2.2 - Innate Immunity Flashcards

1
Q

Definition: pathogenesis

A

The ability of an organism to drive disease. Due to two factors:
- Infectivity
- Virulence
The outcome of the host-pathogen relationship is also determined by the state of the immune system

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2
Q

Definition: infectivity + virulence

A

infectivity The ability of a pathogen to establish itself on/in a host
virulence the ability to drive tissue damage

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3
Q

What are the groups more vulnerable to greater risk of infection

A

Naturally immune supressed:
- Pregnant women
- Elderly (over 65)
- Children below the age of 5

At particularly high risk due to co-morbidities
- Asplenic + hyposplenic patients (need to give vaccination against encapsulated bacteria)
- Patients with damaged or prosthetic heart valves
- Patients with previous infective endocarditis

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4
Q

Definition: immune system

A

Cells and organs (lymphoid organs, eg spleen) that contribute to immune defences against infection sand non-infectious conditions (self vs non-self)

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5
Q

Definition: infectious disease

A

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

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6
Q

Roles of the immune system

A
  • pathogen recognition cell surface and soluble receptors (if cell invades cell → produces complimentary antibodies). We are all born with proteins + structures to recognise microbes that haven’t been encountered yet
  • containing/eliminating the infection killing in clearance mechanisms, to try to make sure the infection doesn’t go systemic
  • regulating itself so that when the infection is gone, the immune system stops → minimum damage to host (resolution). If this mechanism doesn’t work = auto-immune disease
  • remembering pathogens to prevent the disease from recurring
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7
Q

Innate vs adaptive immunity

A

innate provides immediate protection
- Fast (within seconds)
- Lack of specify (so not specific to virus/bacteria etc)
- Lack of memory
- No change in intensity
- Eg skin or phagocytosis
- Death occurs with highly virulent pathogens that don’t give enough time for adaptive immunity to kick in

adaptive provides long-lasting protection
- Slow (days)
- Specificity
- Immunologic memory
- Changes in intensity (better response with repeated exposure to the pathogen)
- Eg past B-cell proliferation (B-memory cells) produce plasma cells → antibodies

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8
Q

What are the different elements that make up innate immunity

A

BARRIERS: these are the first lines of defence: factors that prevent entry + limit growth of pathogens
- Physical barriers
- Physiological barriers
- Chemical barriers
- Biological barriers

PHAGOCYTES + CHEMICALS: second line of defence
These contain + eliminate the infection

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9
Q

Innate immunity: physical barriers

A
  • skin (eg eczema will increase risk of patient having cellulitis)
  • mucous membranes eg mouth (candida), respiratory tract (COVID-19), GI tract (E.Coli) + urinary tract (UTIs)
  • bronchial cilia (disease effecting cilia, such as cystic fibrosis, will increase risk of infection)

☞ Barrier damage can be caused by anything that is disrupting the integrity of the barrier
Eg: drugs, smoking, localised disease (eg eczema, psoriasis)

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10
Q

Innate immunity: physiological barriers

A

the point of these are to expel the microbe out of the body ☞ however, these are also used by the microbe to spread the disease further, such as diarrhoea
- Diarrhoea
- Vomiting
- Coughing
- Sneezing

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11
Q

Innate immunity: chemical barriers

A

low pH
Have this in skin, stomach and vagina

antimicrobial molecules
- IgA (antibody produced by mucosal surfaces, tears and in saliva ☞ binds to the microbe + prevents it from attaching to the cell surface, and therefore stops it entering the host)
- Lysozyme (sebum, perspiration, urine ☞ non-specific enzymes)
- Mucus (mucus membranes ☞ trap the microbes so that cilia can expel)
- Beta defensins (epithelium ☞ anti-microbial properties against microbes)
- Gastric acid + pepsin (acidic)

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12
Q

Innate immunity: biological barriers

A

normal flora
- Non pathogenic microbes (as long as they stay where they are, otherwise become pathogenic)
- Strategically located: eg nasopharynx, mouth, throat, skin, GI tract, vagina
- They are absent in the internal organs

benefits
- Compete with pathogens for attachment sites and resources
- Produce antimicrobial chemicals
- Synthesise vitamins (K, B12, other B vitamins)
- Contribute to immune maturation

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13
Q

What are the encapsulated bacteria

A

if splenectomy, at much higher risk of these
These are bacteria covered with a polysaccharide capsule eg
- Streptococcus pneumoniae
- Haemophilus influenzae
- Neisseria meningitidis
(there are others but these 3 are the most important)

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14
Q

Examples of normal flora that inhabit the skin, mouth and nasopharynx, and the gastrointestinal tract – these can become pathogenic if displaced from their normal location (know a couple of examples from each)

A

the skin
- Staphylococcus aureus
- Staphylococcus epidermis
- Streptococcus pyogenes
- Candida albicans

the mouth and nasopharynx
- Streptococcus mutans
- Streptococcus pneumoniae (encapsulated bacteria)
- Haemophilus species (EB)
- Neisseria meningitidis (EB)

the gastrointestinal tract
- E.coli

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15
Q

Normal flora – clinical problems start when…

A

normal flora is displaced from its normal location to sterile location
- By breaching the skin integrity (ie skin loss, surgery, IV lines, skin diseases, injecting drugs, tatoos)
- Faecal-oral route (ingestion, eg foodborne infection)
- Faecal-perineal-urethral route (eg urinary tract infection)
- Poor dental hygiene/dental work (dental extraction, gingivitis, brushing + flossing) as these form easy haematogenous transmission (blood-borne pathways)

normal flora overgrows + becomes pathogenic when host becomes immuno-compromised
- Eg diabetes (infection risk high due to excess glucose in blood)
- Eg AIDS, malignant diseases and chemotherapy

when normal flora in mucosal surfaces is depleted by antibiotic therapy
- Eg in intestine → severe colitis
- Eg in vagina → thrush

