Chapter 15

Question 1

An Overview of the Body’s Defenses

Answer 1

• Resistance to most plant and animal pathogens
• Species resistance
  
  • Due to physiological processes of humans that are incompatible with those of the pathogen
    
    • Correct chemical receptors not present on human cells
    • Conditions may be incompatible with those needed for pathogen’s survival
• Number of pathogens for which humans don’t have innate resistance

Question 2

Skin in Innate Immunity

Answer 2

• Structures, chemicals, and processes that work to prevent pathogens entering the body
• Skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems
• The Role of Skin in Innate Immunity
  
  • Skin composed of two major layers
    
    • Epidermis
      
      • Multiple layers of tightly packed cells
      • Few pathogens can penetrate these layers
      • Shedding of dead skin cells removes microorganisms
      • Epidermal dendritic cells phagocytize pathogens
    • Dermis
      
      • Collagen fibers help skin resist abrasions that could introduce microorganisms
  • Skin has chemicals that defend against pathogens
    
    • Perspiration secreted by sweat glands
      
      • Salt inhibits growth of pathogens
      • Antimicrobial peptides act against microorganisms
      • Lysozyme destroys cell wall of bacteria
    • Sebum secreted by sebaceous (oil) glands
      
      • Helps keep skin pliable and less likely to break or tear
      • Lowers skin pH to a level inhibitory to many bacteria
• Axillary (Armpit & Groin area) is different from other parts of the body
• Axillary sweat glands have much more different substances in there than those in other parts of the body, which are antimicrobial
• Different sweat and sweat glands. Axillary sweat glands are thought that sweats composition feeds bacteria. The hair provides surface area for bacteria.
  
  • At sexual maturity an increase in sweat and hair. Purpose? Sexual or non-sexual communication. Evolved before humans used speech. Typically shown among females.
• Pheremones - chemicals communicate state of mind using bacteria. Animal communication is mediated by bacteria.
• Any other sweat glands other than the axillary are still involved in killing bacteria.

Question 3

Mucous Membranes and the Lacrimal (tear) Apparatus in Innate Immunity

Answer 3

• Mucous membranes line all body cavities open to environment
• Two distinct layers
  
  • Epithelium
    
    • Thin, outer covering of the mucous membranes
    • Epithelial cells are living
    • Tightly packed to prevent entry of pathogen
    • Continual shedding of cells carries away microorganisms
  • Deeper connective layer that supports the epithelium
• Lacrimal apparatus
  – Produces and drains tears
  – Blinking spreads tears and washes surface of the eye
  – Lysozyme in tears destroys bacteria

Question 4

Normal Microbiota in Innate Immunity

Answer 4

• Microbial antagonism
  
  • Normal microbiota compete with potential pathogens
• Activities of normal microbiota make it hard for pathogens to compete
  
  • Consumption of nutrients
  • Create an environment unfavorable to other microorganisms. Ex: create metabolic trash like lactic acid
  • Help stimulate the body’s second line of defense
  • Promote overall health by providing vitamins to host
• Some bacteria in microbiota are in very tiny numbers vs. some are in vast amount; e.g. microbiota in anus and vagina as a protection.
• Some nutrient, Vitamin B, and K are produced by bacteria in our microbiota; Vitamin K is involved in coagulation; have some ramification
• Any living bacteria secrete waste, which when piled on, make other competing species inhabitable in that same environment e.g. lactic acid, CO2 etc.
• Bacteria in our microbiota can also break down poisons etc.

