Immune Patho II

Part 1: Host Defenses, Infection, & Disease Transmission

3 lines of defense

• 1. Barriers (skin, mucous membranes, secretions)

• 2. Inflammatory response (phagocytic leukocytes, antimicrobial proteins, inflammatory response, fever)

• 3. Adaptive immunity (lymphocytes, antibodies, memory cells)

Skin - epidermis

• Superficial outer layer

• Continuously renews itself

• Has a lot of keratin

• 0.05-0.01mm thick

• No vascular structures

Skin - dermis

• 0.05mm-4mm thick

• Elastin & collagen fibers

• Gives skin strength & helps store water & electrolytes

• Nerves & blood vessels

• Location of sensory receptors

Skin - hypodermis/subcutaneous

• Connective tissue, fat cells, immune cells, blood vessels & nerves

• Connects skin to rest of body

Dermal appendages

• Nails

• Hair

• Sebaceous glands → oil producing, protects skin

• Sweat glands → temp regulation, toxin removal (minor)

**All within the dermis**

Resident microbiota

• Average human has ~30 trillion human cells

  • Also has ~39 trillion bacterial cells

    • Live in nonsterile areas of body, including skin

    • Provide many benefits & usually don’t cause harm

      • Take up space

      • Compete for nutrients

      • Antimicrobial properties (can destroy microbes)

Infection

• Invasion or overgrowth of a micoorgansim within the body, resulting in cellular, tissue, & organ destruction or even death

• To cause infection, organism must penetrate the 3 lines of defense

• Primary pathogens:

  • Bacteria, virus, fungi, parasites

Pathogens

• Any microorganism that produces disease

• 2 types:

  • 1. True pathogens: cause disease in healthy people

    • Bypass normal defenses & cause infection

    • Associated w/ a specific & recognizable disease (Covid, TB)

  • 2. Opportunistic pathogens: part of our normal flora but can cause illness if the conditions are right

    • Often developed by immunocompromised people

    • Ex. Antibiotic-associated diarrhea or yeast infections

Pathogenicity - how easy is it to catch?

• Communicability: ability to spread from person to person

  • Portal of entry is important

• Infectivity: ability to invade & multiply in host

Pathogenicity - how well does it evade host defenses?

• Immunogenicity: ability to produce an immune response

• Antigenic variability: ability to alter antigens recognized by immune cells

• Pathogen defenses: ability to avoid destruction

Pathogenicity - how bad can it harm us?

• Mechanism of action: how a micoorganism damages tissue

• Virulence: capacity to cause severe disease (potency)

  • Toxigenicity: production of toxins

• Coinfection: 2+ pathogens transmitted together

• Superinfection: new infection develops after an initial infection

Transmission

• Infectious organisms reside in reservoirs

• 3 types:

  • 1. Direct transmission → must have physical contact

  • 2. Indirect transmission → fecal-oral, droplets/airborne, vectors (ex. mosquitos, fleas)

  • 3. Vertical (parent to offspring in utero) vs. horizontal (spread from one subject to another)

Transmission - Zoonotic

• Infectious disease that can spread from animals to humans

Chain of infection

• Direct contact: touch

• Droplet: large respiratory particles

• Airborne: small suspended respiratory particles

• **By breaking chain of infection, we can limit pathogen spread**

• Universal precautions: all blood & body fluids treated as potentially infected

Phases of acute infection (important)

• 1. Exposure: contact w/ pathogen

• 2. Incubation: time b/w when a person get infected, & when they start experiencing symptoms

  • Pathogen is multiplying inside body

• 3. Prodrome: mild, vague, nonspecific symptoms

  • Ex. fatigue, low grade fever, nausea

• 4. Clinical illness: specific disease symptoms

  • Can have local manifestations, systemic manifestations, or both

• 5. Convalescence: recovery, fatigue

  • Gradual improvement of symptoms

Tests to identify correct pathogen

• Direct culture: take 2-3 days, some organisms are difficult to grow

• Antigenic tests: rapid, some tests have high false +/- rates

  • Ex. at-home Covid test

• Antibody tests: doesn’t necessarily mean you have an active infection

• Genetic tests (PCR): very accurate but must know genetic sequence to look for, need expensive equipment

• Serum labs: basic blood cultures

  • Ex. WBC count

Part 2: Major Infectious Organisms

1. Bacteria

Bacterial characteristics

• Bacteria are prokaryotes

  • Single cell w/ cell wall

  • Different DNA/RNA replication

  • Different ribosomes

  • Folic acid synthesis

• Classification (shapes):

  • Cocci, Bacilli

  • Staphylo- (cluster), Strepto (chain), etc.

