week 4 Flashcards
signs and symptoms of strep throat:
-begins quickly
-pain with swallowing
-fever
-red and swollen tonsils, sometimes with white patches or streaks of pus
-tiny red spots on roof of mouth
-swollen lymph nodes (anterior neck)
symptoms to rule out strep throat:
-cough
-runny nose
-hoarseness
-conjuntivitis (viral)
what is the centor score?
the probability that the pharyngitis is strep
criteria:
-age (3-14 most common)
-exudate or swelling
-tender/swollen anterior cervical lymph nodes
-temp
-cough
what bacteria causes group A strep?
streptococcal pyogenes
gram + bacteria
what are the characteristics of a scarlet fever rash?
-“sandpaper rash”
-small, numerous papular elevations
-blanches with pressure
-starts on trunk and extends outwards
what is the treatment for BACTERIAL strep?
-penicillin (x10 day course)
possible etiologies of a persistent strep?
GERD
abscess
malignancy
tonsillitis
allergies
appearance of simple squamous:
-oval nuclei parallel to the basal lamina
-flattened, single layer of cells
lining blood vessel or lymph vessel: endothelium
lining a body cavity: mesothelium
appearance of simple cuboidal:
-square cells
-single layer
-round nuclei
-little cytoplasm distributed evenly around nucleus
appearance of simple columnar:
rectangular cells
single layer
usually oval nuclei (not always)
usually nuclei are towards the basal lamina (not always)
may have migrating immune cells
appearance of stratified squamous:
multiple layers
top layer flattened
bottom layer can be cuboidal or columnar in shape
surface modifications
-non-keratinized (usually; means nuclei in the top layer)
-keratinized
-parakeratinized
keratin vs. parakeratin
keratin does not have nuclei in the top layer; parakeratin looks like a keratin layer but nuclei ARE present
where are stratified columnar and cuboidal cells found?
mainly in the ducts of larger glands
what type of epithelium is respiratory epithelium?
pseudo-stratified columnar
cilia
goblet cells present
what are stereocilia?
long microvili that clump together (paintbrush)
made of actin, therefore are NOT true cilia
what are the features of transitional epithelium?
balloon or umbrella cells (larger cells) on the surface
type of pseudo-stratified epithelium because all cells touch the basal lamina but not all cells reach surface (picture says otherwise…)
commonly seen in uroepithelium
-these cells can stretch
-important with the expanding bladder w/ urine
what are discoidal vesicles?
-part of the transitional epithelium
-not actually vesicles-membrane infoldings that are cut to look like vesicles
-artifact (artificial structure that is present from when the slide was cut/prepared?)
-allow for the expansion of the epithelium when the bladder fills with urine
contrast the appearance of microvili on a TEM and a LM?
TEM: appear fingerlike, can distinguish them, can see linear features inside (microfilaments)
LM: cannot visualize them as separate structures, appear as a dense line
what are microvili composed of?
microfilament core (actin)
what are cilia composed of?
core of protein tubulin in a 9+2 arrangement (motor proteins move the cilia)
basal bodies (base of the microtubule arrangement) are composed of 9 triplets of microtubules
what are the permanent type of cell-cell junctions?
-zona occuldens (tight junctions)
-zona adherens (belt desmosome)
-macula adherens (spot desmosomes)
-zonula communicantes (gap junction)
transcellular vs paracellular
transcellular: movement through the cytoplasm
(transporters, channels)
paracellular: in between two cells, prevents movement through cells
(tight junctions, zona occuldens; made of protein strands, the more protein strands, the tighter the junction)
what proteins are involved in zonula occuldens (tight junctions)?
Claudin and Occuldin
Claudin is the protein which confers the barrier properties.
what proteins are involved in the structure of the zonula adherans?
-interacts with the microfilaments of the terminal web (belt around the cell)
-receptors on either cell are cadherins (desmocollins, desmogleins)
what are junctional complexes?
symmetrical structures consisting of 3 components:
-zonula occuldens (tight junction)
-zonula adherans (belt desmosome)
-macula adherans (spot desmosome)
what proteins compose a gap junction (zonula communicantes)?
x6 connexins form a connexon with a gap in the middle
the connexon of one cell lines up with the connexon of another cell so that the holes line up
a gap junction consists of numerous connexons
allows for cell communication (e.g. electrical signal shared between cardiac cells)
what are the 2 layers of the basal lamina?
lamina rara (laminin, entactin, perlecan)
lamina densa (type IV collagen)
what are the 2 possibilities for having a basement membrane?
