Immuno Flashcards
Where are all leukocytes produced? Where do B and T cells mature?
Bone marrow via hematopoiesis; bone marrow and thymus (primary lymphoid organs). T cells move to thymus as they develop
Which cells are part of humoral immunity vs cell-mediated immunity?
B cells, ab, complement, soluble mediators vs T cells, PMNs, NK cells, macs, cellular mediators
Name different barriers of nonspecific/innate immunity
Physical: skin, epithelial tight junctions, physical removal (cough/sneeze, peristalsis, cilia, vomiting/diarrhea, sloughing dead cells), flushing (tears, urine). Chemical: GI tract/stomach acid/lysozymes/pH, mucous membranes, sebum, fatty acids, antimicrobial peptides, pulm surfactant. Biological: microbiome influenced by where you live, diet, exer, stress, dz, meds, gender/age. BOTH INNATE N ADAPTIVE CELLS = PART OF CELL MEDIATED RESPONSE
innate vs adaptive immunity
rapid onset (1d), no memory, general specificity, doesn’t react to self, actions cont to adaptive phase vs delayed onset (7d) since cells = activated by APCs, has memory –> faster & stronger response and resolves at higher titers, highly specific, doesn’t react to self
Active vs passive immunity. Give examples of natural and artificial of each
Ab made during immune response –> MEMORY vs ab passed down. NA actually getting dz; AA vaccines vs NP mom passing ab to fetus via placenta; AP receiving ab or T cells as med tx
MALT vs GALT vs BALT vs NALT
Mucous-associated lymphoid tissue; lymphoid tissue at mucosal surfaces Ex: GALT, BALT, NALT vs Gut-associated lymphoid tissue; Ex: tonsils, adenoids, Peyer’s patches, appendix, igA, M cells, antimicrobial peptide vs Bronchus-associated lymphoid tissue; Ex: goblet cell and mucin production, surfactant, igA vs Nasal-associated lymphoid tissue; Ex: mucous lining of nostril, goblet cell, brush cells, igA
purpose and basic process of hematopoiesis?
generation of immune and non-immune cells, occurs in bone marrow. hematopoietic stem cells differentiate into diff cell type => pluripotent thru mult steps w/ differentiation pathways determined by mix of cytokines, growth factors, etc that the developing cell binds
which cells are APCs?
macs, DCs, B cells
Diff types of T cells?
helper/CD4 T cells and cytotoxic/CD8 T cells (conventional); regulatory/suppressor T cells - tone down immune system after infection and promote self tolerance, NKT, and gamma-delta T cells (nonconventional)
What are NETs?
matrix formed of DNA extruded by PMNs after phagocytosis to which degraded nuclear proteins bind in addition to granular enzymes; traps large particles like bacteria then degrades and kills them; AG INDEP
How to differentiate lymphocytes since they all look similar?
