Infections and Disease

what is the chain of transmission?

what is a pathogen

a microbe that causes disease

what is bacteria?

• single cells / simple structure

• cell wall structure determines which stains bacteria takes up (gram +/-)

• Colonising microbes live on the body for days-months (microbiome)

• Contaminants are not part of the microbiome (normal flora) and can be removed by washing

what is viruses?

• only replicate inside cells.

• Made up of DNA or RNA contained in an envelope → has proteins that enable virus to attach to cells and insert genetic material by combining with cell receptors.

what are other types of microbes?

• Fungi: in patients undergoing chemotherapy or long- term antibiotic treatment due to debilitated state =  opportunistic pathogen e.g. Candida albicans

• Protozoa e.g. giardia, crystosporidium

• Prions = strands of protein, rare

what are 3 modoes of infectious transmission?

Communicable Infections	Contagious Infections	Non-Communicable Infections
Infection that transmits from one person to another (either directly / indirectly)	Easily transmitted from one person to another Viruses	Requires ANOTHER vector to transmit the infection between people E.g malaria using the mosquitoes

what is a microbiome?

The microbes in our microbiome are permanent residents of the body → inhabit our body without causing disease (in individuals who are not immunocompromised)

• Present in most areas of the body in contact with the outside environment e.g., oral microbiome, skin microbiome, urogenital microbiome, respiratory microbiome, gastrointestinal microbiome

  • Microbial communities at each site are very different from each other

• Internal organs, tissues, and fluids are microbe-free

Function: supports immunity, prevents overgrowth of pathogens, produces vitamins + chemicals

what are factors that impact microbiome?

• age

• maternal diet

• gestational diabetes

• environmental exposures

what are reseroivrs of infectious microbes (3)?

Endogeneous	Congenital	Exogenous ‼
Pathogens come from a person’s own microbiome = “self infection”	Pathogens passed from mother → child either  during pregnancy during birth	Pathogens come from a source external from the patient  = “cross infection”

what are 3 types of exogeneous sources of infectious microbes?

People	Symptomatic obvious symptoms minor symptoms Asymptomatic → no symptoms present incubating the disease (first few days) recovering (convalescent // at the end) asymptomatic or subclinical infection chronic (long-term and inapparent, or latent → >3months)  passive (ie healthcare worker, visitor or patient contaminated with infectious agents)
Inanimate Sources	Fomites: Clothing, Medical equipment and devices Vehicles (common): Medications, Food, water, air
Animals / Insects (Arthropods)	Zoonoses: Any disease/ infection that is naturally transmissible from vertebrate animals to humans Over 200 known types Rabies, salmonellosis, Pandemic influenza Insect/arthropod bites (Vectors) Malaria, Typhus, Q fever Plague (zoonosis)

what are carriers of infectious microbes? and the 2 types?

“Carriers” = person who harbours infectious pathogens without discernable clinical disease → are a potential source of infection

• Asymptomatic Carrier: temporary (<6months) OR chronic (6>months)

• Passive (Contact) Carrier: healthcare worker, visitor, patient contaminated w/ infectious agents

compare between the innate and adatptive immune system? what is its definition? function? response? specificity? memory? cells involved?

	Innate	Acquired/Adaptive (3)
Definition	A type of simple immunity which is inbuilt at the time of birth (genetically determined)	A type of complex immunity which is developed through a lifetime.
Main function	To prevent pathogen entry To kill pathogens before spread Physical & chemical barriers (1) Cellular responses (2)	To kill pathogens to prevent further spread To prevent pathogen further attack
Response	Fast	Slow
Specificity	Non-specific	Specific
Memory	No memory	Stores memory
Cells involved	Neutrophils, macrophages, dendritic cells, natural killer cells	T cells, B cells, antibodies, immune memory

what is an antigen?

molecule on the surface of a cell that an organism recognises as foreign→ triggers an immune response

• On the surface of cells in the body, there are ‘marker’ molecules that identify the cell as belonging to the body (‘self’) = protects the body from attacking itself.

