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Infection > innate Immune System > Flashcards

innate Immune System Flashcards

1
Q

Describe the different innate barriers to infection

A

G

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2
Q

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

A

1) Infectivity - The capacity of the pathogen to establish itself within the host
2) Virulence - Capacity of microbe to actually damage the host
3) Host immune response

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3
Q

What is the immune system?

A

Cells and organs that contribute to immune

defences against infectious and non-infectious conditions (self vs non-self)

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4
Q

What is an infectious disease?

A

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

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5
Q

What are the roles of the immune system?

A
  •   Pathogen recognition = Cell surface and soluble receptors
  •   Containing/eliminating the infection = Killing and clearance mechanisms
  •   Regulating itself = Needs to be stopped eventually to ensure minimum damage to host (resolution)
  •   Remembering pathogens = Preventing the disease from recurring
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6
Q

What is the difference between innate immunity and adaptive immunity?

A 
Innate Immunity:
Immediate protection 
•  Fast (within seconds) 
•  Lack of specificity 
•  Lack of memory 
•  No change in intensity
Adaptive Immunity:
Long lasting protection 
•  Slow (days) 
•  Specificity 
•  Immunologic memory 
•  Changes in intensity (Faster and stronger)

You cannot have adaptive immunity if innate immunity has not been activated.

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7
Q

What are the first lines of defence in innate immunity?

A

Factors that prevent entry and limit growth of pathogens

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

If there is anything that is affecting or preventing the integrity of these innate barriers then the patient will have an increase in infection susceptibility.

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8
Q

What are some physical barriers to pathogens?

A

•  Skin (surface area 1-2 m2)

  •   Mucous membranes - in body cavities, dynamic, can sense the pathogens and initiate immune response because they have a high number of immune cells. They can be found:
    •   Mouth
    •   Respiratory tract
    •   GI tract
    •   Urinary tract

•  Bronchial cilia - remove any trapped microorganisms from mucous outside the lung that will be expelled out of lung or swallowed e.g. Problem in CF

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9
Q

What are some physiological barriers to pathogens? Give an example of when each of them are used.

A

•  Diarrhoea
- To expel the microorganisms e.g. Food poisoning

•  Vomiting

  • Again, to expel the microorganism e.g. Food poisoning
  • Hepatitis
  • Meningitis

•  Coughing
- Pneumonia

•  Sneezing
- Sinusitis

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10
Q

What are some chemical barriers to pathogens? Give an example of when each of them are used.

A

•  Low pH

  • Skin (5.5)
  • Stomach (1-3)
  • Vagina (4.4) - caused by bacteria called lactobacillus

•  Antimicrobial molecules
- IgA (Tears, saliva, mucous
membrane )
- Lysozyme (sebum,
perspiration, urine)
- Mucus (Mucous membranes, can trap microorganisms so they can be expelled)
- Beta-defensins (toxic to gram positive and negative bacteria epithelium)
- Gastric acid + pepsin (kills almost all microorganisms)

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11
Q

How can antibiotics lead to vaginal thrush?

A

In the vagina, there are opportunistic fungi that are there but do not grow.

If a patient is treated with antibiotics, you kill the normal flora there that maintain the low pH and so the fungi can now thrive as the pH is high enough for them to grow

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12
Q

How does Immunoglobulin A work?

A

Binds to microbe and prevents it from attaching to the mucous membrane of cells

Since the microbe cannot attach, it will not be able to grow

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13
Q

What are some biological barriers to pathogens? Give an example of when each of them are used.

A

As long as they do not move from their designated places, they are fine.

Should not be in blood, organs or tissues.

•  Normal flora

  • Non pathogenic microbes
  • Strategic locations
    • Nasopharynx
    • Mouth/Throat
    • Skin
    • GI tract
    • Vagina (lactobacillus spp)
  • Absent in internal organs/tissues
•  Benefits
- Compete with pathogens for
attachment sites and resources. 
- Produce antimicrobial chemicals
-Synthesize vitamins (K, B12, other
B vitamins).
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14
Q

Name two examples of normal flora that inhabit the skin and the nasopharynx.

A

Skin:
•  Staphylococcus aureus
•  Staphylococcus epidermidis

Nasopharynx:
•  Streptococcus pneumoniae
•  Neisseria meningitidis

They are opportunistic normal flora that could become pathogenic in certain cases.

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15
Q

When do normal flora become clinical problems?

A

1) Normal flora is displaced from its normal location to sterile location

•  Breaching the skin integrity

  • Skin loss (burns)
  • Surgery
  • Injection drug users
  • IV lines

•  Fecal-oral route
- Foodborne infection, food is contaminated by fecal matter

•  Fecal-perineal-urethral route
- Urinary tract infection (women) caused by incorrect wiping technique (back to front when it should be front to back)

•  Poor dental hygiene/dental work

  • Common cause of harmless bacteraemia
  • Dental extraction
  • Gingivitis
  • Brushing/Flossing

Flora in mouth would get access to blood stream

⇒ Serious infections in high-risk patients (e.g. those without spleen, patients with damaged or prosthetic valves)

2) Normal flora overgrows and becomes pathogenic when
host becomes immuno-compromised
•  Diabetes
•  AIDS 
•  Malignant diseases 
•  Chemotherapy (mucositis)

When normal flora is depleted by antibiotics
•  Intestine -> severe colitis (Clostridium difficile) •  Vagina -> thrush (Candida albicans)

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16
Q

Why are patients with no spleen highly susceptible to blood-borne infections?

A

?

