NURS 3366: MECHANISMS OF DEFENSE

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:%%

1. protection from hazardous environment
2. desquamation of skin
3. 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

1. **Sjogren’s Syndrome:** autoimmune disease that

dries up all lubricating fluids in the body


2. **Dry Eye Syndrome:** manufacturing of tears slows down; due to aging

respiratory system defenses

1. viscosity of mucus
2. cilia of cells in bronchi
3. cough reflex

*stressors that can breach* respiratory defenses:

1. cigarette smoking changes bronchial cells—no more cilia. (__**metaplasia**__)
2. __cough reflex suppression__ such as in head injury or stroke

GI system defenses

1. saliva - contains protective enzymes
2. stomach - HCL destroys most microbes
3. gag reflex / vomiting
4. bowels - normal contain “good flora” & defecation

*stressors that can breach* GI defenses

1. **Sjogren’s Syndrome** - dries up saliva, so less protection in mouth
2. 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

1. flow of urine - washes away microbes
2. vaginal secretions slightly acidic - kills bacteria

*stressors that can breach* GU defenses

1. decreased urine flow → kidney stones/failure
2. 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

1. pleuritis—inflammation of pleura when irritated by, for example, a lung cancer cell.


2. thyroiditis—thyroid is inflamed because of autoimmune attack.

S&S of (normal) systemic inflammation:

1. malaise, aches & pains
2. 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

1. CBC will show increased WBCs: Leukocytosis and Neutrophilia


2. 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

1. **chemotactic defects**: won’t respond appropriately when “summoned.”


2. **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

1. unexplained change in mental status (confusion, not as awake and alert as normal).
2. fever of more than 100.4° F
3. increased HR
4. increased RR
5. 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

1. have normal __**platelet**__ clotting function (**P**)
2. maintain the integrity of the __**gastric**__ mucosa (**G**)
3. promote healthy __**renal**__ function. (**R**)
4. maintain appropriate __**vasomotor**__ tone. (**V**)
5. 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)__

1. differentiate into __plasma cells__
2. 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

1. dermatitis (skin rash → itching and swelling),
2. nasal allergic rhinitis,
3. conjunctivitis - as a result of HLP release from the mast cell.

*systemic allergic hypersensitivity* S&S

1. anaphylaxis
2. urticaria (hives)
3. angioedema - abnormal vasodilation & edema of small bv (lips, tongue, hands)
4. N, V, D, cramps
5. wheezing - bronchial edema - leukotriene induced bronchoconstriction
6. dyspnea; possibly laryngeal edema
7. Hypotension & shock → systemic vasodilation

*allergic hypersensitivity* tx

1. histamine - anti-histamine
2. steroids
3. 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

1. **skin rashes**: “__butterfly” malar rash__ (wolf-like across face)
2. Joints: non-erosive arthritis of at least 2 peripheral joints
3. Serositis: pleura & pericardial sac inflamed → pleurisy & pericarditis
4. proteinuria - kidneys
5. seizures - neurons of brain
6. 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