Exam 1

Question Answer
Immunology study of the body's defense against infections
functions of immunological recognition effector function,regulation, memory
what is immunological recognition recognizing self from non self
what are effector functions cell function that have end results
what is immunological regulation turning off of the immune response after a pathogen has been dealt with
what is immunological memory recognition of a particular pathogen and function of immune response to the point where you don't feel symptoms. goes down with age
example of immunological memory vaccination
types of pathogens viruses bacteria fungi and parasites
bacteria single-celled organisms without a nucleus
viruses non living particles that reproduce by taking over living cells
fungi simple organisms that grow as single cells or thread like filaments
parasites or protozoa single celled organism with nucleus
antigen any molecule that can bind specifically to an antibody, can come from a pathogen or inert substance or from "self"
antibodies are effector molecules of B cells
how does vaccination work you receive a killed virus that has virals proteins (antigen) that the body can make antibodies from those antigens
types of immunity innate and adaptive
innate immunity first line of protections that lasts for hours that was derived from primordial immune responses and has no memory. it keeps infection in check while adaptive immunity produces specific antibodies for the infection
does innate immunity respond in a similar or different way to a repeat infection similar, it has no memory of the infection so it responds in a similar way
adaptive immunity antigen-specific and has delayed onset (days) bc it develops immunological memory that forms in a few hours in B or T cells. its main function is to make sure that the pathogen doesn't escape
what are the functional arms of adaptive immunity humoral antibody-mediated that takes care of bacterial pathogens and cell-mediated-primarily CD8 and T cells that take care of viruses and virus killed cell
natural barriers of innate immunity skin, [mucosal membranes, acidity of the stomach and perspiration, lysozymes in tears—-all capture pathogens and don't allow entrance into cells]
are the components of innate immunity present before or after the onset of infection before
do all pathogens deal with the adaptive immune system no, most microorganisms are readily cleared within few days by the innate system before adaptive is activated
pattern recognition of innate immunity patterns are unique to microbes that are not found in multicellular organisms, so receptors of innate immunity recognize these structures/patterns on the pathogens
what are the receptors of innate immunity that recognize the patterns of pathogens soluble molecules such as mannose-binding lectin (MBL) or complement proteins OR they can be cell-associated receptors such as toll-like receptors (TLRs) that recognize double stranded RNA
humoral immune responses mediated by serum antibodies produced by B lymphocytes
cell-mediated reponse depends on T cells. both T helper (TH/CD4) cells and cytotoxic T lymphocytes (CTLs/CD8) serve as effector cells. TH cells activate CTLs
when does adaptive immunity get activated when there is a recognition of an antigenic challenge–tere are no antibodies for this specific pathogen
characteristics of adaptive immunity antigen specificity (down to the specific strain), diversity (each strain of a bacteria/virus has a specific antibody), immunological memory, self-nonself recognition
problems with self-nonself recognition can lead to problems such as problems with organ transplants, autoimmune disorders such as lupus, crohn's, RA rhematoid arthritis that produces a persistent inflammatory response
why does the flu have no immunity the virus changes and so each new strain of the virus needs the specific antibodies associated with it
stem cells cells that differentiate into all other cell types and can self-renew themselves by cell division.
production of stem cells of the immune system begin in embryonic yolk sac during first weeks of development and by the third month they migrate to fetal liver and then colonize in the spleen (hematopoesis from 3-7 months) and then move to bone marrow
hematopoiesis generation of many different types of immune cells
the pluripotent hematopoietic stem cells in the bone marrow can then develop into two different types of cells common lymphoid progenitor (CLP) and common myeloid progenitor (CMP)
CMP can develop into two types of progenitors granulocyte/macrophage progenitors or megakarocyte/erythrocyte progenitor
megakarocyte/erythrocyte progenitors develop into what erythrocytes (red blood cells) and megakarocytes develops into thrombocytes (platelets)
granulocyte/macrophage progenitors develop into what neutrophils or eosinophils or basophils or unknown precursor mast cells or monocytes (that can further develop into macrophages)
CLPs can develop into what B cells, T cells, NK (natural killer) cells, and immature dendritic cells (that further develop into mature dendritic cells)
all progenitors reside in the bone marrow so where do mature B cells, T cells, NK cells, and mature dendritic cells reside and how do they get there travel to the lymph nodes via blood
where do granulocytes such as neutrophils eosinophils unknown precurosor mast cells and monocytes reside blood
after unknown precursor mast cells mature and monocytes mature into macrophages, where do they go and how and why travel to tissues via blood, so as to provide instant immunity to infections in the tissue since it takes time for antibodies to travel to infected tissue via blood
why do we use inbred mouse strains in experimentation of immunlogy reduces experimental variation, differences in experimental outcomes is often a result of different genetic backgrounds,
how are inbred strains generated 20 or more generations of brother-sister mating
syngeneic when more than 99% of all loci are identical
Sca-1+ stem cell antigen 1, differentiation antigen