AKA a basal lamina that is thick enough to visualize with LM
1) cells have a basal lamina and a reticular lamina (reticular fibers made of collagen III)
2) cells have a fused basal lamina (cells pointing away from each other, each have a lamina rara with their lamina densas fused together)
describe the function and structure of hemidesmosomes:
function: adhere epithelial cells to the basal lamina
interact intracellularly with intermediate fibers
interact extracellularly with the matrix of the basal lamina
receptors: integrins
disruption: causes the epithelium to pull away (e.g. blisters)
what is the function of focal contacts?
adhere the cell to the proteins of the extracellular matrix
integrins=receptors of the ECM
ultimately connect the cell to the actin cystoskeleton
list the types of basal cell: matrix receptors?
-integrins: heterodimers (alpha and beta subunits)
-intergral membrane proteoglycans (e.g. syndecan)
-glyoproteins (e.g. CD44)
how are glands formed? how are the two kinds different from each other?
ORIGIN: epithelial, formed by the invagination of the surface epithelium
EXOCRINE: retain a connection to the surface, forming a duct
ENDOCRINE: lose the connection and secrete into the blood supply, endocrine
what type of glandular cell is a goblet cell?
exocrine (duct)
secretes mucus
found in the respiratory tract, secretes mucus that is moved by cilia
contrast the cellular appearances of mucous cells and serous cells:
mucous cells
-flattened nuclei
-cells appear washed out (mucous lost during processing)
-secrete mucous
serous cells
-rounded nuclei
-stains well
-secrete proteins
what are the 3 types of exocrine secretion?
merocrine
-exocytosis
-e.g. pancreas
apocrine
-piece of cell pinches off
-e.g. milk secretions
holocrine
-whole cell becomes the secretion
-e.g. sebaceous glands
name the 3 types of tonsils with location, cell type, distinguishing characteristics
PALATINE
-oropharynx
-paired
-stratified squamous with several crypts (also s. squamous)
PHARYNGEAL
-in the nasopharynx
-single
-pseudo-stratified columnar with cilia and goblet cells (AKA respiratory epi)
-no crypts but small folds
-adenoid (can become inflamed and hypertrophied)
LINGUAL
-base of the tongue
-numerous
-single crypt
-stratified squamous
what do the following factors cause?
histamine
bradykinin
prostaglandins
nitric oxide
-arteriolar dilation
-hyperemia (redness)
-slowing/stasis of the blood
-fluid extravasation into tissues (swelling)
what responses are the following factors responsible for?
complement C5a (anaphylotoxin/chemotaxin?)
leukotriene B4
chemokines
bacterial products
neutrophil activation
rolling and adhesion
emigration to tissue
chemotaxis
what responses are the following factors responsible for?
serotonin
histamine
C3a, C5a
bradykinin
leukotrienes
endothelial activation
adhesion molecules and increased permeability
plasma proteins “leak” into tissues
what are the 3 components of acute inflammatory exudates?
- neutrophils migrating in response to chemotaxin signals (complement component C5a and LTB4)
- spaces in the tissue that indicate fluid accumulation (edema)
- several other plasma proteins are found in the tissue space - evidenced by fibrin threads (from plasma fibrinogen)
what are the 5 cardinal signs of inflammation?
-rubor (redness, hyperemia, vasodilation)
-tumor (swelling)
-calor (heat, due to hyperemia (vasodilation)
-dolor (pain due to bradykinin and PGE2)
-functio laesa (loss of function due to combined effects)
what suffix indicates inflammation?
