Week 10 and 11 Flashcards
True or false… CD8 T cells have repeated activity until inhibited
True
True or false… some CD4 T cells have direct effector function and can kill
True
Which T cell kills virus-infected cells?
CD8 cytotoxic T cells
Which T cell activates infected macrophages and provides help to B cells for antibody production? They target microbes that persist in macrophage vesicles and extracellular bacteria
CD4 Th1 cells
Which T cells enhance neutrophil response and promote barrier integrity? They target klebsiella pneumoniae and fungi
CD4 Th17 cells
What T cells provide help to B cells for antibody production, especially isotype switching to IgE? They target helminths and parasites.
CD4 Th2 cells
Which T cells help B cells with isotype switching and antibody production?
TfH cells
Which T cells function to suppress other T cell responses?
Treg
True or false… CD8 T cells do not form memory cells
False, they do
___ are the most common T cell activator. They must be activated. Presentation occurs in the ___
Dendritic cells
Secondary lymphoid organs
How do dendritic cells uptake antigen? Describe their MHC expression and co-stimulation delivery.
Antigen uptake - macrophinocytosis and phagocytosis
MHC expression - low on immature dendritic cells, high on dendritic cells in lymphoid tissues
Co stimulation delivery - constitutive by mature, nonphagocytic lymphoid dendritic cells.
Dendritic cells mature through ______. Immature dendritic cells in the peripheral tissues encounter pathogens and are activated by ____. ___ signaling induces ___ and enhances processing of pathogen-derived antigens. ____ directs DC migration into lymphoid tissues and augments expression of co-stimulatory molecules and MHC molecules. The mature DC in T cell zone primes ____.
Antigen activation
PAMPS
TLR
CCR7
CCR7
Naive T cells
Antigen presenting cells distribute differently in lymph nodes. Describe where the different cells are found.
DCs - T cell areas
Macrophages - all areas
B cells - B cell areas
True or false… cross presentation of antigen via MHC 1 and MHC 2 is critical for CD8 T cell activation
True
Circulating naive T cells are exposed to antigen in _____. the naive T cells can get there by two routes. What are they?
Lymph nodes (they travel from node to node to survey lots of antigen)
Blood
Afferent lymph coming from an upstream lymph node
T cell activation requires three signals. What are they and what do they cause?
T cell receptor - activation
Co-stimulatory molecules - survival signal
Cytokines - differentiation, propagation
Co-stimulatory signals are required for T cell activation. ___ on APCs bind to ____ on T cells.
B7
CD28
(This gives a survival signal)
Which cytokine involved in T cell activation gives a propagation/clonal expansion signal?
IL-2
Naive T cell TCR activation in the absence of co-stimulation leads to ___
Anergy
Activation of T cells causes changes. Name 5 potential changes
Differentiation
Clonal expansion
Changes in surface protein expression
Migration to target tissues (lymph nodes or sites of infection/damage)
Effector functions
Resting T cells express a _____-affinity IL-2 receptor. Activated T cells express a ___-affinity IL-2 receptor. IL-2 signals in an ____ fashion.
Moderate
High
Autocrine
____ inhibits continued T cell activation and proliferation. Describe how. Why is this important?
CTLA-4
CTLA-4 (on T cell) binds B7 (on APC) more strongly than CD28. This will deliver inhibitory signals.
T cells dont die after their effector functions, thus must be inhibited. Binding an APC after activation will lead to inhibition.
What are the two ways naive CD8 T cells can be activated?
Dendritic cell sends strong enough signal to induce the CD8 T cell to produce IL-2, to cause it to proliferate and differentiate. Note that costimulatory receptors CD28 and B7 are necessary
Dendritic cells can activate CD4 T cells which will produce IL-2 to cause the CD8 T cell to become activated.
True or false… secondarysignals are necessary for CD8 T cell activation but not for active CD8 T cells to kill
True
The only cells that kill via perforin and granzyme are ___ and ___ cells
NK
CD8 T cells
Th1 cells are involved in ____ immunity whereas Th2 cells are involved in ___ immunity
Cellular
Humoral
Differentiation of T helper cells involves what three things?
Cytokine induction
Transcription factors
Effector cytokines
What two cytokines induce differentiation into Th1 cells? What is the function of these cells?
IL-12
IFN-gamma
Function: activate macrophages
What three cytokines induce differentiation into Th17 cells? What is the function of these cells?