how to purify bone marrow stem cells take bone marrow of a mouse via fluorescent tagged antibodies that isolate Sca-1+. irradiate another mouse to destroy the immune system. insert the irradiated mouse with bone marrow from syngeneic mouse and the complete hematopoietic system is restored
granulocytic cells all live in blood, all have granules, all originate from CMPs of the bone marrow, are the white blood cells. have multi-lobed nucleuses
neutrophills constitute 70% of white blood cells. are dominant first-responders to site of infection, circulate 7-10 hours before migrating into tissues, life span of 2 days, phagocytic and deal with mostly bacteria
another name ofneutrophils are leukocytes
leukocytosis medical term for increase in neutrophils
pus dead neutrophils
neutropinia problem of too few white blood cells
eosinphils motile phagocytic cells that release granules onto mostly parasites and that migrate from blood into tissues. they make 1-3% of white blood cells and contribute to allergy and asthma and deal with mostly antibody-coated parasites
basophils non-phagocytic granulocytes that make up less than 1% of white blood cells that contribute to allergy and asthma that function by releasing pharmacologically active substances from granules
how do allergies work allergen binds to antibodies such as basophils that release pharmacologically active substance histamine from granules that cause increase in blood vessel permiability s. muscle activity (it's why you have take antihistamines)
mast cells precursors are formed in bone marrow and released into blood as undifferentiated cells, they differentiate when they leave the blood and entire tissues
myeloid antigen presenting cells monocytes, macrophage, and dendritic cells are myeloid-derived APCs. the cellular bridges to adaptive immune systems because they make contact with a pathogen at site of infection and communicate this encounter to T cells at interstitial fluid or blood
monocytes reside in blood are undifferentiated
macrophages monocytes that migrated to tissues and differentiated and enlarged themselves to macrophages acquiring increased phagocytic ability providing immune response in tissue prior to infection
dendritic cells extensions that resemble dendrites, arise from CMP and CLP, highly motile, bridge between infection and adaptive immunity by carrying a pathogen from site of infection to nearest lymphnode. use phagocytosis, receptor mediated endocytosis, and pinocytosis
B lymphocytes (prior to antigen encounter) immature go through antigen independent differentiation where they display membrane-bound immunoglobulin or antibody-serve as receptors for antigens called B cell receptors (the receptor is an antibody)
B lymphocytes (after antigen encounter) naive B cells goes through antigen dependent differentiation into active B cells of immunoglobulin secreting cells, plasma cells, or memory B cells
plasma cells have no immunoglobulin, short life span, and are antibody factory
immunoglobulin secreting cells have immunoglobulin and secrete antibodies
B memory cells have immunoglobulin for recognition and long lives and are efficient for APCs
cluster of differentitation nomenclature used to name a protein identified by several different antibodies
T cells forms in bon marrow and matures in thymus. express membrane-bound receptor called T cell receptor TCR
T helper and T cytotoxic CD4 and CD8 cells. ratio CD4:CD8 is 2:1
function of T helper cells to help other cells produce an immune response such as B cells, macrophages, Tc cells by secreting cytokines and activate Tc cells
Tc cells kill virally infected cells
Tregs T regulatory cells supress immune response
once activated T cells become either effector cells (permanent T cells) or memory cells
each T cell has a specific function based on cytokine profile
NK cells primordial Tc cells that release lytic granules that kill some virus-infected cells however have different process than Tc cells since they dont have Tc receptors that can recognize antigens
NKT cells share features of both conventional T cells and NK cells, have TCR and some express CD4, are not as diverse T cells and recognize specific lipids and glycoproteins and can secrete cytokines and release cytotoxic granules
primary lymphoid organs bone marrow and thymus
secondary lymphoid organs lymph nodes, spleen, mucosal ymphoid tissues, it is the site for mature lymphocytes to interact with antigens
function of bone marrow microenvironment for differentiation of stem cells and myeloid cells, site of origin of B and T cells and all other cells of immune response. with immunoglobulin on, cells leave bone marrow via blood to secondar lymphoid tissues
function of bone marrow for B cells antigen-independent maturation of B cells, site for mature re-circulating lymphocyte populations such as B memory cells and plasmablasts
thymus site of T cell differentiation, primary immune tissue, located in thorax, sequestered from antigen via two lobes surrounded by thin capsule of connective epithelium. reaches max size at puberty and then atrophies
thymicite undifferentiated T cells
thymic stroma network of epithelia contains T cell precursors
thymic medulla dendritic cells macrophages and medullary epithelial cells
sub capsular epithelium underlying capsule acts as a barrier
blood circulates under pressure, fluid component (plasma) seeps through what into surrounding tissues capilaries
how plasma returned to blood from tissues venules, to prevent edema
describe the structure of lymphatic vessels porous architecture to allow fluids and cells to enter
thoracic duct largest lymphatic vessel and is where lymphatics empty into and is from where the fluid travels to the subclavian vein
what is lymph blood plasma that carries cells of the immune system
how is lymph flow achieved the heart does not pump lymph instead flow is achieved through movements of the body's muscles
lymphatic system series of one way valves produces one way movement through vessels that picks up foreign antigens and carries them to lymph nodes
describe circulation of lymphocytes in response to infection naive lymphocytes enter lymph nodes from blood. foreign antigens are carried from infected tissues to lymph nodes via lymph vessels. lymphocytes and lymph return to blood via thoracic duct.
