Innate Immunity

Question 1

What is the immune system?

Answer 1

The immune system are cells and organs that contribute to the immune defence against infectious and non-infectious conditions. It can differentiate between self and non-self.

Question 2

What is an infection?

Answer 2

An infectious disease is when a pathogen succeeds in evading and/or overwhelming the host’s immune defences.

Question 3

What must the immune system be able to do?

Answer 3

The immune system must: Recognise pathogens, contain or eliminate the infection, regulate itself and remember the pathogen for future protection.

Question 4

Describe some of the main characteristics of the innate and adaptive immune system

Answer 4

Innate immunity is fast, non-specific, has no memory and does not change its intensity.
Adaptive immunity is slow, very specific, has immunologic memory and can change its intensity.

Question 5

What physical barriers does the innate system comprise of?

Answer 5

• Physical barriers such as the skin, mucous membranes (mouth, respiratory tract, GI and urinary tract) and bronchial cilia.

Question 6

What physiological barriers does the innate immune system comprise of?

Answer 6

Physiological barriers such as diarrhoea, vomiting, coughing and sneezing

Question 7

What chemical barriers does the innate system comprise of?

Answer 7

Chemical barriers such as stomach acid (1-3), skin (5.5) and vagina (4.4) and antimicrobial molecules such as IgA, lysozyme, mucus, beta defensins and gastric acid and pepsin.

Question 8

What biological barriers does the innate system comprise of?

Answer 8

Biological – normal flora of non-pathogenic microbes in strategic locations – nasopharynx, mouth, throat, skin, GI tract and vagina (lactobacillus) these are absent in internal organs. These normal microbes compete with pathogens, produce antimicrobial and synthesize vitamins (K, B12, and other B vitamins)

Question 9

What microbial commensals are commonly found on the skin and in the nasopharynx?

Answer 9

1. On the skin it is common to find Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Candida albicans and Clostridium Perfringens.
2. In the Nasopharynx it is common to find Streptococcus pneumoniae, Neisseria Meningitidis and Haemophilus species.

Question 10

When can commensals become pathogenic?

Answer 10

Problems can arise if normal flora is displaced away from its normal location into what is normally a sterile location. This can happen when the skin is breached such as in burns, cuts, surgery and any form of injection, down a faecal-oral route such as foodborne infection, faecal-perineal-urethral route causing UTI’s or poor dental hygiene/dental work.

Question 11

What are the 3 main classes of people who are at risk of serious infection?

Answer 11

1. Asplenic or Hyposplenic as the spleen is important in antibody production and removing antibody covered bacteria. It also hosts the majority of the body’s monocytes – so reduced capability for phagocytosis
2. Damaged or prosthetic valves
3. Previous infective endocarditis

Question 12

What conditions can allow normal flora to take over?

Answer 12

If the host becomes immune-compromised, then the normal flora can again overgrow and become pathogenic. This occurs in people with diabetes, AIDS, malignant diseases and chemotherapy.

Question 13

What infections can antibiotic use lead to?

Answer 13

If the normal flora is depleted by antibiotic use, then you can get developments of severe colitis (clostridium difficile) and in the vagina thrush can occur due to candida albicans. C.Diff gastroenteritis. This occurs due to the reduced competition.

Question 14

What is the major cellular defense of the innate immune system?

Answer 14

Phagocytes – recognise, follow and engulf pathogens, killing them.

Question 15

Describe the role of macrophages

Answer 15

Present in all organs, the ingest and destroy pathogens, they also present microbial antigens to T cells

Question 16

Describe the role of Monocytes

Answer 16

These are present in the blood, when recruited they move into the tissue and differentiate into macrophages

Question 17

Describe the role of neutrophils

Answer 17

Present in the blood, recruited by chemokines to the site of infection, ingest an destroy pyogenic bacteria (S.Aureus and Strep pyogenes). They become raised during infectio

Question 18

Describe the role of basophils/mast cells

Answer 18

Early actors of inflammation and important in allergic responses

Question 19

Describe the role of eosiophils

Answer 19

Defense against multi-cellular parasites such as worms

Question 20

Describe the role of Natural killer cells

Answer 20

Kill all abnormal host cells such as in viruses and cancers.

Question 21

Describe the role of dendritic cells

Answer 21

Present microbial antigens to T cells

Question 22

How do phagocytes recognise pathogens?

Answer 22

Phagocyte recognise specific molecules on the pathogen these are termed PAMPs – pathogen associated molecular patterns and can include: lipid, carbohydrate, proteins and nucleic acids. Phagocytes have PRRs pathogen recognition receptors.

Another way these pathogens can be recognised is if they have been opsonised. Coating proteins called opsonins that bind to the microbial surfaces leading to enhances attachment of phagocytes and clearance of microbes.

Question 23

Give examples of some opsonins and what type of bacteria they are especially important for clearing?

Answer 23

Examples of these opsonins are Complement proteins such as C3b and C4b, antibodies such as IgG and IgM and acute phase proteins such as CRP and mannose binding lectin MBL. Opsonins are essential for clearing encapsulates bacteria: Neisseria meningitidis, streptococcus pneumoniae and haemophilus influenza b.

Question 24

What other role do PAMPs, PRRs and opsonins play?

Answer 24

PAMPs and PRRs activate the inflammation process whilst opsonins activate the killing process

Question 25

Describe phagocytosis i.e. oxygen independant pathway

Answer 25

1) Chemotaxis and adherence of microbe to the phagocytes
2) Ingestion of microbe by phagocytes
3) Formation of a phagosome
4) Fusion of the phagosomes wih a lysosome to form a phagolysosome
5) Digestion of the ingested microbe by enzymes
6) Formation of residual body containing indigestible material
7) Discharge of waste materias

Question 26

Describe the oxygen dependant pathway

Answer 26

There are two main intracellular killing mechanisms. Oxygen dependant pathway (respiratory burst) – toxic oxygen products created that damage the pathogen and kill it (oxidising agents).

Question 27

What is the complement system and what does it do?

Answer 27

Once the phagocyte is triggered by the PRRs the complement pathway is triggered. There are 20 inactive serum proteins involved most important are C1-C9.

C3a and C5a - recruitment of phagocytes

C3b-C4b - opsonisation of pathogens

C5-C9 - killing of pathogens membrane attack complex

Question 28

How is the complement system activated?

Answer 28

2 different pathways

The Alternative pathway is initiated by cell surface microbial constituents (endotoxins).

The MBL (mannose bining lectin) pathway is initiated when MBL binds to mannose containing residues on proteins on many microbes.

Question 29

What 4 functions do cytokines/chemokines have?

Answer 29

These have 4 important functions:
• At the liver they stimulate the release of CRP and MBL (important for complement system)
• In the bone marrow they mobilize neutrophils
• They have inflammatory roles such as causing vasodilation, increase vascular permeability and to cuase the adhesion of molecules for the attraction of neutrophils
• In the hypothalamus it causes an increased body temperature.

Question 30

What is chronic granulmatous disease?

Answer 30

They cannot perform a respiratory burst

Question 31

What is Chediak Higashi syndrome

Answer 31

They can’t form a phagolysosome.