specific markers by stains (ex: stain CD3, CD4 and CD8 to find CD4+ and CD8+ T cells)
immunoprotection vs immunopathology
protection against pathogens vs inappropriate immune response that dmgs host (over-exuberant immune response, autoimmune dz, rejecting grafts)
barrier defenses vs immune organs vs immune cells vs soluble molec for immune system
keep pathogens out of body (skin, mucous membranes) vs where immune cells = made and reside (spleen, tonsils, lymph nodes) vs fight pathogens (macs, lymphocytes); cells = not technically part of immune response but do secrete during immune response vs help defend against pathogen (complement, cytokines, ab)
lymphatic fluid vs lymphatic vessels vs lymphoid tissues/organs
made of water, immune cells, proteins, electrolytes, dend cells w/ ag, soluble ag, free microbes, ca cells, leuks; plasma leaked from capillaries and into lymph system; if leaked from capillaries and into tissue/interstitium => interstitial fluid (but don’t let fluid stay in tissue –> go to lymph vessels, picks up path and carry to 2nd lymph organ –> innate & adaptive immune cell fight pathogens, DOESN’T CONTAIN RBCs vs collects and returns tissue fluids to lymph organ & collects and returns lymph fluids to bloodstream, same structure as blood vessels: tunica intima, tunica media, tunica adventita; open ended vessels, fenestrations, one-way valves, connects lymph nodes, tethered to surrounding tissue by collagen filaments => anchoring filaments, permeable d/t adjacent endothelial cells, vs survey lymph fluid or pathogens/debris, activate and upregulate adaptive immunity (ex: spleen, lymph node)
3 main functions of lymph system
remove edema fluid from tissues/interstitium, 85% re-enter circ and 15% stay in lymphatic system and returned to circ (if not efficient –> lymphedema); transport lipids from intestine to circulation, special lymph capillaries (lacteals) and blood capillaries w/ villi = along surface of sm intestine, lacteals absorbed lipids and lipid-sol vit –> lacteals contain high fat liquid content => chyle; generate and mediate immunity
primary vs secondary lymph organs
where immune cells develop from stem cells to mature inactivated leukocytes (ex: bone marrow, thymus) vs where mature but naive B/T cells encounter ag; optimize interaction in innate and adaptive immune cells w/ ag and e/o; organ inc in size during activations b/c inc number of B/T cells, APCs activate naive B/T cells (ex: spleen, lymph nodes)
bone marrow vs thymus
in interior of hollow bones, where stem cells become B/T cells => hematopoiesis, 50/50 stem cells & fat cells (fat cells inc in age b/c stem cells already differentiated), stem cells can also become mesenchymal cells (repair connective tissue) or endothelial cells (repair dmged blood vessels) vs in upper anterior chest (cortex = dark purple, contains immature T cells; medulla = light purple, contains mature T cells), where T cell maturation occurs, involutes w/ age, relates to immunosenescence (dec immune fxn), absent thymus => DiGeorge syndrome
spleen vs lymph nodes vs tonsils
upper L abd behind stomach; red pulp - stores blood, macs & dendritic cells, site for extramedullary hematopoiesis if bone marrow fails; white pulp - follicles made of B cells, germinal centers develop w/in follicles and contain activated B cells –> make plasma cells and ab –> activates adaptive immune response, periarteriolar lymphoid sheaths (PALS) formed by T cells; marginal zone - b/w red pulp and white pulp, where ag = trapped and presented to splenic B/T cells; filters blood by removing ag vs similar architectural traits w/ spleen like cortex and medulla (T cell zones = paracortex, B cell zones = follicles and germinal centers, central vasc region = medulla, subcapsular sinus = marginal zone), enclosed by fibrous capsule, concentrated w/ pathogens at entry; enlarge during lymphocyte proliferation => lymphadenopathy, connected by lymph vessels for delivery of ag to B/T cells and release ag-activated T cells and ab vs 3 sets: palatine - back of throat (we see), pharyngeal - adenoids, lingual - base of tongue (we don’t see); have crypts that develop into follicles and catch pathogens from food or oral secretions; fight infxns of upper resp and digestive systems
process of lymph node
activate B/T cells to start primary adaptive immune response or reactive secondary response; pathogens enter -> dend cells present at barrier surfaces and take up pathogen -> enter lymph vessels to go to nearest lymph node via afferent lymphatics or other secondary lymph organ -> present ag to B/T cells -> activated T cell or ab leave lymph node to infected tissue
where are cervical vs axillary vs inguinal vs mesenteric lymph nodes?
neck & shoulders vs armpit vs GU area vs abd cavity near sm intestine
bulk fluid flow
movement of water and solute based upon pressure gradients; fluid filters at arterial end of capillaries into interstitium –> most interstitial fluid = reabsorbed at venous end of capillaries, remaining interstitial fluid enters lymph system => lymphatic fluid
key characteristics of lymph fluid
colorless/clear, similar to plasma but low protein conc, flows thru lymph channels, filtered by lymph nodes
overview of lymphatic flow
relies on muscle contractions (perilymphatic smooth muscle cells, pressure from movement of MSK tissue) (not a pump like cardiovasc system), breathing, 1 way system, massage, or passive compression (OMT), postural changes, contractions of lymph vessel walls; consists of lymph capillaries –> lymph fluid flow into convergent progressively bigger lymph vessels –> trunks –> RUQ lymphatic duct or thoracic duct and re-enter circ at R/L subclavian veins respectively –> superior vena cava
advantages vs disadvantages of edema
“washing” pathogens, ag, cellular debris from tissues vs cause tissue dmg if not removed –> interstitial fluid = reabsorbed into blood or taken up by lymph vessel and returned to blood
how does osteo med enhance lymph system?