periphery and secondary lymphoid tissues trap antigen-bearing dendritic cells and initiate of adaptive immune response and provide signals that sustain recirculating lymphocytes
lymph nodes structure encapsulated bean shaped structures, reticular network, full of lymphocytes, macrophages, and dendritic cells. contains cortex, paracortex, and medulla
lymph nodes function sites of immune responses, that trap antigens. germinal center foci that reach to max size within 4-6 days of antigen challenge and remain active up to 3 weeks or more. they are required for development of memory T and B cells
lymph node cortex contains mostly B cells, macrophages, and follicular dendritic cells
lymph node paracortex primarily T lymphocytes and dendritic cells
lymph node medulla sparsely populated with lymphoid lineage cells (mostly plasma cells)
how do lymphocytes entire lymph nodes via high endothelial venules lined with unusually tall endothelial cells
spleen major role in starting immune responses to antigens in bloodstream. filters blood and traps antigens, important for controlling systemic infections.
does the spleen have lymphatic vessels no. splenic artery carries antigens and lymphocytes into spleen and out via splenic vein
structure of spleen surrounded by capsule from which trabeculae extend into interior. splenic red pulp and white pulp
splenic red pulp has network of sinusoids, populated by macrophages, red blood cells and few lymphocytes. it is the site were old and defective red blood cells are destroyed and removed by macrophages
splenic white pulp surrounds branches of splenic artery. forms periarteriolar lymphoid sheath (PALS) that populated by primarily T cells. primary lymphoid follicles are attached to PALS and are rich in selected B cells with specific BCR and germinal centers
organizton of germinal center of spleen perifollicular zone (PFZ) then PALSthen co-follicular B cell corona (germinal center) then MZ-marginal zone with lymphocytes and macrophages then red pulp
is the spleen part of the lymphatic system spleen. you can live without it depending on the age but you will just have increased incidence of bacterial infections since it does filter blood and the pathogens found in the blood
MALT- mucosa-associated lymphoid tissue mucous membrane lining digestive, respiratory, and urogenital system that are the major sites of entry for most pathogens
structures of MALT Peyer's patches (lymphoid tissue) in intestinal lining that are well organized, clusters of lymphoid cells in lamina propria of intestinal villi, tonsils, appendix.
what has more plasma cells than spleen and lymph nodes MALT because it blocks adherence of pathogens to mucosal lining
peyers patches outer layer is epithelial cells (M cells) that are the entrance for pathogens and the inner lining is lymphoid cells. has T cell areas and germinal center and follicle B cell area
how are antigens transported through peyers patches transport is carried out by M cells that are flattened epithelial cells laced with microvilli and have deep invagination which is filled with B,T cells and macrophages
fixed defenses of immune reponse internal epithelia that has mucosal membranes that secrete mucins that prevent adherence of microorganisms. tears and saliva contain lysozyme and histatins. stomach has acidic pH and digestive enzymes. alpha and beta defensins
alpha and beta defnsins small cationic peptides with beta sheet folds that exhibit antimicrobial activity against broad spectrum of bacteria and fungi . they also shape microbiota and protect stem cells
cutaneous associated lymphoid tissues skin anatomic barrier to external environement
surface kertinocytes layer under skin (epidermis) filled with these cells that set secrete cytokines that set up local inflammatory reaction
langerhans cells layer under skin (epidermis) with surface kertinocytes. they are a type of dendritic cell that phagocytose antigens
intra-epidermal lymphocytes under the epidermis, these cells are mostly T cells and reside in lymph nodes
dermal layer of skin contains scattered t cells and macrophages
pathogenic versus non pathogenic micro organisms pathogenic organisms are able to avoid the innate immune system but non pathogenic microorganisms are dealt with innate immune system
how do pathogenic organisms to overcome innate immune defenses thick polysaccharide capsule that is not recognizable by any phagocyte receptor. ability to grow inside macrophages (mycobacteria) and prevent acidification and fusion with lysosomes. inactivate complement system that gets rid of pathogens
extracellular pathogens lie in interstitial spaces, blood, and lymph. all types of pathogens and are dealt with by antibodies, complement immune system, and phagocytosis and antimicrobial peptides
intracellular pathogens cytoplasmic pathogens that are mostly viruses that are dealth with macrophages, cytotoxic t cells and nk cells
direct mechanisms of pathogenic damage kills cells or the immune reponse of cells against pathogen kills cell itself. exotoxin release, endotoxin release, or direct cytopathic effect that has virus proliferate in cell and then cell lyses killing itself and releasing virus
indirect mechanisms of pathogenic damage by forming immune complexes large amounts of antibodies attach to antigen yet this large structure gets stuck in red blood cells causing them to get stuck in organs causing tissue damage by blocking oxygen
indirect mechanisms of pathogenic damage by anti-host antibody cross reactivity with self antigen so that the antibody attacks itself in order to attack pathogen
indirect mechanisms of pathogenic damage by cell-mediated immunity T cells kills virally effected cells but it is essential cell killing
how do the surface receptors that stimulate the phagocytosis of macrophages and neutrophils and intracellular killing of microbes bound to them they secrete 3 molecules: lipids- can diffuse into/out of blood to interact with white blood cells to bring them into tissue. chemokines- direct cell movement leading cells to site of infection. cytokines- induce inflammation
lps lipopolysaccharide receptor
fMLP peptide attached to amino terminus of proteins of some bacteria that are potent chemotactant for neutrophils
CXC cystine-amino-cystine acid, classifying chemokines
CXCL8 and TNF-alpha do what activate neutrophils, they are release from macrophages to blood to activate neutrophils to show where the site of infection is. they also cause respiratory burst that produces oxygen anions & nitric oxide to kill pathogens by changing pH of environment
inducible nitric oxide synthetase iNOS enzyme is found in what ACTIVATED macrophages and neutrophils. if they are not activated they will not have iNOS.