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16
Q

What is mucositis

A

common side effect of radiotherapy + chemotherapy
- Inflammation of mucosal membranes
- Opportunity for normal flora to get into host
- Leads to more infection by normal flora in cancer patients

17
Q

Innate immunity: second line of defence (ie skin has been breached)

A
  • Non-specific to pathogen
  • Phagocytes + chemicals
  • These drive inflammation
  • This leads to factors that contain + clear the infection
18
Q

Endogenous vs exogenous bacteria

A

endogenous are normal flora, present on skin etc. Can become pathogenic if displaced (eg from cut of skin)
exogenous are not normally present in host. Acquired from the external environment

19
Q

Phagocyte

A
  • Part of innate immunity
  • Non-specific
  • The first cell that deals with pathogen if it has breached the first line of defence
  • Needs to recognise + kill the pathogen
  • There are macrophages, monocytes and neutrophils (separate card)
20
Q

What are the three main phagocytes

A
  • macrophages present in all organs, ingest + destroy microbes (phagocytosis), present microbial antigens to T cells (adaptive immunity) and produce cytokines/chemokines (will increase CRP)
  • monocytes are present in the blood (5-7%). Recruited at infection site + differentiate into macrophages
  • neutrophils are 60% of blood leukocytes. Increased during infection. Recruited by chemokines to the site of infection. Ingest and destroy pyogenic bacteria (staph. Aureus and Strep. Pyogenes). These are short-lived.
21
Q

What are some other key cells of innate immunity

A
  • Phagocytes (macrophages, monocytes + neutrophils) – prev card
  • basophils/mast cells are the early actors of inflammation (vasomodulation) and are important in allergic responses
  • eosinophils act as defence against parasitic infection (helminths). Also important in allergies.
  • natural killer cells kill all abnormal host cells (virus infected or malignant)
  • dendritic cells present microbial antigens to T cells (acquired immunity)
22
Q

How do phagocytes recognise pathogens

A

PAMPs and PRRs
- Phagocytes are looking for something foreign that is not in the host
- They are looking for PAMPs ☞ pathogen associated molecular patterns
- These are present on the microbe
- Could be carbohydrates, lipids, proteins, nucleic acids
- Pathogens have PRRs ☞ pathogen recognition receptors
- These PRRs are mainly ‘Toll-like receptors’ (TLR2, TLR4 etc)
- These TLRs can recognise different structures present on Gram-negative and Gram-positive bacteria etc → therefore TLRs on pathogens are non-specific

Remember that pathogens have PRRs, microbes have PAMPs

opsonisation
- The ability of a host cell to coat a microbe in opsonins (proteins)
- This enhances attachment of phagocytes
- Therefore more efficient clearance of microbes
- Phagocytes have opsonin receptor
- These are essential to clearing encapsulated bacteria

23
Q

What are some common opsonins

A
  • complement proteins such as C3b and C4b
  • antibodies such as IgG and IgM (the phagocyte has receptors to recognise these)
  • acute phase proteins such as CRP and MBL (mannose-binding lectin)
24
Q

Why is opsonisation particularly important for encapsulated bacteria

A
  • Encapsulated bacteria are resistant to phagocytosis
  • Opsonisation is essential in clearing these encapsulated bacteria
25
Q

What are the main steps of phagocytosis

A
  • Microbe detected by phagocyte (ie by PRRs and PAMPs or by oponisation)
  • Microbe adhere to phagocyte
  • Formation of phagosome
  • Fusion of the phagosome to lysosome → phagolysosome
  • Digestion of ingested microbe by enzymes
  • Formation of residual body containing ingestible material
  • Discharge of waste material
26
Q

What is present in the phagolysosome to kill the pathogen

A

oxygen dependent pathway
- aka respiratory burst
- toxic O2 products kill pathogens (ROS, free radicals)
- eg hydrogen peroxide, hydroxyl radical, nitric acid etc
- this is the main pathway that kills the pathogen

oxygen independent pathway
Eg lysozymes, proteolytic enzymes etc

27
Q

What is the complement system

A

☞ serum proteins that are activated when encountering a microbe
☞ once they are activated, they produce complement protein that has anti-microbial properties eg:
- C3a and C5a that are responsible for the recruitment of phagocytes (ie to attract phagocytes towards the infectious microbe by chemoattraction: chemical diffusion gradient)
- C3b opsonisation of pathogens
- C5-C9 killing of pathogens via membrane attack complex

Remember a = attraction, b = binding

28
Q

Why is CRP important

A
  • Infection
  • Severity of inflammation
  • Patient response to treatment
29
Q

What are some conditions where phagocytosis will be reduced

A

decreased spleen function
- Asplenic patients (ie had splenectomy)
- Hyposplenic patients

decreased neutrophil number
- Cancer chemotherapy
- Certain drugs (eg phenytonin)
- Leukaemia + lymphoma

decreaed neutrophil function
- Chronic granulomatous disease (no respiratory burst)
- Chediak-higashi syndrome (no phagolysosomes formation)

30
Q

What are some conditions where phagocytosis will be reduced

A

decreased spleen function
- Asplenic patients (ie had splenectomy)
- Hyposplenic patients

decreased neutrophil number
- Cancer chemotherapy
- Certain drugs (eg phenytonin)
- Leukaemia + lymphoma

decreaed neutrophil function
- Chronic granulomatous disease (no respiratory burst)
- Chediak-higashi syndrome (no phagolysosomes formation)