S3) Innate Immune System

Question 1

What is the immune system?

Answer 1

The immune system is a network of cells and organs that contribute to immune defences against infectious and non-infectious conditions (self vs non-self)

Question 2

Identify 4 roles of the immune system

Answer 2

• Pathogen recognition: cell surface and soluble receptors
• Containing/eliminating the infection: killing and clearance mechanisms
• Regulating itself: minimum damage to host (resolution)
• Remembering pathogens: preventing disease from recurring

Question 3

Compare and contrast the innate and adaptive immunity

Answer 3

• Innate (immediate protection): fast (seconds), lack of specificity and memory, no change in intensity
• Adaptive (long lasting protection): slow (days), specificity, immunologic memory, changes in intensity

Question 4

What is an infectious disease?

Answer 4

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

Question 5

Identify and describe the 3 mechanisms by which micro-organisms trigger the inflammatory cascade

Answer 5

• Pilus enhances attachment
• Lipopolysaccharide endotoxins triggers inflammation
• Polysaccharide capsule promotes adherence and prevents phagocytosis

Question 6

The inflammatory cascade is triggered when an endotoxin binds to macrophages.

Outline its following phases:

• Local
• Systemic
• Sepsis

Answer 6

• Local: cytokines, TNFs and interleukins promote wound repair and recruit the reticuloendothelial system
• Systemic: cytokines released into circulation and stimulate GF, macrophages & platelets (aims to control infection)
• Sepsis: cytokines lead to activation of humoral cascades, RE System, circulatory insult (infection is not controlled)

Question 7

Explain the relationship between sepsis and coagulation

Answer 7

• Cytokines released in sepsis initiates production of thrombin
• Thrombin promotes coagulation and cytokines also inhibit fibrinolysis
• Coagulation cascade leads to microvascular thrombosis → organ ischaemia, dysfunction and failure (sepsis)

Question 8

What are the three factors determining the outcome of the host-pathogen relationship?

Answer 8

• Infectivity
• Host’s immune response
• Virulence

Question 9

The first line of defence consists of factors that prevent entry and limit growth of pathogens.

Identify the different innate barriers to infection

Answer 9

• Physical barriers
• Physiological barriers
• Chemical barriers
• Biological barriers

Question 10

Identify the 3 different physical barriers to infection in the innate immune system

Answer 10

• Skin
• Mucous membranes: mouth, resp tract, GI tract, urinary tract
• Bronchial cilia

Question 11

Identify and describe the 4 physiological barriers to infection in the innate immune system

Answer 11

• Diarrhoea – food poisoning
• Coughing – pneumonia
• Sneezing – sinusitis
• Vomiting – food poisoning, hepatitis, meningitis

Question 12

Identify and describe the 2 different chemical barriers to infection in the innate immune system

Answer 12

• Low pH – skin (5.5), stomach (1-3), vagina (4.4)
• Antimicrobial molecules:

I. IgA (tears, saliva, mucous membranes)

II. Lysozyme (sebum, perspiration, urine)

III. Mucus (mucous membranes)

IV. Gastric acid + pepsin

Question 13

Identify and describe the biological barrier to infection in the innate immune system

Answer 13

Normal flora:

• Non pathogenic microbes
• Found in nasopharyngeal, mouth/throat, skin, GI tract, vagina
• Absent in internal organs/tissues

Question 14

What are the benefits of normal flora as a biological barrier in the innate immune system?

Answer 14

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

Question 15

Describe how the different innate barriers work together to maximise the response against microbes

Answer 15

Innate barriers trigger the second lines of defence:

• Phagocytes
• Chemicals

Question 16

What does the second line of defence in the innate immune system do?

Answer 16

• Causes inflammation
• Contain and clear the infection

Question 17

Provide some examples of opsonins

Answer 17

• Complement proteins: C3b, C4b
• Antibodies: IgG, IgM
• Acute phase proteins: CRP, MBL

Question 18

Opsonis are essential in clearing encapsulated bacteria.

Identify three examples of this type of bacteria

Answer 18

• Neisseria meningitidis
• Streptococcus pneumoniae
• Haemophilus influenzae b

Question 19

Identify the 3 main types of phagocytes

Answer 19

Question 20

State the location and functions of macrophages

Answer 20

• Location: present in all organs
• Functions:

I. Ingest and destroy microbes by phagocytosis

II. Present microbial antigens to T cells

III. Produce cytokines/chemokines

Question 21

State the location and function of monocytes

Answer 21

• Location: present in the blood (5-7%)
• Function: recruited at the infection site and differentiate into macrophages

Question 22

State the location and functions of neutrophils

Answer 22

• Location: present in the blood (60% of blood leukocytes)
• Functions:

I. Increased during infection

II. Recruited by chemokines to the site of infection

III. Ingest and destroy progenitor bacteria e.g. Staph aureus

Question 23

State the function of the following key cells in the innate immunity:

• Basophils/mast cells
• Eosinophils
• Natural Killer cells
• Dendritic cells

Answer 23

• Basophils/ mast cells: early actors of inflammation (vasomodulation) in allergic responses
• Eosinophils: defence against multicellular parasites (worms)
• NK cells: kills all abnormal host cells (viral infected/malignant)
• Dendritic cells: present microbial antigens to T cells (acquired immunity)

Question 24

What is opsonisation?

Answer 24

Opsonisation is the process that involves coating microbial surfaces with opsonin proteins leading to enhanced attachment of phagocytes and clearance of microbes

Question 25

Identify the structures involved in pathogen recognition

Answer 25

• Microbial structures: pathogen-associated molecular patterns (PAMPS) – carbohydrates, lipids, proteins, nucleic acids
• Phagocytes: pathogen recogniton receptors (PRRs)

Question 26

In 7 steps, outline the process of phagocytosis

Answer 26

⇒ Recognition (PAMPS and opsonins)

⇒ Chemotaxis and adherence of the microbe to the phagocyte

⇒ Ingestion of the microbe by the phagocytes

⇒ Formation of phagosome

⇒ Fusion with lysosome to form a phagolysosome

⇒ Digestion of ingested microbe by enzymes

⇒ Discharge of waste materials

Question 27

Identify and describe the 2 different phagocytic intracellular killing mechanisms

Answer 27

• Oxygen-dependent pathway (respiratory burst): toxic O₂ products for pathogens – peroxide, hydroxyl radical, nitric oxide
• Oxygen-independent pathways: lactoferrin and transferrin, proteolytic and hydrolytic enzymes

Question 28

The complement pathway consist of 20 serum proteins.

Identify and describe the 2 activating pathways

Answer 28

• Alternate pathway – initiated by cell surface microbial constituents e.g. endotoxins on E.coli
• MBL pathway – initiated when MBL binds to mannose containing residues of proteins found on many microbes e.g. Candida albicans

Question 29

Describe the antimicrobial actions in the alternate pathway of the complement system

Answer 29

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

Question 30

Provide 4 examples of normal flora that inhabit the skin

Answer 30

• Staphylococcus aureus
• Staphylococcus epidermidis
• Streptococcus pyogenes
• Candida albicans

Question 31

Provide 3 examples of the normal flora which live in the nasopharynx

Answer 31

• Streptococcus pneumoniae
• Neisseria meningitidis
• Haemophilus species