• Can produce endospores

  • Resistant to heat, drying, chemicals (harsh conditions)

  • Ex. Clostridioides difficile

• Various transmission routes & ways to avoid immune detection

Biofilms

• Protective coating around bacteria that protects against antibiotic or host immunity → so they’re resistant to antibiotics

• Highly difficult to remove

• Ex. plaque, implanted devices

Bacterial toxins - Exotoxins vs. Endotoxins

• Exotoxins: enzymes released during growth

  • Damages cell membranes, activates second messengers, & inhibits protein synthesis

• Endotoxin aka Lipopolysaccharide (LPS):

  • Part of Gram-Negative cell wall

  • LPS activates a very strong immune response, which is what damages tissues (inflammation)

    • This is one of the patterns that innate immune cells recognize

Tissue damage from toxins - direct & indirect

• Direct: exotoxin production

  • Pathogen → immune response → inflammation → leads to much of the tissue damage & symptoms

• Indirect: induction of the immune response (endotoxin)

  • Indirect damage = immune-mediated damage

Staphylococcus aureus

• Gram positive cocci

• Often a normal colonizer (lives in body w/out causing issues)

  • Around 30% of people are colonized

  • Sits on skin → so must disinfect skin before procedures

• Is an opportunistic pathogen (usually harmless, but can turn bad)

• Numerous virulence factors (toxins, immune-evasion, biofilms)

• Common cause of healthcare-associated infections

• Antibiotic resistance

• MRSA → specific type of Staphylococcus aureus that’s mutated & is resistant to certain antibiotics, so very difficult to treat

S. aureus skin conditions - Folliculitis

• Superficial inflammation of hair follicles

  • Can be infectious or noninfectious

S. aureus skin conditions - Furuncles

• Boils

• Deeper inflammation of hair follicles

• Develop from preceding folliculitis; spread through follicular wall into surrounding dermis

S. aureus skin conditions - Carbuncles

• Collection of infected hair follicles that may develop into an abscess

• Erthematous, painful, swollen mass that drains through many openings

• Commonly causes systemic symptoms (fever, malaise) & often required medical intervention

S. aureus - Cellulitis

• Infection/inflammation of the dermis &/or subcutaneous tissue

  • Occurs when bacteria gets into deeper layers of skin

  • Frequently occurs when early infections go untreated

• Clinical manifestations:

  • Erythema, edema, warmth, pain

• Risk factors:

  • Bacterial entry: bug bites, cuts, pressure injuries

  • Impaired healing: diabetes, poor circulation, immunosuppression

  • Increased exposure: crowded living conditions, poor sanitation

Clostridioides Difficile (C. diff)

• Gram-positive, anaerobic, spore-forming bacillus

  • Exotoxin

• 2-5% of population are colonized, but not “infected”

• Transmission by fecal-oral route

  • Common cause of healthcare-associated diarrhea

  • Spores can survive on fomites (contaminated surface) for months

  • Hospitalized patients require enteric isolation

C. diff - clinical manifestations, complications, & risk

• Clinical manifestations:

  • Frequent, watery diarrhea (up to 10-15x/day)

  • Fever, loss of appetite, nausea/vomiting

  • Abdominal pain, tenderness. or cramping

• Complications:

  • Toxic megacolon (severely dilated colon, stops working), colon perforation, sepsis, death

• Greater risk for:

  • Antibiotic use

  • 65+ years old

  • >14 days in hospital

  • Immunocompromised

2. Fungi

Fungal infection (mycosis)

• Large eukaryotes:

  • Thick cell walls

  • Single-celled yeasts

  • Mulicellular molds

  • Dimorphic (changes forms) → very common

• Transmission:

  • Inhalation, contamination of wounds, opportunistic (present in body)

Candiasis

• Most common fungal infection, typically due to commensal overgrowth

  • Oral thrush (yellowy-white coating on tongue)

  • Vaginal candidiasis

• Risk factors:

  • Moist environment

  • Recent antibiotic use

  • Pregnancy

  • Diabetes

  • Infants/Immunocompromised

Dermatophytes

• Fungi that infects keratinized tissues

• Dermatophyte infection are called tinea, followed by body area infected

  • Tinea capitis: scalp

  • Tinea pedis: foot (athletes foot)

  • Tinea corporis: body (ringworm)

  • Tinea cruris: groin (jock itch)

  • Tina unguium: nail (onychomyosis)

• Often presents as patches that are dry, scaly, erythematous, & pruritic

3. Parasites

Parasites patho

• Organism that lives on/in host & lives at the expense of the host

• 3 types:

  • 1. Protozoa

  • 2. Helminths

  • 3. Ectoparasites

1. Protozoa

• Eukaryotic, unicellular

• Amoebas, Flagellates, Ciliates, Sporozoan

2. Helminths

• Parasitic worms

• Large, multicellular

• Intestinal & tissue nematodes (ex. hookworm, roundworm)

• Flatworms (ex. liver fluke, lung fluke, tapeworm)

