface for presentation to T cells
Self-antigen epitopes
self-antigen epitopes bind within the MHC I antigen-binding cleft and then are presented on the cell surface for NK cells to recognize and not target the cell for destruction
cross presentation
subset of dendritic cells are able to take foreign antigen from their environment and present the antigen on MHC I without infection
intracellular pathogens
pathogen that have already gained entry into host cells
t cells are formed in
bone marrow
first steps of T cell differentiation happen in
red bone marrow
final steps of T cell maturation occur in
thymus
thymic selection definition
in the thymus, immature T lymphocytes go through a maturation and selection process
First step in thymic selection
development of T cell receptors (TCRs), T cells w/ defective TCRs are removed by negative selection through induction of apoptosis
Second step in thymic selection
involves positive selection of T cells that will interact appropriately w/ MHC molecules that move further in the process of maturation, T cells interacting inappropriately w/ MHC are eliminated by apoptosis
Third (final) step in thymic selection
involves negative selection to remove self-reactive T cells by apoptosis
central tolerance
third and final step of thymic selection prevent self-reacting T cells from entering the blood stream and potentially causing an autoimmune disease
peripheral tolerance
second line of defense against self-reacting T cells that enter the bloodstream. involves mechanisms of anergy and regulatory T cells (Treg)
anergy definition
refers to a state of non-responsiveness to antigen stimulation
anergy in peripheral tolerance
self-reactive T cells that escape the thymus will have a lack of a co-stimulatory signal required for activation, causing anergy and prevents autoimmune function
Treg cells in peripheral tolerance
inhibit the activation and function of self-reactive T cells and secrete anti-inflammatory cytokines
T cell location after maturation
exit the thymus through the bloodstream and lymphatic system to secondary lymph organs such as lymph nodes, tonsils, spleen
naive T cells definition
inactivated T cells that wait for activation through the presentation of specific antigens by APCs
classes of T cells
helper T cells, regulatory T cells, cytotoxic T cells
CD molecules function
cluster of differentiation molecules are used to identify and distinguish between various types of WBCs
cells with CD4
helper T cells, regulatory T cells
cells with CD8
cytotoxic T cells
CD4 cells are activated by antigen presented on
APCs presenting antigens associated w/ MHC II
CD8 cells are activated by antigens presented on
MHC I by a subset of dendritic cells or by nucleated cells infected w/ an intracellular pathogen
Helper T cells function
central orchestrators that help activate and direct functions of humoral and cellular immunity, enhance pathogen killing functions of macrophages and NK cells
regulatory T cells function
involved in peripheral tolerance and prevention of autoimmune responses
cytotoxic T cells function
primary effector cells for cellular immunity, recognize and target cells that have been infected w/ intracellular pathogens, destroying infected cells along w/ pathogens inside
T-cell receptor (TCR) function
involved in first step of pathogen epitope recognition during the activation process
TCR structure
similar to antibodies, has variable region and a constant region
TCR epitope specificity achieved by
genetic rearrangement which happens in the thymus during the first step of thymic selection
first step in activation of helper T cells
TCR recognition of the specific foreign epitope presented within the MHC II antigen-binding cleft
second step in activation of helper T cells
involves interaction of CD4 with a region of the MHC II molecule separate from the antigen binding cleft
second interaction in helper T cell activation function
ensure that the helper T cell is recognizing both the foreign epitope and the “self” antigen of the APC; both recognitions are required for activation of the cell
third step in activation of helper T cells
APC and T cell release cytokines that activate the helper T cell, causing it to proliferate and differentiate into helper T cell subtypes with different functions
Helper T cell subtypes
T helper 1 (TH1) cell, T helper 2 (TH2) cell, T helper 17 (TH17) cell, or a memory helper T cell
effector cell definition
short-lived cells that perform various functions of the immediate immune response
memory helper T cells function
long lived cells programmed to remember a specific antigen or epitope in order to mount a rapid, strong, secondary response to subsequent exposures
TH1 cell function
stimulate cytotoxic T cells to enhance their killing and promote their differentiation into memory cytotoxic cells, stimulate macrophages for more effective intracellular killing of pathogens, stimulate NK cells to kill more effectively
TH2 cell function
stimulate B cell activation and differentiation into plasma cells and memory B cells, direct antibody class switching in B cells, regulate eosinophils
TH17 cells function
stimulate immunity and memory to extracellular pathogens, stimulate neutrophils and an inflammation response
first step in cytotoxic T cell activation
recognition of antigen presented on MHC I receptor
second step in cytotoxic T cell activation
interaction of CD8 with the MHC receptor complex
third step in cytotoxic T cell activation
production of cytokines by APC and cytotoxic T cell activate clonal proliferation and differentiation into effector cytotoxic T cells and memory cytotoxic T cells
effector cytotoxic T cells function
target pathogens for destruction
co-stimulation for activation of CD8 T cells
proliferation and differentiation is also stimulated by cytokines secreted from TH1 cells activated by the same foreign epitope
effector CD8 T cell mechanism of destruction
CD8 T cell recognize infected cells through antigen presentation of pathogen-specific epitopes associated with MHC I. TCR of CD8 binds to epitope and releases perforin and granzymes that induce apoptosis
