Innate immune system, fever, intro to antibiotics

Question 1

Immunity

Answer 1

• The ability to resist organisms or toxins that tend to damage the tissues and organs.

Question 2

Acquired immunity

Answer 2

• Immunity that does not develop until the body is attacked by a bacterium, virus, or toxin.
• It often takes weeks to months for this type of immunity to develop

Question 3

Innate Immunity

Answer 3

• Immunity that comes from general process - not from processes directed at the specific organism.
• It is the first line barrier and rapid response mechanism to prevent invasion.
  
  • Protects the body during period between microbe exposure and start of adaptive response
• Components are inherited from parent to child (present at birth).

Question 4

Components of the Innate Immune system

Answer 4

1. Physical barries - tight junctions in skin, epithalial and mucous membrans, mucus, vascular endothelial cells that prevent penetration of the intestines.
2. Enzymes in epithelial and phagocytic cells (lysozymes)
3. Inflammation- related serum proteins - complement componenets, C-reactive protein
4. Antimicrobial peptides on cell surface and in phagocyte granules
5. Cell receptors that sense micro-organisms and signal a defensive response
6. Cells that release cytokines and other inflammatory mediators
7. Phagocytes - neutrophils, monocytes, macrophages
8. The microbiome - collection of bacteria, fungi, and viruses that live in and on the body. Microbiome plays a role in the maturation of the immune system, protects aginst pathogen overgrowth, and aids in the balance between inflammation and immune homeostasis.

Question 5

Main function of the innate immune system

Answer 5

• Detection of micro-organisms and first-line defense against invasion and infection
  
  • Response of innate immune system is due to proteins ability to recognize and interact with components specific to the microbe (Pattern Recognition Receptors)
• Regulation of inflammation - swelling, redness, heat, and pain are due to the actions of innate immunity
• Maintenance of immunologic homeostasis in host
• Activation and instruction of adaptive immune responses

Question 6

Pattern Recognition Receptors (PRR)

Answer 6

• Receptors that recognize a specific components of the microbe. There are 2 groups of PRRs

1. Secreted and circulating pattern recognition receptors - mediate direct microbial killing, act as helper proteins for transmembrane receptors, and enhance phagocytosis.
2. Cell-associated pattern recognition receptors - membrane bound PRRs. They are found on mnay cells of the innate immune system and various antigen-presenting cels. On these cells, transmembrane signaling PRRs induce rapid upregulation of other PRRs on activation.

Question 7

Pathogen-associated molecular patterns (PAMPs)

Answer 7

• Patterns that are highly conserved in pathogens, allowing them to be recongized by PRRs
• Features:
  
  • Only produced by microbes
  • Typically invariant strucutres shared by enture classes of pathogens
  • Structures are necessary for integrity, survival, and pathogenicity of the micro-organism (makes it so PAMPs can’t mutate to avoid host defense)

Question 8

Cells of the Innate immune system

Answer 8

• Neutrophils, monocytes, macrophages, eosinophils, basophils, mast cells, natural killer cells, epithelial cells, platelets, innate lymphoid cells, dendritic cell, and adipocytes
• Phagocytes (neutrophils, monocytes, and macrophages) are the critical component.

Question 9

Neutrophils

Answer 9

• Most abundent circulating phagocyte
• First cell recuited in areas of infection/inflammation (neutrophils are attaracted to chemotactic factors generated at these sites.
• Once they reach infected site, neutrophils phagocytose the invading micro-organisms that have been opsonized (prepared for phagocytosis) by innate and acquried immune preocesses.
• Once ingested, microbicidal mechanisms kill the microbes

Question 10

Monocytes and macrophages

Answer 10

• Monocytes - develop in the bone marrow and circulate before entering tissue
  
  • Most serve to renew macrophage population by differentiating into macrophages characterisitic for the tissue
• Macrophages - express many PRRs on cell surface
  
  • Respond rapidly to presence of microbes
  • Digest microbes and present microbial antigens to lymphocytes to initiate adaptive immune response
  • Secrete various proteins that mediate host defense and inflammation

Question 11

Eosinophils

Answer 11

• Release extracellular traps carrying gransules that secrete their contents when stimulated
• Play role in resisting parasitic infection
• These cell circulate, but are mainly found in the lamina propria of the GI tract

Question 12

Basophils

Answer 12

• Leukocytes that only appear in the blood
• Play a role in inflammation and in the allergic response