how are macrophages and neutrophils activated to make iNOS through contact through toll like receptros or exposure to cytokines
iNOS enzymes that oxidize L-arginine to yield L-citrulline and nitric oxide (to kill pathogens) that are contained in vacuoles/endosomes
respiratory burst in macrophages and neutrophils initiated by activation of NADPH oxidase. abrupt rise in oxygen consumption and increase in glucose consumption. large amounts of ROI generated via influx of K+ ions that causes pH change in lysosomal vacuoles to activate microbial proteins and peptides.
order of events for respiratory burst activated nadph oxidase converts oxygen to superoxide O2-, a second enzyme converts the superoxide into hydrogen peroxide , then another enzyme converts hydrogen peroxide tino hypochlorite ions and hydroxyl radicals
nadph enzyme reaction NADPH + 2 O2 ——-(NADPH oxidase)—–> NADP + 2O2- + H+
how does the NADPH oxidase get assembled ingestion of microorganisms activates the phagocyte to assemble the multi-subunit enzyme NADPH oxdiase from its components–the 2 transmembrane subunits and 4 associate factors
chronic granulomatous disease most common form of the disease is X-linked with a defect in gp91phox
granulomas swirls of immune cells trying to kill infected cells but can't so there are lots of dead cells that are necrotic and hard. found in TB
mannose binding lectin MBL non-toll like receptor. expressed by liver. soluble, found in blood. binds to a particular spatial arrangement of mannose or fucose residues that activates macrophage
TLR-4 dimer (md-2 and CD14) LPS (gram negative bacteria) and lipoteichoic acids (gram positive bacteria)
cooperation of TLR-4 and CD14 in macrophages LPS in blood is bound to acute-phase protein LPS-binding protein (LBP). the LPS-LBP complex transfers LPS to CD14 on surface of phagocytes . the LPS-CD14 interaction with TLR-4 results in activation of macrophage
cellular location of mammalian TLRs in endosomes and phagolysosomes. signal back into nucleus to change gene expression
contact of bacterial component by toll-like recceptor causes secretion of "pro-inflammatory" cytokines such as Interleukin-1, IL-6, tumor necrosis factor- TNF alpha, CXCL8 and IL-8 to activate neutrophils and to to cause respiratory burst.
what are highly inflammatory cytokines IL-1 and IL-6
too much IL-1 and IL-6 can cause shock or sepsis
LPS activate what into what resting immature dendritic cells (migrate to lymphoid tissue) to mature cells. they lose phagocytic properties and acquire T cell stimulating properties. express co-stimulatory molecules
what cytokines act upon lymphocytes and the liver and produce enhanced responses and induce acute-phase protein structures IL-1 and IL-6
what cytokine acts upon phagocytes and produces chemoattractant for neutrophils CXCL-8 and IL-8
what cytokine acts upon naive T cells and diverts immune response to type 1, pro-inflammatory, cytokine secretion IL-12
inflammation delivers additional effector molecules to site of infection, provides physical barrier to prevent spread of infection, and promotes the repair of injured tissue
inflammatory reponses pain, redness, heat, swelling which all reflect changes in lochoal blood vessels
how do inflammatory responses come about macrophages release immediate inflammatory mediators: prostaglandins-vasodilators, leukotrienes-increase vascular permeability, platelets activating factor-platelet aggregation, and also release chemokines-leukocyte migration, cytokines
what are the induced innate responses to infection cytokines chemokines adhesions molecules interferons and acute phase proteins
process of inflammation 1.cytokines released by macrophages cause dilation of local small blood vessels, 2. increased expression of adhesion molecules cause leukocytes to go to periphery blood vessel 3. leukocytes go to site of infection 4. blood clotting occurs in microvessels
cytokines released by macrophages for inflammation are IL-1, IL-6, and TNF-alpha
acute phase proteins induced by TNF-alpha , IL-1, IL-6 (action on hepatocytes). shift in proteins synthesized and secreted by the liver into plasma.leads to leukocytosis
actue phase response C-reactive protein, mannose binding lectin, opsonin
c-reactive protein binds to phosphorycholine of distinct bacterial and fungal cell wall lipolysaccharides and opsonizes (tags it for recognition) bactera. it is a pentamer of identical subunites
mannose binding lectin in acute phase response opsonin for monocytes (cells that do not express macrophage mannose receptor)
opsonin a substance that promotes the phagocytosis of antigens by binding to them (e.g. an antibody)
acute phase response SP-A and SP-B pulmonary surfactants
leukosytosis increase in neutrophils
chemokine receptor receptros are integral membrane proteins and contain 7 membrane spanning helices (nonmenclature is CCR or CXCR)
CXCR4 HIV-1 coat proteins gp120 bind to CD4 and gp41 binds to co-receptor of CD4 in membrane of host cells. use CCR and CXCR4
chemokine and recruitment function acts on leukocyte in blood to extravasate into tissue. direct leukocyte in blood along a gradient to site of infection
local effects of Tnf-alpha macrophage activated to secrete TNF-alpha into tissue that increases release of plasma proteins into tissue and increase phagocyte and lymphocyte migration into tissue and increase platelet adhesion to blood vessel wall
systemic effects of TNF-alpha macrophages activated in liver and spleen secrete TNF-alpha into bloodstream. systemic edema causes decreased blood volume since all blood goes to site of infection. hypoproteinemia and neutropenia followed by neutrphilia. causes sepsis and organ failure