-itis
exceptions: pleurisy (inflammation of the pleura) and cellulitis (infection that causes inflammation)
what bacteria cause purulent inflammation?
pyogenic bacteria
staphylococci
strep pyogenes
e. coli
Neisseria spp. (N. meningitidis, N. gonorrhea)
what stage of inflammation is characterized by pus formation?
acute suppurative inflammation
clinical examples of purulent inflammation:
-lobar PNA
-bronchopneumonia
-acute appendicitis
-acute suppurative tonsillitis
contrast suppurative acute inflammation vs fibrinous acute inflammation:
SUPPURATIVE - high # of neutrophils, more cells than fibrin and fluid
FIBRINOUS - more fibrin compared to cells and tissue fluid
where is fibrinous inflammation most common?
in serous tissues such as the pericardium and the pleura
how does acute pericarditis occur?
inflammation causes a fibrin coat to form on top of the visceral layer of the serous pericardium
when is acute serous inflammation usually seen (what injuries and tissue types)?
burn injuries and in serous membrane lined cavities (e.g. pleural effusion)
what is a granuloma?
inflammation found in many diseases
characterized by the presence of giant cells
form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate them
giant cells = macrophages fused together to form a multi nucleated cell
what are the 2 types of giant cells?
Langhan’s giant cells
-immunological cause
-e.g. infectious organisms such as bacteria and fungi
Foreign Body giant cells
-non immunological cause
e.g. glass, splinters, silica, asbestos etc.
compare and contrast the appearance of Langhan’s and Foreign Body giant cells:
although both are comprised of several macrophages fused together, the nuclei arrangement differ.
Langhan’s - nuclei form a horseshoe shape and somewhat resemble one next to the other
FB cells - the nuclei are distributed randomly, no horseshoe shape
how can streptococcus be characterized?
gram (+) bacteria
cocci arranged in chains (or pairs)
non-motile
catalase negative (distinguishes from staph)
non-spore forming
most are facultative anaerobes (some obligate)
what 3 methods are used to classify each species within the streptococcal genus?
- hemolytic patterns
- Lancefield groupings
- biochemical/physiological properties on other tests
what streptococcal species are capable of alpha hemolysis?
S mutans
S mitis
S pneumoniae
what streptococcal species are capable of beta hemolysis?
S agalactiae
S pyogenes
what streptococcal species are associated with gamma hemolysis?
nonenterococcus (S bovis)
enterococcus (E faecium, E faecalis)
what is the hemolytic patterns test used for?
distinguishes strep bacteria based on how well they can lyse RBCs in a blood agar
alpha: partial
beta: full
gamma: none
how is the serologic properties test used to distinguish strep?
-divide into groups based on the antibodies that recognize surface antigens (Lancefield groups)
-based on antigenic differences in cell wall carbs (group A - V), cell wall pili associated protein, and polysaccharide capsule group B (GBS)
how is the bacitracin sensitivity test used?
-divides B hemolysis groups into groups A and B
-bacitracin is an Abx that interferes with peptidoglycan synthesis
group A - inhibited (S agalactiae)
group B - not inhibited (S pyogenes)
B-BRAS
how is the optochin test used?
-distinguishes S pneumoniae from other alpha hemolytics
-optochin inhibits its growth
“overpass: OVRPS”
viridians - resistant
pneumoniae - sensitive
explain how the bile sensitivity test is used?
-another test that distinguishes S pneumoniae from other alpha hemolytics
-S pneumoniae is bile soluble
-viridians are bile insoluble
explain how the camp test is used:
-to distinguish S agalactiae from other B hemolytics
-releases CAMP factor
-not fully B hemolytic on its own but the CAMP factor helps enlarge its zone of hemolysis
-forms a characteristic arrow shape
S agalactiae colonization site:
vagina
S gallolyticus colonization site:
gut
S pneumoniae colonization site:
upper respiratory tract
S pyogenes colonization site:
throat, skin
Viridians group streptococci colonization site:
oral cavity
what are the 6 steps of a viral infection?
