ryan lecture 9 + 11

SIRS

systemic inflammatory response syndrome

SIRS criteria

high temp

high hr

high rr

high wbc count

sepsis criteria

sirs + source/suspicion of infection?

4 hypersensitivity types

I

II

III

IIII

type I

IgE mediated hypersensitivity

type I step 1

activation of a B cell

“sensitization” to antigen

type I step 2

B cells produce IgE

IgE production is favored when

Il-4 > IFN-y present

type I step 3

IgE binds mast cell eosinophil or basophil via Fc receptor

type I step 4

when IgE binds antigen, crosslinking occurs

type I step 5

cell releases inflammatory mediators

histamines*, cytokines, platelet activating factor

edema

due to increased vascular permeability

inflammatory mediators can directly trigger sensory neurons:

opportunity for therapeutic intervention

wheezin and trouble breathing…

constricted airways

mucus secretion

edema

what must occur since this is IgE mediated

prior sensitization (prior activated B cells via T cell help)

examples of type I

atopic dermatitis

anaphylaxis

allergic asthma

atopic dermatitis is not the same as

contact dermatitis

anaphylaxis treatment

epinephrine *always on list

corticosteroids

anti-histamines

type II hypersensitivity

IgG mediated cytotoxic hypersensitivity

IgG (or an antibody) implies

prior exposure and T cell help (class switching)

type II antibody dependent

antigen-antibody complex* forms on a host cell

antibodies can be made against…

1. intrinsic antigens

2. extrinsic antigens

intrinsic antigens

pre-existing host cell antigen

extrinsic antigens

“novel” antigens created when a cell’s self-antigen is altered and now seems foreign

example of extrinsic antigen

a drug bound to cell

antibodies are usually either…

IgG or IgM

IgG/M are secreted by

self-reactive B-cells

mechanisms of cytotoxicity include

1. activation of complement

2. opsonization

activation of complement =

C5a promotes recruitment of neutrophils → degranulate → kill cell

opsonization =

antibody and/or complement enhance phagocytosis (macs. and neuts.)

more mechanisms of cytotoxicity

activation of the complement cascade: MAC

result of MAC =

cell lysis (instead of hole in bacteria hole in RBC or could be different cell in your body)

antibody-dependent cell mediated cytotoxicity

several cell types can participate (neuts., macs., NKs)

immune complex is formed on the…

cell surface directly

biggest difference between type 2 and type 3 hypersensitivity

the type 2 is the cell surface/formed on cell

type III hypersensitivities involve

1. Ag-Ab complexes

2. antigens are soluble

example =

vasculitis

vasculitis

Ag-Ab complexes adhere to vessel wall → activate complement → vessel dialation/incr. perm./cytokine release

type IV (delayed-type)

t-cell** mediated hypersensitivity

type IV requires two things

1. prior sensitization

2. involve T lymphocytes

TB diagnostic tool (people and cattle)

use type IV to determine if patient has had prior exposure to TB antigen

examples of contact hypersensitivity

chemicals

metals

poison ivy

5 signs of inflammation

redness

heat

swelling

pain

loss of function

redness cause

vasodilation

swelling cause

vasodilation

swelling causes

vasodilation

increased vascular permeability

immune cell influx

pain causes

nocioreceptor stimulation (physical and chemical)

immune cell influx

loss of function causes

physical disruption of tissues

immune cell influx

remodeling of tissues over time

purposes of inflammation

destroy

expel

aid in healing

stimuli that can induce inflammatory responses

PAMPS

DAMPS

foreign material

Who recognizes the stimulus?

APCs: macrophages, DCs

how

binding to PRRs

DAMP emphasized corresponding receptor

TLR4 ?

what also contributes to inflammatory process (physical thing)

phospholipid component of cell membrane

after PRR binds to PAMP (or DAMP)

1. signaling cascade initiated

2. NF-kb activated

   1. genes expressed: cytokines, chemokines, adhesion molcules, co-stim

after sensing stimuli released by macrophages

cytokines

chemokines

eicosanoids

released by mast cells

histamine

another mediator is also activated

plasma enzyme

plasma enzyme mediators

complement

kinins

plasmin

effects of mediators that are released: acute inflammation*

small blood vessels dilate

vascular permeability increases

neutrophils migrate to site of infection

inflammatory response overview

1. detect stimulus

2. release signals to communicate

3. call in other cells

4. resolve sustain or ramp-up

first responders

neutrophils

neutrophils are short-lived

hours to days

neutrophils recruited by

chemokines

neutrophils perform

phagocytosis

neutrophils release variouis inflammatory mediators

histamine

ROS

cyto/chemokines

NETs

peptides

after neutrophils migrate to site of infection…

they attack

they attack by

phagocytosis

degranulation

NETs

NETs are released in response to cytokines

IL-8 and PAMPs

how we seeing neutrophils in a patient

marginating (attaching to walls)

diapedesis

traveling to infection site

eosinophils release many mediators (important one is)

major basic protein (helminths)

during resolution of inflammation neutrophils…

apoptosis

if infection doesn’t clear

more neutrophils recruited

becomes chronic inflammatory response

chronic inflammatory cell types

macrophages

lymphocytes

plasma cells

outcomes of infection

complete resolution without sequelae

healing by CT replacement

chronic infection/inflammation

infection extending beyond original insult =

systemic inflammation and sepsis (flashcard 1)