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Transcript
Lecture 13: Innate Immunity
Silverthorn Chapter 24
Immune System Overview
The immune system is responsible for patrolling the body and identifying SELF vs NONSELF. The identification of NON SELF
substances relies on the presence of an ANTIGEN: a specific chemical (usually a protein) that initiates an immune response.
The immune responses can be divided into TWO categories (though there is significant overlap between the two categories)…
INNATE IMMUNITY: Non-Specific
ACQUIRED IMMUNITY: Specific
- Present from birth
- Acquired over time…
- Fast response
- Takes days to mount effective response
- Fights all foreign cells with same strategies
- Mounts a specific response to each invader
- Phagocytosis
- Antigen causes a specific response
- Characterized by inflammation
- Can “remember” a repeat offender
- Complement
INNATE IMMUNE RESPONSE (patrolling WBC that attack anyone they identify as foreign, based on broad-ranging qualifications)
Inflammation
Characterized by 4 signs: Redness, Swelling, Heat, Pain
Purposes:
1.
2.
3.
4.
Attract blood cells to injury site
Create a physical barrier that prevents spread of invader
Promote tissue repair once infection has been dealt with (not immune!)
Caused by inflammatory cytokines (proteins produced in one cell (often WBC) that impact function of another cell) that
promote:
A. INCREASED PERMEABILTY OF CAPILLARY MEMBRANE:
i. Opens capillary pores, allowing plasma proteins to enter interstitial space
ii. Increase osmotic pressure in interstitum b/c proteins go OUT!
iii. Enables diapedesis (easier to get through) (di a peh dEEsis) Migration of immune cells from blood to tissue
iv. WBC who go through membrane follow chemotaxins (a molecular trail marking the way to the site of inflammation)
Movement of immune cells toward infection site (Chemotaxins are chemicals that attract immune cells to damaged
site)
v. Also increases plasma proteins getting to site of inuury, including:
a. Antibodies
b. Complement proteins
c. Clotting factors (for repair, but also keep pathogens isolated to the area of damage!)
vi. Causes SWELLING and PAIN
B. VASODILATION:
i. Dilates blood vessels, increasing blood flow to area
ii. Causes REDNESS an d HEAT
Complement
Complement is a cascade of chemical reactions that pop cellular invaders and promote inflammation
1. A group of 25+ plasma proteins that create a cascade
A. Culmination of cascade: membrane attack complex (MAC)
i. MAC pokes holes in the cell membranes of bacteria and virus-infected cells, allowing ions (and water) to enter and lyse
the cell.
Bio 7: Human Physiology
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Spring 2014: Riggs
B. Intermediates in cascade:
i. Inflammatory mediators
ii. Opsonins (encourage phagocytosis!)
2. Antibodies can stimulate complement!
A. Binding reveals that complement binding site in its armpit!!!
B. This activates complement protein 1, and STARTS THE CASCADE!!!
Non-specific phagocytosis
Phagocytes remove sketchy substances.
1. Who does it?
A. Natural Killer lymphocytes, Macrophages/Monocytes, Neutrophils, Eosinophils, Dendritic cells
2. How do they know who to eat?
A. PRR (Pattern Recognition Receptors) on phagocyte surface including TOLL-LIKE RECEPTORS
i. Recognize and bind to common pathogen molecules called Pathogen Associated Molecular Patterns (PAMPs)
a. Flaggelin
b. Peptidoglycan
c. Lipoplysaccharide (endotoxin)
ii. BINDING causes phagocytosis
B. Sometimes foreign invaders cannot be phagocytosed unless they are coated with OPSONINS (particles that bind to bacteria
and enable phagocytes to recognize them as “food”)
C. Antibodies can act as opsonins!
3. What happens after phagocytosis?
A. Ingested pathogen enclosed in a vesicle binds with a lysosome and gets digested
B. Sometimes pathogen body parts are posted on MHC platforms and used to activate acquired immunity…
Natural Killer Cells
NKC’s are specialized lymphocytes that make up 2% of the population that destroy SELF cells that are malfunctioning
1. Identify cells lacking normal MHC-1 proteins…removal of these proteins happens to a cell infected by a virus, and ALSO
cancerous cells!
2. Kill self cells by promoting apoptosis.
Fever
Fever is a symptom caused by cytokines called pyrogens (pg 751)
1. Advantages of fever:
A. Enhances WBC activity…(some immune reactions happen BETTER at higher temps!)
B. Pyrogens decrease plasma iron concentrations, which might inhibit bacterial growth
C. High temp can inhibit bacterial growth
2. Disadvantages:
A. Fever 106+ can cause brain damage
B. Makes you feel like hell…
3. Temperature is controlled in the hypothalamus…Pyrogen mechanism of action:
A. Resets the thermostat to a higher level!
B. Normal temp now feels cold; body responds by inducing temp raising mechanisms
i. Ex: Shivering!
ii. (And blanket gathering!)
Bio 7: Human Physiology
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Spring 2014: Riggs
External Brain 13: Innate Immunity
Study Guide
1. What are the four cardinal signs of inflammation?
2. What are the physiological causes that result in the four cardinal signs of inflammation?
3. Define diapedesis and chemotaxis.
4. What is complement?
5. What is the Membrane Attack Complex?
6. How do antibodies initiate complement?
7. How do non-specific phagocytes know what organisms to ingest?
8. What is an opsonin?
9. What are natural killer cells? Compare them to the lymphocytes involved in the acquired immune response.
10.Briefly describe how body temperature is maintained. Relate this to a fever.
11. What is a pyrogen?
12.What are some advantages of fever?
Bio 7: Human Physiology
46
Spring 2014: Riggs