Chapters mentioned: Mechanisms of Defense: Inflammation and Immune Function
Innate (AKA “natural”) resistance
the defense mechanisms we are born with
1st Line of Defense
Non-specific, Immediate, physical barriers
EX of defensive roles for 1st:
protection from hazardous environment
desquamation of skin
secretion of sweat (has anti-fungal/anti-bacterial properties)
stressors that can breach this defense
lacerations, abrasions, & punctures
eyes Defense
Tears and Eyelashes
stressors that can breach eyes defenses
Sjogren’s Syndrome: autoimmune disease that
dries up all lubricating fluids in the body
Dry Eye Syndrome: manufacturing of tears slows down; due to aging
respiratory system defenses
viscosity of mucus
cilia of cells in bronchi
cough reflex
stressors that can breach respiratory defenses:
cigarette smoking changes bronchial cells—no more cilia. (metaplasia)
cough reflex suppression such as in head injury or stroke
GI system defenses
saliva - contains protective enzymes
stomach - HCL destroys most microbes
gag reflex / vomiting
bowels - normal contain “good flora” & defecation
stressors that can breach GI defenses
Sjogren’s Syndrome - dries up saliva, so less protection in mouth
anything that changes the bowel flora can leave us open to invading microbes; ex of something that might change the bowel flora: antibiotics
genitourinary (GU) system defenses
flow of urine - washes away microbes
vaginal secretions slightly acidic - kills bacteria
stressors that can breach GU defenses
decreased urine flow → kidney stones/failure
anything the changes vag. pH (EX: douching)
2nd Line of Defense
INFLAMMATION, non-specific, immediate
SHEP
swelling, heat, erythema (redness), pain
___________ is a normal, important body mechanism that helps us defend against stressors and begin the healing process.
Inflammation
Inflammation is
acute and short-lived (2 weeks)
mast cell degranulation leak chemical granules called
local inflammatory mediators
What are the three local inflammatory mediators?
Histamine, Leukotrienes, & Prostaglandin (HLP)
HLP causes capillaries to
vasodilate and become more permeable
If more inflammation is needed, what systemic inflammatory mediators will come to the area via the bloodstream?
acute phase reactants (APR)
What are the three APR?
CRP (C-reactive protein) , complement, circulating prostaglandins
Function of APR
opsonize (coat) and directly kill bacteria
serous exudate
clear, gold color of plasma leaking out in the area (blister)
serosanguinous
if there is blood (similar to blister)
purulent exudate
also, known as pus, thick & whitish or yellowish color, a microbe is present
Chemotactic substances
biochemical mediators that summon OTHER substances to a certain area, or to increase in amount.
Granulating tissue
pink, healthy, healing tissue
Degranulation
breaking apart of mast cells with spillage of granules of biochemical mediators into tissue.
local external example
laceration or abrasion to skin.
local internal examples
pleuritis—inflammation of pleura when irritated by, for example, a lung cancer cell.
thyroiditis—thyroid is inflamed because of autoimmune attack.
S&S of (normal) systemic inflammation:
malaise, aches & pains
FEVER (response from increased PG’s & APR)
fever can dilate blood vessels →
too much vasodilation = low BP
fever increases metabolic rate→
may cause decompensation in very ill, debilitated, and/ or elderly patients.
Systemic Inflammation Lab Test
CBC will show increased WBCs: Leukocytosis and Neutrophilia
serum CRP will often be elevated
“Not enough” inflammation
Anyone with not enough inflammation will be extra susceptible to infections.
Quantitative Defect
Leukopenia and Neutropenia
Qualitative Defect
chemotactic defects: won’t respond appropriately when “summoned.”
impaired function; ex—phagocytes damaged by diabetes mellitus have decreased ability to fight microbes.
“____too much” inflammation
inflammation goes into “overdrive” and/or becomes chronic; EX: SIRS, sepsis, septic shock, & chronic inflammation disorders
SIRS – systemic inflammatory response syndrome
excessive systemic inflammation contributes to widespread impaired tissue function and organ damage.
