4. Innate immunity

Question 1

List and describe the factors determining the outcome of the host- pathogen relationship

Answer 1

Infectivity- This is the ability of the microbe to establish itself on the host or within the host

Virulence- This is the capacity of the micorbe to do damage to the host

Question 2

define the immune system

Answer 2

The cells and organs that contribute to immune defences against infectious and non-infectious conditions (self vs non-self)

Question 3

define infectious diseases

Answer 3

This is when the pathogen succeeds in evading and/or overwhelming the host’s immune defences

Question 4

What are the three risk groups more susceptible to infection? (Not caused by disease, other environmental factors or induced)

Answer 4

Children, elderly, pregnant women

Question 5

What does the spleen do?

Answer 5

It filters bacteria out of the blood, produces phagocytes to fight off foreign invaders.

Question 6

Give the roles of the immune system

Answer 6

• Pathogen recognition- cell surface and soluble receptors
• Containing/eliminating infections- killing/clearance mechanisms
• Regulating itself- minimum damage to the actual host ie autoimmune - The immune system needs to know when to stop to prevent it from enacting damage against itself.
• Remembering pathogens- prevention of recurring, great in vaccinations

Question 7

What is innate immunity?

Answer 7

• Nonspecific protection against foreign substances indiscriminantly.
• Fast (within seconds), immediate
• Lack of memory - no antibodies
• No change in intensity

Question 8

What is adaptive immunity?

Answer 8

• Your immune responses to a specific invader, in which both B and T lymphocytes respond to.
• Slow (takes days), long lasting
• Specific
• Immunologic memory
• Changes in intensity with exposure

Question 9

List the 4 different innate barriers to infection and their collective function

Answer 9

1. Physical barriers
2. Physiological barriers
3. Chemical barriers
4. Biological barriers

Collectively these barriers work to prevent entry and limit growth of pathogens.

Question 10

Describe the physical barriers involved in innate immunity

Answer 10

1. Skin (surface area 1-2 m2)
2. Mucous membranes (lines cavities inside the body and prevents an ingress of pathogens)
   - Mouth
   - Respiratory tract
   - GI tract
   - Urinary tract
3. Bronchial cilia
   These are present in the lungs and expel out mucus trapped microbes via the cilia

Question 11

Describe the physiological barriers involved in innate immunity

Answer 11

Expulsion of pathogens from the body
• Diarrhoea- food poisoning
• Vomiting- food poisoning, hepatitis and meningitis
• Coughing- pneumonia
• Sneezing- sinusitus
This however spreads the pathogens to others.
However it’s important to understand that these actions aren’t exclusively associated with infection.
E.g coughing is also associated with asthma.

Question 12

Describe the chemical barriers involved in innate immunity

Answer 12

Low pH
1. Skin (5.5)
2. Stomach (1-3)
3. Vagina (4.4)
Microbes can't survive in these low pHs. 

Antimicrobial molecules
1. IgA (Tears, saliva, mucous
membrane )- attaches to microbes and prevents it from binding to their host cells
2. Lysozyme (sebum, perspiration, urine)
3. Mucus (Mucous membranes)
4. Beta-defensins (epithelium)
5. Gastric acid + pepsin

Question 13

Describe the biological barriers involved in innate immunity

Answer 13

Normal flora

• non pathogenic microbes in strategic locations

Question 14

Where are normal non pathogenic microbes found?

Answer 14

o Nasopharynx
o Mouth/Throat
o Skin
o GI tract
o Vagina (lactobacillus spp)
• Absent in internal organs/tissues

Question 15

What are the benefits of normal flora?

Answer 15

• Compete with pathogens for attachment sites and resources
• Produce antimicrobial chemicals
• Synthesize vitamins (K, B12, other B vitamins)
• Immune maturation

Question 16

Give examples of normal flora that inhabit the skin

Answer 16

• Staphylococcus aureus (week 1, case 1)
• Staphylococcus epidermidis
• Streptococcus pyogenes
• Candida albicans
• Clostridium perfringens

Question 17

Give examples of normal flora that inhabit the nasopharynx

Answer 17

• Streptococcus pneumoniae (week 3, case 2)
• Neisseria meningitidis (week 3, lecture case)
• Haemophilus species

Question 18

Where are mucous membranes found?

Answer 18

respiratory tract, gastrointestinal tract, genitourinary tract, mouth

Question 19

When do normal flora become pathogenic?

Answer 19

When displaced from their normal location to other sites in the body

Question 20

How can normal flora be displaced from its normal location to sterile locations?

