Lecture 2 Immune System I: Innate

Question 1

What does immunis mean in Latin?

Answer 1

Exempt

If you recover, you never get it again

Question 2

What happened in 18th century in origin of immunology?

Answer 2

Jenner defined vaccination

Question 3

What systems make up the immune system?

Answer 3

Lymphatic system
Blood

Question 4

What organs are in the immune system? (4)

Answer 4

1. Bone marrow
2. Thymus
3. Lymph nodes
4. Spleen

Question 5

What are the two types if cells in immune system?

Answer 5

Innate & Adaptive

Question 6

Give 3 examples of molecules in immune system?

Answer 6

Antibodies
Cytokines
Complement

Question 7

How do we fight infection? (3) what are the innate and adaptive stages

Answer 7

1. Stop pathogen entering - innate
2. If it enters, flush it out, kill it, control it
3. Once you’ve defeated it, remember it - adaptive

Question 8

How does skin stop pathogens entering? (4)

Answer 8

Mechanical barriers I

• Dead skin cells on surface prevent viral infections
• Population of harmless bacteria on surface of the skin compete for binding sites with pathogens
• sebaceous gland
  
  • fatty acids
  • lactic acid
  • low pH (3-5)- inhibits microbial growth
• skin is dry which inhibits bacterial growth

Question 9

How do tight junctions stop pathogens from entering ?

Answer 9

Mechanical barriers II

Tight junctions to stop ingested antigens passing into body

Question 10

How do Mucosal surfaces stop pathogens entering? (3)

Answer 10

Mechanical barriers III

Mucus traps microorganisms which are then shed from the body

Mucosal surfaces have: cilia and mucus secreting cells e.g. respiratory mucous membrane

Mucus is slippery

Question 11

What are the pH and environment physiological barriers? (2)

Answer 11

1. Low pH in stomach - kills pathogenic microorganisms
2. Normal commensal microbiota - out compete pathogenic strains for nutrients

Question 12

What are the chemical mediator physiological barriers? (4)

Answer 12

1. Anti-microbial peptides - Defensins damage pathogens
2. Anti-microbial proteins - Lysozyme in tears & saliva
3. Cytokines - Interferons induce anti-viral state in cells
4. Complement - M-A-C lyses bacteria

Question 13

Why are parasites effective pathogens?

Answer 13

• Evade the innate immune response
• Vectors burrow straight through skin
• Hook on to avoid being flushed

Question 14

What happens once a pathogen has broken through innate barriers?

Answer 14

Inflammation

Question 15

What are the 3 Phagocytes that are innate immune cells?

Answer 15

1. Macrophages - ‘Big -Eaters’
2. Neutrophils
3. Dendritic cells

Phagocytes - cells that eat

Question 16

What does NET stand for ?

Answer 16

Neutrophil Extracellular Traps

Question 17

What do NETs do?

Answer 17

Trap bacteria during appendicitis

Question 18

What are the granulocytes which are innate immune cells ?

Answer 18

1. Neutrophils
2. Basophils
3. Eosinophils
4. Mast cells

Granulocytes- granule containing cells

Question 19

What are the 4 signs of inflammation?

Answer 19

1. Heat (calor)
2. Redness (rubor)
3. Swelling (Tumor)
4. Pain (dolor)

Question 20

5 stages of local inflammatory response? (Glass in skin)

Answer 20

1. Chemokine release
2. Activation of clotting and complement cascades
3. Neutrophils secrete chemokine to recruit monocytes from blood
4. Phagocytosis of pathogens
5. Macrophages migrate into tissue & screte IL-1 & TNF-alpha to recruit lymphocytes, monocytes & neutrophils

Question 21

What happens during chemokine release in inflammatory response? (3)

Answer 21

1. CXCL8/IL-8 release from damaged endothelial cells
2. TNF-alpha release from macrophages to help recruit neutrophils and allow migration from blood
3. Histamine release from mast cells- vasodilation and increased blood vessel permeability

Question 22

Signs of inflammation

Answer 22

Increased blood supply
Increased blood vessel permeability
Increased leukocyte migration to area

Question 23

Inflammation - glass cut through skin (4)

Answer 23

1. Tissue damage & bacteria cause resident sentinel cells to release chemoattractants & vasoactive factors that trigger a local increase in blood flow and capillary permeability
2. Permeable capillaries allow influx of fluid (exudate) and cells
3. Phagocytes and antibacterial substances destroy bacteria
4. Neutrophils and other phagocytes migrate to site of inflammation (chemotaxis)

Question 24

Systemic acute- phase response (3)

Answer 24

1. Fever (speeds up phagocytosis & body reactions but is costly)
2. Leukocytosis (white cell production increase)
3. Acute phase protein production by the liver
   - C-Reactive Protein (CRP)
   Binds to microbes, activates complement proteins to aid phagocytosis
   - Type-1 Interferons, IL-6, CXCL8 - activate neutrophils & macrophages

Question 25

What is the complement system ?

Answer 25

A group of serum proteins in the blood that performs critical defence against pathogens, especially extracellular bacteria >35 proteins in this system Most complement proteins made in liver Some produced in large quantities during acute phase response stimulated by the pro-inflammatory cytokines IL-6 & TNF- alpha Has links to both innate & adaptive immunity

Question 26

What are the 7 different functional categories complement proteins can be put into?

Answer 26

1. Initiators- bind pathogens components or antibodies 2. Enzymes (convertases) 3. Opsonins - promote phagocytosis 4. Anaphylatoxins - cause inflammation 5. Membrane attack proteins - lyse pathogens 6. Complement receptors - on phagocytes or neutrophils 7. Regulatory proteins - limit complement activation

Question 27

How does the body sense infection ?

Answer 27

1. Innate immune system detects molecules from pathogens: Pathogen Associated Molecular Patterns (PAMPs) 2. It does this by using Pattern Recognition Receptors (PRRs)

Question 28

7 stages of phagocytosis

Answer 28

1. Bacteria have Pathogen Associated Moleculat Patterns (PAMPs) 2. Phagocytes have Pattern Recognition Receptors PRRs 3. Bacterium becomes attached to pseudopodia 4. Bacterium is ingested forming phagosome 5. Phagosome fuses with lysosome 6. Bacterium is killed & digested by lysosomal enzymes & reactive oxygen species 7. Digestion products are released from cell

Question 29

In phagocytosis what are the 2 separate killing mechanisms after each negation of the bacteria?

Answer 29

Oxygen-dependent killing And Oxygen-independent killing

Question 30

What is oxygen-dependent killing

Answer 30

- oxidative burst - superoxide and other toxic oxidants are generated - acts as anti-microbial

Question 31

What is oxygen-independent killing?

Answer 31

- lysozyme- hydrolytic enzyme - defensins- peptides kill many bacteria

Question 32

Why are parasites effective pathogens?

Answer 32

Too big to be phagocytosed

Question 33

Function of anti-microbial peptides and give example

Answer 33

Insert into and disrupt the pathogens membrane causing cell death E.g. defensin

Question 34

Function of anti-microbial proteins?

Answer 34

Cleave peptidoglycan in bacterial cell wall E.g. lysozyme