superantigens definition
bacterial and viral pathogens that produce toxins that cause unregulated and excessive T cell activation
superantigen function
bind to MHC II molecules of APCs and TCR without specific foreign epitope recognition that results in cytokine storm
cytokine storm definition
excessive uncontrolled release of cytokines
B cells are formed in
bone marrow
B cells mature in
primarily bone marrow, spleen
first step in B cell maturation
assessment of the functionality of their antigen-binding receptors which occurs through positive selection for B cells w/ normal functioning receptors. negative selection is used to eliminate self-reacting B cells
negative selection of self reacting B cells involves elimination by
editing or modification of the receptors so they are no longer self-reactive, or induction of anergy in the B cell
second step in B cell maturation
immature B cells that pass selection in bone marrow travel to the spleen for final stages of maturation where they become naive
naive B cell definition
mature B cells that have not yet been activated
B-cell receptors (BCRs)
membrane-bound monomeric forms of IgD and IgM
BCRs recognize epitopes on ___
free antigens or with epitopes displayed on the surface of an intact pathogen
T cell-independent activation of B cells definition
activation of B cells without the cooperation of helper T cells, occurs when BCRs interact w/ T-independent antigens
first signal in T-cell independent activation of B cell
multiple BCRs cross link w/ T-independent antigens, providing first signal of activation
T-independent antigens examples
polysaccharide capsules, lipopolysaccharide
what happens to cells only getting one signal of activation
the cell either dies or becomes non-responsive
second signal in T-cell independent activation of B cells
signal comes from other sources such as interactions of toll-like receptors w/ PAMPs or interactions w/ factors from the complement system
third step in T-cell independent activation of B cells
undergoes proliferation and differentiates into plasma cells that secrete IgM that have the same antigen specificity as BCRs
plasma cells function
antibody factories that secrete large quantities of antibodies
T cell-dependent activation occurs in response to
free protein antigens or to protein antigens associated w/ an intact pathogen
First step in T cell-dependent activation of B cells
interaction between BCRs and a free protein antigen stimulate internalization of the antigen, interaction w/ antigens associated w/ an intact pathogen initiates the extraction of pathogen before internalization
Second step in T cell-dependent activation of B cells
protein antigen is processed and present w/ MHC II and recognized by helper T cells specific to the same antigen
Third step in T cell-dependent activation of B cells
TCR of helper T cell recognizes foreign antigen, CD4 interacts w/ MHC II
linked recognition definition
coordination of B cells and helper T cells that are specific to the same antigen
Fourth step in T cell-dependent activation of B cells
TH2 cells release cytokines that activate B cell to proliferate, after several round of proliferation, TH2 cytokines stimulate differentiation of B cells into memory cells and plasma cells
antibody class switching process
cytokines secreted by TH2 stimulate plasma cells to switch from IgM production to production of IgG, IgA, or IgE
primary antibody response initial stage
lag period or latent period of approx. 10 days where no antibody can be detected in the serum
what happens during the lag period of primary response
naive mature B cell binding of antigen w/ BCRs, antigen processing and presentation, helper T cell activation, B cell activation, clonal proliferation, plasma cell production, memory cell programming, antibody production
secondary response lag peroid
high production of IgG, antibodies produced are more effective and bind w/ higher affinity, plasma cells survive longer leading to antibody levels remaining elevated for a longer period of time
active immunity definition
refers to activation of an individual’s own adaptive immune defenses
passive immunity definition
refers to the transfer of adaptive immune defenses from another individual or animal
natural active immunity definition
adaptive immunity that develops after natural exposure to a pathogen
natural passive immunity definition
involves natural passage of antibodies from a mother to child before and after birth
artificial passive immunity definition
refers to the transfer of antibodies produced by donor to another individual
artificial active immunity definition
involves the activation of adaptive immunity through deliberate exposure of an individual to weakened or inactivated pathogens
herd immunity definition
majority of population is immune to pathogen, protects susceptible individuals because the disease cannot spread effectively
variolation definition
refers to the deliberate inoculation of individuals w/ infectious materials from scabs or pustules of smallpox victims
classes of vaccines
live attenuated, inactive, subunit, toxoid, conjugate
live attenuated vaccines contain
weakened strain of whole pathogen
inactive vaccines contain
whole pathogen killed or inactivated w/ heat, chemicals, or radiation
subunit vaccines contain
key antigens of a pathogen, not whole cells or viruses
toxoid vaccines contain
inactivated bacterial toxins
conjugate vaccines contain
capsule polysaccharide conjugated to a protein
enzyme immunoassay (EIA) components
use antibodies to detect presence of antigens, enzymes, colorless substrate that is converted to colored end product, conducted in microtiter plate
widely used EIAs
enzyme-linked immunosorbent assays (ELISAs)
direct ELISA steps
antigens immobilized in well of microtiter plate. antibody that is specific for antigen is conjugated to an enzyme and added to well. after washing to remove unbound antibodies, colorless substrate is added. presence of enzyme converts substrate into colored end product.
