How does you body respond to the presence of microbes 3
- Tolerance - nothing if microbes are friendly/harmless
- Segregation - Keep microbes out of places they should normally be (harmless and harmful microbes)
- Combat - mount and immediate/aggressive anti-microbial response (harmful)
Functions of human immune system 3
- Create a physical/biological/chemical barrier that prevents foreign from entering “internal” body sites
- Recognize and eliminate foreign material
- cancer cells, transplants
- pathogenic micro-organisms - Create memory of old encounters of foreign material
How to deal with different kinds of pathogens
Viruses: defense needs to recognize and eliminate “self” cell acting as host for virus
Bacteria, fungi, parasites: Requires ability to recognize and eliminate nonself microbe while not harming host tissues
Solutions to deal with different kinds of pathogen
Using multiple mechanisms that coop with eachother and back each other up (redundancy)
Defense against foreign microbes occurs by two mechanisms:
- Innate immunity
Non specific defense systems
-respond same way (no preference)
-No memory (repeat exposure don’t improve defenses)
(external barrier defenses and internal cellular/ biological defenses)
Defense against foreign microbes occurs by two mechanisms:
- Acquired/adaptive immunity
Specific defense systems
-individual response designed for each diff. microbe
-memory (a second exposure to the same microbe gives faster and stronger response)
(Antibody-mediated/ humoral immunity and cell-mediated immunity)
Innate Immunity
1.External surface entry barriers
(Intended to block microbes from entering sterile internal tissues)
4
A) Structural Defenses (skin, mucous membranes)
- Hard to penetrate barrier that protects deeper tissues
- Continual loss of dead skin cells removes attached microbes
- Dry, salty environment (of skin) limits growth of microbes
B) Mechanical Defenses
-Flushing action of fluids (urine, tears, saliva)
-Ciliated cells in lungs move mucus (Along with attached microbes) toward mouth -> swallowed and eliminated
(swallow and digest 1 Liter of mucus)
C) Microbial defenses
-Normal microbial flora (eg gut bacteria) out competes pathogenic microbes for nutrients and for attachment sites on tissue surfaces
D) Biochemical Defenses
-Chemical produced by body that harm microorgnanisms or restrict their growth
Eg: Lysozyme
-enzyme in human fluid breaking bond between NAG - NAM in bacterial Peptidoglycan
Innate Immunity
Internal Cellular and Biological Defenses
Come into action if pathogen overcomes surface barriers
4
A) Phagocytosis
B)Inflammation
C)Complement
D)Fever
Phagocytosis
Digest and remove foreign material that
Mainly white blood cells:
-Monocytes, neutrophils, eosinophils (circulate in blood)
-Macrophages (monocytes which moved from blood to deeptissue/organ)
-Dendritic Cells (in tissues close to body surfaces)
- Note: Phagocytosis is a non-specific mechanism → any microbe can be ingested & killed by any phagocytic cell
- ie. no different phagocytic cell for every different species of bacteria
How does phagocyte recognize foreign microbe and not one of your own cells
Pattern recognition receptors - proteins on surface of phagocytes that recognize characteristic molecules found in microbes but not in host cells
eg. Peptidoglycan and LPS (bacteria), chitin (fungi)
How are bacteria actually killed once ingested by phagocyte
Various degradative enzymes and toxic molecules found in lysosome of phagocyte
What happens to the stuff phagocytes spit out
Further degraded and absorbed but can irritate surround tissues if present in large amounts
defensive actions of phagocytes can contribute to the symptoms associated with an infection
Can Bacteria defend themselves against phagocytosis ?
-Produce Capsular polysaccharide
(harder for phagocyte to grab on and ingest)
-Secrete “toxins” that target and destroy phagocytes
-Survive after being ingested
(escape the phagosome-lysosome compartment and enter and grow in cytoplasm
Other ways that cells of the innate immune system can kill microbes (ie. besides phagocytosis)
- Killing something bigger than you (parasite)
-Extracellular killing by eosinophils
(secrete toxic proteins that perforate parasite wall) - Killing something that’s hiding in your own cell (virus)
-Extracellular killing by NATURAL KILLER (NK) cells
(recognize a Virus infected host cell and destroy it by secreting degradative enzymes)
Inflammation
Rapid biological response to tissue dmg as result of:
- cuts, burns, bites, exposure to chemicals
- The action of microbes when causing disease
Five main signs(PRISH):
- Pain
- Redness (erythema)
- Immobility (loss of function)
- Swelling (edema)
- Heat
Purpose of inflammation
- Attract phagocytes and other immune cells to the site of injury
- Begin the processes that will repair and heal injured tissues
Inflammation is a correct and appropriate response to damaged tissues or to the presence of microbes
S&S of Inflammation due to chemicals released after tissue dmg
Eg. Histamine
- Vasodilation (increases blood flow -erythema, Heat)
- Increases permeability of blood vessels (edema)
- Stimulates nerve endings (Pain)
Prostaglandin
-Vasodilation, Fever, increased sensitivity to pain + numerous molecules, proteins involved in repair of tissue, coagulation of blood, stimulation of immune system cells
inflammation can be treated with various drugs that counteract the inflammatory chemicals:
Anti-histamines - Reduce vasodilation & pain
Aspirin, Ibuprofen - Block the synthesis of prostaglandin
Corticosteroids - Multiple effects on cells to suppress the production or release of inflammatory chemicals
Acute Inflammation
- Immediate & beneficial response to tissue injury or microbes
- (1-2weeks) once cause or dmg healed
- no long term consequences
- no treatment needed unless pain severe
Chronic Inflammation
- Delayed and potentially harmful response occurs if issue persists or other conditions (arthritis, ulcerative colitis, asthma)
- Slow to resolve
- Result in tissue dmg and scarring due to phagocytic cell activity
Complement
30 different proteins found in blood serum
- Complemented action of antibodies
- 10% total serum protein
3 Complement Functions
- Make phagocytosis more efficient by “opsonization”
- Complement proteins coat surface of bacterial cells
- receptors on macrophage to better attach to bacterial - Destroy bacteria by forming membrane attack complexed
- insert into bacterial cell membrane to create pore = leakage = death - Regulate inflammation and other immune system responses
- cause vasodilation
- help remove antibody + antigen complexes from circulation
Fever
Biological response to pyrogenic (fever inducing) agents
- External pyrogens- Bacterial LPS, fungal wall components
- Internal pyrogens- Chemicals from phagocytes
Pyrogens cause hypothalamus to produce prostaglandins which set body temp higher
non-pyrogenic = no swelling?
Benefits of fever
- Slows growth of temp sensitive microbes
- reduce availability microbes for growth (low serum levels of iron, zinc, coper)
- Increases metabolic activity of phagocytic cells
- Stimulates acute inflammation
Low grade fever beneficial
High grade fever treated with drugs that block prostaglandin synthesis (asprin)
Summary Innate Immune System
two of three lines of defense against pathogens
- surface entry barriers
- internal (chemical/cellular) barriers
-non specific and lack memory
