Lecture 9 Flashcards
Whats techoic aicd
Major component found in cellgram + cell walls, not found in gram negative
Technolci acid consists of
polymers of glycerol phosphate. Varying R groups.
Varying R groups can lead to
Adherance to tissue
technoic acid is
highly immunogenic (antigenic). antibodies against indiviudals with subseuqent infection by an organism with same technoic acid
what makes the negative cell wall in gram postive
TAs
Whats the complement cascade in vetebrates
technoic acid can induce
complemt is a human blood plasma that enhances phaogcytosys
Whats a syndrome
set of symptoms characteristic of a particular disease
some diseases of group A strep
cutaneous, invasive: like strept throat
necrotizing fascilits
toxic like syndrome
which bacteria is part of group A strep
Streptoccocus pyogenes
Streptococcus pneumonia
Whats the toxic like symdrome
- organisms invade host via a cut
- the bacteria releases degrdative enzymes and other cytokines resulting in an inflammatory response.
- The infection enters the blood stream -> leading to damange in blood vessels, lympocytes, releasing more cytokines -> inflammatory response
- Tissue damange and signigicant release of cytokines -> septic sholc
Whats systemic repsonse
Whole body response to an infection rather than a local one
Whats septic shock
result in fever, tarhybia , electrolyte imblaance, multiple organ failure, death
What makes S pyogen infections destructive
- secretion of streptokinase (wall off blood clots)
- scercete hemolysisn that kill strpetolyisin that kill host RBC and release cytokinase
extracellular procease/nucleases
leukocykins:kill WBC
- may contain a cell wall and capsule
Adaptive immune resposne is also known as
speciifc immune respise
Whats another group A strep
Streptococcus pneumonia
How many types of Streptococcus pneumonia are there
90 serotypes dues to
antigenic capsule variants
Whhat are some diseases caused by group A strep, cutaneous
cellulitis: subcutaneous spreading infection with swelling (edema)
➢ impetigo: crusty lesions on skin (common in children)
Whhat are some diseases caused by group A strep, Invasive
strep throat: severe sore throat
pharyngitis (infection
of pharynx); tonsillitis (cause of over half the severe sore throat infections).
- severe sore throat plus fever
- toxic like syndrome
- necrotizing fasciztiz
Important to treat Strep A rapidly and completely because can lead to:
possible sequelae (follow up diseases) of streptococcal diseases:
❖ glomerulonephritis : an inflammation of the kidney: in 10% of
cases can lead to kidney dialysis for life
❖ rheumatic heart disease: an autoimmune disease causing
damage to cardiac tissue
❖ scarlet fever or even toxic shock syndrome
Which strain can lead to toxic like syndrome
Streptococcus pyogenes
What is necrotizing fasciitis
caused by certain strains of S. pyogenes
▪ is the flesh eating disease,
Cellulitis is a milder form of this disease, but can become dangerous in short
order if untreated
What is Necrotizing Fasciitis
the organisms enters the soft tissues usually via a wound (scratch, cut)
organism reach fascia (membranes that surround muscle and separate muscle from fat)
fascia is relatively thin and is destroyed easily. It is destroyed as the bacteria move along
destruction of fascia detaches the skin from blood supply and the
skin dies
rate of destruction can be as fast as one inch per hour (similar to
gas gangrene)
Symptomso f necrotizing fasciitis
- flu-like symptoms (fever, chills, malaise)
- rash, similar to scarlet fever (spreading redness,
sometimes swelling, may be hot to the touch) - some peeling of skin (exfoliation)
- tissue necrosis (sometimes treatable by amputation
and antibiotics) - the person may go into shock due to drop in blood
pressure, can lead to organ failure an death (septic)
Symptoms of necrotizing fasciitis are similar to
common in severe diabetes
and leprosy, conditions which reduce the blood and nerve supply to the skin
What makes S. pyogenes infections so destructive
S.pyogenes as well as certain other strains of streptococci secrete a number of extracellular enzymes that damage the host tissue:
+ streptokinase which dissolves blood
clots
+ hemolysins destroy RBC are
considered membrane-disrupting exotoxins
+ extracellular proteases and nucleases also contribute to tissue damage and invasiveness
+ leukocydins that kill WBC including phagocytes
+ S. pyogenes may contain a capsule and/or cell wall components that contribute to virulence. (For example cell wall proteins F, G and M)
hemolysins are
membrane-disrupting exotoxins
streptolysin O
oxygen sensitive)
streptolysin S
oxygen stable
What are phagocytes
Monocytes, macrophages, and neutrophils are phagocytes
A phagocyte is a type of
white blood cell
What are the components of Streptococcal gram positive cell walls that contribute
to virulence
cell wall proteins F, G and M
Whats protein F
a protein extending from the surface which increases adherence by binding to a glycoprotein found in the extracellular
matrix of many mammalian cells called fibronectin, aids in binding of pathogen to eukaryotic cells
What is protein G
streptococcal surface protein that are Fc receptors - can bind Immunoglobulins
What are immunoglobulins
any of a class of proteins present in the serum and cells of the immune system, which function as antibodies.
