Lecture 15+16 Flashcards

1
Q

recognition for the innate immune system

A

By pattern recognition receptors-PRRs that recognize broad structural motifs present in the invader, but absent in the host:

PAMP’s or DAMP’s

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2
Q

PAMP’s (pathogen-associated molecular patterns)

A

Essential to microbial survival and metabolism which makes them relatively invariant and evolutionary stable

examples:

peptidoglycan 
flagellin
LPS
mannose
nucleic acids
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3
Q

Phagocytosis: Opsonization

A

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

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4
Q

Opsonins

A

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

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5
Q

complement molecules

A

opsonize the antigen

Opsonized antigen binds to CR1 receptor on the phagocyte

Main opsonins: C3b, C4b, and C1q

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6
Q

Mechanisms of Phagocytic Killing

A
  1. oxygen dependent
  2. 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)

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7
Q

NADPH oxidase deficiencies

A

X linked
deficiencies are associated with catalase positive infections

ex. E coli

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8
Q

Chronic Granulomatous Disease

A

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,

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9
Q

The Nitroblue -tetrazolium (NBT) test

A

The higher the blue score, the better the cell is at
producing reactive oxygen

yellow is negative

this tests for CGD

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10
Q

Chediak-Higashi Syndrome (CHS)

A

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

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11
Q

signs and symptoms of inflammation

A
  1. rubor
  2. dolor
  3. tumor
  4. calor
  5. loss of function
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12
Q

inflammatory response

A
  1. injury/ immediate reactions
    Injury/damage causes release of chemical mediators,
    cytokines, histamine
    attracts leukocytes to the site of injury
  2. Vascular reactions
    histamine leads to vasodilation (redness and heat)
    Delivers leukocytes, fluid, and clotting factors to the site of injury
  3. Edema and Pus Formation
    swelling helps to contain the infection and attract neutrophils

debris and wbc’s form pus
bradykinin stimulates pain

  1. Resolution/Scar formation

macrophages clean the area; fibroblasts form granulation tissue
lymphocytes mediate long-term immunity

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13
Q

selectins

A

CAM

Glycoproteins
Bind to carbohydrates
Expressed on leukocytes and endothelial cells

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14
Q

Mucins

A

CAM

Proteins
Present CHO ligands to selectins
Present on endothelial cells and neutrophils

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15
Q

Integrins

A

CAM

Proteins; heterodimers
Expressed on leukocytes
Bind to Ig superfamily molecules

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16
Q

ICAMs

A

Ig CAMs
Expressed on endothelial cells
Bind to integrins

17
Q

Leukocyte Extravasation

A
  1. rolling
    Mediated by binding of selectins (endothelium) to
    mucin-like CAMs (leukocyte)
  2. activation
    Chemokine binding induces conformational change in
    integrins (leukocyte)
  3. Arrest/Adhesion
    Integrins now capable of binding Ig-superfamily CAMS
    (endothelium)
  4. Transendothelial migration
    Migration through tight junctions of inflamed
    endothelium
18
Q

Leukocyte Adhesion Defect (LAD)

A

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

19
Q

kinin system

A

Hagman factor (factor XII) activation leads to bradykinin formation

↑ vasodilation, permeability, pain, smooth muscle contraction

20
Q

Clotting system

A

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

21
Q

Fibrinolytic system

A

Hagman factor activation leads plasmin activation

Plasmin breaks down clots and activates complement

22
Q

Complement system

A

Anaphylatoxins activate mast cells; ↑ permeability

23
Q

Chronic Inflammatory Response

A

lasting longer than 2 weeks
unsuccessful acute response

IFNg and TNFα play a major role

24
Q

Acute Phase Response

A

Mediated by IL-1, IL-6, TNFα

increase acute phase proteins

↑ Leukocytosis

25
Q

The viral toll-like receptors

A

3,7, and 8

26
Q

The bacterial toll-like receptors

A

1,2,6,4, and 5

27
Q

The increase in the odds of having the disease after a positive test

A

likelihood ratio of a + test (LR+)

sensitivity / 1 - specificity

28
Q

The decrease in the odds of having the disease after a negative result

A

likelihood ratio of a - test (LR -)

1 - sensitivity / specificity

29
Q

high LR+ result

A

rule out

low would be rule in

30
Q

Low LR - result

A

rule out

high would be rule in

31
Q

PPV =

A

PPV = TP / TP + FP

want low FP

32
Q

NPV =

A

NPV = TN / TN + FN

lower false neg is optimal