Session 2: Innate Immunity

Question 1

You have been called to care for a 60-year-old patient in the intensive care unit who was admitted following a car accident. He is currently unconscious and has signs of cerebral oedema. The patient has a tube into his trachea, a central venous line and urinary catheter inserted. He was given a high-dose of corticosteroids to reduce his cerebral oedema and anti-convulsant phenytoin. What causes an increased risk of developing a serious infection here?

Answer 1

Tube in trachea Central venous line Urinary catheter Corticosteroids Phenytoin

Question 2

Define immune system.

Answer 2

Cells and organs that contribute to immune defences against infectious and non-infectious conditions. (Self vs. non-self)

Question 3

Define infectious disease.

Answer 3

When the pathogen succeeds in evading and/or overwhelming the host’s immune defences.

Question 4

What are the four roles of the immune system?

Answer 4

Pathogen recognition (cell surface and soluble receptors) Containing and eliminating the infection (killing and clearing mechanisms) Regulating itself (to minimise damage to host) Remembering pathogens to prevent disease from recurring

Question 5

How does innate immunity and adaptive immunity change from person to person?

Answer 5

Most of us have the same innate immunity. However our adaptive immunity can be very different.

Question 6

Complete table

Answer 6

Question 7

What are the first lines of defence? (barriers)

What’s their function?

Answer 7

Physical barriers

Chemical barriers

Physiological barriers

Biological barriers

To prevent entry** and limit **growth of pathogens.

Question 8

Give examples of physical barriers.

Answer 8

Skin

Mucous membranes in mouth, resp. tract, GI tract and Urinary tract.

Bronchial cilia

Question 9

Give examples of physiological barriers.

Answer 9

Diarrhoea in food poisoning

Vomiting (food poisoning, hepatitis, meningitis)

Coughing (pneumonia)

Sneezing (sinusitis)

Question 10

Give examples of chemical barriers.

Answer 10

Low pH from skin, stomach and vagina.

Antimicrobial molecules

Question 11

Give examples of antimicrobial molecules.

Answer 11

IgA

Lysozyme

Mucus

Beta-defensins

Gastric acid + pepsin

Question 12

Give examples of biological barriers.

Answer 12

Normal flora

Question 13

Beneficial characteristics of normal flora.

Answer 13

Non pathogenic microbes as long as they stay where they are supposed to be. They compete with pathogens for attachment sites and resources which makes it harder for pathogens to adhere.

Produce antimicrobial chemical

Synthesize vitamins like K, B12 and other B vitamins.

Immune maturation

Question 14

Examples of normal flora organisms found on skin.

Answer 14

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus pyogenes

Candida albicans

Clostridium perfringens

Question 15

Examples of normal flora organsisms that inhabit nasopharynx.

Answer 15

Streptococcus pneumoniae

Neisseria meningitidis

Haemophilus species

Question 16

What happens if organisms that inhabit flora in their normal place move to another place?

Answer 16

They can become pathogenic in other places.

If normal flora is displaced from its normal lcoation to sterile location.

Question 17

Give examples of how normal flora can enter an environment they are not supposed to be in.

Answer 17

Breaching skin integrity.

Skin loss (burns)

Surgery

IV lines

Skin diseases

Injection drug users

Tattooing/body piercing

Where it is common for S. aureus and S. epidermidis to breach into tissue where they are not supposed to be and cause infection.

Fecal-oral route:

Foodborne infection

Fecal-perineal-urethral route

UTIs in women because of poor wipeing technique

Poor dental hygiene/dental work:

Dental extraction

Gingivitis

Brushing/flossing

Question 18

Displacement of normal flora due to dental hygiene/dental work can cause serious infections in everyone but especially high-risk patients.

What are high-risk patients?

Answer 18

Asplenic or hyposplenic patients

Patients with damaged or prosthetic valves

Patients with previous infective endocarditis

Question 19

Give examples of when normal flow overgrows and becomes pathogenic when the host is immuno-compromised.

Answer 19

Diabetes

AIDS

Malignant disease

Chemotherapy (mucositis)

Question 20

Give examples of when normal flora in mucosal surfaces is depltetd by antibiotic therapy.

Answer 20

Intestine -> severe colitis and clostridium difficile

Vagina -> thrush by candida albicans

Question 21

What are the second lines of defence?

Answer 21

Phagocytes

Chemicals and inflammation

These are factors that will contain and clear the infection once it has invaded.

Question 22

Explain the role of macrophages.

Answer 22

Present in all organs.

They ingest and destroy microbes by phagocytosis.

They also present microbial antigens to T cells in adaptive immunity.

They also produce cytokines and chemokines.