uptake fluid and tissue ag into lymphatics, release leuks into lymphatics, inc ab responses
why do lymph pump techniques?
tx for thoracic cage (for resp), abd (spleen, liver, pancreas, bladder, colic, menstrual cramps, flatulence, post-surgical scars), feet/legs (pedal pumps); techniques reduce edema, inc circ and immune cell output into lymph system, clear pathogen, and improve immune surveillance
thoracic pump v auricular pump (Galbreath Maneuver)
inc lymph drainage from head and neck; tx upper & lower RTI, CHF, asthma, COP, post-surgical edema/lymphatic congestion); hands on ribs 2-4, pt inhales by mouth and exhales passively, dr follows force of exhale, dr maintains force, pt inhales again but dr put sl resistance and maintains force during exhale, rpt 4-5x, abruptly remove hand 1/3 of last inhalation vs mandibular manipulation to open/close Eustachian tube in “pumping action” –> drain ear; tx middle ear infections; dr has 1 hand on chin (thumb and forefinger on jawbone, other hand on forehead to hold pt in place, as pt opens mouth –> dr gently moves lower jaw to the side away from ear w/ acute otitis media (AOM) and holds it there for 3-5s, releases jaw, rpt 3x
factors leading to disruption of blood flow? results?
dmg of vessel (infectious or physical processes –> chronic inflamm), removal of vessel during surgery. results in scar tissue or fibrosis reduces lymphatic flow in vessel –> buildup of lymph fluid in tissue => lymphedema; dz condition - elephantiasis, after breast surgery, ca, infections
innate non-immune cells: epithelial cells. innate immune cells: dend cells vs macrophages vs neutrophils
barrier cells. sentinel cell, APC, phagocyte vs sentinel cell, APC, phagocyte vs phagocyte
PRR
pattern recognition receptors, INNATE receptors; recognize general structures like path-assoc molec patterns (PAMP) and dmg-assoc molec patterns (DAMP); 1 receptor can recognize same PAMP and DAMP on diff pathogens –> diversity and efficiency of immune system
soluble PRR: collectins vs compliment
in plasma, ex: mannose binding lectin (MBL), PAMPs = carbs w/ terminal fructose and mannose vs in plasma, ex: C1 and C3, PAMPs = microbial surfaces
steps when ligand binds to PRR
ligand binds to PRR -> complement binds to PRR –> complement protein binds to complement receptor (CR) on phagocyte –> phagocytosis starts
Cell surface/membrane bound PRR: toll like receptors (TLR) vs c type lectin receptors (CLR)
In plasma membrane or endosomal membrane, form dimers when ligand binds (leu-rich repeats = impt for ligand binding), toll/interleukin-1 receptor domain for signaling vs “C-type” = binds carb ligand in ca2+-dependent manner, CArbohydrate Recognition Domain (CARD or CRD) for binding, binds carbs residues like mannose –> phagocytosis, cytokine production, defense against fungi, dectin
Cell surface human TLRs: TLR1 vs TLR2 vs TLR4 vs TLR5 vs TLR6
Mono/macs, DC, PMN, B cells; ligand = bacterial lipoproteins vs mono/macs, DC, PMN, mast cells; ligand = bacterial and fungal glycolipids and lipoproteins like peptidoglycan, lipoteichoic acid, lipoabarinomannan; forms heterodimer w/ TLR1 or TLR6; good for gram pos and mycobacteria infections vs mono/macs, DC, PMN, mast cells, epithelial cells; ligand = LPS (bacterial lipopolysaccharide) of gram neg bacteria; binds DAMPs vs mono/macs, DC, PMN, epithelial cells; ligand = flagellum vs mono/macs, PMN, mast cells, B cells; ligand = lipopeptides (eg. Mycobacterium, Mycoplasma)