IL-16
TGF-beta
IL-23
Function: enhance neutrophil response
What cytokine induces differentiation into Th2 cells? What is the function of these cells?
IL-4
Activate cellular and antibody response to parasites
What two cytokines induce the differentiation into TFH cells? What are these cells’ function?
IL-6
IL-21
Activate B cells. Maturation of antibody response.
What cytokine induces differentiation into Treg cells? What is a function of these cells?
TGF-beta
Function: suppress other effector T cell function
Th1 cells activate macrophages. What do activated macrophages do? (4 things)
Express co-signaling ligands
Kill intracellular pathogens
Release cytokines and antimicrobial effectors
Present antigen
____ T cells form granulomas when pathogen cannot be cleared? What are granulomas?
Th1
A compact aggregate of leukocytes that sequester pathogen. Involved in chronic inflammation, may be infectious or no infectious agents, several types of granulomas
True or false… pyrogenic granulomas are true granulomas
False
True or false… Th1 cytokines enhance the induced immune response to increase inflammation
True
How do Th2 cells promote tissue protection and repair?
Recruitment and activation of mast cells and eosinophils
B cell activation (different than Th1)
Cytokine release
True or false… TFH cells activate B cells and induce class switching
True
True or false… Treg cells suppresses other T cells, but must be interacting with the same APC in order to do so
True
What four things do Treg cells do?
Prevent T cell activation in the lymph node
Stops adaptive immune response
Prevents autoimmunity
-TGF beta differentiation
Describe how Th17 and Treg cells regulate mucosal inflammation
Th17 is involved in tissue repairs, neutrophil recruitment, antimicrobial peptide production
Treg cells inhibit mucosal inflammation
Persistent Th17 function will result in autoimmunity
What is hypertrophy?
Increase in cell size
Atrophy - decrease in cell size
What is hyperplasia?
Increase in cell number
What is metaplasia?
Replacement of one type of cell with another type
What is dysplasia?
Disordered growth
Describe how hypertrophy in the heart can result in ischemia?
Blood vessels are more widely dispersed in the heart, limiting the dispersement of blood flow
Atrophy can be caused by…
Lack of hormonal signals Loss of innervation Lack of use Loss of blood supply Starvation Individual cell death
Note that dementia is atrophy in the brain
What is cachexia?
Fatty atrophy
(Starvation)
Fatal at 68% of normal body weight
Where is a common place where hyperplasia occurs?
Prostate
(Also liver, kidney, breast, endometrium)
Note that hyperplasia and hypertrophy often occurs together
Name three examples of metaplasia
Smoker’s airways
Cervix
Barrett’s esophagus
Define dysplasia
Disordered hyperplasia without maturation
Preneoplastic
Name three examples of dysplasia
Uterine cervix
Bowel in inflammatory bowel disease
Esophagus with Barrett’s
What types of cells are most prone to injury? Give examples
High metabolic activity (cardiac myocytes, renal tubular cells, hepatocytes)
Rapidly proliferating (testicular germ cells, intestinal epithelium, hematopoietic cells)
What are the two degrees of cell injury? Define them and give some examples
Reversible - damage not enough to kill cell (toxic liver injury, severe exercise, hypoxia (loss of ATP), anaerobic glycolysis with lactate and acidosis)
Irreversible - apoptosis or necrosis. More severe damage involving holes in membranes, long calcium influx, mitochondria loss
True or false… apoptosis is energy-requiring programmed cell death that usually only involves one cell at a time and does not involve inflammation
True
How does apoptosis work?
Caspase cascade is initiated because cytochrome C is released from mitochondria. Cytochrome C activates P53 which will then go to activate the caspase cascade.
What is the TdT stain used for?
Identifying DNA
True or false… apoptosis results in a shriveled cell with a pyknotic nucleus, with peripheral clumping of chromatin
True
What are the early events of necrosis?
Cell membrane disruption, calcium signal depletion, loss of ATP (loss of ions will cause cells to swell)
Cell contents leak and cause acute inflammation.
What is gangrene?