Answer 20

1. Skin flora
   - Skin loss (burns)
   - Surgery
   - IV lines
   - Skin diseases
   - Injection drug users
   - Tattooing/ body piercing
2. Fecal-oral flora
   - Foodborne infection
3. Fecal-perineal-urethral flora
   - Urinary tract infection
4. Oral/ teeth flora
   - Dental extraction
   - Gingivitis (inflammation of the gums)
   - Brushing/ flossing)

Question 21

There are certain patients that are at a high risk of infections due to specific conditions name them

Answer 21

1. Asplenic (and hyposplenic) patients
2. Patients with damaged or prosthetic valves
3. Patients with previous infective endocarditis
4. Patients with diabetes
5. AIDS patients
6. Patients with malignant diseases
7. Patients undergoing chemotherapy(muscositis - inflammation of mucosal membrane which increases surface area for attachment for pathogens to get in)

A lot of these patients(4,5,6,7) are immuno-compromised meaning that their immune system is working below the normal rate

Question 22

The use of antibiotics can affect the normal flora levels in mucosal surfaces give an example in the intestine

Answer 22

In the intestine you can have severe colitis due to the development of the bacterium Clostridium difficile.
The normal intestinal flora have been dramatically reduced due to the use of antibiotics which reduces competition for pathogens and allows the bacterium to grow.

Question 23

The use of antibiotics can affect the normal flora levels in mucosal surfaces give an example in the vagina

Answer 23

In the vagina you can have thrush because of the development of the Candida albicans fungi.
The normal vaginal flora have been dramatically reduced due to the use of antibiotics which reduces competition for pathogens and allows the fungi to grow.

principle is that antibiotics deplete the good bacteria, allowing infection to occur

Question 24

List the second lines of defence in the innate immune response and give their role

Answer 24

1. Phagocytes
2. Chemicals
3. Inflammation
   These factors are used if the innate barriers fail - they will contain and clear the infection.

Question 25

What are the functions of macrophages

Answer 25

- Present in all organs - Ingest and destroy microbes (Phagocytosis) - Present microbial antigens to T cells (adaptive immunity) - Produce cytokines/chemokines

Question 26

What are the functions of monocytes

Answer 26

- Present in the blood (5-7%) | - Recruited at infection site and differentiate into macrophag

Question 27

What are the functions of neutrophils

Answer 27

-Present in the blood (60% of blood leukocytes) -Increased during infection -Recruited by chemokines to the site of infection -Ingest and destroy pyogenic bacteria: Staph. aureus and Strep. pyogenes

Question 28

What are the functions of basophils/mast cells

Answer 28

- Early actors of inflammation (vasomodulation, regulation of blood flow) - Important in allergic responses

Question 29

What are the functions of eosinophils

Answer 29

Defence against multi-cellular parasites (worms)

Question 30

What are the functions of natural killer cells

Answer 30

Kill all abnormal host cells (virus infected or | malignant)

Question 31

What are the functions of Dendritic cells

Answer 31

Present microbial antigens to T cells (acquired immunity)

Question 32

Define pyogenic

Answer 32

pus producing

Question 33

What does pus contain?

Answer 33

Neutrophils

Question 34

How do phagocytes recognise pathogens?

Answer 34

* PAMPS and PRRs | * Opsonins

Question 35

Describe how phagocytes recognise pathogens by PAMPS and PRRs

Answer 35

One way in which pathogens can be recognised is through the use of PAMPS and PRRs. PAMPS (pathogen associated molecular patterns) are microbial structures found on the surface of the pathogen these can be recognised by phagocytes using PRRs (pathogen recognition receptors). An example of this would be toll like receptors (TLR) E.G lipopolysaccharide (LPS) and TLR4.

Question 36

What do cytokines do?

Answer 36

further stimulate Th, B, and Tc cells

Question 37

What is the PRR used against lipopolysaccharide? In which type of bacteria is this found?

Answer 37

TLR4 Gram negative bacteria

Question 38

Describe how phagocytes recognise pathogens by opsonins

Answer 38

Another way in which pathogens can be recognised would be through the opsonisation of microbes. Opsonins are coating proteins that bind to the microbial surfaces and allow enhanced attachment of phagocytes to the microbes to increase the level of clearance. They signal for the engulfment and the degradation of infectious microbes when opsonin receptors on phagocyte bind to the opsonin. Examples include C3b and IgG.