Cytosolic PRR: TLR vs Nucleotide-binding domain Leu-Rich (NLR) protein receptors vs RIG-Like Receptors (RLR) vs Cytosolic DNA Sensors (CDS)
Some = membrane anchored (TLRs), most = free floating in cyto. All the endosomal TLRs vs NOD1 and NOD2 bind bacterial cell wall components like caspase recruitment domain, best in GI tract, activates innate immune response by cytokine production and inflammasome activation, recognizes PAMP/DAMP in cyto vs Retinoid-inducible gene; bind duplexes RNA in cyto as RNA-RNA homodimer or RNA-DNA heterodimer; for viral infection —> produces type I interferons (IFNs) —> activates innate immunity, stops viral replication in infected cells, makes neighboring cells resistant, activates DCs to start adaptive immune response vs detects 2x-stranded DNA in cyto, when activated —> type I IFNs = produced or autophagy started, sting pathway (stimulator of IFN genes)
Cytosolic PRR: endosomal TLR: TLR3 vs TLR7 vs TLR8 vs TLR9
DC, NK cells, B cells; ligand = viral dsRNA —> good for viral infections, artificial ligand/agonist = polyl:C (polyinosinic-polycytidylic acid) vs mono/macs, DCs, PMN, B cells; ligands = ssRNA —> good for viral infection, synthetic ligand/agonist = imiquimod, R848; expression = inc and induced on stimulated APCs vs mono/macs, DC, PMN, mast cells; ligand = viral ssRNA —> good for viral infection, agonist = imiquimod, R848; expression = inc and induced on stimulated APCs; not basally expressed by cells but inducable vs mono/macs, DC, PMN, NK cells, B cells; ligand = unmethylated CpG oligonucleotides (ODN) from bacteria and viruses, agonist = CpG ODN or vaccine adjuvant; can also be activated by apoptotic DNA
Inflammasome
Multi-protein complex w/ NLR –> activate caspase and active IL-1 or IL-18 –> inflammation; can be Immuno protective (infections, vaccines) or immunopathogenic (gout, mesothelioma, autoimmune dz)
endocytosis vs exocytosis
all nucleated cells taking up liquid, large polar macromolec/particles from surrounding medium; macro/micropinocytosis and phagocytosis vs export material, form of active transport
why do cells vs immune cells endocytose?
uptake nutrients or drugs, receptor downregulation vs remove pathogens or dead cells or debris, present ag, also fxns mentioned earlier
macro vs micropinocytosis
actin-mediated membrane ruffling “gulps” large vol of extracellular fluid/particle; in all euks vs cell membrane invaginates “sip” small amounts of fluid and sm particles; receptor-mediated clathrin-coated pits; cavelolin-mediated pits
phagocytosis and its stages
cells bind and engulf particles –> form vesicle => phagosome, occurs in prof phagocytes (neu, tissue-specific mono/macs, DCs) and nonprof phagocytes (eos, mast, fibroblasts, epi/endothelial cells, mesenchymal cells, immature cell types). detecting P/DAMPS, phagocyte tracks target, phagocyte binds and endocytoses target, phagosome fuses w/ lysosome => phagolysosome and degrades target
2 subsets of phagocytosis: opsonized vs nonopsonized
engulf microbes coated w/ C’/ab bind to C’/Fc receptors; fast, efficient vs engulf microbes bind to innate PRRs; slow, limited, inefficient; non-opsonic receptors: TLR, scavenger receptors on mac/DC, C-type lectins
prof phagocytes vs nonprof phagocytes
neu, tissue-specific mono/mac, DC; detect and bind PAMPs to trigger phagocytosis vs eos, mast cells, fibroblasts, epi/endothelial cells, mesenchymal cells, immature cell types; phagocytosis = not their first fxn b/c limited receptors but can be induced to do so
