Lecture 15+16 Flashcards
recognition for the innate immune system
By pattern recognition receptors-PRRs that recognize broad structural motifs present in the invader, but absent in the host:
PAMP’s or DAMP’s
PAMP’s (pathogen-associated molecular patterns)
Essential to microbial survival and metabolism which makes them relatively invariant and evolutionary stable
examples:
peptidoglycan flagellin LPS mannose nucleic acids
Phagocytosis: Opsonization
Phagocytes have specific receptors for this mechanism:
✓CR1 – complement receptor
for C3b fragment
(complement cascade)
✓Fc receptors for Fc region of
immunoglobulins
(antibodies)
In Addition of an opsonin, to ensure cell is readily identified, and more efficiently taken by phagocytes
Opsonins
Antibodies Opsonize the antigen
fc region of antibody binds to phagocytic cell receptors
Phagocytic cells do not have Fc receptors for IgM, but IgM activates complement to do the opsonization
Main opsonin: IgG
complement molecules
opsonize the antigen
Opsonized antigen binds to CR1 receptor on the phagocyte
Main opsonins: C3b, C4b, and C1q
Mechanisms of Phagocytic Killing
- oxygen dependent
- Oxygen-dependent degradation: (Oxidative Burst)
NADPH oxidase produces superoxide which will recombine with other molecules to form a radical
superoxide dismutase produces hydrogen peroxide
myeloperoxidase uses the hydrogen peroxide to produce bleach (hypochlorite)
NADPH oxidase deficiencies
X linked
deficiencies are associated with catalase positive infections
ex. E coli
Chronic Granulomatous Disease
does not have NADPH oxidase and no formation of reactive oxygen species
suffer from recurrent bouts of infection due
to the decreased capacity of their immune system to fight off disease-causing organisms
ex:
pneumonia, superficial skin infections, abscesses,
The Nitroblue -tetrazolium (NBT) test
The higher the blue score, the better the cell is at
producing reactive oxygen
yellow is negative
this tests for CGD
Chediak-Higashi Syndrome (CHS)
autosomal recessive disorder
arises from a mutation of a lysosomal trafficking regulator protein (Microtubule dysfunction) leading to lack of phagolysosome formation
will have large lysosome vesicles in phagocytes
more prone to infection
anemias
hepatomegaly
dohle bodies in neutrophils
albinism, neutropenia, periodontal disease, recurrent pyrogenic infections
signs and symptoms of inflammation
- rubor
- dolor
- tumor
- calor
- loss of function
inflammatory response
- injury/ immediate reactions
Injury/damage causes release of chemical mediators,
cytokines, histamine
attracts leukocytes to the site of injury - Vascular reactions
histamine leads to vasodilation (redness and heat)
Delivers leukocytes, fluid, and clotting factors to the site of injury - Edema and Pus Formation
swelling helps to contain the infection and attract neutrophils
debris and wbc’s form pus
bradykinin stimulates pain
- Resolution/Scar formation
macrophages clean the area; fibroblasts form granulation tissue
lymphocytes mediate long-term immunity
selectins
CAM
Glycoproteins
Bind to carbohydrates
Expressed on leukocytes and endothelial cells
Mucins
CAM
Proteins
Present CHO ligands to selectins
Present on endothelial cells and neutrophils
Integrins
CAM
Proteins; heterodimers
Expressed on leukocytes
Bind to Ig superfamily molecules
ICAMs
Ig CAMs
Expressed on endothelial cells
Bind to integrins
Leukocyte Extravasation
- rolling
Mediated by binding of selectins (endothelium) to
mucin-like CAMs (leukocyte) - activation
Chemokine binding induces conformational change in
integrins (leukocyte) - Arrest/Adhesion
Integrins now capable of binding Ig-superfamily CAMS
(endothelium) - Transendothelial migration
Migration through tight junctions of inflamed
endothelium
Leukocyte Adhesion Defect (LAD)
Deficiency of the β-2 integrin subunit (CD18)
formation of the β-2 integrins by dimerization
with different CD11 subunits
neutrophils cannot extravasate and fight
against bacteria in tissues
hallmarks:
recurrent skin infections, delayed umbilical
separation, absence of pus
kinin system
Hagman factor (factor XII) activation leads to bradykinin formation
↑ vasodilation, permeability, pain, smooth muscle contraction
Clotting system
Hagman factor activation leads ↑ thrombin and clot formation that stop bleeding
forms a fibrinous meshwork at an injured or inflamed site
prevents the spread of infection and keep microbes at the site of inflammatory cell activity
provides a framework for repair & healing
main substance: fibrin
Fibrinolytic system
Hagman factor activation leads plasmin activation
Plasmin breaks down clots and activates complement
Complement system
Anaphylatoxins activate mast cells; ↑ permeability
Chronic Inflammatory Response
lasting longer than 2 weeks
unsuccessful acute response
IFNg and TNFα play a major role
Acute Phase Response
Mediated by IL-1, IL-6, TNFα
increase acute phase proteins
↑ Leukocytosis
The viral toll-like receptors
3,7, and 8
The bacterial toll-like receptors
1,2,6,4, and 5
The increase in the odds of having the disease after a positive test
likelihood ratio of a + test (LR+)
sensitivity / 1 - specificity
The decrease in the odds of having the disease after a negative result
likelihood ratio of a - test (LR -)
1 - sensitivity / specificity
high LR+ result
rule out
low would be rule in
Low LR - result
rule out
high would be rule in
PPV =
PPV = TP / TP + FP
want low FP
NPV =
NPV = TN / TN + FN
lower false neg is optimal