3. Ectoparasites

• Arthropods that depend on a blood meal from humans

• Fleas, ticks, lice, mites

Parasite transmission

• Rarely transmitted from human to human; transmitted mainly through vectors

  • Malaria by mosquito bites

  • Trypanosomes by tsetse fly

  • Leishmania spp. by sand fleas

  • Others found in contaminated water or food (ex. Giardia duodenalis)

• Typically have complex life cycles that require multiple hosts to complete their life cycle

Toxoplasma Gondii

• Causative agent of toxoplasmosis

• Parasitic protozoa

  • Reservoirs: undercooked contaminated meat, cat feces, contaminated water

    • **Pregnant woman should not change cat litter**

  • Transmission: fecal-oral route or eating contaminated meat

• Many infections are asymptomatic, but can also cause flu-like symptoms

  • Fever, headache, myalgias, pharyngitis (sore throat), rash, cervical lymphadenopathy (swollen neck lymph nodes)

4. Viruses

Virus patho

• Basic structure: nucleic acid surrounded by protective protein (capsid)

• Virion only contains bare necessities:

  • Genetic material, viral-specific proteins/enzymes, protective coating

  • Cannot replicate on their own

• Disease occurs when virus takes over host cell, interfering w/ normal function & sometimes causing cellular death

Viral infection stages

• 1. Attachment

  • Virus into body

  • Finds right cell w/ right receptor (lock & key)

• 2. Uncoating

  • Virus takes off its coat surrounding genetic material

  • Genetic material is released into host cell

• 3. Replication

  • Virus takes over

  • Uses host cell as a factory

• 4. Release

  • Multiplied virus is released

  • Through budding or by rupturing host cell

Viral latency

• Survival strategy where a virus remains dormant in a cell w/out producing more viruses → can last for years

• Viral genome is left behind in the cell

  • IF the virus can integrate its DNA into host cell, it can be transmitted to daughter cells

  • The daughter cells can then make new viruses at a later time

Examples of latent viruses

• Herpes Simplex Virus 1 & 2 (cold sores, genital warts)

• **Varicella Zoster Virus (chicken pox = shingles when reactivated)**

• Human Immunodeficiency Virus (HIV, AIDS)

• Epstein Barr Virus (infectious mononucleosis, various lymphomas)

Influenza A

• Highly contagious respiratory virus spread through respiratory droplets

• Single-stranded RNA virus w/ a range of hosts

  • Humans, birds, pigs, bats, horses, dogs

• Mutates quickly & changes

  • Antigenic Drift → small genetic changes that slowly change over time

  • Antigenic Shift → major genetic changes that occur very quickly

    • Flu pandemic, Covid-19 pandemic

Influenza A - Clinical Manifestations

• Localized:

  • Dry cough, sore throat, nasal congestion, nasal drainage, shortness of breath

  • Symptoms caused by inflammation of immune response, not virus

• Systemic:

  • Chills, fever, body aches, anorexia, weakness, malaise

• Can progress to pneumonia, sepsis, & death in severe cases

Viral Hepatitis

• Group of viral infections that cause liver inflammation & damage

• A & E = fecal-oral route, most commonly through food

• B, C & D = body fluids (sex, childbirth, vaccinations)

  • Must have B to get D

Acute Viral Hepatitis stages

1. Incubation

• Phase lasts 2-6 weeks for HepA, & up to 6 months for HepB

• Asymptomatic

2. Prodrome

• Nonspecific GI symptoms (nausea, vomiting, right upper quadrant abdominal pain, fatigue, malaise, fever)

3. Icteric

• Jaundice, dark urine, clay-colored stools, significantly elevated liver enzymes

4. Recovery

• Symptoms resolve as pathogen is destroyed, typically occurs 4-8 weeks after symptom onset

Chronic Hepatitis

• Liver inflammation lasting longer than 6 months

  • HepB & HepC

• Persistent infection can lead to progressive liver damage

  • Fibrosis (due to inflammation)

  • Cirrhosis (long term fibrosis)

    • Portal hypertension

    • Ascitis

    • Hepatocellular carcinoma

• Can be asymptomatic

Herpes Simplex Virus (HSV)

• HSV-1

  • Contact w/ infected saliva

  • Cold sores or fever blisters

• HSV-2

  • Genital infections

  • Skin-to-skin mucous membrane contact during viral shedding

• Lesions are painful, erythematous vesicles

• Both can go latent! (inactive, no more symptoms)

  • Comes down same nerve route (so after going away, it’ll come back in the same spot)

Varicella Zoster Virus

• Varicella (chickenpox)

  • Initial infection transmitted by respiratory droplets

  • Full body pruritic fluid-filled blisters that crust over time

• Herpes Zoster (shingles)

  • Reactivated zoster virus (usually 50+ years old)

  • Pain & paresthesia localized to a dermatome, followed by vesicular eruptions

  • Can’t “catch” shingles, but if exposed to vesicles the person can get chickenpox if not vaccinated or previously infected