TNF-alpha induces septic shock vasodilation, loss of blood pressure, increased vascular permeability, loss of blood volume, disseminated intravascular coagulation (generation of clots). leads to multiple organ failure due to lack of oxygen and death
interferons IFN-alpha and IFN-beta primarily involved in anti-viral activities. synthesis is in response to double stranded RNA–recognized by TLR-3. induces state of replication resistance inside cell and acts on both infected and nearby cells
interferons increase MHC class I expression receptor that is sensed by Tc cells that then activated NK cells
IFN receptor signal through JAK-STAT intracellular signaling pathway which results in the inhibition of translation and viral replication which is PKR kinase induced and phosphorylates elF2 (translation initiation factor)
adhesion molecules selectins, integrins, and immunoglobulin superfamily
selectins p-selectin binds to carbohydrates and initiates leukocyte-endothelial interaction and is on activated endothelium and platelets
integrins bind to cell-adhesion molecules and extracellular matrix. it is expressed on cells that move throughout blood (monocytes, T cells, neutrophils, dendritic cells, macrophages)
immunoglobulin superfamily various roles in cell adhesion. ICAM-1 is on activated endothelium, ICAM-2 on resting endothelium and dendritic cells,VCAM-1 on activated endothelium, PECAM on activated leukocytes and endothelial cells
steps in recruitment expression of selectins (low affinity) then binding of ICAMs on endothelium to integrins on leukocytes then integrins extravasate
LFA-1 and CR3 (integrins bind to ) ICAM-1 and 2
chemokine binding to endothelium to immunoglobulin causes conformational change
4 steps in extravasation rolling adhesion, tight binding, diapedesis (moving from blood to tissue), migration
rolling adhesion selectin-mediated adhesion to leukocyte is weak and allows leukocyte to roll along the vascular endothelial surface with blood
tight binding interaction between leukocyte integrins (LFA-1 and CR3) with ICAM-1
diapedesis interaction between LFA-1 and CR3 with ICAM-1 and CDC31 or pCAM(expressed on leukocyte and at the intercellular junctions of endothelial cells. pulls in leukocyte
migration depends on chemokines CXCL8 and CCL2 that creates gradient across membrane to pull leukocyte into cell
complement a set of serum proteins that cooperates with both innate and adaptive immune systems to eliminate blood and tissue pathogens. opsonize bacteria making them susceptible to receptor-mediated phagocytosis
how do complement proteins interact with one another catalytic cascades
what are the 3 pathways for complements classical pathway, mb-lecting pathway, alternative pathway that all lead to the production of C3 convertase that makes oppsonins
what triggers complement actibation antibody binding to pathogens
classical pathway C1q binds to antibody-antigen complex or directly to surface of pathogens via C-reactive proteins
C1q composed of six identical subunits with globular heads and long collagen-like tails
binding of C1q to antibody/antigen complexes (low affinity) pentameric immunoglobulin M molecules bind to antigens on bacterial surface in staple form. C1 binds to single immunoglobulin molecule
binding of C1q to antibody/antigen complexes (high affinity) immunoglobulin G molecules bind to antigens on bacterial surfaces and CI1 binds to two or more immunoglobulin molecules
classical pathway to C1s serine protease subunits of C1q + 2(C1s + C1r) make C1 once immunological response starts. Binding of C1 to immunoglobulins via C1q activates C1r autocatalysis of C1s that activates it
C4 to C3 convertasae C4 is cleaved by C1s into C4a + C4b. C4b + C2 are covalently linked to membrane through thioester bond. C1s cleaves C2 into C2a and C2b. C4b + C2a make C4bC2a can cleave C3 convertase
C3 to opsonin C3 is cleaved by C3 convertase into C3a + C3b. C3a becomes a inflammtorymediator and C3b is cleaved and inactivated by MCP to become iC3b an opsonin attached to surface of pathogen that cannot bind to factor B or C4b2a
how cleavage of C4 and C3 makes C4b and C3b attach to pathogen surfaces cleavage of C3 and C4 exposes a reactive thioester bond that cause hydroxyl and amino groups on cell membrane proteins and carbohydrates to subject an neucleophilic attack
what complement proteins bind covlently to microbial surfaces C4b and C3b
lectin complement pathway from MBL to C3 convertase MBL is combined with 2 units of MASP-1 and MASP-2 to form a complex MASP-2 (serine protease). MASP-2 cleaves C4 into C4a and C4b and cleaves C2 into C2a and C2b. C4b and C2a combine to C4b2a to make C3 convertase
MBL monomers have what that let them do what trimeric clusters of carbohydrate-recognition domains that bind to mannoseficolins and fucose residue with high affinity on pathogens
ficolins have similiar structures to MBL but have different binding domains that let them bind to oligosaccharides containing acetylated sugars
high concentration of C3 in serum leads to what hydroylsis of C3 which starts the alternative pathway of complement
alternative pathway of complement from C3 to C3 convertase C3 undergoes spontaneous hydrolysis=C3(H2O) that binds to factor B which is cleaved by factor D into Ba and Bb. Bb combines with C3(H2O) to make C3(H2O)Bb a C3 convertase that cleaves C3 into C3a + C3b. C3b is inactivated unless binds to pathogen surface
alternative pathway of complement from C3b to opsonin C3b combines with factor B. factor B is cleaved by factor D into Ba and Bb and Ba gets expelled while Bb stays with C3b. C3bBb is a type of C3 convertase that cleaves C3 into C3a and C3b that becomes opsonin.