• Particular lymphocytes will recognise a particular epitope (the part of an antigen molecule to which an antibody attaches itself)  as they have complementary binding sites = antigen receptors

what is the 1st line of defence?

natural barriers (mechanical / chemical / reflexes)

• Physical Barriers: skin, mucous membranes, hairs, cilia, secretions, flushing

• Reflexes: blink, sneeze, vomiting, defecation

• Normal Microbiome → will inhibit growth of pathogen (competition)

what is the 2nd line of defence? its steps in general?

rapid innate = non-specific immune response

1. activation: Detection of a pathogen = the pathogen’s antigens are detected by WBCs using PRR (pattern recognition receptors) that recognise PAMPS (pathogen-associated molecular patterns) on a pathogen’s surface

2. inflammation

3. immune recruitment

4. pathogen removal

explain inflammation: what is it triggered by? aim? actions? signs?

Triggered: tissue damage/presence of pathogens

Aim: eliminate pathogen, clear necrotic cells from infection, initiate tissue repair

Actions: 

1. mast cells and basophils release histamine

2. Macrophages release cytokines = activate other cells of the immune system

Signs: redness, heat, swelling, pain = isolate and eliminate pathogen + begin tissue repair

what are the steps for immune recruitment?

Neutrophils = first phagocytes involved 

Macrophages = always present in tissues → phagocytoses any foreign materials (eats them)

Monocytes circulate blood until attracted to inflamed tissue → transform into phagocytic cells: dendritic cells or macrophages

1. detection of pathogen = PAMPS (pathogen associated molecular patterns) on pathogen surface are recognised by pattern recognition receptors (PRRs) on phagocytes

   1. Effect: release of soluble molecules (complement proteins, cytokines, chemokines) = recruits immune cells

what are the steps for pathogen removal / phagocytosis?

1. engulfment (ingestion) = phagocyte engulfs the pathogen into a vesicle - phagosome

2. forms phagolysosome = phagosome fuses with lysosome (contains digestive enzymes) 

3. digestion = enzymes + acids break pathogen into non-infectious components

4. exocytosis = waste materials are expelled from cell

5. in APCs (i.e macrophages/dendritic cells) fragments of the antigen are presented on the MHC II molecules = activate adaptive immune system

what are the 2 types of inflammations?

1. Acute inflammatory response: recognition → recruitment → elimination → resolution + repair

2. Chronic Inflammation → autoimmune disease (asthma, inflammatory bowel disease, neurodegeneration …)

• Constant inflammation is bad → immune system produces persistent cytokine production = tissue damage

what is the 3rd line of defence? and its general steps

adaptive immunity = specific + has a memory

1. antigen presentation

2. anti-body mediated immunity / humoral

3. cell-mediated immunity

what are the steps in antigen presentaiton?

Antigen Presentation Controlled by: T cells and B cells → act against the specific invader to destroy it at a cellular level The TH cell is specific to the pathogen’s antigen  Once activated, will initiate the humoral (antibody mediated) and cell-mediated immunity

Antigen presenting cells (APC) = dendritic cells (most common) or macrophages Pathogens engulfed by APC > broken down > antigen fragment produced > loaded onto MHC II molecule (inside APC) > MHC-II antigen complex migrates to cell surface > APC migrates to lymph nodes > activates specific naive helper T-cells (TH) = has a specific receptor to that antigen > TH cell divides to activate antibody-mediated and cell-mediated immunity

what are the steps required in anti-body mediated immunity?

Antibody-mediated immunity (humoral) For: pathogens in body liquid (blood, tissue fluid) By: B Cells

TH cells secrete cytokines →  activates B-cells → undergoes differentiation + proliferation→ produces many plasma B-cells and some memory cells → plasma cells  produce huge quantities of antibodies → float in liquid → recognise antigen on pathogen → bind to it →  inactivate it →  mark it for destruction by phagocytosis Antibodies: Y-shaped molecules that consist of 4 chains of protein (2 long/2 small) Antigen + antibody = antigen-antibody complex

what are these types of antibodies:

IgM

IgG

IgA

IgE

IgD

• IgM = produced early + effective at activating complement system

• IgG = abundant in blood + tissues → is the memory // supports opsonisation 

• IgA protects mucosal surfaces

• IgE helpful for allergy 

• IgD = a receptor on naive B cells

what are the steps in cell-mediated immunity?