- attachment
- penetration
- uncoating
- replication
- assembly
- release
where do DNA viruses replicate?
in the host nucleus, using the host’s machinery
exception: pox viruses
where do RNA viruses replicate?
in the host’s cytoplasm, using its own machinery and the host’s ribosomes
exception: influenza virus which replicates in the nucleus
what is the most common cause of viral pharyngitis?
adenovirus
what is the most common cause of bacterial pharyngitis?
group A strep - S pyogenes
what is the most common cause of fungal pharyngitis?
candida albicans
term for “pain with swallowing”
odynophagia
describe the process for CD4 activation:
- TCR binds to the antigen peptide presented by the MHC II molecule
- co-receptor CD4 binds directly to MHC II
- co-stimulator B7 (DC) binds to CD28 (CD4)
- TCR and co-receptors move to the center of the TCR base to form a ring “immune synapse”
- tyrosine kinase (Lyc) of CD4 co-receptor phosphorylates CD3 and zeta
- activates transcription factors NF-kB and NFAT
- increases IL-2 and IL-2Ra expression
- autocrine stimulation
- cell proliferation
in what x2 ways can helper T cells help CD8 cells during weak immune responses:
-directly secrete IL-2 that acts directly on the CD8 cells
-indirectly by activating more DCs to increase the expression of co-stimulator B7, therefore resulting in more DCs interacting with CD8s
in what ways is CD8 activation different from CD4 activation?
- cross presentation - CD8 T cells can also be activated by the presentation of extracellular antigens by dendritic cells on MHC I (instead of MHC II)
- CD8 may require help from CD4s if the immune response is weak and there isn’t sufficient IL-2 being produced
what are the 3 major subsets CD4 cells and what kinds of pathogens do they respond to?
Th1 - intracellular pathogens
Th2 - helminths, injury
Th17 - extracellular pathogens
what cytokines differentiate a CD4 cell into Th1?
IL-12 and TFN gamma
what ligand does a Th1 cell express on its surface once it makes physical contact with the macrophage?
CD40
what cytokine does Th1 release once it binds to the CD40 receptor on macrophage?
IFN gamma
what cytokines do Th2 cells respond to?
IL-4 and IL-13
what cytokines do Th2 cells secrete in response to IL-13 and IL-4?
IL-4, IL-5, IL-13
what cytokines induce the differentiation/proliferation of Th17 cells?
IL-1, IL-6, IL-23, TGF-beta
what cytokines do Th17 cells secrete? What are the functions?
IL-17 - stimulate the recruitment of neutrophils and monocytes
IL-22 - increase the barrier integrity of the epithelial cells
both 17 and 22 - produce antimicrobial peptides
what type of antigens do T independent reactions detect?
non-peptide antigens
(i.e. polysaccharides, nucleic acids, lipids)
what type of B cells are involved with T independent reactions?
marginal zone B cells (B-7 cells)
what type of antigens do T dependent B cells detect?
peptide antigens only
what is the result of T dependent reactions?
-isotope switching
-affinity maturation
-long lived plasma cells and memory B cells
-the presence of helper T cells that can react with B cells that are specific for the same antigen
what is the result of T independent reactions?
-mainly IgM antibodies
-low affinity antibodies
-short lived plasma cells
-transient responses
what is the process for B cells recognizing antigens? (recognition/activation phase)
- B cell antigen receptors cross-linked by antibody
- Ig-alpha and Ig-beta are phosphorylated
- other proteins get involved - series of intermediates
- activation of transcription factors Myc, NFAT, NF-kB, Ap-1
- increase of gene expression for proteins that are involved with B cell survival, proliferation/differentiation
what transcription factors are released by B cells during the activation phase?
Myc, NFAT, NF-kB, and AP-1
what is the post activation fate for T independent reactions?
-extensive cross-linking of BCRs due to multivalent antigens (i.e. repeating sugar units of polysaccharides)
-stimulates proliferation/differentiation without T cell help
-activated B cells synthesize IgM (may secrete some)
-early phase of humoral immune response
this response is enhanced when:
-antigens are multivalent
-antigen activates complement and innate receptors strongly
what is the post activation fate of T dependent reactions?
-interactions of T and B cells
-B and T cells specific for an antigen come together physically in the secondary lymphoid organ
RESULTS:
-increased survival, proliferation
-interaction with helper T cells
-responsiveness to cytokines
-increased expression of CCR7 - migration from the follicle to the T cell zone (where they meet the T cells)
-generation of plasma cells - Ig secretion
what x2 things do T cells use to promote B cell proliferation and differentiation?
-CD40 ligand (CD40L)
-cytokines
B cells are activated by CD40L engagement and cytokines
where does the initial T-B cell interaction take place?
in the T cell zone (outside of the follicle)
contrast primary and secondary follicles:
primary follicles do not have a germinal center
secondary follicles DO have germinal centers
what processes occur in the dark zone of the follicle?