what are the 2 pathways C3bBb can take in the alternative pathway of complement on host cells the complement regulatory proteins (CR1, H, MCP, DAF) bind to C3b and displace Bb OR pathogens that lack complement-regulatory proteins, properdin (factor P) can stabilize C3bBb by binding to it
what is so unique about C3bBb it is a fluid-phase C3 convertase. forms of it on host cells are immediately inactivated by complement regulatory proteins but bacterial surfaces do not express complement-regulatory proteins and favor the binding of factor P (properdin)
C3 of alternative pathway active fragment is C3band it binds to pathogen surface, binds B for cleavage by D, C3bBb is C3 convertase and C3b2Bb is C5 convertase
Factor B active fragment is Ba and Bb. Ba function is unknown, Bb is active enzyme of the C3 convertase C3bBb and C5 convertase C3b2Bb
factor D plasma serine protease, cleaves B when it is bound to C3b to Ba and Bb
Factor P plasma proteins with affinity for C3bBb convertase on bacterial cells
C1q binds directly to pathogen surfaces or indirectly to antibody bound to pathogens thus allowing autoactivation of C1r
C1r cleaves C1s to active protease
C1s cleaves C4 and C2
C4 C4b covalently binds to pathogen and opsonizes it and binds to C2 for bleavage of C1s. C4a is peptide mediator of inflammation (weak)
C2 C2a is active enzyme of classical pathway C3/C5 convertase and cleaves C3 and C5. C2b is precursor of vasoactive C2 kinin
C3 for classical complement pathway C3b binds to pathogen surface and acts as opsonin and initiates amplification via alternative pathway, binds C5 for cleavage by C2b. C3a peptide mediator of inflammation (intermediate)
what is the C3 convertase for classical C4b2a
what is the C3 convertase for lectin C4b2a
what is the C3 convertase for alternative C3Bb (also C3(H2O)Bb)
how do the classical and lectin pathways get from C3b molecule to C5b C3b combines with C3 convertase: C4b2a to make C5 convertase (C4b2a3b) that cleaves C5 into C5a and C5b. C5a is inflammatory mediator and C5b is an opsonin
how does the alternative pathway get from C3b to C5b C3b combines with C3bBb to make C5 convertase (C3bBbC3b or C3b2Bb) that cleaves C5 into C5a (inflammatory) and C5b (opsonin)
what are the initiating serine proteases for all 3 pathways alternative-D, lectin-MASP, classical-C1s
what are the proteins that covalently binding to cell surface for all 3 pathways alternative-C3b, classical and lectin- C4b
what are the proteins involved in C3/C5 convertase for all 3 pathways alternative-Bb, lectin and classical- C2a
what are the proteins that control activation for all 3 pathways alternative- CR1 and H, classical and lectin – CR1 and C4BP
what are the proteins for opsonizatino for all 3 pathways C3b
what are the proteins that initiate the effector pathway for all 3 pathways C5b
what are the proteins that cause local inflammation for all 3 pathways C5a, C3a
what are the proteins that are used for stabilization for all 3 pathways alternative- P, lectin and classical dont have a stabilization molecule
what are the receptors that recognize complement proteins (CRs) CR1 binds to C4b and C3b. CR5 binds to C5b. the binding stimulate phagocytosis
how do CRs recognize complement proteins C3b can be cleaved into derivatives that do not form functional C5 convertase iC3b acts as an opsonin
CR3 has specficity for what and does what iC3b and it stimulates phagocytosis
CR2 receptor has specificity for C3d, iC3b, C3dg and is part of B-cell co-receptor. is involved in B cell signaling through BCR. amplifies antibody response and links innate and adaptive
purpose of inflammatory mediators increase vascular permeability and expression of adhesion molecules
how does C5a cooperate with opsonin to induce phagocytosis bacteria is coated with complement by alternative and MBL pathway. when only C3b binds to Cr1, bacteria are not phagocytosed but when C5a binds to CR1 as well it activates phagocytosis in macrophages
membrane attack complex highly effective against strains of Neisseria (Neisseria Meningitides- causes endemic and epidemic meningitis, Neisseria Gonorrheae- causes gonorrhea)
Neissera encapsulated bacteria is particularly vulnerable to MAC during division when bacterial membrane is exposed
C5a small peptide mediator of inflmmation (high activity)
C5b initiates assembly of membrane-attack system
C6 binds to C5b forms acceptor for C7
C7 binds to C5bC6, amphiphilic complex inserts in lipid bilayer
C8 bindsto C5bC6C7, initiates C9 oplymerization
C9 polymerizes C5b678 to form a membrane-spanning channel, lysing cells
MAC function forms hydrophillic channel allowing for free passage of solutes and water which causes loss of homeostasis and loss of proton gradient across membrane
C1 inhibitor C1INH binds to activated C1r, C1s removing them from C1q. also binds to activated MASP-2 removing it from MBL
C4-binding protein C4BP binds to C4b displacing C2a, cofactor for C4b cleavage by Factor I