Cell-Mediated Immunity For: infected host cells By: T Cells

CD8 cytotoxic T cells kill virus-infected cells, tumour cells or transplanted cells by inducing apoptosis. CD4 helper T cells coordinate:  immune responses through cytokines activating macrophages supporting B cells guiding the type of immune response required.

compare a human’s immnue primary and secondary response using antibody exposures?

Primary Response	Secondary Response
Slow process Unknown pathogen Cell mediated response first Memory B and T cells for future infection Antibody levels rise gradually, with early IgM followed by class-switched antibodies such as IgG, IgA or IgE depending on the context	Faster process Known pathogen Antibody-mediated response first Utilises memory B and T cells  Antibodies are usually higher affinity because B cells have undergone affinity maturation, and (Ig G) class-switched antibodies are produced quickly.

what is the purpose of vaccinations?

A substance used to stimulate the immune system’s response to a certain pathogen

• Antigen introduction to initiate primary response and store memory

• Vaccines allow for Herd Immunity: most people get immunised so those who cannot (old, sick) will still be protected

• Booster vaccines are used to stimulate the stronger secondary immune response for longer-lasting immunity

what do allergies require prior? what antibody is involved?

requires prior sensitization to the allergen (= any substance that can elicit an allergic immune response → antibody IgE)

what is autoimmunity?

• Self-tolerance: normal unresponsiveness of the immune system to self antigens

  • The immune system loses tolerance for self antigens → tissue destruction.

  • Cause is often unknown but may be: Genetic, Traumatic (Infections, drugs, diet, environmental), Immune dysregulation (e.g., with ageing)

what is anaphylactic reaction

antigen / allergen —> production of IgE antibodies —> IgE binds to surface of mast cell / basophils

subsequent exposure to allergen —> antigen attatches to antibody molecules = releases histamines + other mediators

what is hearing loss? caused in?

A partial or complete decrease in the ability to perceive sound in one or both ears.

Mechanism: Caused by pathology (issue) in

1.  the external/middle ear (conductive) 

2. the inner ear/auditory nerve (sensorineural).

what is otalgia? classified as?

Pain originating within or referred to the ear.

Mechanism: Classified as 

1. primary (pathology within the ear itself)

2. referred (pain originating from cranial nerves innervating the ear, such as the trigeminal or glossopharyngeal nerves).

what is aural fullness? associated with?

A subjective sensation of pressure, clogging, or stuffed feeling inside the ear.

Mechanism: Commonly associated with Eustachian tube dysfunction, middle ear effusion (accumulation of fluid), or endolymphatic hydrops.

what is tinnitus? symptoms?

The conscious perception of sound in the absence of a corresponding external acoustic

stimulus.

Mechanism: Typically presents as ringing, buzzing, or hissing, often resulting from aberrant neural activity in the auditory pathway.

what is otorrhea? symptoms?

Any discharge or drainage exiting the external auditory canal.

Mechanism: May consist of serous fluid, pus, or blood → indicating pathology in the external ear canal or a perforated tympanic membrane in middle ear disease.

what is vertigo? cause?

A false sensation of movement or spinning of oneself or the surrounding environment.

