Review 1.2 Flashcards
CR1
complement receptor 1
binds C3b and C4b
major activator receptor for macros and PMNs
CR3
binds C3bi- bound complexes
CR2
mainly found on Bcells, involved in their activation
CR4
similar to CR3, but also adhesion molecule.
development of B lymphocytes
steps.
RAG
encode enzymes that play an important role in the rearrangement and recombination of the genes of immunoglobulin and T cell receptor molecules during the process of VDJ recombination.
what tests B lymphs when they are graduating?
stroma cells, they secrete cytokines at them.
how are histones modified?
acetylation- activates, methylation- inactivates.
SCID
severe combined immunodeficiency disease
gamma chain deficiency- cytokine receptor. shared by IL-2 family of receptors.
type 1 interferons
antiviral response that results in cells having a higher level of resistance to infection than unactivated cells.response driven by JAC STAT pathway.Main effect: resistance of viral replication, and infection.recognized by NK cells.
immunomodulatory.
type 2 interferons
produced by Nk cells. AKA gamma interferon. Activates Macrophages.
what induces liver to produce acute phase proteins?
IL-6
c-reactive protein
opsonin, induces phagocytocis
C’ functions
opsonization and phagocytocis- binds C3b, recognized by phagocyte, then its eaten.stimulation of inflammatory reactions- recruits and activates leukocytes by C5a and C3acomplement mediated cytolysis- recruits components, forms pore, osmotic lysis of microbe.
C3 convertase
cleaves C3 so that it can tag bacteria for destruction.C3a, part of C3 will then recruit phagsAKA C3bBb
3 ways that complement is activated
Classical - least important.
Lectin - activated by acute phase proteins. has to go to liver first.
Alternative - doesn’t need antibody, most important. first to act.
they all lead to cleavage of C3 to C3a and b. C3b can also cleave C3 to make more C3a
amplification
C3 cleavage
Alternative pathway
main way to activate complement. C3 cleavage driven by:
Factor B- forms C3bBb complex aka C3 convertase
Factor D- cleaves B when bound to C3b to Ba and Bb
Properdin- stabilizes complexes formed by other factors. positive regulator. accelerator.
regulation of C3 activation
Factor H+ Factor I- inhibitor, slows down consumption of C3^^^ if missing this then you are more susceptible to encapsulated bacteria.
C5
initiates assembly of membrane attack complex in solutionactivated by C5 convertase, activates terminal part of complement
MAC
membrane attack complex. formed by complement, poly 9 forms the pores.
C8 deficiency
recurrent Neisseria infections to to lack of MAC
C3 mutations
no complement response!!!!!severe, recurrent infections
C5 mutations
increased complement activation, deplete C3, recurrent infections.
MBL
member of the collectin family of proteinsuses specific set of MASP proteasescleaves C4, then C2.
Classical C3 convertase
C4bC2b
calssical pathway
utilizes bound antibodyneed to bind multiple arms of C1.
best antibody for activation of c’
IgM
regulation of complement
- specific activation 2. short half life 3. regulation
C1 inhibitor
serine protease inhibitor.
SERPIN family.
also helps regulate clotting
CD59
inhibits formation of MAC, AKA MAC-inhibitory protein
Paroxysmal nocturnal hemoglobinuria
missing CD59.
complement induced RBC lysis. via random activation of MACs on RBCsacquired. CD59 just goes missing.
PIGA - x linked
Familial Atypical Hemolytic Uremic Syndrome
associated with lack of control of convertase activation. means complement cascade is always activated.
missing Factor H, factor I, mutation in C3, increased C3 consumption.
what is controlled most carefully?
C3 convertase. its generation and stability.
which is a most common infection with complement deficiencies?
Neisseria species
MIC
MHC class I-related chainfor infected cells that have had their receptors down regulated by viruses, NK cells recognize these and kill the cell.
LAD
leukocyte adhesion deficiency:
inability of leukocytes to migrate into sites of infection: history of overwhelming infections. often lethal.
early symptom:
** delayed loss of umbilical cord***
no PMNs and macros in sites of infection.higher levels in blood.
type 1 interferons
antiviral response that results in cells having a higher level of resistance to infection than unactivated cells.
response driven by JAC STAT pathway.
Main effect: resistance of viral replication, and infection.
recognized by NK cells.immunomodulatory.
type 2 interferons
produced by Nk cells. AKA gamma interferon. Activates Macrophages.
what induces liver to produce acute phase proteins?
