Innate Immune System Flashcards by RG Cattermole

What is the difference between infectivity and virulence?

Infectivity is ability to establish inside host

Virulence is ability to damage host

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Define immune system?

Cells and organs that contribute to immune defences against infection and non-infections (i.e cancer/foreign objects). Differentiates between self-non-self

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What is an infectious disease?

When a pathogen succeeds in overwhelming a host defence response to evade

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What are 4 broad roles of the immune system?

Pathogen recognition
Containing infection
Minimising host damage
Memory for pathogens

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4 characteristics of innate immunity?

Fast
Lack of specificity
Lack of memory
No change in intensity

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4 characteristics of adaptive immunity?

Fast
Specific
Memory
Changes in intensity (same microbe 2nd time round much bigger immune response)

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What are the roles of first lines of defence of innate immunity (2)?

Limit entry

Prevent growth

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What are the 4 types of first line defence of innate immunity?

Physical
Chemical
Biological
Physiological

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What are the three physical barriers?

Skin
Mucous membranes
Cilia

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How do cilia help prevent infection?

Goblet cells secrete mucus catch pathogen cilia beat and mucus is coughed up. Upper resp tract has normal flora but lower resp tract should be sterile

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What are the 4 physiological barriers?

Coughing
Sneezing
Vomit
Diarrhoea

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What are 2 types of chemical barrier and name examples for each

pH
Skin 5.5
Vagina 4.4
Stomach 2-3

Antimicrobial molecules
Gastric pepsin and acid
Lysozymes
IgA
Mucous
Beta - defensins

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What do each of the antimicrobial molecules do?

Gastric pepsin and acid - kills most microbes
Lysozymes - breaks bacterial cell wall
IgA - in tears sweat etc prevents microbe binding
Mucous - trap to expel
Beta - defensins - antimicrobial peptides toxic for both gram + and -

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What is the biological barrier made up of and where?

Normal flora:

Skin
Nose/Pharynx
Mouth/Upper respiratory tract
GI - intestine
GU - vagina

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Are normal flora seen around internal organs? blood?

No No

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Name some benefits of normal flora

Compete with pathogens for resources and attachment sites so reduces their ability to establish
Makes vitamins e.g. Vit K
Antimicrobial properties

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Give some examples of normal flora of the skin (5)

Step pneumonia
Staph aureus
Staph epidermis
Candida albicans 
Clostridium perfringens

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What does opportunistic mean? How is Candida albicans opportunistic?

Means normally unharmful and at low numbers, if normal flora reduced e.g. with antibiotics may be given the chance to grow and cause pathology e.g. Thrush

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Give some examples of normal flora of the nasal cavity (3)

Strep pnuemoniae
Neisseria meningitidis
Haemophillus species

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What is first vs second line defence of innate immunity?

First - barriers to entry of pathogen

Second - cells that contain and clear infection

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How can normal flora become pathogenic/pathology related to reduction in normal flora? Give examples

DISPLACEMENT of flora from normal location to another site - e.g. staph aureus or strep viridans
Reduced normal flora by antibiotics = pathogen can invade - e.g. cdiff
Increased flora to pathological level e.g. if host immunocompromised like AIDS - e.g. candida albicans

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What is the most common cause of normal flora being displaced to another site?

Poor dental hygiene/dental work

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Which patients would need antibiotic prophylaxis before dental work (4)?

HIV - immunocompromised
Asplenic/Hyposplenic
Damaged or prosthetic valves
Previous infective endocarditis

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Give some examples of what causes a patient to be immunocompromised/deplete normal flora and therefore at risk of overgrowth of microbes e.g. candida albicans

HIV
Diabetes
Malignancy
Chemo
Antibiotics

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How can chemotherapy predispose to infection by normal flora in terms of first line defence barriers?

Can cause mucositis - inflammation of mucosal membranes makes it easier for bacteria to permeate

How does taking antacids predispose to colonisation of normal flora?

Increases pH, low pH is an innate barrier so increases chance of bacteria being able to establish and replicate

What does the 2nd line defence do? What is in included?