sandwich ELISA steps
primary antibody binds to well. blocking agent is added to bind remaining nonspecific protein binding sites in the well. sample is added; if antigen is present, it binds to the antibody. unbound sample is washed away. antibody-enzyme conjugate added. unbound secondary antibody-enzyme conjugate is washed away. substrate is added; if present, enzyme converts substrate to colored product
direct ELISA tests for
whether or not a sample has the antibody for a specific antigen
sandwich ELISA test for
whether or not a sample has a specific antigen present and how much of the specific antigen is present
indirect ELISA test for
detects or quantifies the amount of antigen-specific antibody in sample
indirect ELISA steps
antigen is bound to well. blocking agent is added. sample added; if antibody is present, it binds to antigen. unbound sample is washed away. antihuman enzyme-linked antibody added. unbound antihuman antibody is washed away. substrate is added; if present, enzyme converts substrate to colored product
immunofiltration process
large volume of liquid is passed through a porous membrane into an absorbent pad. an antigen attached to the porous membrane will capture antibody as it passes
immunochromatographic assay steps
fluid applied on an absorbent pad on test strip. fluid flows by capillary action through a strip of beads w/ antibodies attached to their surfaces. antibody beads will bind antigens. the antigen-antibody complexes flow over second strip that immobilizes antibody-antigen; strip will retain beads that have bound antigen. third control strip binds any beads.
hypersensitivity reactions definition
undesirable reactions produced by normal immune defenses
type I hypersensitivity quick definition
allergies involve IgE antibody against soluble antigen, triggering mast cell degranulation
type II hypersensitivity quick definition
involves IgG and IgM antibodies directed against cellular antigens, leading to cell damage mediated by other immune system effectors
Type III hypersensitivity quick definition
involve the interactions of IgG, IgM, sometimes IgA antibodies w/ antigen to form immune complexes. accumulation of immune complexes in tissue leads to tissue damage mediated by other immune system effectors
Type IV hypersensitivity quick definition
T cell-mediated reactions that can involve tissue damage mediated by activated macrophages and cytotoxic T cells
allergen definition
type of antigen that triggers an allergic reaction immune response
type I hypersensitivities involve two components
sensitization and subsequent exposure
sensitization to an allergen steps
APC processes antigen and presents it to TH2 cell. TH2 cell releases IL-4 and IL-12, which activate B cell. B cells proliferate and differentiate into plasma cells that synthesize and secrete IgE antibody. IgE binds to mast cells by Fc region, sensitizing the mast cells.
