Session 3 Lecture 2 Flashcards by A A

Define virulence ?

The capacity of the microbe to damage the host

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Define immune system

Cells and organs that contribute to immune defences against infectious and non-infectious conditions (selfvsnonself)

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Define an infectious disease

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

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What is the largest lymphoid organ in the body?

Spleen

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What are the four main features of the immune response?

Pattern recognition, Containing/eliminating the infection, Regulating itself and remembering pathogens

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What is meant by pattern recognition in the immune response?

Cell surface and soluble receptors determine whether something is self or non self

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What is meant by ‘regulating itself’ in the immune response?

Minimum damage to the host (resolution)

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What are the two different types of immune response?

Innate immunity and adaptive immunity

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Describe the features of innate immunity

Immediate protection - Fast, Lack of specificity, Lack of memory and No change in intensity

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Describe the features of adaptive immunity

Long lasting - Slow, Specificity, Immnunologic memory and Changes in intensity

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What would happen if you don’t have an innate immune response?

You would not get an adaptive immune response either because the innate activates the adaptive.

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What are the first line of defence in the body?

Physical barriers, physiological barriers, chemical barriers and biological barriers.

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What is the aim of the first lines of defence?

They prevent entry and limit growth of pathogens

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Give some examples of physical barriers

Skin, mucous membrane and bronchiole cilia

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Give some example of physiological barriers

Diarrhoea, vomiting, coughing and sneezing

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Give some examples of chemical barriers

Low pH and antimicrobial molecules

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Give some examples of biological barriers

Normal flora

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Give examples of normal flora that inhabit the skin

Staphylococcus aureus, streptococcus pyogenes

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Give examples of normal flora that inhabit the nasopharyx

Streptococcus pneumoniae, neisseria meningitidis

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With regards to normal flora, when to clinical problems start?

When the normal flora is displaced from its normal location to a sterile location

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How can normal flow be displaced from its normal location?

Breaching skin integrity, faecal oral route, faecal-perineal-urethral route (UTI) and poor dental hygiene.

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What are considered to be high risk patients? (With regards to a serious infection caused by normal flora)

Patients who

Asplenic/hyposplenic
Damaged or prosthetic valves
Previous infective endocarditis

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What are the second lines of defence?

Phagocytes, chemicals and inflammation

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What is the aim of the second lines of defence?

They will contain and clear the infection

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What are the main phagocytes?

Macrophages, monocytes and neutrophils

What is the function of macrophages?

- Phagocytosis - Present microbial agents to T cells - produce cytokines/chemokines

Where are macrophages found?

Present in all organs

Where are monocytes found?

Present in the blood (5-7%)

What is the function of monocytes?

Recruited at infection site and differentiate into macrophages

Where are neutrophils found?

Present in the blood (69% of blood leukocytes) Increase during infection

What is the function of neutrophils?

- Recruited by chemokines to the site of infection | - Ingest and destroy progenitor bacteria; staph aureus and strep pyogenes

What other key cells are involved in innate immunity?

Basophils/mast cells, eosinophils, natural killer cells and dendritic cells

What is the function of basophils/mast cells?

- Early actors of inflammation (vasodilation) | - Important in allergic responses

What is the function of eosinophils?

Defence against multi-cellular parasites (worms)

What is the function of natural killer cells?

Kill all abnormal host cells (virus infected or malignant)

What is the function of dendritic cells?

Present microbial antigens to T cells (acquired immunity)

Once a phagocyte and microbe interact, what happens next?

- Recognition process | - Killing process of infectious microbe

What are PAMPs?

Pathogen associated molecular pattern. They are molecules associated with groups of pathogens that are recognised by cells of the innate immune system.

What are PRRs?

Pathogen Recognition Receptors. These are proteins expressed by cells of the innate immune system to identify two classes of molecules - PAMPs and DAMPs.

What is the difference between PAMPs and DAMPs?

PAMPs are associated with microbial pathogens and DAMPs are associated with cell components that are released during cell damage/death.

Why we do need receptors inside cells as well?

Because viruses replicate inside the cell and we need to be able to detect this.

What is opsonisation of microbes?

Coating proteins called opsonins that bind to the microbial surfaces leading to enhanced attachment of phagocytes and clearance of microbes.

Give some examples of opsonins

Complement proteins - C3b, antibodies IgG, acute phase protein CRP

What is a phagolysosome?

This is when a lysosome has bruised with a phagocytic vesicle.

What are the two different phagocyte intracellular killing mechanisms?

- Oxygen dependent pathway | - Oxygen independent pathway

What is the oxygen-dependent pathway?

When phagocyte ingests bacteria, its oxygen consumption increases. This increases produces reaction O2 containing molecules that are anti-microbial. Eg hydrogen peroxide and nitric oxide

What is respiratory burst?

This is the rapid release of reactive oxygen species from different cell types.

What is the oxygen independent pathway?

This is when phagocytes kill microbes by oxygen independent ways. There are four different types.

What are the different methods of killing a cell via the oxygen independent pathway?

Use: lysosome; lactoferrin; cationic proteins or proteolytic hydrolytic enzymes

How does lactoferrin kill a microbe?

Removes the essential iron from bacteria

How do cationic proteins kill a microbe?

These are electrically charged proteins that damage the bacteria membrane

What does the complement system consist of?

Complement pathways | 20 serum proteins (most important C1-C9)

What are the different pathways of the complement system?

- Alternative pathway | - MBL pathway

How is the alternative pathway initiated?

Cell surface microbial constituents

How is the MBL pathway initiated?

MBL binds to mannose containing residues on proteins found on many microbes

What does MBL stand for?

Mannose binding lectin

What are the functions of C3a and C5a?

Recruitment of phagocytes

What are the functions of C3b - C4b ?

Opsonisation of pathogens

What are the functions of C5 - C9 ?

Killing of pathogens membrane attack complex

What do cytokines/chemokines cause?

Chemoattraction, phagocyte activation and inflammation

What antimicrobial actions does the bone marrow do?

Neutrophil mobilisation

What antimicrobial actions does the hypothalamus do?

Increased body temperature

What anti-microbial effects does the inflammatory response have?

- Vasodilation - Vascular permeability - Adhesion molecules therefore attraction of neutrophils

What anti-microbial effects does the liver have?

- CRP | - MBL - complement activation

With regards to infection, when do clinical problems start?

When phagocytosis is reduced

Why might you have reduced phagocytosis?

- Decreased spleen function - Decreased neutrophil number - Decreased neutrophil function

Why might you have decreased neutrophil number?

Cancer chemotherapy, certain drugs or leukaemia/lymphoma

Why might you have decreased neutrophil function?

- Chronic granuloma disease (no respiratory burst) | - Chediak-Higashi syndrome (no phagolysosome formation)