Question 39

What are phagocyte microbe interactions

Answer 39

Recognition processes and killing processes

Question 40

What does the binding of PAMPs and PRRs simulate?

Answer 40

When PRRs bind to PAMPs - simulates release of cytokines/ chemokines for inflammatory response

Question 41

Give examples of opsonins

Answer 41

``` Complement proteins • C3b • C4b Antibodies • IgG • IgM Acute phase proteins • C-reactive protein (CRP) • Mannose-binding lectin (MBL) ```

Question 42

What is Encapsulated bacteria and why are opsonins important

Answer 42

Bacteria that possess thick carbohydrate coats that protect them from phagocytosis. Encapsulated bacteria cause extracellular infections and can be dealt with by phagocytes only if the bacteria are first coated with antibody and complement. Opsonins allow this coating and recognisition

Question 43

What are examples of encapsulated bacteria? Which organ is essential in their clearance?

Answer 43

1. Strep pneumoniae 2. Haemophilus influenzae B 3. Neisseria meningitidis Spleen

Question 44

What are acute phase proteins?

Answer 44

* A class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. They are produced by the liver. * Enhance the inflammatory response and aid innate immunity * They include opsonins and complement proteins (but not antibodies as these are produced by B cells not the liver)

Question 45

What are the two pathwyas of phagocytosis

Answer 45

There are 2 types of pathways in which phagocytes kill pathogens 1. Oxygen dependent (respiratory burst) Toxic O2 products for the pathogens: Hydrogen peroxide, Hydroxyl radical, Nitric oxide, Singlet oxygen, Hypohalite 2. Oxygen independent Lysosome, lactoferrin, cationic proteins, proteolytic and hydrolytic enzymes

Question 46

What is the complement system?

Answer 46

a group of 20 serum proteins that act in a cascade to destroy invading microbes; these function to keep blood pathogen-free • Most important C1-C9

Question 47

Give examples of complement proteins. What are their function?

Answer 47

* C3b and C4b - opsonisation of pathogens * C3a and C5a - recruitment of phagocytes * C5 - C9 - killing of pathogens, membrane attack complex

Question 48

What are the two activating pathways of the complement system?

Answer 48

o Alternative pathway Initiated by cell surface microbial constituents (endotoxins on E. Coli) o MBL pathway Initiated when MBL binds to mannose containing residues of proteins found on many microbes (Salmonella spp. Candida albicans)

Question 49

How are the activities of PAMPS + PRRs different to opsonins?

Answer 49

When PRRs bind to PAMPs - simulates release of cytokines/ chemokines for inflammatory response whereas When opsonin receptors bind to opsonins - signals killing of microbe

Question 50

Which immune cells are important for chemoattraction?

Answer 50

Neutrophils, monocytes

Question 51

Give an overview of phagocytosis

Answer 51

- chemotaxis and adherence of microbe to phagocyte - ingestion - phagosome formation - fusion of phagosome with lysosome - digestion - formation of residual body containing indigestible material - discharge of waste

Question 52

What are the three main cytokines? What do they do?

Answer 52

TNF alpha, IL-1, IL-6 Systemic actions • Act on liver to produce acute phase proteins(opsonins): CRP MBL (-> complement activation) • Act on bone marrow to mobilise neutrophils • Act on hypothalamus to increase body temperature Local inflammatory actions • Act on vessels for vasodilation, vascular permeability, expression of adhesion molecules to attract neutrophils

Question 53

Summary of the innate immune response

Answer 53

Innate barrier breached: entrance and colonization of the pathogens. The mast cells and the macrophages are the first immune cells present at the site of infection when the innate barriers are breached. The macrophages immediately starts using their PRRs to see if they recognise any PAMPs. Once recognised they begin phagocytosis with the help of opsonins. They also produce cytokines/ chemokines. Cytokines and chemokines trigger vascular changes (vasodilation/increased vascular permeability). They also trigger chemoattraction, there's movement of neutrophils and monocytes from the blood into the site of infection. There's also action on the hypothalamus which causes fever preventing pathogen proliferation. The liver is affected and undergoes an acute phase response e.g CRP proteins are made. Inflammation at the site occurs resulting in redness, swelling, heat and pain.

Question 54

What are clinical problems that start when phagocytosis is reduced

Answer 54

- decreased spleen function - asplenic./ hyposplenic - decreased neutrophil number - chemotherapy, certain drugs e.g. phenytoin, leukaemia and lymphoma - decreased neutrophil function - chronic granulomatous disease (no respiratory burst), chediak-higashi syndrome (no phagolysosome formation)