what happens during subsequent exposure to allergen
allergens bind to multiple IgE on mast cell surface, cross-linking the IgE molecules. this activates the mast cell and triggers degranulation of inflammatory molecules that cause symptoms of allergy symptoms
localized type I hypersensitivity examples
hay fever, asthma, rhinitis, hives
systemic type I hypersensitivity examples
anaphylactic shock
late-phase type I hypersensitivity reaction
may develop 4-12 hours after early-phase reaction and are mediated by eosinophils, neutrophils, and lymphocytes that have been recruited by chemotactic factors released from mast cells
type II (cytotoxic) hypersensitivities mediated by __ binding to ___
IgG and IgM antibodies binding to cell surface antigens or matrix-associated antigens on basement membranes
IgG and IgM antibodies function in type II hypersensitivity
can either activate complement, resulting in inflammatory response and lysis of target cells, or they can be involved in ADCC with cytotoxic T cells
examples of type II hypersensitivities
hemolytic disease of the newborn, hemolytic transfusion reactions
hemolytic transfusion reaction (HTR) cause
IgG and IgM bind to antigens on transfused RBCs, targeting donor cells for destruction, activating complement and MAC to mass hemolyze transfused blood cells
hemolytic disease of the newborn (HDN) cause
after primary exposure to Rh+ RBCs and activation of primary immune response, in a secondary exposure IgG from mother crosses the placenta, targeting the fetus’s RBCs for destruction
unique characteristic of type III hypersensitivities
antibody excess coupled w/ relatively low concentration of antigen results in the formation of small immune complexes that deposit on the surface of epithelial cells lining small blood vessels or on surface of tissues
immune complex accumulation leads to:
IgG binding to antibody receptors on localized mast cells, resulting in mast-cell degranulation, complement activation w/ production of proinflammatory C3a and C5a, increased blood vessel permeability w/ chemotactic recruitment of neutrophils and macrophages
how type III hypersensitivities cause tissue damage
immune complexes on tissue surface cannot be phagocytized, neutrophils degranulate instead damaging immune complexes as well as localized cells
Type III hypersensitivities examples
serum sickness, systemic lupus erythematosus, rheumatoid arthritis
type IV hypersensitivities subcategories
CD4 TH1-mediated reactions (delayed-type hypersensitivities), CD4 TH2-mediated reactions, CD8 CTL-mediated reactions
CD4 TH1 mediated reactions (delayed-type hypersensitivities) process
sensitization step involves introduction of antigen into the skin by phagocytosis by local APCs, which activate helper T cells, stimulating proliferation and differentiation into TH1 memory cells. upon subsequent exposure, TH1 memory cells release cytokines activating macrophages which cause tissue damage
CD4 TH2 mediated reaction process
soluble antigen is inhaled, resulting in eosinophil recruitment and activation w/ release of cytokines and inflammatory mediators
CD4 TH1 mediated reaction examples
contact dermatitis due to latex, tuberculin reaction
CD4 TH2 mediated reaction examples
chronic asthma and chronic rhinitis
CD8 CTL mediated reaction process
APCs process and present antigen w/ MHC I to naive CD8 T cells, when CD8 T cells are activated they proliferate and differentiate into CTLs that target and induce apoptosis in cells presenting the same antigen w/ MHC I (cells could be self cells that have absorbed the antigen or transplant cells displaying the antigen)
CD8 CTL mediated reaction examples
contact dermatitis from poison ivy, tissue-transplant rejection
desensitization process
elicit production of different interleukins and IgG antibody responses instead of IgE. Excess allergen specific IgG bind to the allergen, acting as blocking antibodies to neutralize the antigen before it can bind to IgE on mast cells
autoimmune disease definition
immune system mistakenly identifying the body’s own cells as the enemy, body is attacked by its own specific adaptive immune response
tolerance definition
lack of an anti-self immune response in normal, healthy states
mechanisms responsible for autoimmune disease
include type II, III, and IV hypersensitivity reactions
causes of autoimmune disorders
individual’s genetic makeup and effect of environmental influences
autoimmune disease examples
addison disease, celiac disease, type I diabetes, graves disease, hashimoto thyroiditis, multiple sclerosis, myasthenia gravis, psoriasis, rheumatoid arthritis, systemic lupus erythromatosus
Addison disease cause
destruction of adrenal gland cells by cytotoxic T cells
celiac disease cause
antibodies to gluten become autoantibodies that target the cells of the small intestine
Type I diabetes cause
cytotoxic T-cell destruction of the insulin producing beta cells of the pancreas
Graves disease cause
autoantibodies target thyroid-stimulating hormone receptors, resulting in overstimulation of the thyroid
hashimoto thyroiditis cause
thyroid gland is attacked by cytotoxic T cells, lymphocytes, macrophages, and autoantibodies
Multiple sclerosis cause
cytotoxic T cell destruction of the myelin sheath surrounding nerve axions in the CNS
Myasthenia gravis cause
autoantibodies directed against acetylcholine receptors within the neuromuscular joint
Psoriasis cause
cytokine activation of keratinocytes causes rapid and excessive epidermal cell turnover
Rheumatoid arthritis cause
autoantibodies, immune complexes, complement activation, phagocytes, and T cells damage membranes and bone in joints
Systemic lupus erythematosus cause
autoantibodies directed against nuclear and cytoplasmic molecules form immune complexes that deposit in tissues. phagocytic cells and complement activation cause tissue damage and inflammation
