S2) Innate Immune System Flashcards

1
Q

What is the immune system?

A

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)

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2
Q

Name 3 categories of people which naturally have a weaker immune system

A

Elderly persons (>65 yo)

Children (< 5 yo)

Pregnant women

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3
Q

Identify 4 roles of the immune system

A
  • 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
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4
Q

Compare and contrast the innate and adaptive immunity

A
  • Innate (immediate protection): fast (within seconds), lack of specificity and memory, no change in intensity
  • Adaptive (long lasting protection): slow (days), specificity, immunologic memory, changes in intensity
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5
Q

What is an infectious disease?

A

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

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6
Q

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

A
  • Pilus enhances attachment
  • Lipopolysaccharide endotoxins triggers inflammation
  • Polysaccharide capsule promotes adherence and prevents phagocytosis
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7
Q

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

Outline its following phases:

  • Local
  • Systemic
  • Sepsis
A
  • 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)
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8
Q

Explain the relationship between sepsis and coagulation

A
  • 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)
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9
Q

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

A
  • Infectivity
  • Host’s immune response
  • Virulence
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10
Q

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

Identify the different innate barriers to infection

A
  • Physical barriers
  • Physiological barriers
  • Chemical barriers
  • Biological barriers
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11
Q

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

A
  • Skin (surface area 1-2m^2)
  • Mucous membranes: mouth, resp tract, GI tract, urinary tract
  • Bronchial cilia
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12
Q

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

A
  • Diarrhoea – food poisoning
  • Coughing – pneumonia
  • Sneezing – sinusitis
  • Vomiting – food poisoning, hepatitis, meningitis
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13
Q

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

A
  • 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

V. Beta defensins (epithelium)

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14
Q

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

A

Normal flora:

  • Non pathogenic microbes
  • Found in strateigic locations - nasopharyngeal, mouth/throat, skin, GI tract, vagina (lactobacillus spp)
  • Absent in internal organs/tissues
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15
Q

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

A
  • Compete with pathogens for attachment sites and resources
  • Produce antimicrobial chemicals
  • Synthesise vitamins (K, B12, other B vitamins)
  • Immune maturation
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16
Q

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

A

Innate barriers trigger the second lines of defence:

  • Phagocytes
  • Chemicals
17
Q

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

A
  • Causes inflammation
  • Contain and clear the infection
18
Q

Provide some examples of opsonins

A
  • Complement proteins: C3b, C4b
  • Antibodies: IgG, IgM
  • Acute phase proteins: CRP, MBL
19
Q

Opsonis are essential in clearing encapsulated bacteria.

Identify three examples of this type of bacteria

A
  • Neisseria meningitidis
  • Streptococcus pneumoniae
  • Haemophilus influenzae b
20
Q

Identify the 3 main types of phagocytes

A
21
Q

State the location and functions of macrophages

A
  • Location: present in all organs
  • Functions:

I. Ingest and destroy microbes by phagocytosis

II. Present microbial antigens to T cells

III. Produce cytokines/chemokines

22
Q

State the location and function of monocytes

A
  • Location: present in the blood (5-7%)
  • Function: recruited at the infection site and differentiate into macrophages
23
Q

State the location and functions of neutrophils

A
  • 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

24
Q

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

  • Basophils/mast cells
  • Eosinophils
  • Natural Killer cells
  • Dendritic cells
A
  • 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)
25
Q

What is opsonisation?

A

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

26
Q

Identify the structures involved in pathogen recognition

A
  • Microbial structures: pathogen-associated molecular patterns (PAMPS) – carbohydrates, lipids, proteins, nucleic acids
  • Phagocytes: pathogen recogniton receptors (PRRs)
27
Q

In 7 steps, outline the process of phagocytosis

A

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

28
Q

Identify and describe the 2 different phagocytic intracellular killing mechanisms

A
  • 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
29
Q

The complement pathway consist of 20 serum proteins.

Identify and describe the 2 activating pathways

A
  • 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
30
Q

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

A
  • C3a and C5a: recruitment of phagocytes
  • C3b-C4b: opsonisation of pathogens
  • C5-C9: killing of pathogens, membrane attack complex
31
Q

Provide 4 examples of normal flora that inhabit the skin

A
  • Staphylococcus aureus (cellulitis)
  • Staphylococcus epidermidis (meningitis)
  • Streptococcus pyogenes
  • Candida albicans
32
Q

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

A
  • Strephtococcus mutans
  • Streptococcus pneumoniae
  • Neisseria meningitidis
  • Haemophilus species
33
Q

Provide an example of the normal flora which live in the gastrointestinal tract

A

E. Coli

34
Q

When do clinical problems start?

A

Normal flora overgrows and becomes pathogenic when host becomes immuno-compromised

When normal flora in mucosal surfaces is depleted by antibiotic therapy

When normal flora is displaced from it’s normal location

35
Q

Give 4 ways that normal flora can be displaced from the normal location to sterile location

A

Breaching the skin integrity

o Skin loss (burns) o Surgery
o IV lines
o Skin diseases

o Injection drug users
o Tattooing/body piercing

Fecal-oral route

o Foodborne infection

Fecal-perineal-urethral route

o Urinary tract infection (women)

Poor dental hygiene/dental work o Dental extraction
o Gingivitis
o Brushing/Flossing

Common cause of harmless bacteraemia

14

14

36
Q

Give examples of when Normal flora overgrows and becomes pathogenic

when host becomes immuno-compromised

A
o Diabetes (session 3, case 2) o AIDS
o Malignant diseases
o Chemotherapy (mucositis)
37
Q

Give examples of when normal flora in mucosal surfaces is depleted

by antibiotic therapy

A
  • Intestine -> severe colitis (Clostridium difficile)
  • Vagina -> thrush (Candida albicans)