Question 5

Other First-Line Defenses

Answer 5

• Antimicrobial peptides
  
  • Present in skin, mucous membranes, neutrophils
  • Act against a variety of microbes
  • Work in several ways
• Other processes and chemicals
  
  • Many organs secrete chemicals with antimicrobial properties

Question 6

Other System’s Defenses

Answer 6

• Digestive system
  
  • Saliva
    
    • important to oral help, is antimicrobial
    • dry mouth common due to medication
    • contains lysozyme
  • Stomach acid
    
    • denatures proteins so enzymes can digest
    • protects against food poisoning
    • proton-pump inhibitor = proton pumps make the stomach more acidic. more likely to have c. dfiff with antihystamine useage
  • Intestinal secretions
    
    • peristalsis helps move food and bacteria away
      
      • similar fuction to vomitting
• Urinary System
  
  • washes microbes away
  • biofilms common on catheters
• Reproductive System
  
  • Vagina
    
    • Acidity promotes growth of friendly bacteria, which kills more bacteria than the action of the low pH itself
      
      • Protects both mother and child
    • e.g. Lactobacillus compete other bacteria from growing
    • Menstral cycle washes out microbes
  • Prostate
    
    • Produces semen (not sperm) which has iron binidng proteins
• Iron
  
  • binds to proteins to keep bacteria away from them because they feed on the iron instead of the protein.
  • Too much iron can be bad because it encourages bacterial growth

Question 7

The Body’s Second Line of Defense

Answer 7

• Operates when pathogens penetrate the skin or mucous
membranes
• Composed of cells, antimicrobial chemicals
– Many of these components are contained or originate in the
blood

– Second line of defense is still INNATE

Question 8

Defense Components of Blood

Answer 8

• Plasma (liquid portion of blood)
  
  • Mostly water containing electrolytes, dissolved gases, nutrients, and proteins
    
    • Serum is the fluid remaining when clotting factors are removed
    • Includes iron-binding compounds, complement proteins and antibodies
• Cells and cell fragments in plasma are called formed elements
• Three types of formed elements
  
  • Erythrocytes
    – Carry oxygen and carbon dioxide in the blood
  • Platelets
    – Involved in blood clotting
  • Leukocytes
    – Involved in defending the body against invaders
    
    • Divided into granulocytes and agranulocytes

Question 9

Schematic representation of hematopoiesis

Answer 9

Question 10

Leukocytes: Granulocytes

Answer 10

• Granulocytes
  – Contain large granules that stain different colors
  
  • Three types
    – Basophils – stain blue with basic dye methylene blue
    – Eosinophils – stain red/orange with acidic dye eosin
    – Neutrophils – stain lilac with mix of acidic and basic dyes
• Neutrophils and eosinophils
  – Phagocytize pathogens
  – Capable of diapedesis (squeeze through tissues)

Question 11

Leukocytes: Agranulocytes

Answer 11

• Agranulocytes
  – Cytoplasm appears uniform under a light microscope
  – Two types
  
  • Lymphocytes
    – Most involved in adaptive immunity (T, B Cells)
  • Monocytes
    – Leave the blood and mature into macrophages

Question 12

Macrophages

Answer 12

• Tissue Macrophage
• Liver Kupffer Cells
• Pulmonary Alveoli Dust Cells (alveolar macrophage)
• Skin/mucosa Langerhans Cells
• Central Nervous System Microglia
• Bone Osteoclast

Question 13

Lab Analysis of Leikocyctes

Answer 13

• Lab analysis of leukocytes (counting # WBCs)
  
  • Differential white blood cell count can signal signs of disease
    
    • Increased eosinophils indicate allergies or parasitic worm infection; Helminth = parasitic worm
    • Bacterial diseases often show increase in leukocytes and neutrophils
    • Viral infections show increase in lymphocytes

Question 14

Phagocytosis

Answer 14

• Phagocytosis
  – Cells capable of phagocytosis are called phagocytes
  – Phagocytosis is not completely understood
  – Can be divided into six stages
  
  • Chemotaxis
  • Adherence
  • Ingestion
  • Maturation
  • Killing
  • Elimination
  • Can An Indian Man Kill Elvis?