CR1 as a regulatory protein binds to C4b displacing C2a or to C3b displacing Bb, cofactor for Factor I
Factor H binds to C3b displacing Bb,cofactor for Factor I
Factor I serine protease that cleaves C3b and C4b, aided by H, MCP, C4BP, or CR1
DAF-Decay-accelerating factor membraine protein that displaces Bb from C3b andC2a from C4b
MCP-membrane cofactor protein membrane protein thta promotes C3b andC4b inactivation by factor I
CD59 (protectin) prevents formation of membrane attack complex on autologous or allogeneic cells
what does each B cell express a unique immunoglobulin
isotype class of heavy chain polypeptides (IgM, IgD, IgG, IgA, IgE)
mature naive or resting B cells express only what on surfaces IgM and IgD
avidity overal strength of binding
strength of one binding site affinity
antibodies can bind to how many identical antigens 2
how do bacterial toxins get handled by antibodies toxins get attached to cells with receptors for the toxins that then release antibodies to neutralize the toxin while being phagocytosed by macrophages
how do bacteria in extracellular space get handled by antibodies bacteria attach to Fc receptors that opsonize the bacteria which is then phagocytosed by the macrophage that it is attached to
how do bacteria in the plasma get handled by antibodies the complement system gets activated which causes the bacteria to be ingested while lysing the cell during cell division
name all the different immunoglobulin molecules M D G E A
IgM, IgD, IgG, IgE, IgA are all what of antibody structures isotypes
what distinguishes the isotype structure of antibody molecules the number of interchain disulfide bonds, number of oligosaccharide moieties, number of C domains (IgM and IgE have extra domains), and the length of the hinge region
what two immunoglobulins can form dimeric and pentameric forms and with what IgM and IgA, with J chain
what's the difference between the four subclasses of IgG the structure of the hinge between the constant and variable region
if there is a difference in amino acid sequence within an isotype, what is this difference called allotypic difference
differences in amino acid sequence within the binding site of the same isotype is called what idiotypic difference
what is a proteolytic cleavage by papain it cleaves the disulfide bond between the constant regions, the constant heavy chains and the constant light chains attached to the variable region. results in 3 parts, 2 V+C and 1 C+C (that has disulfide bond)
what is a proteolytic cleavage by pepsin it separates the C and V regions. the 2 V regions along with their CL regions stay intact via the hinge. however the CH region is spliced along the top parts of it
describe the structure of an antibody molecule constant region (containing c terminus) with 2 beta sheets attached together by disulfide bonds that is attached 2 other arms. each arm has constant region and variable region. each region has 2 beta sheets held together by disulfide bondss
where does an antigen bind to an antibody in the variable region where the n terminus of the molecule is `
each domain of an immunoglobulin has a similar structure called Ig fold
Ig fold 2 beta pleated sheets that are antiparralel linked by disulfide bonds creating called a beta barrel
within the V regions what are the 3 regions of elevated variability hyper variable (HV) region called complementary determining regions or CDRs that make contact with antigens
how do antibodies recognize antigens juxtaposition of the CDRs of both heavy and light chains form a pocket that recognized antigen
haptens small molecules that can be recognized by antibodies but cannot stimulate the production of anti-hapten antibodies. they demonstrate a wide range of epitopes
what do haptens need to create a response with antibodies they need to be linked to a larger carrier protein such as BSA
epitope the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells
what can the hapten-carrier system be used for besides starting an immune reponse it can be tool to probe the effects of minor variations in chemical structures on immune specificity
the variability in amino acids in CDRs creates what surfaces on antibodies that are distinct that create antigen-antibody conjugates
the same antibody can recognize what on antigens different types of epitopes
linear epitopes recognize a specific sequence of amino acids (2 or 3)
conformational epitopes are also called what and what are they? discontinuous epitopes. they recognize specific structures on the antigen or specific amino acids that are not in sequence but create such a structure that is recognizable by the antibody and can also be bound to the antibody
what defines the variable regions of the Ig heavy and light chain polypeptides framework and hypervariable regions
clonal selection hypothesis lymphocyte has 1 receptor with unique specificty. interaction b/w antigen + receptor (high affinity) leads to lymphocyte activation. differentiated effector cells derived from activated lymphocyte will have receptor of that lymphocyte.