SIRS S&S
unexplained change in mental status (confusion, not as awake and alert as normal).
fever of more than 100.4° F
increased HR
increased RR
abnormal white blood cell count (WBC)
Sepsis
SIRS + Infection
Septic Shock
sepsis + low BP
extreme vasodilation = no arterial vessel “tone” as arteries become too relaxed, “floppy”
Septic Shock S&S
SIRS S&S + low BP
causes ischemia to organs so patient can have renal failure, respiratory failure, heart failure or death.
non-medicinal interventions for inflammation
Ice on the area of swelling → cold numbs pain → vasoconstriction of bv → diminished swelling and pain
medicinal therapeutics
anti-inflammatory medications and prostaglandins (PGs)
anti-inflammatory medications MOA
suppress the effects of prostaglandins : STEROIDS, and NSAIDs—“non-steroidal antiinflammatory drugs
Prostaglandins (PGs)
Pro-inflammatory PG’s - stimulate further inflammation by increasing vascular permeability and also induce fever &
pain
Protective PG’s - PGRVI
side effects of anti-inflammatory drugs
have to do with suppressing the “protective” and “pro-inflammatory” effect
* (ideal effect would be to be specific and suppress pro-inflammatory only.)
arachidonic pathway
birth pathway to PG’s
phospholipases
they are enzymes that catalyze the creation of arachidonic acid from the phospholipids of the cell membrane
Protective PG’s
have normal platelet clotting function (P)
maintain the integrity of the gastric mucosa (G)
promote healthy renal function. (R)
maintain appropriate vasomotor tone. (V)
maintain normal immunocyte function. (I)
Protective PG’s: Steroid Side Effects
P - easy bleeding and bruising
G - ulcers
R - kidney failure
V - vasoconstriction → HTN
I - higher risk of infections
when pt is taking a steroid for a long time ⬆️
steroids
________ suppress both proinflammatory AND protective PG’s high up in the arachidonic pathway by blocking prostaglandins and leukotrienes
Steroids are used to treat
acute back injuries, asthma, allergic reactions, bad rashes, lupus & other autoimmune diseases
non-steroidal antiinflammatories – NSAIDs
work lower in the arachidonic pathway and are used for headaches, general aches, and pains
examples of NSAIDs
aspirin, ibuprofen (Motrin), naproxen
Acquired (AKA “adaptive”) immunity-- 3rd line of defense
delayed, specific, & immunocyte involvement
Which T-cell is known as an introductory cell?
CD4 cells (helper-T)
B-lymphocytes (B-cells)
differentiate into plasma cells
create antibodies to the microbe that has attacked the body → memory B-cells
Antigens
“name tag,” “invader”: substance that induces the formation of Ab bc it’s recognized by the immune system as a threat
response to antigens that are foreign to our bodies is normal; response to our own “self” antigens is abnormal.
Antibodies
IgG & IgE: “protect & defend”: made by immune system in response to & counteract a specific antigen
T-Cell in charge →
Cell-Mediated Immunity
B-Cell in charge →
Humoral Immunity
Active acquired immunity
their own immunocyte system developed the antibodies that established immunity
NATURAL active acquired immunity
when a person’s plasma cells build up Ab in response to a microbially induced illness
Summary: you get an infection when someone sneezes on you and you create your own Ab or memory T-cells so you’ll never get that dz again.
ARTIFICIAL active acquired immunity
when a person’s plasma cells build up Ab in response to receiving inoculations (vax) of a weakened or inactive microbe
Passive acquired immunity
they have been given someone else’s antibodies; they did not develop the antibodies on their own
NATURAL passive acquired immunity
mom → baby; via placenta/breast milk; MatAb
Summary: mom’s Ab are temporary & only protect for approx. 2-3 mths, then disintegrate
ARTIFICIAL passive acquired immunity
Ab injected during treatment; emergencies or as a stop-gap measure until active immunity develops
Summary: exposed to a dz you’re not vaxxed against → get an IgG shot → gives Ab for right now (last 2 weeks)
neutralization (inactivation):
neutralizes viruses by preventing attachment and entrance of viruses into host cells
opsonization
“coats” bacteria—this promotes phagocytosis by optimizing recognition and “digestibility” of antigen for phagocytes
makes it tastyyyyy
Hypersensitivities— “too much” immunocyte response
immunocyte response that is supposed to help us goes “too far” and harms us.