Question 15

Terminology regarding Phagocytosis

Answer 15

• Chemotaxis - cell moving towards or away from a chemical stimulus
  
  • Includes chemotactic factors, attract phagocyte to site of infection/damage
  • Movement toward a gradient
  • chemotactic factors - **chemokines ** (-kines = “movement”)- released by tissue, attracts phagocytes
• Adherence - phagocytes stick to pathogen via glycoproteins
  
  • Phagocytosis can be enhanced via **opsonins - **antimicrobial proteins that coat pathogens and allow them to undergoe phagocytosis. Opsonization is the process of coating the pathogen (happens before the ingestion)
  • Phagosome is formed with pathogen
• Ingestion - **pseudopodia - **phagocyte extends pseudopodia, surrounds pathogen, found inside a phagosome
• Maturation - Phagosome fused with lysosome. 30 min to kill pathogen then is a residual body
  
  • Lysosomes have different pH via hydrogen pump (increased H+ content inside thus lower pH)
• ​Elimination - removal of leftover product i.e residual body via exocytosis

Question 16

Nonphagocytic Killing

Answer 16

• Nonphagocytic Killing
• Killing by **eosinophils **
  
  • Attack parasitic helminths by attaching to their surface
    
    • Secrete toxins that weaken or kill the helminth
    • Eosinophilia (elevated eosinophils) is often indicative of a helminth infestation
  • Eosinophil mitochondrial DNA and proteins form structure that kill some bacteria
    
    • Eosinophil catapaults mitochondrial DNA to form some fibers which eventually kill some bacteria
• Killing by natural killer lymphocytes
  
  • Secrete toxins onto surface of virally infected cells and tumors
  • Differentiate normal body cells because they have membrane proteins similar to the NK cells that kills some bacteria
• Killing by neutrophils
  
  • Produce chemicals that kill nearby invaders
  • Generate extracellular fibers called neutrophil extracellular traps (NETs) that bind to and kill bacteria

Question 17

Nonspecific Chemical Defenses Against Pathogens

Answer 17

Nonspecific Chemical Defenses Against Pathogens

• Toll-like receptors (TLRs)
  
  • Play a key role in the innate immune system.
  • Integral membrane proteins produced by phagocytic cells
  • Bind pathogen-associated molecular patterns (PAMPs)
  • Initiate defensive responses
    
    • Apoptosis
    • Secretion of inflammatory mediators
    • Production of stimulants of adaptive immune response
• NOD proteins
  
  • Cytosolic proteins that bind PAMPs
  • They are part of pattern recognition receptors and play key roles in regulation of innate immune response. NLRs can cooperate with Toll-like receptors and regulate inflammatory and apoptotic response.
• Although microflora, sperm, etc. are not self cells, they are not killed by lymphocytes
• Cancer cell is both a self and a non-self in some sense but are targeted by immune system
• Phagocytes are just agent of the bigger overarching immune system.
• Interferons
  
  • ​Protein molecules released by host cells to nonspecifically inhibit the spread of viral infections
  • Cause many symptoms associated with viral infections (thus, can in turn be harmful to us)
  • Two types
    – Types I (alpha and beta)
    – Type II (gamma)
• Complement
  
  • Set of serum proteins designated numerically according to their order of discovery
  • Complement activation results in lysis of the foreign cell
  • Complement can be activated in three ways
    
    • Classical pathway
    • Alternate pathway
    • Lectin pathway
  • Inactivation of complement
    
    • Body’s own cells withstand complement cascade
      
      • Proteins on many cells bind and break down activated complement proteins

Question 18

Pathogen-associated Molecular Patterns (PAMPs)

Answer 18

• PAMPs are NOT found in us normally thus good stratety for our body to detect something as foreign things
  
  • Glycocalyces,
  • Peptidoglycans,
  • Glycopolysaccharides,
  • dsRNA (asso. w/ interferons, which is also not normally found in our body),
  • Non-methylated C on CG pairs (methylation asso. w/ suppression of gene expression where human genome is full of methylated C’s; thus unmethylated ones are more likely from other foreign organisms)
  • Flagellin (except only in sperms)
• Toll-like receptors are receptors for PAMPs

Question 19

The actions of alpha and beta interferons

Answer 19

1. Virus infects cell
2. Viral replications in cell triggers transcription and translation of alpha or beta interferon (IFN) depending on type of host cell.
   