Question 13

Mast cells

Answer 13

• Found in the interstitium of peripheral tissue
• Express TRL
• On PRR activation, mast cells release tumor necrosis factor alpha and IL-8
• Produce classic inflammatory mediators (histamine, heparine, leukotrienes, platelet-activating factor), proteases, and AMPs
• Have immunomodulatory, antimicrobial, and antiprotozoan function

Question 14

Natural Killer Cells

Answer 14

• Lymphoid cells that don’t express antigen-specific receptors
• When activated, NK cells release granules that damage the target cell membrane and induce apoptosis
• Distinguish and avoid healthy host cells through receptors that recognize MHC class 1 molecules expressed on healthy (bindings of these receptors inhibits NK activity)

Question 15

Dendritic cell

Answer 15

• Major antigen presenting cell - starts life in unprogrammed, innate, state
• Phagocytotic
• Plays role in linking adaptive and innate immunity
• Capture, process, and present antigens to t-cells to induce adaptive immunity or tolerance to self-antigens

Question 16

How does innate immunity work with adaptive immunity?

Answer 16

• Innate immune system communicates directly with adaptive immune cells
  
  • Release mediators that activate and instruct antigen-specific T and B lymphocyte responses
• Cells of innate immune system provide a first line response. However, they cannot function optimally without specific antibodies and sensitized T cells

Question 17

Skin layers

Answer 17

Question 18

Skin as a barrier

Answer 18

• The most important function of the skin is to form a barrier between organism and environment
  
  • The physical barrier of the skin is mainly the stratum corneum layer
• The skin prevents excessive water loss (inside-outside barrier) and entry of harmful substanes (outside-inside barrier)

Question 19

Outside-inside barrier of the skin

Answer 19

• Portects against
  
  • Mechanical assaults (irritation, UV radiation, heat and cold shock)
  • Microbial assaults (bacteria, fungus, virus)
  • Chemical assaults (irritants, allergens)

Question 20

Skin flora

Answer 20

• Micro-organism that reside on the skin
• Generally, skin flora is non-pathogenic and may have some benefit to the host - ex. can prevent pathogenic bacteria from colonizing skin surface (competes for nutrients, secretes chemicals against them, or stimulates skin immune system)
• However, skin microbes can cause skin disease and enter blood, creating life-threatening conditions

Question 21

Main “areas” of skin and its flora

Answer 21

• Sebaceous - Propionibacteria and staphlyococci species dominate (have greater species richenss than moist or dry areas)
• Moist - corynebacteria and staphylococci dominate
• Dry - b-proteobacteria and flavobacteria dominate

Question 22

Skin Defenses

Answer 22

• Antimicrobial peptides (cathelicidines) - controls proliferation of skin flora. Also causes secretion of cytokines which induce inflammation, angiogenesis (process where new blood vessels form from old ones), and re-epithalization (wound healing).
• Acidity - superficial layers of skin are naturall acidic (pH 4-4.5) due to lactic acid in sweat and those produce by skin flora. At this pH, mutualistic flora is able to gorw, but not some more virulent types
• Immune system - if activated, skin produces cell-mediated immunity against microbes
  
  • Increase stratum corneum turnover to shed fungus and bacteria from the skin

Question 23

Bacteria Classification

Answer 23

• Gram Staining
  
  • Gram positive - stains PURPLE. Larger peptidoglycan cell walls holds strain
  • Gram negative - stains PINK
• Morphology
  
  • Cocci - Spherical
  • Bacilli - Rod shaped
• Arrangement
  
  • Chains
  • Clusters
• Size
• Growth requirements
  
  • Anaerobic - can grow WITHOUT oxygen
  • Aeorbic - can only grow WITH oxygen

Question 24

Complement

Answer 24

• Proteins produced in the liver - exist in the body in unactivated (zymogen) state until needed.
• Can be activated via
  
  1. Classical Pathway (antibody-antigen complexes)
  2. Lectin Pathway (mannose-binding lectin binds to pathogen surface)
  3. Alternative pathway (mcirobe directly binds to complement protein)
• Results in
  
  • Inflammation - vasodilation increases permeabilization and allows antibodies, WBCs, etc. to leak out of the blood vessels and into the infected area.
  • Formation of membrane attack complexes - punches hole in bacterial cell wall
  • Opsonization - complement proteins caot surface of bacterium and signals phagocytosis.