Module 2: Mechanisms of Defense (MOD) PART 1

an interaction and coordination of responses to stressors

What is a Mechanism of Defense (MOD)?

1. Invasion by foreign body like a microbe or splinter

2. Development of unnatural dangers like cancer cells

Provide 2 examples of stressors that may cause the body to activate a MOD.

Innate Resistance and Acquired Immunity

What are the 2 big categories of the Immune System?

defense mechanisms we're born with which includes a 1st and 2nd line of resistance

What is Innate (aka natural) Resistance?

body's physical barriers which are immediate (occurs at same time w/ contact stressor) and also non-specific (response is same no matter the stressor)

What is the 1st line of resistance in Innate Resistance?

inflammation which is also immediate and nonspecific

What is the 2nd line of resistance in Innate Resistance?

states of resistance related to our species...humans being naturally resistance to some infectious agents that cause illness in other species and vice versa

Innate Resistance can also include what? (aside from 1st and 2nd line of defense)

1. Canine distemper can't be "caught" by humans

2. West Nile Virus can infect birds/humans/horses but NOT dogs or cats

Give 2 examples of Innate Resistance relating to our species.

1. Being able to resist certain dz or conditions b/c immunocyte involvement

2. This type of response is delayed (occurs later) and specific (different immunocytes respond to diff stressors)

What is Acquired Immunity (AKA 3rd line of defense)?

Lymphocytes—aka B & T cells

What are Immunocytes?

skin and its glands, membranes, glands of body openings....remember that these respond immediately

The first line of resistance includes what parts of your body?

1. Protect more vulnerable areas underneath from simple environment hazards

2. Desquamation of skin—shedding cells means bacteria shed too

3. Various glands in skin secrete sweat...antibacterial & antifungal

What are the 3 examples of the defensive roles that Skin and its glands play?

1. Attack cell walls of certain bacteria

2. Contribute to making skin acidic (ph 3-5), making it inhospitable to most bacteria

How is Sweat antibacterial & antifungal?

lacerations, abrasions, punctures, etc

What stressors can breach the skin and its glands?

1. Eyelashes

2. Tears

Eyes' Defense count as a membrane/glands of body openings. What 2 things falls under this?

Blinking --> lacrimal glands spread tears over eyes --> tears drain into lacrimal ducts --> eyes washed regularly

Explain how Tears defend eyes.

1. Dry Eye Syndrome—making tears slows down; happens to almost everyone at some degree with age

2. Sjogren's Syndrome—autoimmune dz drying up all lubricating fluids in body

What 2 stressors can breach the Eyes' Defense?

1. Viscosity of mucus in nose plus hair traps bacteria (same w/ wax and hair in ears)

2. Cilia of cells in bronchi—can sweep away foreign bodies

3. Cough reflex—if foreign body inhaled and reach carina, this is activated

Respiratory System Defenses count as membrane/glands of body openings. What 3 things falls under this?

1. Cigarette smoking changes bronchial cells—no more cilia (metaplasia)

2. Cough reflex suppression like in head injury or stroke

What 2 stressors can breach the Respiratory System Defenses?

1. Saliva—has enzymes

2. Stomach—HCl destroy most microbes

3. Gag reflex/vomiting—get rid of injurious agents like harmful bacteria

4. Bowels

Gastrointestinal (GI) System Defenses count as membrane/glands of body openings. What 4 things falls under this?

1. Normal bowel has many "good flora" aka unharmful microbes that keep out malicious microbes by competing for food

2. Defecation—get rid of injurious agents like harmful bacteria

Describe Bowels in the context of GI system defenses.

1. Sjrogen's—dries up saliva so less defense in mouth

2. Anything changing bowel flora can leave us open to invading microbes (example: antibiotics)

What 2 stressors can breach GI system defenses?

1. Flow of urine—wash away microbes

2. Vaginal secretions—slightly acidic thus killing bacteria

Genitourinary (GU) System Defenses count as membrane/glands of body openings. What 2 things falls under this?

1. Decreased urine flow—kidney stones or kidney failure

2. Anything changing vaginal acidity—harsh soaps & douching

What 2 stressors can breach the GU system defenses?

1. Being immediate and nonspecific

2. Expected manifestations like "normal" degree of swelling/heat/erythema /pain (SHEP)

Inflammation is a state of INNAE defense characterized by what 2 things?

- Defend against stressors

- Begin healing process

- AND call in 3rd line of defense as needed

Inflammation is a normal, important body mechanism that helps us do what?

an abnormal state (inflammation is normal!!!)

Since inflammation is an uncomfortable process, it's often mistakenly thought of as...