what does clonal selection hypothesis about self molecules lymphocytes bearing receptors specific for ubiquitous self molecules are deleted at an early stage in lymphoid cell development and are therefore absent from the repertoire of mature lymphocytes
how many loci are there for antibody genes one heavy chain locus and two light chain loci
first mechanism that generate diversity among antibodies combinatorial diversity of heavy and light chains– pairing of individual heavy chains with different light chains
second mechanism that generates diversity among antibodies combinatorial diversity where any function VH segment can recombine with any DH segment and any JH segment. AND any function VL segment can recombine with any JL segment
only recombination recognition sequences that have what can recombine with each other different spacer lengths
describe mechanism of recombination of forward-orientated V gene when a forward-oriented V gene segment recombines with downstream gene segment (face each other), alignment of the RSS regions loops out intervening DNA. loop is excised taking two RSS region with it
describe the mechanism of recombination of reverse-orientated V-gene when genes face in same direction, alignment of RSS regions forms the intervening DNA into a coiled configuration. after recombination the coiled region is retained in chromosome in an inverted orientation
what are the proteins required for carrying out recombination called V(D)J recombinase
RAG I and II VDJ recombinases for variagle region somatic recombination. they create hairpins that are cleaves. Terminal deoxynucleotidyl transferase (TdT) are added.
3rd mechanisms for creating diversity among antibodies junctional diversity. enzymatic processes creates diversity in joint between gene segments. RAG creates DNA hairpins. TdT adds nucleotides. Exonucleases delete gene segments.
each B cell expresses a unique immunoglobulin
what is the first immunoglobulin expressed during development IgM
what immunoglobulin molecules are expressed on surface together in mature, resting, naive B cells IgM and IgD but very little IgD.
how are IgM and IgD so similar yet different they are produced by differential cleavage of a common mRNA transcript. 2 cleavage and polyadenylation sites, pA1 and pA2
when cell is activated what happens to IgM and IgD it ceases to make both and only produces IgM
what does each heavy chain gene have membrane-coding (MC) and secretion-coding exon (SC)
what does each mRNA transcript of heavy chain have 2 cleavage sites for polyadenylation, pAm and pAs
what does the membrane form of heavy chain gene have 25 amino acid hydrophobic tail
what does the secreted form of heavy chain gene have has hydrophillic COOH end
isotype refers to class of heavy chain polypeptides
constant region has what types of chains has only 2 types of chains, lambda and kappa
what is the proximal part of a TCR constant heavy chain region
describe the chains of antibody structure the constant region of the c terminus has both heavy sheets. the n terminus arms has a constant region and variable region. each region has a heavy and light chain
TCR comprised of two distinct chains, alpha and beta linked by disulfide bond. each chain has a V and C region. also carbohydrate moeties. also has a hydrophobic transmembrane region that keeps it anchored to the membrane of T cells
MHC molecules there are two classes, 1 and 2 that are expressed in different tissues and cell types. Class 1 has one transmembrane part while Class 2 has two transmembrane parts
what type of cells are MHC class I expressed in T cells, B cells, macrophages, dendritic cells, and neutrophils
what type of cells are MHC class II expressed in B cells, some macrophages, dendritic cells, and epithelial cells of the thymus
MHC Class 1 structure forms basket alpha helices surrounding it and beta sheets at the bottom.
what is in MHC Class 1 if not an antigen a self-peptide to keep it stabilized but it does not activate T cells
how does the self-peptide bind to MHC Class 1 the peptide (8-10 amino acids) has very little secondary structure and so its side chains make contact with side chains of the cleft- the alpha helices-
how does TCR bind to peptide:MHC class 1 complex V region of TCR makes contact with peptide:MHC class 1. if the peptide is viral, contact with TCR will alert TCR it is not self-peptide and will activate the T cells
anchor residues contact points on peptide where peptide bonds with MHC class 1 molecule. these points usually have some form of conservation of charge and/or structure, basically these particularly amino acids of the peptide have similar properties
MHC Class 1 is polymorphous one MHC class 1 can bond with different peptides
TCR needs to be able to bind to what in order to be activated the peptide and the MHC Class 1 molecule
MHC Class 2 structure similar deal as MHC Class 1 except binding region is more flexible and more open for longer polypeptides–up to 13 amino acids and more.
what defines the specificity of TCR peptide it recognizes and the by the MHC molecule bound to it. They need to be able to bind to both or they will not be able to recognize it
where do T cells learn self from non-self thymus
CD4 Co-receptors contains 4 Ig-like domains and binds to beta 1 and beta 2 (only beta 2 actually) domains of MHC class II
CD8 Co-receptors heterodimer of alpha and beta chain. binds with alpha chains (alpha 3 domain) of MHC Class 1
what is the difference between developing T cells and mature T cells in terms of co-receptors developing T cells are double positive thymocites meaning they express both CD-4 and CD-8 co-receptors. however after maturation, they down regulate and express only one
why does it make sense that CD4 binds to MHC class 2 only and CD8 binds to MHC class 1 only CD4 activates B cells and MHC class 2 is found on mostly B cells, macrophagesm, + dendritic cells. CD8 activates cytotoxic T cells (Tc) and MHC Class 1 is found in mostly T cells (also B cells, macrophages, + dendritic cells)
immunological synapse binding of CD8 to MHC 1 or CD4 to MHC 2. linking T cells to target/antigen-presenting cells to kickstart immunological response

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