17
Q

Why should Antibiotic prophylaxis be given to those without a spleen?

A

?

18
Q

What are the second lines of defence?

A

Phagocytes

Chemicals

That lead to inflammation

These factors will contain and clear the infection

19
Q

How would taking anti-acids for a stomach ulcer lead to food poisoning?

A

Anti-acids alter and increase the acidic pH of the stomach.

This is bad because the acidic environment prevents bacterial growth in the stomach and colonisation in the intestines.

20
Q

Why would eczema, dermatitis or insect bites cause cellulitis?

A

Cellulitis is an infection of soft tissue on the skin so any condition that affects the skin integrity

21
Q

What are the three main phagocytos and what are their functions?

A

Macrophages:

  • Present in all organs
  • Ingest and destroy microbes (Phagocytosis)
  • Present microbial antigens to T cells (adaptive immunity)
  • Produce cytokines/chemokines

Monocytes:

  • present in blood
  • recruited at site of infection and then differentiate to macrophages

Neutrophils

  • present in blood
  • look for it in full blood count because it’s increased during infection
  • Recruited by chemokines to the site of infection
  • Unlike macrophages, neutrophils die, they are the major WBC component of pus
  • Ingest and destroy pyogenic bacteria: Staph. aureus and Strep. pyogenes
22
Q

What are the functions of basophils/mast cells?

A

Early actors of inflammation (vasomodulation)

Important in allergic responses

23
Q

What is the function of eosinophils?

A

Defence against multi-cellular parasites (worms)

24
Q

What is the function of NKCs?

A

Kill all abnormal host cells (virus infected or malignant)

25
Q

What is the function of Dendritic cells?

A

Activate adaptive immunity

Present microbial antigens to T cells (acquired immunity)

26
Q

What is vasomodulation?

A

the dilatation of blood vessels, which decreases blood pressure.

This also the proteins and immune response cells to get to the site of infection quickly

27
Q

How are pathogens recognised by macrophages?

A

Microbial structures that are not present on host cells:

1) Pathogen-associated molecular patterns (PAMPs) on microorganisms : e.g. Carbohydrates, Lipids, Proteins, Nucleic acids

The phagocytes have Pathogen Recognition Receptors (PRRs): e.g.Toll Like Receptors

They are used to detect the PAMPs on the microbe. Not only at cell surface, but also inside the cell so can detect and sense viral infection that are replicating inside the cell

2) Opsonisation of microbes

28
Q

Name one example of microbial PAMPs and PRRs in:

1) Gram negative bacteria
2) Gram positive bacteria
3) All mycobacterium
4) Bacterial flagella

A

1) Lipopolysaccaride (LPS) which is a major component of gram negative microorganisms - TLR4 (Toll like receptor 4)
2) Peptidoglycan - TLR2
3) Lipoarabinomannan - TLR2
4) Flagellin - TLR5

29
Q

What is opsonisation?

A

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

This is where CRP plays a role. - It goes up during infection and can be used to monitor disease progression and patient response to treatment

30
Q

How do the PAMPs/PRRs work alongside opsonins/opsonins receptors?

A

The PRRs are activated it initiates phagocyte activate and start producing immune response cells to trigger the inflammatory cascade and clear the infections by releasing cytokines and chemokines.

Meanwhile the opsonin activates phagocytosis and killing process.

31
Q

What are some examples of opsonins?

A

Complement proteins

Antibodies - IgG can bind to microbe specifically and because the phagocyte has the receptor for this antibody, it can be further recognised and engulfed.

Acute phase protein - CRP can enhance recognition

32
Q

Why is it a problem for a bacteria to be encapsulated?

A

Harder to detect opsonins

33
Q

How are microbes phagocytosed?

A

1) Chemotaxis and adherence of microbe to phagocyte
2) Ingestion of microbe by pathogen
3) Formation of phagosome
4) Fusion of phagosome to lysine to form a phagolysosome
5) Digestion of ingested microbe by enzymes
6) Formation of residual body containing ingestible material
7) Discharge of waste materials

34
Q

What are the two main ways in which phagocytes kill microbes intracellularly?

A

1) O2-dependent
- respiratory burst
- O2 radicals are highly toxic

2) O2 independent
- lysosomes

35
Q

What are the two main activating complement pathways?

A

1) Alternative pathway

2) MBL pathway

36
Q

Whichever complement pathway is activated there are 3 specific anti microbial actions. What are they?

A

1) C3a and C5a: Recruitment of phagocytes - they guide phagocytes to where the microbe is - they are chemoattractants
2) C3b-C4b: Opsonisation of pathogens - stick to the pathogens and a make them easier to find

3) C5-C9: Terminal proteins - assemble together and form pores – Killing of pathogens
- Membrane Attack complex
- punch holes into the bacteria and kill it

37
Q

What are the roles of cytokines and chemokines?

A
  •   Chemoattraction
  •   Phagocyte activation
  •   Inflammation
38
Q

What are examples of cytokines and chemokines? Wh

A

TNFa
IL-1
IL-6

They are released by activated macrophages when they are activated by PAMPs via PRR

39
Q

Which bodily structures do TNF, IL-1, IL-6 act on?

A

They act on:
•  Liver (opsonins)
- CRP
- MBL (-> complement activation)

•  Bone marrow
- Lead to neutrophil mobilization

•  Inflammatory actions

  • Vasodilation
  • Vascular permeability so that the immune cells can get to site of inflammation
  • Adhesion molecules -> attraction of neutrophils

•  Hypothalamus
- Increased body temperature

Infection (6 decks)

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