1. Skin is breached --> red and sore --> clot formation to stop bleeding --> scab forms and seals breach --> less painful as it heals

2. Cut becomes infected --> inflammation increases and becomes more painful but eventually heals

3. Upper resp. infection --> fever and aches miserable but u finally get well

Give 3 examples of normal inflammation situations.

1. Short-lived...acute

2. "Gets out of control", occurs inappropriately, and/or becomes chronic (2+ weeks)

- Ex: bacteria w/ cell walls resistant to breakdown by phagocytes

- Ex: irritants that cause a prolonged inflammatory response

1. A normal inflammatory process is usually short-lived or long-lived?

2. When do we realize that an inflammatory process is considered a disorder?

Shift substances from blood into injured/irritated tissue

The inflammatory response facilitates shifting what?

- To "clean up area and begin clotting process --> promote healing

- Stimulate and enhance immunocyte response (3rd line of defense) as needed

Why does the inflammatory response facilitate shifting substances from blood into injured/irritated tissue?

irritation/injury of tissue triggers same response anywhere in body --> stimulate LEAKINESS in 3 ways

What is Step 1 of the Inflammatory Response?

- Irritated/injured cells that make up tissue undergo disruption to metabolic pathway

- Leads to loss of cell membrane integrity and leaking of fluid/other substances from all injured cells in area

What is the FIRST way that LEAKINESS is stimulated?

MASS CELL DEGRANULATION OCCURS

- Here and there throughout any tissue area in body are a specialized type of cell called MAST cells

- When stimulated by injury/irritant, they degranulate—leak chemical granules

- They're LOCAL inflammatory mediators called Histamine (H), Leukotrienes (L), and Prostaglandins (P)

What is the SECOND way that LEAKINESS is stimulated?

- HLP causes capillaries in area to swell up but also "relax" at same time (this is called vasodilation)

- Capillary becomes more permeable, then "leaks" plasma from blood vessel into tissue space

- "Leaked" plasma has neutrophils, clotting factors, & fibrin

What is the THIRD way that LEAKINESS is stimulated?

- SYSTEMIC inflammatory mediators summoned

- They come to area via bloodstream to pour "FUEL ON FIRE"

- These are called Acute Phase Reactants (ex: CRP aka C-reactive protein, circulating prostaglandins, AND COMPLEMENT SYSTEM)

If MORE inflammation is needed, what happens?

b/c 2nd line is immediate and non-specific!

No matter where inflammation is occurring, the elements of all these steps in the process will be there in one way or another. Why?

1. VASODILATION and LEAKINESS of capillaries & other blood vessels

- there'll always be a degree of vasodilation and increased capillary permeability in area

Always think of what things when you think of INFLAMMATION?

Leaked plasma contains NEUTROPHILS (phagocytic WBC from blood) and MACROPHAGES (phagocytic cells in tissue)

- they phagocytize (eat/destroy) dirt/debris/dying tissue/and or microbes they find in tissue area

Now what is Step 2 of the Inflammatory Response?

1. Combo of plasma, phagocytes, dead tissue cells, bacteria, fibrin, etc results in thick fluid called EXUDATE

2. When there's little microbe involvement, exudate is clear gold and is called SEROUS EXUDATE. If there's some blood it's called SEROSANGUINOUS

3. If more microbe & WBC involvement (infection), exudate becomes thick & white/yellow...PURULENT exudate/pus

Describe Step 2 of the Inflammatory Response. (3 points for this flashcard)

- When bacteria/viruses/other microbes are part of the mix above, macrophages will have phagocytized & processed them now and need help from 3rd line of defense

- 3rd line of defense is lymphocytes...help kill microbes and create memory (immunity) of microbe

Now what's Step 3 of the Inflammatory Response?

1. Secrete chemotactic substances to "call" immunocytes (usually T-cell CD4 lymphocytes) to come to area via bloodstream

2. Display remnants of microbes on cell membranes as a guide to the T-lymphocyte "this is our enemy...create more defenses"

What do Macrophages do to involve the Lymphocytes?

biochemical mediators that summon OTHER substances to certain area or to increase in amount

What are Chemotactic Substances?

Clotting factors, platelets, and fibrin come together in various way in the area to create healing, GRANULATING, tissue.

What is Step 4 of the Inflammatory Response?

laceration/abrasion to skin

Inflammatory Response can be local (internal/external) or systemic. Give an example of Local External.

Appendix irritated by food/microbe --> Normal inflammation responds --> AppendicITIS (becomes dz process bc its ultimately bad for body, but INITIAL inflammation was a normal defense)

Inflammatory Response can be local (internal/external) or systemic. Give an example of Local Internal.