Necrosis of whole anatomical areas
Describe the cellular changes in necrosis
Cytoplasm is deeper red (loss of mRNA). Cells swell. Nuclei not basophilic. Hemorrhage, acute inflammation, then chronic inflammation and fibrosis
What are the three different types of nuclear changes in cell death? Describe them
Nuclear pyknosis - shriveled and dark
Karyolysis - digested, pale nucleus
Karyorrhexis - nuclear fragmentation
Name 6 different patterns of necrosis. Describe them
Coagulative - with ischemia - makes infarct
Liquefactive - loss of substance - in brain or lung abscess
Fat necrosis - necrosis in fat
Caseous necrosis - necrotizing granulomas - combination of liquefactive and coagulative fungal TB infection
Gangrenous necrosis - necrosis of anatomic area
Fibrinoid necrosis
Coagulative necrosis is common in the ___
Heart
Forms a scar or thin area - leads to ventricular anuersym
-note that in the last stage of coagulative necrosis, it is fibrous
Name some differences between necrosis and apoptosis
Necrosis: Injury-induced uncoordinated death Early cell membrane disruption Cell swelling Cells die in large groups Acute inflammation Always pathological
Apoptosis: Programmed cell death Activation of caspases No swelling Usually one cell at a time No inflammation involved Can be a normal phenomenon
What are three brown storage products?
Lipofuscin - degraded lipid lysosomes.
Bilirubin - hemoglobin breakdown product
Hemosiderin - iron containing pigment
What is hemosiderin?
Hemochromatosis. Hereditary iron storage disease
What is anthracosis?
Carbon pigment
Mostly in or near lungs
(Coal worker’s lung. “I have the black cough. *cough cough” - zoolander)
What is the role of macrophages, platelets, lymphocytes, and other blood cells in tissue healing?
Make proper cytokines to promote healing (TGF -beta)
Matrix metalloproteinases
Macrophages phagocytose and eliminate foreign material
What are the roles of fibroblasts in tissue healing?
Make collagen and rest of extracellular matrix
Contractile myofibroblasts shrink wound
What are the roles of endothelial and epithelial cells in tissue healing?
Endothelial cells - make new blood vessels
Epithelial cells - migrate and proliferate to cover wound or regenerate organ
What are the steps in tissue healing?
Inflammatory response and clot formation
Fibroblasts, endothelial cells, and others migrate to clot and form granulation tissue and new epithelium
Granulation tissue matures forming a scar with mature vessels and abundant collagen (10% strength at week 1)
Scar matures - collagen remodeling and loss of excess blood vessels (occurs in months to years. ~80% of normal strength at 3 months
Repair after an inflammatory process may form a cavity in the ___ or in the ___. In other locations, it may form a scar because…
Brain
Lung
The damage is too severe for simple regeneration
Typically in tissue healing, ~____% of strength is achieved in the first week. After about three months ~___% of strength is achieved.
10
70-80
What happens if tissue repair is too much or too little?
Too much - hypertrophic scar formation, keloid formation (extends beyond site of injury), Desmond/fibromatosis ( a benign neoplasm)
Too little - infection or mechanical stress
What are some things that can lead to too little tissue healing?
Steroids, poor perfusion, diabetes, malnutrition (especially vitamin C)
What are the three patterns of inflammation? Describe them.
Acute - begins almost immediatly, lasts minutes to days. Includes neutrophils, vessels, mast cells
Chronic - begins at least 6 hours (to days) later. Includes lymphocytes, macrophages and plasma cells
Granulomatous - variant of chronic inflammation. Aggregates of epithelium histiocytes/macrophages, giant cells, lymphocytes
Note that mixes of all three of these can occur
What are the five clinical signs of inflammation?
Rubor - redness Tumor - swelling Calor - warmth Dolor - pain Loss of function
What causes the pain in inflammation?
PgE2
Bradykinin
Substance p
What is exudate
Fluid coming from vessels into the site of inflammation. Fluid rich in protein (such as clotting factors, Ig, complement, etc.)
Which has a lower specific gravity, exudate or transudate?
Transudate (Lower specific gravity, protein, and LDH than exudate)
If you have leukocytosis with neutrophilia, what should you suspect?
Bacterial infection
If you have leukocytosis with lymphocytosis, what should you suspect?
Viral infection
If you have eosinophilia, what should you suspect?
Parasitic infection, autoimmune, or allergic
Causes a type 2 response
How many mm of RBCs sink in one hour in a vertical capillary tube, normally?
less than 20mm
What are the laboratory signs of inflammation?
Increased sedimentation rate
Because…
Increased plasma fibrinogen, red cells clump and sink faster
Fibrinogen is an acute phase reactant made in liver
Nonspecific disease indicator
Index of activty of a known disease
What are some other acute phase reactants? Describe them.
