Innate Immunity - Intro

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11.19.17

2 more days until break

Music mood: Mili - Miracle Milk

Parasitology

Influenza

Happy flu season! I’ve just been stuck inside for 5 days with a mild case, so this is a bit bitter

There are 3–5 million cases of flu per year, and ~375,000 deaths, usually in older, younger, and immunocompromised individuals.

Enveloped, Single-stranded RNA virus

First identified in 1933, but existed long before

Generally considered an infection of the bronchi

so effectively a form of bronchitis – i.e. it causes inflammation of the bronchi 

There are 3 types - A, B and C

B & C appear restricted to humans 

C is less common

A is found in wide range of species including pigs and poultry as well as man

Type A appears to be responsible for more severe disease

Basics

Transmission by aerosols

Incubation ~2 days

Contagious during first 3-5days of illness

Symptoms – fever, myalgia, headache, dry cough, sore throat, aches, fatigue

Recovery ~7-10 days for most

Complications – most frequent = secondary bacterial pneumonia, rarely = viral pneumonia, myocarditis, encephalitis

No specific treatment

Vaccination for high risk groups including the elderly, health care workers, those with underlying respiratory conditions.

Avian

The main reservoir is wildfowl that are resistant to the disease

doesn’t usually affect animals other than poultry and pigs

However some transfer events occur

Seasonal

Incidence highest in winter

Strains vary from year to year -  hard to predict and vaccinate (this year’s vaccine has been pretty rubbish)

Pandemic

Can be caused by any strain that has not been seen in the human population for many years

New strains evade the herd immunity that exists to previously encountered strains

1918 /19 –( Spanish) estimated 40-50 million deaths worldwide

1957 – Influenza A/H1N1 (Asian)

1968 – Influenza A/H3N2 (Hong Kong)

Eventually the virus runs out of susceptible hosts and the epidemic fizzles out

Experts generally agree another pandemic is inevitable, and may be imminent – maybe we have had some minor pandemics 

16000 confirmed H1N1 deaths in 2009 affecting over 200 countries

Consensus is that the prompt action of the Hong Kong authorities probably prevented a pandemic in 1997

The prediction is scary - for industrialised countries they predic 1.0 – 2.3 million hospitalisations

280,000-650,000 deaths 

in two years

A network of 112 centres monitor flu isolates to identify unusual strains that can then be examined further

The WHO has a Pandemic Preparedness Plan in place http://www.who.int/influenza/preparedness/pandemic/en/

Diagnosis

Generally based on GP diagnosis

Virus isolation / virus demonstration from nasopharyngeal secretions during acute phase

Demonstration of viral antigen in secretions

Antibody rise using paired sera ( 1st sample taken between days 1-3 of illness, 2nd taken around day 12 of illness) by haemagglutination inhibition or complement fixation test

Molecular methods evolving rapidly – in particular in response to the recent epidemic/pandemic strains emerging

A range of respiratory illnesses have the same symptoms, only laboratory testing can confirm the aetiological agent

Treatment/Vaccination 

In the UK NICE argue that immunisation against predicted strains is the best form of defence – traditionally focused on the elderly and those with underlying lung problems, but recently started rolling out a childhood vaccine (nasal spray)

Vaccines generally based on the H & N surface structures which mutate, however hopes of an M protein based vaccine which will give longer lasting protection raised recently

Antivirals

Antivirals not recommended in otherwise healthy people (amantadine should not be used at all) - should ride it out

However when incidence reaches a certain level zanamivir and oseltamivir should be used in those considered high risk for the development of complications – PROVIDED THAT TREATMENT IS STARTED WITHIN 48 HOURS OF ONSET OF SYMPTOMS

Resistance is becoming an issue

Gram staining

Medically Important Bacteria: Clasification

Staphylococcus epidermidis is a coagulase negative, Gram-positive coccus. The organism uses sophisticated regulatory networks to adapt its metabolism to suit varying environmental conditions. S. epidermidis relies on biofilm formation to protect cells from the host immune system and other anti-microbial molecules.

Haematology

White Blood Cells (Leukocytes)

Neutrophils, eosinophils and basophils = granulocytes (polymorphonuclear leukocytes)

Monocytes & lymphocyes = mononuclear

Neutrophils

Most numerous (~60% of WBC)

Nucleus divided into lobes

Cytoplasm contains small granules

Stains pink with Romanowsky dyes

Lifespan of 6-10hrs

Exit into tissues - non-specific defence against bacteria and fungi

Eosinophils

1% of circulating leukocytes 

Large cytoplasmic granules - stain strongly with acidic dye eosin

Nucleus is bilobed

Circulate for 4-5hrs

Exit to tissues –> 

Defence against parasites 

Dampen allergic response

Tissue eosinophils are also capable of responding to bacterial and fungal infection in a similar way to neutrophils.

Basophils

Least numerous (<1%)

Large granules stain strongly with basic dye methylene blue

Involved in anaphylactic hypersensitivity and inflammatory reactions

Monocytes

5% of circulating leukocytes

Large cell

Kidney/clefted shaped nucleus

Scattering of delicate azurophilic granules

Circulate for 10hrs

Mature into phagocytic tissue macrophages

Responsible for the removal of aged RBCs and other debris

Process and present antigens to T-lymphocytes 

(Macrophages are formed in response to an infection or accumulating damaged or dead cells. Large, specialized cells that recognize, engulf and destroy target cells.)

Lymphocytes

Second most common leukocyte (33%)

Much less cytoplasm - nucleus almost fills cell

Variable lifespan

Receptors on surface recognise foreign substances

Several types of lymphocyte - click here

BACTERIAL MENINGITIS Timeline, Organisms, Presentation

Actinomyces israelii

Gram+, anaerobic, non-spore forming, branching rod

Endogenous transmission (dental crevices -bad higiene, dental trauma- ; female genital tract -IUD-)

Dx: branching rods in “sulfur granules”; colonies resemble a molar tooth.

Not painful but very invasive penetrating tissues, including bone.

Draining abscess (sinus tracts) CULTURE THAT PUS

Disease: ACTINOMYCOSIS in low O2 tissues

Cervicofacil: “Lumpy jaw”, mycetoma on jaw line

Pelvic: from IUD

CNS: solitary abscess

Abdominal: qx, trauma

Thoracic: aspiration