1. Inflammation of pleura when irritated by, for example, a lung cancer cell

2. Thyroid inflamed b/c of autoimmune attack

THESE ARE BOTH LOCAL INTERNAL BTW

1. What's Pleuritis?

2. What's Thyroiditis?

1. Steps in systemic response basically same as local but without a specific focus...systemic happens when body needs extra help of the systemic "cavalry"—like more leukocytes (leukocytosis) and more acute phase reactants (often causing fever)

2. Any stressor which activates and involves local inflammatory response can activate systemic too

Give a quick overview of NORMAL SYSTEMIC inflammatory response.

1. Malaise, aches, pains

2. Fever (from response to increased prostaglandins & acute phase reactants)

3. Lab tests

S&S of systemic inflammation may include:

- Fevers are beneficial since directly kill some microorganisms via heat

- HOWEVER...they can dilate blood vessels...too much vasodilation = low BP

- Fever also increases metabolic rate --> may cause decompensation in very ill/debilitated/elderly patients

Describe the purpose and effects of Fevers.

- CBC will show increased WBCS aka leukocytosis

- Leukocytes (WBCs) increase in number as they're summoned to areas of inflammation

- WBC subtype that's usually most increased are NEUTROPHILS --> Neutrophilia

- Serum CRP (C reactive protein) will be high b/c it's an acute phase reactant—"fuel on fire"

What will Lab tests show in Systemic Inflammation?

5k-10k

What's the normal Leukocyte/WBC range?

50-75%

What's the normal percentage range of Neutrophils?

Quantitative and Qualitative defects

"Not enough" inflammation is an abnormality of inflammation. This can be attributed to what 2 things?

1. Leukopenia—deficiency in WBCs

2. Neutropenia—specific deficiency in neutrophils

What are the 2 Quantitative defects? (ex: from chemotherapy)

1. Chemotactic defects—won't respond appropriately when summoned

2. Impaired function—ex: phagocytes damaged by diabetes mellitus have decreased ability to fight microbes

What are the 2 Qualitative defects?

extra susceptible to infections

Anyone with "not enough" inflammation will be

- These are a group of disorders that stem from genetic defect in synthesis of complement proteins

- Patients w/ defects in these have problems very similar to those seen in patients with antibody deficiencies (or any other defense mechanism deficiency)

- They will be EXTRA SUSCEPTIBLE TO INFECTIONS

Describe Complement Deficiencies.

Inflammation goes into overdrive and/or becomes chronic

- Ex: SIRS, sepsis, septic shock, and chronic inflammation disorders

"Too much" inflammation is an abnormality of inflammation. What is this?

- Occurs when normal systemic inflammatory response goes into overdrive—normal braking system of inflammatory process doesn't occur

- Instead, widespread systemic inflammation occurs in entire body instead of locally

What's Systemic Inflammatory Response Syndrome (SIRS)?

widespread impaired tissue function and organ damage

Excessive systemic inflammation contributes to?

1. Unexplained change in mental status (confusion, not awake/alert as normal)

2. Fever more than 100.4 F

3. Increased heart rate

4. Increased respiratory rate

5. Abnormal WBC count

SIRS is present when 2 (usually more) of what 5 S&S are present?

98.6 F

ALWAYS ALWAYS remember that the normal body temperature is what?

occurs when there's known or suspected infection AND person has SIRS

SIRS + Infection = SEPSIS

What's Sepsis?

occurs when sepsis (infection + SIRS) is complicated by LOW BP

What is Septic Shock?

low BP that causes S&S --> poor tissue oxygenation

What is "Shock"?

1. Occurs in every 1 out of 3 hospital deaths

2. Mortality rate of 50-60%

1. How often does Sepsis Occur?

2. Septic shock carries a mortality rate of?

increases by 10%

Every hour that treatment of sepsis is delayed means mortality increases by?

extreme vasodilation

High lvls of inflammatory mediators triggers widespread what?

- No arterial vessel "tone"

- Arteries become too relaxed/floppy --> blood pools in periphery instead of being part of circulation

- Eventually low volume volume reduces amt of O2 being brought to tissues

All of this contributes to LOW BP that's part of shock

Describe the extreme vasodilation that comes w/ high lvls of inflammatory mediators.

the muscles in their walls constrict & dilate as body needs

Normal arteries have a certain "vasomotor tone". What does this mean?

1. SIRS S&S

2. Low BP causes ischemia to organs --> renal failure, respiratory failure, heart failure, or death

S&S of Septic Shock?