neutrophils
first recruited (arrive in 30min) to inflamm site and responds immediately, they don’t return to blood –> turn to pus via NETosis but can be pathogenic –> autoimmune dz, destroy bystander cells, occlude vessels; contain 2 main pop of granules: azurophilic granules - contain myeloperoxidase (MPO), proteolytic enzymes, defensins vs specific/secondary granules - contain lactoferrin; have limited PRR receptors; in acute infxns, they inc prod of colony stimulating factors to make more neutrophils (if they leave bone marrow too early => immature neutrophils –> have band nuclei –> neutrophilia w/ L shift”); do phagocytosis
mono/macs
in blood/tissue, resident macs - in tissue as sentinel cells before infxn, recruited macs - go to tissue via chemotactic gradient –> arrive 20-40hrs of infxn; secrete cytokines; APC; phagocytosis; lots of PRRs; DO BETTER AT KILLING (RESP BURST, O2 IN/DEP) as opposed to DCs
DC
immature/unactivated DC - reside in tissue as sentinel cells, do phagocytosis and macropinocytosis; mature DC - migrate to draining lymphoid organs in targeted fashion; lots of PRRs; DO BETTER AT AG PRES as opposed to macs
How can pathogens evade phagocytosis?
Avoid contact, survive in phagocyte, kill phagocyte, disrupt cell signaling
exocytosis and its 3 pathways
deliberate, well organized, active ATP dep process transporting molec to extracellular space. constitutive - in all cells to release plasma membrane protein and enzymes; regulated secretory - specific extracellular signals tell specialized cells to release neurotransmitter, hormone; lysosome-mediated secretory - phagocytes do “frustrated phagocytosis” (release lysosomal contents like ROS and proteases into extracellular environ –> tissue dmg); pathways = impt for effector fxn of mast cells and eosinophils
lysosomes
membrane-enclosed organelles that contain enzymes to break down protein, nuc acids, carbs and lipids; degrades material from outside and inside of cell; PART OF 02 IN/DEP PATHWAYS
O2-dep vs O2-indep pathways vs N2-dep pathway
neutrophil ingests material –> inc O2 consumption –> oxidative or respiratory burst mediated by NADPH oxidase –> produces O2- –> antimicrobial; NADPH oxidase exists in eosinophils > neutrophil > mono > mac; O2- = dismutated to O2 + H2O2 via superoxide dismutase; MPO = in neutrophil granules and catalyzes rxn b/w H2O2 and Cl –> hypochlorite ClO- aka bleach –> CIO- kills phagocytosed bacteria vs release granules containing proteolytic enzyme like defensins, lysozyme, cationic protein, proteases; less effective than O2-dep; lactoferrin remove essential iron from bacteria; proteases and hydrolytic enzymes digest bacterial molec; acidic pH of phagolysosome activate degradative enzyme and denature bacterial protein; electrically charged protein dmg bacterial membrane; enzymes = more stable than ROS/RNS –> active in extracellular environ vs nitric oxide NO- formed by conversion of arg + citrulline in presence of O2 catalyze by nitric oxide synthase (NOS); NO- + O2- –> peroxynitrite ONOO- via NADPH oxidase; effects of NO- production: antimicrobial, 2nd messenger, vasodilation, reduced PLT adhesion, reduced leuk trafficking
interdependent pathways w/ ROS and RNS species
primary goal: destruction of ingested microbe; initiated/upregulated by phagocytosis; affected by other immune responses like IFN gamma and TNF inducing prod of NOS; tightly regulated
respiratory burst. color on NBT?