CRP - c reactive protein. Becomes abnormal faster than sedimentation rate. Can increase up to 1000 fold. Mild increases in otherwise healthy subjects indicate risk of atherosclerosis
Procalcitonin - specific for bacterial infection. Can help determine if antibiotics are needed
SAA (serum amyloid A protein)
Ceruloplasmin (copper binding protein)
What are the cells involved in chronic inflammation?
Lymphocytes (sometimes plasma cells too)
Macrophages
Fibroblasts and new vessels in tissue repair
Giant cells are involved with…
TB granuloma
True or false… granulomas can calcify
True
Calcification often develops in areas of necrosis
What is a type two immune response?
A response that involves Th2 lymphocytes, eosinophils, mast cells and basophils
This is a reaction to parasites, allergies, and allergic-like diseases
True or false… basophils are the rarest type of blood cell. Like mast cells, they are coated with IgE, and are involved in allergies and responses to parasitic infection
True
Is appendicitis acute inflammation or chronic inflammation?
Acute
True or false… asthma is an allergic-like disease involving a type 2 response
True
What is the definition of SIRS in kids?
Core temp >38.5 or <36C
Tachycardia (> 2 SD above normal for age) or bradycardia (<10th percentile for age)
Mean respiratory rate > 2 SD above normal for age
High or low WBC, or >10% immature neutrophils
How is T cell function different in infants?
Anti-inflammatory cytokine production diminished
Less Immunoglobulin synthesis (B cells)
Neutrophils differ from adult functional capacity
At what months of life are children at an increased risk for serious bacterial infection?
0-3 months
What is an SBI?
Serious bacterial infection
Such as…
Meningitis, bacteremia, UTI, pneumonia, osteomyelitis,
____ accounts for most of the SBIs infants within their first 3 months of life
UTIs
What are the three most common bacterial pathogens of neonatal SBI?
Group B streptococcus (S. Agalactiae)
E. Coli (and other gram negative enteric bugs)
Listeria monocytogenes
What are the most common viral causes of neonatal sepsis?
HSV 1 and 2
VZV
Enteroviruses
Influenza
Adenoviruses
RSV
True or false group B strep is alpha hemolytic and are common colonizers of the pharynx
False.. it is beta hemolytic and they are not common colonizers of pharynx (they colonize the GI and GU tracts)
What are some important virulence factors of group B strep?
Pilus-like structures
Alpha C surface protein
Beta-hemolysis/cytolysin
Capsular polysaccharides
What are the clinical manifestations of GBS infection? What is the onset for early-onset, late-onset, late, late-onset?
Early-onset = <7days
Late-onset = 7-89 days
Late,late-onset = 90+ days
Early-onset GBS infection is commonly associated with maternal OB complications, and has the highest morality rate of 5-10%. What are some symptoms of this disease?
Respiratory distress, poor feeding, bradycardia, lethargy
What is the number one cause of early neonatal morbidity and mortality in the US?
GBS
Universal screening for GBS occurs in all pregnant women in __ - ___ weeks gestation using a vaginal-rectal specimen.
35-37
What is the drug of choice for treating neonatal GBS?
Penicillin
True or false… intrapartum antibiotic prophylaxis (IAP) only reduces early-onset GBS
True
True or false… listeria monocytogenes has incomplete beta-hemolysis, grows well at refrigerator temps, and has polar flagella, and is a gram positive rod
True
True or false… it is ok to narrow your antibiotics based on your gram stain
False
How is early-onset sepsis or late-onset meningitis acquired regarding listeria monocytogenes?
Early-onset: aquired in utero. Associated with prematurity
Late-onset meningitis: onset about 2 weeks of age, acquired via birth canal
What is the drug of choice for treating neonatal listeria infection? Do cephalosporins work well?
Ampicillin (plus gentamicin)
Cephalosporins dont have activity!!!
Think ____ with E.coli sepsis
Galactosemia
What is the best choice for empiric antimicrobial therapy for a febrile neonate?
Ampicillin, cefotoxamine, gentamycin
Also note that you use acyclovir for HSV
What is the number one case of neonatal conjunctivitis?
Chemical irritation from silver nitrate
True or false… chlamydia trachomonas is the number one reportable STD in the US. 50% of infants are born to infected mothers. They will either develop conjunctivitis or pneumonia
True
What is the treatment give to prevent neonatal conjunctivitis?
Erythromycin (taken orally, not ocularly!!!)