subcategories of hypersensitivity responses
allergic, autoimmune, and alloimmune
allergic response (“allergic reaction”):
hypersensitivity to a target antigen (environmental, medical, or pharmaceutical), called an allergen.
autoimmune response:
hypersensitivity to self-antigens (the target antigen) – a reaction of our body to our own antigens.
alloimmune response:
hypersensitivity to another person’s antigens (the target antigen), such as when an organ is transplanted
allergic hypersensitivity
IgE mediated; exposure through inhalation, ingestion, injection, or skin contact → trigger primary response SENSITIZATION → creation of Ab that lies out in the lymph system
Allergic pathologic response
if an individual is genetically predisposed → IgE binds to mast cells → sensitizing the cell
local allergic hypersensitivity S&S
dermatitis (skin rash → itching and swelling),
nasal allergic rhinitis,
conjunctivitis - as a result of HLP release from the mast cell.
systemic allergic hypersensitivity S&S
anaphylaxis
urticaria (hives)
angioedema - abnormal vasodilation & edema of small bv (lips, tongue, hands)
N, V, D, cramps
wheezing - bronchial edema - leukotriene induced bronchoconstriction
dyspnea; possibly laryngeal edema
Hypotension & shock → systemic vasodilation
allergic hypersensitivity tx
histamine - anti-histamine
steroids
leukotriene blockers (Singulair)
autoimmune hypersensitivity
to self-antigens -- a reaction of our body to our own antigens
Autoimmune Hyper. EX:
rheumatic heart disease: heart valve cells appear to be a close enough match to the strep antigen → autoAb begin attacking them → heart valve can malfunction-- become floppy & leaky instead of opening & closing tightly.
Humoral Autoimmune Response
autoAb attack causing opsonization → phagocytized tissue cells by macrophages as if they were bacteria
Humoral Tissue Specific AutoImmune Dzs
Graves, Goodpasture’s Synd., Myasthenia gravis, Autoimmune hemolytic anemia
Cell-mediated Autoimmune Response
auto-T-cell response - “attacker” is our own T-cells
Cell-mediated Tissue Specific AutoImmune Dzs
Multiple sclerosis, Type-1 Diabetes, Celiac Dz
Systemic Autoimmune Dzs
Ab & self-antigen pair up → immune complex → irritates bc & vasculitis = surrounding tissue inflamed
Systemic Lupus Erythematosus
Ab → autoAb when encountered Nucleic Acids → attach themselves to DNA → immune complexes → circulated & deposited in connective tissue bv: kidneys, lungs, joints, skin → vasculitis
SLE S&S
skin rashes: “butterfly” malar rash (wolf-like across face)
Joints: non-erosive arthritis of at least 2 peripheral joints
Serositis: pleura & pericardial sac inflamed → pleurisy & pericarditis
proteinuria - kidneys
seizures - neurons of brain
fatigue
SLE diagnosis
elevated CRP - non-specific
ANA - antinuclear Ab that looks for immune complexes
Rheumatoid Arthritis (RA)
Immune Complex: Ab + Collagen → systemic S&S
pain tends to be worse in morning & lessens as
day goes on
RA S&S
fatigue, joint pain, swelling and deformation, inflammatory S&S of eyes, heart, lungs, almost any tissue
RA diagnosis
elevated CRP and + Rheumatoid (Rh) factor
alloimmune hypersensitivity
hypersensitivity to someone else’s cells; ex: organ transplant; “compatibility” issues
Types of alloimmune hyper.
Histocompatibility and ABO/Rh
Histocompatibility compatibility issues
test done on both donors to see if the HLA’s match on their cells
if immunocytes attack → rejection
S&S: pain over area, fever
immunosuppressant drug
to minimize rejection, transplant patients are put on _________ _______ immune system “lethargic” so it won’t attack transplanted tissue.
ABO compatibility issues
A, B, AB, O
receiving wrong blood type → hemolysis
“clumping” effect → block bv in kidneys (failure) → ischemia to distal tissues (transfusion reaction) → S&S: rash, fever, low BP, &/or body aches
Rh factor compatibility issues
a person is either born with or w/out the Rh factor on their RBC as part of inheritance
EX: a person w/out the Rh factor who is given RH+ blood will be ok the 1st time they get blood since there’s no Ab development