ch 4: overview of adaptive immunity Flashcards
describe some of the disadvantages of the innate system
the process of innate is limited in recognizing diverse pathogens due to lack of receptor diversity
what is the adaptive immune response based on?
specificity and diversity, it focuses on targeting specific antigens
what is the marker that innate immune receptors recgonize?
PAMPs
adaptive immune cells recognize pathogens presented by ____ _____________
MHC molecules
what is one of the biggest differences between innate and adaptive?
adaptive has immune memory, or the ability to say the system will respond much faster than normal to combat future infections
describe T cell receptors
composed of two protein chains, alpha and beta or delta and gamma. each chain has a constant region (close to membrane) and variable region. the variable region is what holds the antigen binding site.
each T cell receptor is capable of recognizing ____
one specific antigen
peptides are presented to T cell receptors by ___________
MHC molecules
differentiate MHC class I and II
- MHC I present intracellular antigens
- MHC II present extracellular antigens
- MHC I bind to CD8 coreceptors
- MHC II bind to CD4 coreceptors
define immunoglobulins
act as B cell receptors, made up of two heavy chains and two light chains. they contain two antigen binding sites and can be present on the surface of a B cell or secreted by plasma cells. they also can recognize only one specific antigen.
what makes immunoglobulins different from T cell receptors?
immunoglobulins do not require an MHC molecule to present an antigen and they can recognize any biological macromolecule (protein, carbohydrate, lipid, nucleic acid)
what are the five major functions of soluble immunoglobulins?
- neutralization of foreign particle/pathogen
- opsonization of foreign particle/pathogen
- complement activation
- activation of innate immune cells (NK cells, mast cells)
- protection of internal/mucosal tissues
what is MHC polymorphism
subtle changes in the protein produced by an MHC.
why is MHC matching for transplants important?
it can help prevent the immune system from recognizing the transplant as foreign if the MHC matches the host MHC1
why does adaptive require such a long period of time to respond?
- the diversity of T cell receptors and immunoglobulins means few T and B cells can recognize a new pathogen
- antigen needs to be delivered and presented in secondary lymphoid tissues and organs
- antigen specific B and T cells need to be activated, proliferated, and differentiated in secondary lymph nodes before they can migrate to sites of infection
T cells mature in the _____ and B cells develop in the _________
thymus, bone marrow
both T and B cells undergo ______ _________ to rearrange genes and test their functionality of receptors
somatic recombination
describe antigen processing
- intracellular antigens, including those from intracellular pathogens such as viruses and Shigella bacteria, are digested in the cytoplasm
- extracellular antigens, including those from extracellular pathogens such as Vibrio cholerae bacteria, are digested within a phagolysosome
dendritic cells present peptide fragments to T cells by which two processes
- cytosolic pathogen proteins are processed in the cytosol and presented to MHC I
- extracellular pathogen proteins are processed in phagolysosomes are presented to MHC II
describe T cell clonal selection and expansion
the T cell receptor engages with the MHC molecule with the correct antigen and drives proliferation of the T cell. in MHC I, CD8 T cells differentiate into cytotoxic T cells. in MHC II, CD4 T cells differentiate into helper T cells.
what do cytotoxic and helper T cells do?
cytotoxic T cells monitor intracellular infections and can target cells for destruction. helper T cells can migrate to parts of the lymph node to activate other cells such as B cells and macrophages to aid in infection
how can B cells be differentiated?
cytokine signals from helper T cells can cause differentiation of B cells into plasma cells or memory B cells
what is somatic hypermutation?
it is a random mutation at the variable regions of the immunoglobulin gene that drive altered affinity of that immunoglobulin for its antigen. the immunoglobulin gene is randomly altered in a subset of activated B cells to promote the production of B cells containing immunoglobulins with higher affinity for antigen. REFINEMENT OF ANTIBODY
where do dendritic cells process foreign antigens?
draining lymphoid tissues
in the absence of __________ and ________ B and T cell activation would not take place
dendritic cells, antigens
rearrangement
- combination of different subunits (alpha and beta chain for T cell receptors, and heavy and light chain for B cell receptors) result in receptor diversity
- occurs only in developing T and B cells
T cell receptor rearrangement
- alpha chain has variable regions linking V and J
- beta chain has variable regions linking V, D and J
B cell receptor rearrangement
- heavy chain contains V, D and J segments
- light chain contains V and J segments
- 5 different constant regions that can be used as heavy chain components for isotype switching
where are RSSs found?
at the downstream ends of V segments, both the upstream and downstream ends of D segments, and the upstream end of J segments
structural features of RSSs that that allow for V(D)J recombination events to occur specifically and efficiently at lymphocyte receptor genes
- conserved heptamer
- conserved nonamer (farthest from coding segment)
- a spacer (23 or 12 bp) (provide full DNA helix twist)
function of TdT
ability to add additional nucleotides known as N nucleotides before the segments are joined together through DNA repair
what is class switch recombination?
change to the constant region (B cell specific)
key proteins in VDJ recombinase?
RAG1 and RAG2 which bind and recognize RSSs that border V, D, and J DNA segments
positive selection
selects cells with functional receptors
negative selection
selects against cells with self-reactive receptors
describe positive selection
binding -> cell proceeds to next step in development
no binding -> cell dies by apoptosis
describe negative selection
tight binding -> cell dies by apoptosis
moderate/weak binding -> cell survives and proceeds to next step
describe the three MHC classes
- class I: present peptides from proteins made inside the cell
- class II: present peptides from extracellular proteins taken into phagolysosomes
- class III: immune regulatory proteins and some complement proteins
describe MHC I presentation
- proteins in cytoplasm digested by proteasome into peptide fragments
- fragments are transported into ER and loaded onto MHC I molecules
- MHC I peptide complex exists the ER and travels to plasma membrane via secretory pathway
- CD8 T cell recognizes the complex and activates it on cell surface
describe MHC II presentation
- MHC class II molecules translated and transported into ER
- MHC class II molecules travel through the secretory pathway to a secretory vesicle, where they wait for further action driven by a phagolysosome
- extracellular molecules and pathogens are endocytosed by professional APCs, including macrophages, dendritic cells, and B cells
- endosome containing the extracellular material matures into a phagolysosome, which results in the digestion of proteins by lysosomal proteases
- phagolysosomes fuse with secretory vesicles containing MHC II, which can bind to peptides generated during lysosomal digestion
- newly loaded MHC II travel to the cell surface where they present peptides generated by the digestion of extracellular material to T cells
CD3 complex
formed through the association of T cell receptors and other transmembrane proteins with cytoplasmic tails with signaling motifs to create T cell receptor signaling that activates T cells
naive B cells initially secrete ____
IgM
naive B cells can undergo class switching to produce _____, _____, or _____
IgG, IgA, IgE
Ig-alpha and Ig-beta
the two proteins B cell receptors associate with that have cytoplasmic domains and signaling motifs