Contain and clear infection Phagocytes --> neutrophils/macrophages Inflammation

Do phagocytes recognise pathogens?

Yes

Name some roles of macrophages. Are they present in all organs?

APC Phagocyte Produce cytokines Angiogenesis Yes

What is the most common leukocyte present in the blood?

Neutrophils 60%

What is the major WBC component of pus?

Neutrophils - so especially phagocytose pyogenic bacteria e.g. staph aureus staph pyogenes

What recruits neutrophils?

Chemokines at site of infection

Name three encapsulated bacteria splenic patients are particularly susceptible to developing

Neisseria meningitidis Strep pneumoniae Haemophillus influenzae

What is the broad role of cytokines

Cell signalling | Eg recruitment of cells in inflammation

Give two ways a phagocyte can recognise a pathogen

PRRs/PAMPs | Opsonisation

How do PAMPs PRRs work?

PRRs on phagocytes recognise PAMPs on microbes. There a variety of PRRs that recognise different things so can recognise a wide range of microbes This allow the pathogen to attach to phagocytose

What is the most common type of PRR?

Toll like receptor

Why do PRRs not target host cells?

Because they don't have PAMPs

What is the PRR for gram neg bacteria that targets lipopolysaccharide (PAMP)?

Toll like receptor 4 (TLR4)

What is the PRR for gram pos bacteria that targets peptidoglycan (PAMP)?

Toll like receptor 2 (TLR2)

What is the PRR for gram neg lipopolysaccharide?

TLR4

What is the PRR for gram pos peptidoglycan?

TLR2

What is the PRR for all mycobacteria

TLR2

What is an opsonin?

A coating protein that binds to microbes and leads to enhanced attachment of phagocytes

Give three classes of opsonins and name some

Complement proteins - c3b c4b Antibodies - IgG IgM Acute phase proteins - CRP MBL (mannose binding lectin)

Why is opsonisation really important for encapsulated bacteria?

As they resist phagocytosis

How does a phagocyte come into contact with a pathogen?

Chemotaxis | Sometimes can randomly bump

After the phagocyte has recognised the pathogen then what?

Phagocytosis

What are the 7 stages of phagocytosis

1) Chemotaxis- adherence to microbe 2) Ingestion of microbe 3) Phagosome 4) Lysophagosome 5) Digest material - enzymes 6) Residual body 7) Eliminate waste

What are two intracellular phagocyte killing mechanisms?

Oxygen dependent - using ROS - e.g. hydrogen peroxide, hydroxyl radical Oxygen independent - e.g. lysosomal enzymes

What two things help phagocytes in 2nd line defence?

Complement system | Cytokines

What are three roles of complement system?

1) Recruitment of phagocytes - chemotaxis 2) Opsonisation 3) Membrane attack - killing of bacteria

Which complement proteins do each of the 3 roles of the complement system?

1) c3a c5a 2) c3b c4a 3) c5-c9

What are the antimicrobial actions of the complement system?

Same as asking what the three roles are Recruitment Opsonisation Membrane attack

What are two pathways of complement from the lecture?

Alternative pathway - C3 - initiated by cell surface microbial constituents MBL pathway - initiated when MBL binds to mannose containing residues of proteins found on many microbes

What are three roles of cytokines

Chemoattraction Phagocyte activation Inflammation

What cytokines do macrophages release?

IL-1 IL-6 TNF-alpha

What do these do (4)?

1) Stimulate liver to produce opsonins - CRP/MBL 2) Stimulate neutrophil mobilisation from bone marrow 3) Inflamm actions - vasodilation, vasc permeability, adhesion molecules (attraction of neutrophils) 4) Hypothalamus - increased body temperature

Which disease has no respiratory burst? Which enzyme is missing?

Chronic granulomatous disease (no NADPH oxidase)

Which disease has no phagolysosome formation?

Chediak-Higashi syndrome

What 3 conditions can reduce neutrophil number and therefore reduct innate immunity?

Chemo Leukaemia/lymphoma Certain drugs - phenytoin

Lack/dysfunction of what organ can lead to reduced phagocytosis?

Spleen | Splenic macrophages