How does protein G work
- These proteins bind to and immobilize the Fc region of antibo in an upside down position (some bind to both IgG and IgA)
- will bind all Fc regions not just to antibodies specific to Streptococcus
- when antibodies are bound in the upside down position to the Fc receptors on protein G the antibodies are unable to interact
with phagocytes that could destroy the bacterial cell (block phagocytosis protecting the bacteria)
Does s pyogenes have a capsule
yes, and it increases virulence
What is protein M
Fimbriae-like, “hairy” extensions associated with virulent
strains which can increase attachment and block the complement
system
Whats fibronectin
glycoprotein found in the extracellular
matrix of many mammalian cells
What does protein M bind to
fibrinogen, fibronectin, factor M
How does protein M prevent phagocytosis
it binds to serum factor H, destroying C3 convertase and preventing opsonization by C3b and hence pagocytosis
What are the 5 classes of immunoglbulins:
GAMDE
Whats IgG
the most abundant antibody found internally: high in plasma
(liquid portion of blood)
Whats IgA
the most abundant secreted immunoglobulins (i.e. in mucous,
breast milk)
Whats IgM
rapidly increase in new infection, expressed on surface of B cells
Whats IgF
found primarily on the surface of lymphocytes: helps to induce the synthesis of IgG and IgA to specific organisms
Whats IgE
can be secreted and is particularly active against parasites
What are lymphocytes
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells B cells
All of the immunoglobulins function in
the adaptive (specific) immune response
Function of an antibody moleucle
a) recruits phagocytes to destroy the cell
b) recruits specific complement proteins resulting in a complement cascade and opsonization
that aids in the destruction of the bacterial cell
What do antibodies bind to on the surface of S. pyogenes
binds to Fc receptor
on protein G on
surface of S. pyogenes
therefore nonfunctional
antibody
Where do phagocytes bind to on the amtibody normally
phagocytes can bind to Fc
region via Fc receptor on the phagocyte surface
-> complement cascade/engulfing
How does the antibody become ueless
since G protein binds to Fc region the antibody is in a useless upside down position phagocytes can’t bind
how does S. pyogenes evade the immune system of the host
inhibit phagocytic leukocytes (WBC)
-> contributes to virulence
Whats the M protein
a family of fibrillar proteins that extend from the Steptococcal cell
wall
How does the M protein work
functions in a manner similar to a capsule, it binds to a
complement regulatory protein that inactivates C3b, interfering
with complement activation and the subsequent formation of more
C3b
-> (i.e. results in ineffective opsonization)
What does M protein binding leading to
ineffective opsonization
How does M proteins cause an autoimmune response
It has amino acid similarity to mammalian proteins like myosin and keratin
antibodies
raised to M proteins can cross react with host proteins
under certain conditions, antibodies can react with the mitral valve (damages
heart)
subsequent streptococcal infections may cause further damage
(sequelum of streptococcal disease)
psoriasis (recurrent inflammation of the skin/scalp often accompanied by arthritis)
-> v
Whats the alternative pathway
C3b attaches to bacterial surfaces -> other complements protein attach -> opsinzaition -> forms an enzyme that initates the complement cascade
When doesnt the host cell not induce response
Host cell suface contains moleucles that bind complement regulatory protein
When C3B binds to the host cell surface -> complement regulatory protein inactiates it
How does M protein inactivate c3b
the bacteria cell contains M protein that bidns with the complement regulatory protien.
When c3b attaches -> compelement regulatory protein inactivates it.
-> M protein is hijacking the host protien
Acquired immunity has 2 types
- Active and Passive
Active: you develop your own antibodies after exposure to the infection
+ vaccination (artificial)
+ after an infection (natural)
Passive: you gain your antibodies from your mother (natural) or serum medication (artificial)
What are some protective neutralization outcomes for host of antibody
- Neutralization
- Antibodies prevent attachment to host cells (attaching on flagella)
3.clumping antigens -> 1 mouthful of phagocytic ell
- IgG antibodies have effect similar to C3b complement protein, facilitiating attachhment of phagocytic cell
- Binding of Ab triggers complement cascade -> complement protein attaches to Fc regions triggering cascade
-> leads to inflmmatory resposne and production of opson C3b - multiple IgG moleucles trigger descruction by natural killer cells via atachment to Fc region
What are the neutralization reactions via antibodies that lead to destruction of antidgens (adaptive immunity)
Usually: dimeric exotoxins produced by pathogen damange the host cell
Neutralization by antiboy: binds to the exotoxins and leaves the cell undamanged
Neutralization of a virus: antibodies to virus bind to the virus and leave the cell uninfected