Mechanism: A specific type of dizziness resulting from an asymmetry or dysfunction within

the vestibular system (peripheral or central)

what is otitis media?

an inflammation or infection of the middle ear, the air-filled space located directly behind the eardrum.

what are the 4 types of diseases of the External Auditory Canal? explain each ones symptoms

1.  Earwax Plug	Earwax (epithelia debris) accumulation that blocks EAC → Complete obliteration of EAC Symptom: hearing loss / aural fullness Treatment: Ear wash with syringe to remove earwax.
2. Foreign Body	Invertebrates: insects, worms Solid objects: small stones, balls (kids)
3. Acute External Otitis	Cause: mostly bacterial infection Symptoms:  Pressure on the tragus + sign Otorrhea and oedema of the EAC Painful otoscopy Hearing loss due to occlusion of the EAC Treatment: otic drops (antibiotic + corticosteroid). Avoid water entry.
4. Otomycosis (fungal external otitis)	Symptoms: itchiness and otorrhea Cotton-like areas in the EAC, with black pigmentation

name 3 diseases of the middle ear?

1. acute otitis media

2. otitis media with effusion

3. chronic otitis media

explain acute otitis media? causes? symptoms?

Inflammation of the middle ear < 3 wk of duration

Cause: Bacterial infection from 

1. Streptococcus pneumoniae

2. Haemophilus influenzae.

Symptoms: Severe otalgia and fever 

• Reddened tympanic membrane +  under tension.

• Problem: Recurrent acute otitis media: children > 3 AOM in 6 mo

explain otitis media with effusion (OME)? causes? other names? risk factors? symptoms? treatments?

“Glue ear; Serous otitis media”

• Most common otitis in infants and children

• Non-purulent infection = doesn’t produce pus etc

Risk factors (same as AOM)

• Eustachian tube dysfunction: Failure in middle ear ventilation that generates chronic negative pressure.

• Adenoid hypertrophy: Physical obstruction in the nasopharynx that prevents normal ear drainage.

Symptoms

• Chronic inflammatory process with intact tympanic membrane

• Metaplastic transformation of the respiratory epithelium of the middle ear → into secretory glandular epithelium with thick mucus (glue ear)

Treatment

1. Saline nasal rinses

2. If adenoid hypertrophy =  Adenoidectomy

3. If hearing loss or glue ear >6 months = chronic issue → myringotomy (makes hole to drain ear canal) and ventilation tubes

explain chronic otitis media (COM)? what are the 2 clinical forms? their symptoms?

Septic (bacterial) or inflammatory process of the middle ear of long-standing evolution with periods of remission and relapse (>6months)

2 clinical forms > It presents with permanent injury to the middle ear

1. Inflammatory COM (SOM - Serous Otitis Media) → proliferation of mucosa BUT no infection

   1. Retraction pockets: thin layers cannot maintain the shape of the tympanic membrane

   2. Tympanosclerosis: calcification of tympanic membrane (more whiter)

   3. Adhesive otitis: the retraction pockets keep growing

2. Suppurative Chronic Otitis Media (COM) → bacterial infection

   1. Tympanic perforation (central, marginal): due to thin tympanic membrane

   2. Disruption of the ossicular chain

   3. Tympanosclerosis

   4. Symptoms: 

      1. Otorrhea

      2. conductive hearing loss (if hearing loss > 60 dB)

      3. perforation / granulation of tissues (either central or marginal)

      4. aural polyp obliterating EAC

name the otitis media with severe infections that are intratemporal?

1. acute mastoiditis

2. acute petrositis

3. labryinthisis

4. facial palsy

name the otitis media with severe infections taht are intracraneal?

1. otogenic meningitis

2. brain abscess

3. sigmoid sinus / lateral sinus thrombophlebitis (really severe)

explain acute mastoiditis? diagnosis? treatment?

Definition: Bacterial infection will extend to the mastoid process 

• Most common complication esp for children 3mo-3 years old

Diagnosis

• Fever + Severe ear pain

• Retroauricular oedema ( swelling from fluid buildup) 

• erythema (skin redness)

• erasing of retroauricular crease with pinna displacement

• Otoscopy= acute otitis media (AOM)

Treatment:  abscess drainage, Myringotomy, ventilation tube,

explain acute petroitis? cause? symtoms? treatment?