IL-6
acute phase proteins
manose binding lectin, c- reactive protein
c-reactive protein
opsonin, induces phagocytocis
C’ functions
opsonization and phagocytocis- binds C3b, recognized by phagocyte, then its eaten.
stimulation of inflammatory reactions- recruits and activates leukocytes by C5a and C3a
complement mediated cytolysis- recruits components, forms pore, osmotic lysis of microbe.
C3 convertase
cleaves C3 so that it can tag bacteria for destruction.C3a, part of C3 will then recruit phags AKA C3bBb
3 ways that complement is activated
Classical - least important.
Lectin - activated by acute phase proteins. has to go to liver first.
Alternative - doesn’t need antibody, most important. first to act. they all lead to cleavage of C3 to C3a and b. C3b can also cleave C3 to make more C3a
C1-9 with 4 out of line.
the classical pathwaylectin pathway doesn’t use C1 alternative activates C3 directly.
regulation of C3 activation
Factor H+ Factor I- inhibitor, slows down consumption of C3^^^ if missing this then you are more susceptible to encapsulated bacteria.
MAC
membrane attack complex. formed by complement, poly 9 forms the pores.
C3 mutations
no complement response!!!!
!severe, recurrent infections
C5 mutations
increased complement activation, deplete C3, recurrent infections.
C1inh mutation
angioedema, HAE
Classical C3 convertase
C4bC2b
best antibody for activation of c’
IgM
CR1
major activation receptor for macros and PMNs
immune complex disease
lack CR1 or liver receptors inability to clear bloodstream of immune complexeskidney is site of deposition. Nephritis.
regulation of complement
- specific activation 2. short half life 3. regulation
C1 inhibitor
serine protease inhibitor.
SERPIN family.
also helps regulate clotting
HAE
Heredetary C1 inhibitor deficiency, angioedema due to overactive complement.
CD59
inhibits formation of MAC
immunoglobulin gene rearangement
no proliferation during DJ and VDJ rearangement
proliferation after successful VDJ rearanement depends on the pre-receptor
no proliferation during VJ rearangement
lectin pathway
The lectin pathway is homologous to the classical pathway, but with the opsonin, mannose-binding lectin (MBL), and ficolins, instead of C1q.
how do A-B type toxins work?
two different ways of entering cells.
B- binding site
A- toxic part, after T bores out of phagozome.
how can bacterial toxins affect host cells and the course of an infection?
they can make bacteria better survive host response.
how can toxins be used for treatment?
Botulinum toxin
how are toxins inactivated?
antibody, drugs.
endotoxin vs exotoxin
endotoxin is LPS, part of bacteria.
exotoxin actively secreted to cause disease
Necrosis
injury induced, uncoordinated
early cell membrane disruption
cell swelling
cells die in large groups
acute inflammation
PATHOLOGIC!!!!
Apoptosis
Programmed cell death
activation of caspade cascade
nuclear pyknosis
one cell at a time
no inflammation
normal phneomena
coagulative necrosis
with ischemia, makes infarct
liquefactive necrosis
loss of substance, in brain or abcess
fat necrosis
necrosis in fat
casueous necrosis
necrotizing granulomas, combo of liquefactive and coagulative.
fungal or TB infection
gangrenous necrosis
necrosis of whole anatomical area.
leukocytosis with neutrophilia
acute inflammation, left shift, depleted neutros
leukocytosis with lymphocytosis
chronic inflammation, viral!
eosinophilia
parasitic infection, autoimmune, asthma/allergy, tumors
increased sedimentation rate
sign of inflammation, fibrinogen is acute phase.
how many RBCs sink in one hour in a vertical capillary tube.
steps in tissue healing
inflammatory response, clotting factors leak in.
clot forms
fibroblasts and others cells migrate in, form granulation tissue
maturation of granulation tissue
scar maturation- 70-75% strength after months
problems in tissue repair
slow
too much- hypertrophic scar, keloid, desmoid
too little- wound dehiscence, cardiac rupture after infarct
how does antibiotic resistance happen?
antibiotic kills most bugs except resistant ones, resistant bacteria take over, HGT leads to resistance in other bugs!!!
mechanisms of resistance to antibiotics
drug cant get it, drug gets pumped out, drug gets inactivated, target is altered or over-expressed so that drug can’t affect it.
how many human infections may involve biofilms?
65%, if you dont count periodontal disease!
autoclaves
sterilize equipment with high P and T.
121 degrees for 15 minutes.
spores
tough!!!!
might not get killed by autoclave, and especially not by hand sanitizers.
why? they are dormant. protected.