B cell proliferation, somatic hypermutation
what processes occur in the light zone of the follicle?
isotope switching, affinity maturation, generation of plasma/memory cells
IgM effector function:
complement activation of classical pathway
M for Mozart, a classical composer
effector function of IgG:
recognize extracellular stages of most bacteria and viruses
coats/opsonizes microbes for phaGocytosis
transfer of neonatal antibodies from mother to fetus
IgE effector function:
elimination of helminths (too large for phagocytosis)
recognized by eosinophils, basophils, and mast cells
IgA effector function:
mucosAl immunity
IgD effector function:
signals that B cells are mature, ready to depart the bone marrow into circulation in search of its antigen
what is the process for isotope switching?
the constant region of IgM/IgD is switched for another antibody type, but antigen specificity (VDJ) remains UNCHANGED
-Tfc cells determine which isotope will be made
-induced by CD40L mediated signals and cytokines
-AID enzyme takes the mu heavy chain and moves it downstream to another constant chain region
(gene region is consistent with antibody name, e.g. alpha region - IgA)
what is the purpose of somatic hypermutation?
high frequency point mutations in Ig variable genes
-mediated by AID
-results in B cell clones with varying affinities for its antigen
-occurs in the dark zone
what is affinity maturation?
follicular dendritic cells display antigens to B cells
-successful B cells (bind antigen tightly) - survive
-unsuccessful (poor binding) - die
“survival of the fittest”
what are the 2 fates for successful B cells (passed through affinity maturation)?
Plasma Cells - will secrete antibodies, long lived
Memory B cells - do not secrete antibodies, circulate in the blood, mucosa, and tissues and wait for a second attack, can last a lifetime
what are the 5 effector functions of antibodies?
- neutralization of microbes and microbial toxins (all isotypes)
- opsonization for phagocytosis (IgG)
- antibody dependent cellular cytotoxicity (IgG, natural killers)
- recruitment of eosinophils, basophils, and mast cells (IgE)
- complement activation - classical pathway (IgM, IgG)
contrast bacteriostatic and bactericidal drugs:
bacteriostatic: stop bacterial growth and allow the host immune system to kill the organism, it itself does not decrease bacteria
bactericidal: kills the organism itself, superimposes the effect of the host’s defense, decrease in bacteria graphically
**bactericidal drugs are important for severe infections, necessary in immunocompromised patients
what enzyme do B-lactam antibiotics target?
-transpeptidase (PBP)
-blocks peptidoglycan cross-linking (cell wall formation)
-causes cell lysis
what are penicillin binding proteins (PBPs)?
-cell wall synthesizing enzymes
-binding sites for B-lactam antibiotics
-PBPs have varying affinities for B-lactam antibiotics
what is the function of Murein (peptidoglycan) hydrolases?
they are autolysins that degrade the cell wall, creating weak points through which the cell membrane can extrude, eventually rupturing and killing the cell
contrast gram (+) and gram (-) defenses against B-lactams:
gram +
-outer envelope composed of peptidoglycan, capsular proteins, and carbohydrates
-only have the one plasma membrane
-does not present a significant barrier to the Abx
gram -
outer envelope is a second membrane that is covalently linked to the peptidoglycan layer by lipoprotein bridges
-this outer membrane is a physical barrier to penetration
contrast the synthesis and dispersal of B lactamase in gram positive and negative bacteria:
gram +
-produced in large amounts but are released in the surrounding medium
-able to diffuse away
-relatively high substrate affinity
-inducible
gram -
-released in small amounts
-retained in the periplasmic space between the cytoplasmic and outer membranes (unable to diffuse away)
**therefore, antibiotics that traverses the porin pores of the outer membrane will encounter a B lactamase in the enclosed environment before it reaches the PBP (effective!)
what are the 3 inhibitors of B lactamase and how do they function?