process in PMNs and macs where O2 = consumed to degrade large particles/pathogens; challenge = generating toxic byprod b/c O2 –> O2- –> H2O2/ClO-/OH.; magnitude of response: PMN > mac»_space;> DC; insoluble blue endproduct in phagoycyte’s cyto on NBT
cytokine producers (5)
mac, DC, ILC (innate lymphoid cell), NK cell; Th cells
cytokine families (6)
o Interleukin (IL) – trigger leuk prolife, differentiation, activation
o Interferon (IFN) – interfere viral replication and mediate antiviral effector fxns
o Tumor necrosis factor (TNF) – activate early immune response
o Colony stimulating factor (CSF) – act on progenitor cell to induce prolif and differentiation on immune cells
o Growth factors – trigger cell prolif for injury repair
o Chemokines – recruit leuk to infxn/injury site
IFN alpha/beta vs IFN gamma
by virus infected cells, DC, leuk, fibroblast; interfere viral rep, induce antiviral response, make nearby cells resistant vs by NK and T cells; inc NK and T cells => pos feedback loop, inc MHC expression for ag pres, activate mac for phag
TNF
by mac, DC, mast, NK cells; synergize w/ IL1&6 –> acute inflam, cyto/chemokine prod, apop; conc-dep: high [TNF] –> dec heart contractility –> sepsis, dec anticoag –> thrombosis, or cachexia
chemokines
- Induce directed movement (chemotaxis) for migration of immune cells to injury site via spatiotemporal gradient
- Involves inc leuk adhesion for extravasation of cells
- Helps w/ homeostasis, angiogenesis, and wound healing
TGF beta
similar to IL10: dec immune response by dec ag pres, dec B/T and NK cells, inc B cell apop, inc Treg differentiation, inc igA
complement: classic vs mannose binding lectin vs alt. what do they share in common?
igG/igM gives signal –> C1q binds to Ag-Ab complex –> activates C2 and C4 to form C3 convertase –> cleaves C3 –> C5 convertase cleaves C5 –> active C5b-9 forms MAC –> lysis of cell vs MBL bind to specific carb –> C2 and C4 form C3 convertase ——> MAC vs spont cleavage of C3 in serum –> C3. C’ reactive proteins bind to C3 convertase –> cleaves C3 ———-> MAC and lysis
cells of innate vs adaptive immunity
granulocytes, macs, mast, NK, complement vs B/T cells
NK cells
kill human cells infected by virus; produce IFN gamma to activate macs; do ADCC: NK w/ Fc receptors kill cells coated w/ ab
neutropenia vs CGD vs LAD1 vs Chediak Higashi syndrome vs MPO deficiency vs NK cell deficiency vs TLR signaling defects vs Mendelian susceptibility to mycobacterial dzs vs C1 inhibitor vs IL12/IFN gamma
defect in bone marrow –> dec neu –> fever, mucosal sores; dx = leukocytosis; primary neutropenia = from bone marrow vs mutation in NADPH oxidase –> make little to no ROS for phagocytes –> recurrent bacterial and fungal infxn, perianal or oral abscess; dx = neg NBT, tx = IFN gamma w/ prophylactic abx and antifungal vs defect in CD18/beta2 integrin –> little to no adhesion/migration –> recurrent bacterial and fungal infxn vs mutation in LYST gene –> defect in making phagolysosome –> WBCs have giant granules –> recurrent pyogenic bacterial infxn vs dec phago and NETosis –> DM, Candida vs little to no NK cells vs little to no TLR, CD40, IFN type I vs caused by nontuberculous environmental mycobacteria, BCG, salmonella, and intracellular bacteria vs hereditary angioedema vs dec CD4, CD8, Th1 –> environ mycobacteria, viruses, intracellular infxn
anaphylatoxins
C5a > C3a > C4a in order of potency; induce anaphylaxis by inc inflamm, release histamine and degranulation in mast cells, inc vasopermeability
are gram neg or gram pos more sensitive to complement?
gram neg b/c MAC can penetrate gram neg outer membrane than gram pos membrane
neu respond to ___? mac respond to ___?
IL17. IFN gamma
CD18 + CD11a =
LFA-1
What’s the most common deficiency of complement?
C2 deficiency
adjuvant
a factor that helps ab bind to ag better, usually in vaccines
where are mast cells found?
tissue
which complement receptor is on RBC vs B cells?
CR1 vs CR2