   1. Interferon serves as signal that something is up, i.e. cells are under seige.
3. Interferon is released, diffuses to neighboring uninfected cells, and binds to receptors.
4. Binding triggers transcription and tanslation of inactive antiviral proteins (AVPs).
5. Meanwhile, the infected cell dies and releases the virus.
6. When the second cell becomes infected with viruses, double-stranded RNA of the virus activates AVPs.
7. Active AVPs degrade mRNA and bind to ribosomes, which stops protein synthesis and viral replication.
   
   1. Shut off the synthesis of material in the cells; no host mRNA, etc.; very harsh on cells

• Interferons are very species specific
• Interferons are also used for treating Hep B and C, where Hep C has no vaccine available; also used for herpes, certain cancers, etc.
• Although this defense mechanism is very harsh on cells, virus will hopefully die off more readily and thus havve a chance of receovering in long-term; alluding to how chemotherapy works.

Question 20

Pathways by which Complement is activated

Answer 20

• Classical pathway: when antibody binds to antigen which lead to complement cascade
• Alternative pathway: when endotoxin and glycoproteins are bound by Factors B, D, and P that lead to complement cascade
• Lectin pathway: when lectins bind to mannose (sugar found specifically in bacteria) which lead to complement cascade.
• All three pathways first lead to opsonization inflammation where opsonin coats the antigen, making it more likely to be phagatocyzed by phagocitic cells

Question 21

Inflammation

Answer 21

• Nonspecific response to tissue damage from various causes
• Characterized by redness, heat, swelling, and pain
• Two types
  
  • Acute
  • Long-lasting (chronic)

Question 22

Acute Inflammation

Answer 22

• Develops quickly and is short lived
• Is typically beneficial
• Is important in the second line of defense
  
  • Dilation and increased permeability of the blood vessels
  • Migration of phagocytes
  • Tissue repair
• Four signs of acute inflammation:
  
  • tumOR - “swelling”
  • rubOR - “redness”
  • calOR - “heat”
  • dolOR - “pain”
• All due to blood flow into the area; e.g. dalor (blood pressing on nerve endings)
• Not just limited to reaction to microbials, can be due to anything
• e.g. gingivitis - both inflammation AND infection

Question 23

Increased vascular permeability during inflammation

Answer 23

• Vasodilation due to inflammation
  
  • vs. Vasoconstriction - opposing effect
• Diapedesis - molecules work their way through blood vessel membranes
• During normal permeability of venule, only small amount of fluid escape the blood vessels.
• During increased permeability of venule (vasodilation) due to inflammation, interstitial spaces are enlarged and thus more fluid and antimicrobial chemicals, e.g. monocytes, squeeze through i.e. diapedesis.

Question 24

An overview of the events of inflammation

Answer 24

1. A cut penetrates the epidermis barrier, and bacteria invade.
2. Damaged cells release prostaglandins, leukotrienes, (both of which are called eicosanoids) and histamine
3. Prostaglandins and leukotrienes make vessels more permeable. Histamine causes vasodilation, increasing blood flow to the site.
4. Macrophages and neutrophils (both of which are phagocytic) squeeze through walls of blood vessels (diapedesis).
5. Increased permeability allows antimicrobial chemicals and clotting proteins to seep into damaged tissue but also results in swelling, pressure on nerve endings, and pain.
6. Blood clot forms
7. More phagocytes migrate to the site and devour bacteria
8. Accumulation of damaged tissue and leukocytes forms pus.
   
   1. Pus contains dead/alive macrophages, dead/alive tissues, and dead/alive pathogens
   2. Abscess - walled off and isolated site of pus
   3. Pustule, pimples are also types of pus.
9. Undifferentiated stem cells repair the damaged tissue. Blood clot is absorbed or falls off as a scab.
   
   1. Scar tissue is the next best thing to stem cells

Question 25

Fever

Answer 25

• A body temperature over 37C
• Results when pyrogens trigger the hypothalamus to increase the body’s core temperature
• Various types of pyrogens
  
  • Bacterial toxins
  • Cytoplasmic contents of bacteria released by lysis
  • Antibody-antigen complexes
• These signal for the production of interleukin-I (IL-1)
• Fever alerts the person that something isn’t right in the body.
  
  • Homeopathic medicine - incuding even more fever may be beneficial (theory has died out).