-clavulanate
-sulbactam
-tazobactam
possess the B lactam structure which make them substrates for B lactamases
irreversibly inhibit B lactamase enzymes
serve as a diversion so that more antibiotic can reach PBPs
the inhibitors in themselves do not possess antimicrobial affects but when they are combined with penicillin = SYNERGISTS/BACTERICIDAL EFFECT
how do macrolides exert a bacteriostatic effect?
bind to the 50s subunit and prevent bacterial protein synthesis
mechanisms of resistance against macrolides:
- drug efflux by an active pump mechanism
- production of methylase enzymes that modify the ribosomal target and decrease drug binding
- hydrolysis of macrolides by esterases
to what degree are each of the macrolides absorbed?
erythromycin - inactivated by acid, administered in enteric coated capsules or as an ester
clarithromycin - absorbed rapidly but undergoes first pass metabolism
azithromycin - absorbed rapidly
how are each of the macrolides excreted?
erythromycin - bile and urine, no need to adjust for renal failure patients
clarithromycin - renal and non-renal, decrease dose in renal failure
azithromycin - biliary excretion, very long half life (40-70 hrs) due to tissue binding
what is the drug of choice for group A strep pharyngitis?
x10 day course of penicillin V or amoxicillin
macrolide if allergic to penicillin
one time dose of penicillin G benzathine
(10 days maximizes bacterial eradication)
what collagen type is associated with the lamina densa?
collagen IV
what collagen type is associated with the reticular lamina?
type III
what collagen type is associated with anchoring fibrils?
collagen VII
where is a fused basal laminae basement membrane seen (which organ)?
in the kidney glomeruli; forms a filtration barrier
how do collagen VII anchoring fibrils appear on microscopes?
striated
perpendicular to the basal lamina
what is an example of a unicellular exocrine gland?
goblet cell
what are serious demilunes?
serous cells that secrete proteins
form a cap on mucous acini clusters
“half moon” shape
secrete proteins into the mucous excretion
what are cytocrine secretions?
passing the secretion directly to another cell
melanocytes
what is the name of the mucosal lymphoid tissue?
MALT
mucosa associated lymphoid tissue
involved in the immune response
what are the symptoms of post-streptococcal glomerulonephritis? (PSGN)
result of untreated strep (dark urine 2-4 weeks post-strep)
sx:
-periorbital edema
-cola colored urine/hematuria
what are the symptoms of N gonorrhea caused pharyngitis?
sore throat
pharyngeal exudates
anterior cervical lymphadenopathy
symptoms of allergic pharyngitis:
presents with system allergic sx
e.g. allergic conjunctivitis, cobble stoning of posterior pharynx
who are at most risk for developing fungal pharyngitis?
immunocompromised patients
treatment for N gonorrhea pharyngitis?
ceftriaxone
what does bacitracin do?
interferes with peptidoglycan synthesis in some bacterial species
what infections does S agalactiae cause?
MOPS!
Meningitis
Osteomyelitis
Pneumonia
Septicemia (sepsis)
Common population: newborns following vaginal birth
what infections do S gallolyticus cause?
bacteremia
subacute endocarditis
most common population: patients with colon CA
S pneumoniae infections:
MOPS!
Meningitis
Otitis Media **
Pneumonia
Sepsis
most common population: children and elderly, immunocompromised, asplenic individuals
S pyogenes infections:
pyogenic infections
toxin mediated infections
autoimmune sequelae
necrotizing fasciitis
most common: children
viridians group infections:
S mutans and S mitis:
dental caries
S mutans:
subacute bacterial endocarditis
S sanguinis:
subacute endocarditis, damaged heart valves
most common: S mutans and mitis in all populations, S sanguinis in patients with damaged heart valves
what are some examples of dsDNA viruses?
adenovirus
viral conjunctivitis
pox viruses/small pox
example of ssDNA viruses:
parovirus B19 (fifth disease)
example of ssRNA virus:
ebola
rabies
measles
example of dsRNA virus:
rotavirus
what type of RNA do retroviruses contain? what enzyme?
ssRNA (+) - sense
reverse transcriptase (RT)
example of a retrovirus:
HIV
what kind of cells do HIV viruses target?