Definition: the inflammation of mastoiditis extends to the petrous apex of the mastoid process

• Rare condition

Cause: Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus

• Children: AOM/ Adults: COM

Symptoms: otorrhea, severe pain, fever, poor general condition

• Confirmed by a CT diagnosis: petrous apicitis are erosive lysis with ill-defined irregular edges

Treatment: 

• IV antibiotics

• Mastoidectomy: surgical procedure that removes diseased air cells from the honeycomb-shaped mastoid bone located just behind the ear.

explain labryinthitis? the types? symptoms? treatment?

Acute OM/Chronic OM extended to inner ear towards anterior (cochlea) and posterior (vestibular organs) labyrinth

1. Serous Labyrinthitis: sensorineural hearing loss + vertigo = Mild, reversible.

2. Purulent Labyrinthitis: Sudden sensorineural hearing loss + vértigo intense = Severe, irreversible

3. Perilymphatic fistula: Cholesteatoma erodes horizontal semicircular canal

Symptoms

• History of middle ear effusion (serous otitis media, chronic otitis media –otorrhea–)

• Sensorineural hearing loss due to cochlear involvement

• Vertigo: spontaneous nystagmus or nystagmus induced by increased pressure in the middle ear (Valsalva, ear aspiration)

• CT scan of the middle ear to assess middle ear and labyrinth effusion (or opacification)

Treatment

• Hospitalization + IV antibiotic therapy

• Surgery: myringotomy and possible mastoidectomy if COM is present

• Vestibular rehabilitation

explain facial palsy’s relation to OM?

Facial palsy due to otitis media

• caused by AOM in children 

• COM with/without cholesteatoma in adults.

Treatment:

• due to AOM: myringotomy, antibiotics, hospital admission?

• due to COM: mastoidectomy with facial nerve decompression

what is the weber test?

using a tuning fork on the midline to see where it lateralises (where it is heard):

• normal = heard in midlline

• conductive hearing loss = heard in worse ear

• sensorineural hearing loss = heard in better ear

what is the rinne test?

• tuning fork placed on the mastoid bone directly behind your ear = bone conduction

• When you stop hearing the sound, they move the fork just outside your ear canal = air conduction

• ask you which position sounds louder.

Understanding the Results

• Positive Rinne Test (Normal or Sensorineural Loss): You hear the sound louder next to your ear canal than on your bone (Air Conduction > Bone Conduction). This means your outer and middle ear work normally.

• Negative Rinne Test (Conductive Loss): You hear the sound louder or longer on your bone than next to your ear (Bone Conduction ≥ Air Conduction). This means something is blocking sound from traveling through your ear canal or eardrum (like earwax, fluid, or an infection).

compare between the conductive hearing loss and sensorineural hearing loss for: definition / ear structure affected / weber test results / rinne test results / air-bone gap / stapedial reflex / common treatment?

Features	Conductive Hearing Loss (CHL)	Sensorineural Hearing Loss (SNHL)
Definition	A barrier to sound transmission through the outer or middle ear.  Inner ear structures remain fully functional.	Pathology localized to the inner ear (cochlea), auditory nerve (CN VIII), or central auditory pathways.
Anatomical Site Affected	Outer / middle ear	Inner ear / auditory nerve
Weber Test (uses tuning fork)	Heard in worse/affected ear	Heard in better/unaffected ear
Rinne Test	Negative (BC ≥ AC)	Positive (AC > BC)
Air-Bone Gap	Present (≥ 15dB) The sound/ buzzing is present	Absent (< 15dB)
Stapedial Reflex	Absence of acoustic reflex	Typically present (except in severe / retrocochlear loss)
Common Fix	Hearing aids (otosclerosis) Surgical	Amplification (hearing aids, cochlear implants)

what is otosclerosis? relevance? symptoms? diagnosis? genetic cause? treatment?