Question 23

What are monocytes?

Answer 23

‘Macrophages’ present in blood (5-7%)

They are recruited at infection site and differentiate into macrophages in tissue.

Question 24

Explain the role of neutrophils.

What bacteria are they effective against?

Answer 24

Present in the blood (60% of blood leucocytes)

They increase in number during infection and recruited by chemokines to the site of infection.

Ingest and destroy pyogenic bacteria like Staphylococcus aureus and Streptococcus pyogenes

Question 25

Give a few other key cells that are important in innate immunity.

Answer 25

Basophils/mast cells Eosinophils Natural killer cells Dendritic cells

Question 26

Explain role of basophils/mast cells. Effective against?

Answer 26

Early actors of inflammation by vasomodulation Important in allergic responses

Question 27

Explain of eosinophils in innate immunity. Effective against?

Answer 27

Defence against multi-cellular parasites (worms)

Question 28

Explain role of natural killer cells. Effective against?

Answer 28

Kill all abnormal host cells like virus infected or malignant cells.

Question 29

Explain the role of dendritic cells.

Answer 29

Present microbial antigens to T cells in acquired immunity.

Question 30

How does pathogen recognition work?

Answer 30

The important features of pathogen recognition are PAMPs and PRRs. **_PAMPs:_** These are pathogen associated molecular patterns present on the **_microbe_**. Examples such as carbohydrates, lipids, proteins and nucleic acids. **_PRRs:_** These are pathogen recognition receptor which are present on the **_phagocytes_**. They are toll like receptors that recognises PAMPs in order to phagocytose the microbes.

Question 31

What are opsonins and what are their role?

Answer 31

They are coating proteins that bind to the surface of the **_microbe_** in order to enhance attachment of phagocyes to the microbe and clear the microbes easier.

Question 32

Examples of opsonins.

Answer 32

C3b, C4b which are complement proteins Antibodies like IgG and IgM. Acute phase proteins like CRP and MBL

Question 33

For what types of bacteria is opsonisation very important?

Answer 33

For encaspulated bacteria like Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae b

Question 34

Explain phagocytosis and killing of pathogens.

Answer 34

A phagocyte recognise a pathogen by the PRR and PAMP interaction as well as by opsonins. 1 - Chemotaxis and ahderence of microbe to phagocyte 2 - Ingestion of microbe by phagocyte 3 - Formation of phagosome inside the phagocyte (a vesicle containing the microbe) 4 - The phagosome now fuses with a lysosome to form a phagolysosome 5 - The lysosome brought with him/her digestive enzymes which digest the ingested microbe. 6 - Formation of residual body containing indigestible material 7 - Discharge of waste materials.

Question 35

What are the intracellular killing mechanisms of the phagocytes?

Answer 35

Oxygen-dependent pathway which is respiratory burst. Free radicals destroy the microbe. Oxygen-independent pathways which involve lysozymes, lactoferrin or transferrin, cationic proteins and proteolytic and hydrolytic enzymes.

Question 36

What is the complement system?

Answer 36

It consist of complement pathways of 20 serum proteins. The most important serum proteins are C1-C9. They have to activating pathways (alternative pathway and MBL pathway)

Question 37

In a few sentences explain the alternative pathway. Also explain MBL pathway.

Answer 37

Initiated by cell surface microbial constituents like endotoxins on E. coli. Initiated when MBL binds to mannose containing residues of proteins found on many microbes like Salmonella spp. and Candida albicans

Question 38

Give examples of actions of C1-C9.

Answer 38

C3a and C5a recruit phagocytes acting as cytokines. C3b and C4b are opsonins C5-C9 kills pathogens, have an attack complex and make hole in the membrane of pathogens.

Question 39

Role of cytokines and chemokinse.

Answer 39

Chemoattraction Phagocyte activation Inflammation

Question 40

Systemic actions of cytokines such as TNFalpha, IL-1 and IL-6.

Answer 40

In the liver as opsonins. CRP and MBL. Bone marrow for neutrophil mobilisation Hypothalamus to increase body temperature

Question 41

Local inflammatory actions of cytokines and chemokines.

Answer 41

Blood vessels get vasodilated. Also increases vascular permeability and expression of adhesion molecules on the endothelium for attraction of and adhesion of neutrophils.

Question 42

Give causes of reduction of phagocytic activity?

Answer 42

Asplenic and hyposplenic patients Decrease in neutrophil numbers like in cancer chemotherapy, certain drugs like phenytoin and leukaemia and lymphoma. Decrease in neutrophil function like in chronic granulomatous disease where respiratory burst doesnt work. In Chediak-Higashi syndrome where phagolysosomes fail to form.