CD4
also monocytes, macrophages, and dendritic cells
products of dsRNA viruses:
multiple RNA molecules that code for MULTIPLE proteins
product of (+) ssRNA viruses:
genome is directly translated
single large protein that can be processed into smaller proteins
product of (-) ssRNA:
needs RNA replicase to synthesize a sense RNA strand
then produces one protein that can be processed into multiple smaller proteins
what are the 3 infection types?
persistent infections
-replicate for long periods of time
-integration into host genome, evasion of host defenses, viral mutations
-e.g. HBV
latent infections
-lacks trigger for replication, lays dormant
-“reactivated” - immunosuppression therapies
-e.g. herpes, cold sores
abortive infections
-error prone replication, effective host defenses
-cell cannot successfully replicate
what are F fusion proteins?
fuse multiple cells together, called syntica
therefore, don’t have to leave to infect other cells
e.g. RSV, retroviruses, herpes
what are inclusion bodies?
viral particles aggregate inside the affected cell
i.e. Molluscum bodies
what two enzymes do neutrophils, in conjunction with lysosomes (phagosomes), use to kill antigens?
perforin
granzymes
characteristics of lobar PNA:
suppurative inflammation - pyogenic
alveoli filled with WBCs (mainly neutrophils), fibrin, and fluid
become solidified vs. its normal spongy nature
what are the 3 types of inflammation:
acute serous
acute fibrinous
acute suppurative
transudate vs exudate
transudate has a low specific gravity with low protein content
exudate has higher specific gravity with high protein content
how are neutrophils and necrotic tissue removed once the inflammation/infection resolves?
phagocytosis (macrophages) and leave via lymph drainage
describe abscess formation:
acute inflammatory response fails to destroy/remove the cause of the tissue damage
continues, usually with a component of chronic inflammation
most common cause: pyogenic bacteria
inflammation progresses producing a liquefaction of tissue into pus
fibrous tissue seals off the cavity
how can plasma cells be identified?
purplish cytoplasm and “clock face” nuclei
(differentiated B cells that produce antibodies)
how can lymphocytes be identified?
dark round nuclei with a very thin rim of basophilic cytoplasm
how can macrophages be identified?
oval/kidney beaned nuclei, pale cytoplasm
(phagocytic and antigen presenting cells)
how can eosinophils be identified?
bilobed nuclei, bright pink granules
(hellminths)
role of fibroblasts?
secrete ECM, including collagen
when an injurious stimulus has been removed, they disappear from the tissue over the course of weeks/months
what is a granuloma?
inflammation characterized by the presence of giant cells (macrophages fused together)
Langhans (immunological)
Foreign Body (non-immunological)
example of immunological granuloma:
tuberculosis
areas of infected/caseous tissue (tubercles) are surrounded by Langhans giant cells
what is flux?
the number of molecules that pass through a permeable membrane at a given time
flux depends on what variables?
-temperature
-molecule mass
-viscosity of medium
-thickness of membrane
-surface area of membrane
doubling the concentration of one molecule will _______ the flux as a result
double
magnitude and direction of diffusion depends on the _______ of concentrations
net difference
what is permeability coefficient?
rate at which polar/charged molecules diffuse across membranes
rate limiting factor: hydrophobic interior of membranes
what is Fick’s Law of Diffusion?
J=PA(Co-Ci)
J=rate of diffusion
P=permeability
-KD/x
K-lipid solubility (good for diffusing across membranes)
D=diffusion coefficient, based on size and viscosity
x=thickness of membrane
A=surface area of the membrane
Co-Ci = concentration difference
membranes have the highest permeability for what ion? why?
K+
has the most open K+ channels on the membrane
extracellular ions:
Na+
Ca2+
Cl-
HCO3-
intracellular ions:
K+
anions
“K in”
simplified Nernst Equation:
membrane potential = (60/ionic valence) x log (concentration outside/concentration inside)
equation for net driving force of an ion:
net driving force = actual membrane potential - equilibrium potential
what is ionic current?
AKA current flow
occurs when there is a movement of an ion across a cell membrane
2 conditions:
1. there is a driving force for the ion
2. membrane has conductance to the ion (membrane channels are open)
I = ionic conductance x (driving force)
conductance = 1/resistance
what is the Chord Conductance Equation?
calculates membrane potential based on the conductances of ions
low conductance = low contribution to the membrane potential
what is the role of adhesion molecules during T cell activation?
TCR only binds peptide-antigen complex with a low affinity
adhesion molecules on T cells recognize their ligands on APCs
stabilize the binding of the T cell to the APC
what are the variant and invariant parts of the T cell receptor?