Definition	Bone dysplasia (abnormal growth of bone) of the human otic capsule and stapes footplate Abnormal remodelling of the middle ears  The stapes begins to calcifies = affects the ossicular chain
Relevance	Leading treatable cause of adult-onset progressive hearing loss
Pathology (issue)	abnormal bone remodeling of normal endochondral bone resorbed →  replaced by vascular, hypercellular otosclerotic bone = fixation of the stapes footplate = conductive or mixed hearing loss.
Symptoms	Onset early 30s More common in women (2X) and European descent Conductive progressive hearing loss evolve to SNHL High-frequency tinnitus
Diagnosis	Otoscopy = normal Audiometry Weber Test: lateralised to the affected / worse ear Rinne Test: negative in affected ear Tympanometry: resistance of tympanic membrane Reduced tympanic membrane pressure: Jerger typo As in advanced phases Lack of acoustic reflex
Genetic Condition	Autosomal Dominant  Familiar clustering 40-50% cases AD inheritance with reduced penetrance 25-40% variable expressivity Candidate genes
Treatment	Hearing Aids Surgery → insertions of prosthetic stapes

what is ototoxicitiy? its clinical consequences? relevance? genetic relevance? prevention methods? risk factors?

Define	Drug-induced injury to cochlear and/or vestibular structures Drug (Aminoglycoside / Cisplatin) enters hair cells through channels transporters = mitochondrial dysfunction = outer hair-cell death = permanent loss of hair cell = hearing loss
Clinical Consequences	Tinnitus SNHL Imbalance Oscillopsia:  stationary objects appear to bounce, shake, or jump in your field of vision
Relevance	damage may be permanent  The only way to try and prevent is to monitor hearing BEFORE implementing the drugs Baseline and serial monitoring: high-frequency audiometry and otoacoustic emissions. Ask specifically about tinnitus, hearing in noise, imbalance and oscillopsia.
Genetic Susceptibility to mitochondrial-mediated ototoxicity	Disruption of Protein Synthesis (Genetic Susceptibility) Ribosomal Targeting: Aminoglycosides structurally resemble bacterial components and bind directly to the mitochondrial ribosome (due to mutation) Protein Halting: This binding halts the translation of essential proteins required for the inner mitochondrial membrane respiratory chain.
Risk Factors	cumulative dose renal impairment Age previous hearing loss + noise exposure genetic susceptibility. Combination therapy increases risk, especially aminoglycosides plus loop diuretics.
Prevention	Using least ototoxic effective regimen and adjust dosing for renal function. Respond early: communicate with oncology, infectious diseases, audiology and ENT teams. Support patients with hearing rehabilitation, tinnitus care and vestibular rehabilitation.

what are the main ototoxic drugs?

• Platinum chemotherapy: cisplatin, carboplatin, oxaliplatin.

• Aminoglycosides: gentamicin, amikacin, tobramycin.

• Loop diuretics: furosemide, bumetanide, ethacrynic acid.

• Other agents: macrolides, vancomycin, salicylates, quinine and antimalarials.

CALM EAR: 

• Cisplatin / Carboplatin

• Aminoglycosides

• Loop Diuretics

• Malaria Drug - Quinine

• Erythromycin

• Aspirin / Salicylates

• Rare reaction of Vancomycin

what is autoimmune ear disease? key players? activation? clinical profile? symtpoms? therapy?

	Autoimmune Inner Ear Disease
Definition	Adaptive immune system mistakenly attacks specific self-antigens within the inner ear tissues
Key Players	T lymphocytes Specific autoantibodies
Activation	Slow, targeted response Requires prior antigen recognition + memory
Clinical Profile	Rapidly progressive, fluctuating Bilateral sensorineural hearing loss
Key Symptoms	Severe vertigo Tinnitus Aural fullness
Therapy	Medication / drugs e.g immunosuppressants

what is autoinflammatory inner ear disease? key players? activation? clinical profile? symtpoms? therapy?

	Autoinflammatory Inner Ear Disorder
Definition	Tissue damage caused by overactive innate immune system = fails to regulate the inflammatory response
Key Players	Macrophages Neutrophils Protein complexes = inflammasomes
Activation	Immediate, non-specific response
Clinical Profile	Pro-inflammatory Cytokines → destroys cochlear hair cells Links to genetic mutations / syndromes
Key Symptoms	progressive deterioration of hearing loss / imbalance / tinnitius / aural fullness
Therapy	Frequent biologic agents