lecture 3 Flashcards
Adaptive immunity
Cell mediated (t-cells)
antibody mediated (b cells)
5 thing of adaptive immunity
- Discrimination (responds selectively to non-self)
- Specificity (activated T or B cells respond to specific non-self antigens)
- Diversity (generates cell receptors & antibodies)
- Tming (turned on after activation by innate response)
- Memory (response to a second exposure is so rapid that there is usually no noticeable illness)
Humoral immunity
- Antibody mediated
- B cells circulate antibodies that bind microorganisms, toxins, and extracellular viruses to neutralize them or destroy them
Cellular immunity
- T lymphocytes
- CTL (cytotoxic T cells) directly target cells infected with intracellular pathogens
- T helper cells– direct CTL to target cell lysis
antigen
self or non-self substance that elicits an immune response
Epitopes
antigenic determinant sites, site where antigen binds to antibody
Valence
of antigenic determinant sites on the surface of antigen
Antibody affinity
strength which an antibody binds to its antigen
haptens
small molecules that become immunogenic when combined with a carrier protein
Naturally acquired active immunity
immune systemc ome sin contact w antigen such as a pathogen causes an infection
Naturally acquired passive immunity
transfer of antibodies from mother to child
Artificially acquired active immunity
Vaccines
Artificially acquired passive immunity
antibodies or lymphocytes produced by one host are introduced into another
MHC
(major histocompatibility complex)
collection of genes encoding proteins that enable the host to distinguish between self and non-self
Human leukocyte antigen (HLA)
location of Human MHC on chromosome 6
- 3 classes
1. Class 1- found on cell w nucleus
2. Class 2 - appear on cells that can process antigens and present them to T lymphocytes
3. Class 3 - irrelevant
Class 1 MHC
Identify all healthy nucleated cells in the body as self
- stimulate immune response when cells from host are introduced to another host
- basis for tissue typing for organ transplant
Class 2 MHC
- produced only by dendritic cells, activated macrophages, mature B cells, and some innate lymphocyte cells (ILCs)
- key to adaptive immunity
- bind large non-self peptides
Antigen processing
mechanism of how peptides bind to MHC molecules
Class 1 MHC antigen processing
bind peptides by sampling the proteins in the cytoplasm of all nucleated cells
Endogenous antigen processing
only peptides that fit perfectly within the binding spot of MCH 1 are binded
Exogenous antigen processing
foreign particles that have been taken up by phagocytosis can be bound to MHC class 2 molecules
Antigen-presenting cells (APCs)
immune cells that place non-self antigen on MHC class 2 molecules
B cells
produce and secrete antibodies
T cells
initiate, orchestrate, and carry out an adaptive immune response
T-cell receptor proteins
- alpha & beta t cells
- gamma & delta t cells (rare)
Positive selection of T cells
determine which of the 2 TCR
co-receptors a mature T cell will have
CD4 co-receptor
interacts with MHC 2
CD8 co-receptor
interacts with MHC 1
Negative selection of T cells
t cells screened so any t cell that strongly recognizes self-antigen undergoes self death (apoptosis)
T-cell receptors (TCR)
detect antigen fragments presented by MHC molecules on the surface of other cells
TCR structure
heterodimeric polypeptide receptor & 6 accessory polypeptides (CD3)
Heterodimer
forms transmembrane receptor stabilized by disulfide bonds
TCR 3D Pocket
a&b chains interacts to creat 3D pocket
each pocket is unique to a specific antigen fragment
Immune synapse
3D change in the TCR -> T cell nucleus gets message -> genes expressed
Signal 1 to activate t cell
APC has antigen fragment in its MHC and is recognized and bound by TCR
Signal 2 to activate t cell
B7 (CD80) protein on the surface of an APC (usually DCs) binds to the CD28 receptor on the T cell
Anergic
t cells that receive signal 1 but not 2
can only recognize antigen but not responds
Signal 3 to activate t cell
release of cytokines by immune cells including APC and T cell
cytokines stimulate the target t CELLS TO DIFFERENTIATE INTO EFFECTOR CELLS WHICH WILL REMOVE THE PATHOGEN OR MEMORY CELSS
Effector t cells
carry out specific functions to protect the host against foreign antigen
Memory cells
mature, educated cells that are quickly reactivated when the host is reintroduced to their specific antigen
CD4+T
t helper and regulatory cells
CD8+T
CTLs and memory cells
T-helper cells (CD4+T cells)
adaptive immune system master regulators
(naive CD4+T cells = TH1, TH2, TH17, Treg)
IFN-y & IL release by DC
induces activity of transcription factor T-bet in TH0 cells
TH1
promotes cytotoxis T lymphocyte activity, activates macrophages, and mediate inflammation by producing interleukins, IFN-y, anf TNF-a, TNF-b
TH2 cells
DC -> IL-4 -> GATA-3 -> TH2
stimulate antibody responses and defend against worm parasites by producing cytokines (IL-4, IL-5, IL-6, & IL-3)
TH17
respond to bacterial invasion by secreting IL-17 and defensins and recruiting neutrophils and inducing a strong inflammatory response.
Treg
dial back an immune response by producing the anti-inflammatory cytokines IL-10 & TGF-b
maintain mucosal immunity homeostasis
CD8+T cells
destroy unhealthy host cells
if non-self recognized -> cytotoxic T lymphocyte (CTL)
CTL (cytotoxic T lymphocyte)
destroy host cells w pathogens
2 ways granzymes are released NK cell mediated death or Perforins generate pores in target cells and then apoptosis
B cell purpose
make antibodies (substances that identify antigens and neutralize them)
B-cell development
begins in bone marrow & eliminates developing B cells that recognixr self antigens
Plasma cell
mature, differentiated B lymphocyte that synthesizes and secrete antibody
B cell binding
does not need APC (antigen presenting cell) to bind to antigen
B cell receptors
made of membrane-bound antibodies
IgM or IgD
antibody attached to naive B cell membranes so that the antibody is is facing outwards
- activate B cells
B-cell receptor (BCR)
- transmembrane antibody (IgD or IgM) & heterodimer protein complex (Iga & Igb)
T-cell dependent B-cell activation
simultaneous activation of both T and B cells with the same antigen
B cell internalize the antigen receptor complex by receptor-mediated endocytosis
antigen is broken down and peptide from the antigen is transferred to a MHC class 2 molecule
T-dependent antigens
antigens that trigger t-cell-dependent B-cell activation
T-independent antigens
antigen that triggers a B cell to produce immunoglobulin without T-cell cooperation
- tend to be polymeric composed of repeating sugars or amino acids
Immunoglobulin (Ig)
glycoprotein made by plasma cells in response to the introduction of an antigen
Antibody structure
4 polypeptide chains connected by disulfide bridges (2 identical heavy and 2 identical light chains)
Constant regions
cL and cH ( light and heavy) do not vary significantly b/w antibodies of the same class
Variable Regions
vL and vH (light and heavy) diff amino acids sequences and these regions fold together to form the antigen binding sites
- structural diversity accounts for the ability of antibodies to bind to a seemingly infinte # of antigens
Fc (crystallizable fragment)
stem portion of the Y portion of an antibody molecule where macrophages bind to the Fc region
Fab
tips of the y part of the antibody
antigen-binding fragment that bind with compatible epitopes
(a specific part of an antigen that triggers an immune response by binding to a receptor on a B cell)
5 Ig classes
IgG, IgA, IgM, IgD, IgE