TCR is variant (differs between clones, specific to each antigen, lacks ability to transmit signals to the nucleus)
CD3 and zeta chain are invariant (invariant among T cell clones, bind to TCR and perform signaling functions)
what are M1 macrophages?
“classical macrophage activation”
activated in response to IFN-gamma in the Th1 pathway
what are M2 macrophages?
“alternative macrophage activation”
in response to IL-4, IL-13 during Th2 injury pathway
result: enhanced fibrosis, tissue repair, scarring
what 2 things do T cells rely on to get to their target/effector site?
adhesion molecules
chemokines
in what 2 ways can the T independent response be enhanced?
if the antigen crosslinks the B cell antigen receptors
if the antigen triggers the innate/complement response well
what is the binding process for phagocytosis by antibody coated antigens?
The Fc portion of the phagocyte receptor recognizes the Fc portion of the antibody
antibody mediated phagocytosis is a major defense against_______.
encapsulated bacteria
i.e. strep pneumoniae
where does antibody mediated phagocytosis take place?
spleen
what antibodies do natural killer cells bind to during antibody mediated cytotoxicity?
IgG
what causes post streptococcal glomerulunephritis (PSGN)?
IgM or IgG, complement antigen complex deposition in the basement membrane of the glomerulus
what type of Abx is penicillin?
B-lactam
important structural feature of penicillin:
carbonyl carbon - nitrogen (amide) bond
what stage of cell wall synthesis do B lactam antibiotics inhibit?
inhibit peptidoglycan cross linking
occurs outside of the cell
what are the B lactam binding sites?
penicillin binding proteins (PBP)
they are cell wall synthesizing enzymes
what is penicillin’s binding site?
transpeptidase (PBP)
what is the next step after the antibiotic binds the PBP?
Murein (peptidoglycan) hydrolases are autolysins that degrade the cell wall, creating weak points for the cell membrane to extrude through the cell wall. leads to lysis.
how are the genes for B lactamase conferred?
in a plasmic, either via transduction or conjugation
contrast Penicillin G and Penicillin V absorption (in acid):
Penicllin G: unstable in acid, absorption is highest when the stomach is empty (30% absorbed)
Penicillin V: acid stable, more consistent blood levels can be achieved
how is Benzathine Penicillin G administered?
parental preparation, IM injection
what is the absorption like for Benzathine Penicillin G?
blood levels low but sustained
when is Benzathine Penicillin G used?
only use for groups that are notably sensitive to the antibiotic (due to the low levels)
AKA group A B hemolytic strep (GAS, S pyogenes)
distribution of penicillin?
widely distributed in the body except for in the CSF, joints, and occular fluids (EXCEPT in times of inflammation)
how are penicillin G and aminopenicillins (amoxicillin) excreted?
primarily by the kidney, so you have to adjust for renal failure/decreased renal function
what is Probenecid?
an organic acid that competes for secretion in the kidneys (would prevent penicillin G and aminopencillins from being excreted) but rarely used because of its toxic side effects
what is the major determinant of penicillin hypersensitivity?
penicillenic acid
how does penicillenic acid cause hypersensitivity reactions?
reacts with sulfhydryl groups in tissues to form HAPTEN-protein conjugates
what is a minor determinant of penicillin hypersensitivity?
penicilloyl
a derivative is used for skin testing for penicillin allergy
adverse effects of penicillin?
Oral - GI distress or diarrhea
Parenteral- phlebitis (IV) and pain (IM)
when does neurotoxicity occur in Penicillin administration?
myoclonus or seizures, confusion, agitation, hallucinations, lethargy
seen in high plasma levels due to failure to adjust for renal patients
why is interstitial nephritis sometimes seen with penicillin G?
sx: fever, rash, hematuria with eosinophilia, proteinuria
reversed when drug is stopped
cause: allergic reaction in which penicillin binds to the basement membrane of the glomerulus, forming an antigen elicited production of antibodies
distribution of macrolides?
wide distribution into intracellular fluids EXCEPT for CNS
side effects of erythromycin:
n/v/d, cramps (oral or IV)
QT prolongation
cholestatic jaundice w/ erythromycin estolate
OVERALL: worst tolerated macrolide
