BIOS 250 - Unit 4: Microbial Diseases

Hypersensitivity

Potentially damaging immune response against an antigen

Type I hypersensitivity

• Rapid-onset allergic reaction due to cross-linking of antigen-specific IgE on the outside of mast cells, resulting in release of inflammatory mediators

• Allergens

• Ex: Allergy-induced asthma, anaphylaxis, hay fever, hives (urticaria)

Type II hypersensitivity

• Cytotoxic reaction triggered by IgG and IgM antibodies binding to antigens on cell surfaces

• Red blood cell types

• Antibodies attack human cells (blood cells)

• Ex: Hemolytic disease of the newborn (HDN), hemolytic transfusion reactions (HTR)

Type III hypersensitivity

• Inflammatory reaction induced by formation of immune complexes and their deposition in tissues and blood vessels

• IgG, IgM, and IgA mediated

• Too much antibody produced in reaction to antigen → Results in antigen-antibody clumps

• Ex: Systemic lupus erythematosus, rheumatoid arthritis, post-streptococcal glomerulonephritis

Type IV hypersensitivity

• Delayed T-cell-mediated inflammatory reaction that takes longer to manifest than the first three hypersensitivity types, due to the need for activation of antigen-presenting cell and T-cell subsets

• Allergens

• Ex: Contact dermatitis, type I diabetes mellitus, multiple sclerosis

Autoimmune disorders

• Diseases in which the body is attacked by its own specific adaptive immune response

• Loss of tolerance to self, resulting in immune-mediated destruction of self cells and tissues

• Vague and weak understanding of how it starts, but regulatory T cells inhibit autoreactive T cells

• Types → Organ-specific and systemic

Celiac disease

• Disease largely of the small intestine caused by an immune response to gluten that results in the production of autoantibodies and an inflammatory response

• Organ-specific autoimmune disorder

• Type IV hypersensitivity

• T cells triggered by gluten

• Anti-tTG antibodies to gluten IgA antibodies

• Target small intestine

Type I diabetes

• Hyperglycemia caused by an autoimmune disease affecting insulin production by β cells of the pancreas

• Organ-specific autoimmune disorder

• Type IV hypersensitivity

• T-helper cells target Beta cells

• Beta cells produce insulin (no insulin = high blood sugar)

• Insulin therapy

Myasthenia gravis

• Autoimmune disease affecting the acetylcholine receptors in the neuromuscular junction, resulting in weakened muscle contraction capability

• Organ-specific autoimmune disorder

• Type II hypersensitivity

• Anti-AChR antibody blocks signal from acetylcholine → Leads to paralysis

Rheumatoid arthritis

• Autoimmune disease in which immune complexes form and deposit in the joints and their linings, leading to inflammation and destruction

• Systemic autoimmune disorder

• Type III hypersensitivity

• Chronic inflammation

• Immune modulators and anti-inflammatory drugs

Transplant

• The replacement of tissue or an organ

• Rejection may occur if immune response is not suppressed (MHC dependent)

Hyperacute transplant rejection

Immediate transplant rejection that is catastrophic

Acute transplant rejection

Days to week transplant rejection by T cells and antibodies

Chronic transplant rejection

Several months to a year transplant rejection due to low immune resistance

Autograft

• Tissue transplanted from a location on an individual to a different location on the same individual

• No rejection concerns

Isograft

• Tissue grafted from one monozygotic twin to another

• Little concern of rejection

Allograft

• Transplanted tissue from an individual of the same species that is genetically different from the recipient

• Rejection possible

Xenograft

• Transplanted tissue from a donor that is of a different species than the recipient

• Rejection possible

Graft-versus-host disease

• Specific type of transplantation reaction in which a transplanted immune system (e.g., a bone marrow transplant) contains APCs and T cells that are activated and attack the recipient’s tissue

• Opposite of recipient rejection

Acute GVHD

• Weeks

• Damages the skin, GI tract, liver, and eyes

Chronic GVHD

• Months

• Not well understood

Primary immunodeficiency

• Genetic condition that results in impaired immune function

• Present from birth

Severe combined immunodeficiency disease (SCID)

• Genetic disorder resulting in impaired function of B cells and T cells

• No memory

• Treatment: Bone marrow transplant (comes with risk)

Secondary immunodeficiency

• Impaired immune response due to infection, metabolic disturbance, poor diet, stress, or other acquired factors

• Acquired B and T cell defects

• Causes: Systemic disorders, immunosuppressive treatments, prolonged illness

• Treatment: Reversible if cause resolved

• Ex: HIV

Cancer cells

• Cells that lose control of their cell cycle

• Cells that rapidly divide but don’t function properly

• Lose contact inhibition

Contact inhibition

Process where normal cells stop dividing upon contact with neighboring cells

Tumor

• Collection or aggregate of cells

• Can be benign (noncancerous) or malignant (cancerous)

Benign tumor

• Noncancerous

• Confined to one location

• Can be removed with surgery

Malignant tumor

• Cancerous

• Move to other areas of the body to form more tumors

Oncogenesis

• Genetic mutations over time

• Proto-oncogenes, tumor suppressor genes, DNA repair genes

• Carcinogen

Chemotherapy in cancer defense

• Classic → Poor selective toxicity

• Targeted → Much better but can improve

Adaptive immune system in cancer defense

• Works unless cancer cells have mechanisms to suppress

• Typically, via cytokine and hormonal control

Epidermis

• The outermost layer of human skin

• Dry, desquamation

Dermis

• The second layer of human skin, found between the epidermis and the hypodermis

• Blood vessels, nerves, muscle

Skin lesions

• Abnormal areas of skin that differ in color, texture, or size from surrounding tissue

• Ex: Crust, cyst, macule, papule, pustule, ulcer, vesicle, wheal

Nasolacrimal duct

• Tear duct connecting the lacrimal glands to the nasal cavity

• Production and control of tears

Conjunctiva

• The mucous membranes covering the eyeball and inner eyelid

• Microbiota not well characterized

Vitreous humor

Sterile watery material

Common sites of eye infections

• Conjunctiva (conjunctivitis)

• Eyelids (blepharitis)

• Cornea (keratitis)

• Lacrimal sac (dacryocystitis)

Staphylococcus aureus

• Bacterial skin infection

• Exposure: Skin-to-skin contact, broken skin

• Virulence: Staphylolysins, leukocidins, protein A

• Infection: Folliculitis, furuncles, carbuncles, staphylococcal scalded skin syndrome (SSSS)

• Treatments: Trimethoprim, tetracycline, linezolid

Folliculitis

A skin infection characterized by localized inflammation of hair follicles, typically producing an itchy red rash

Furuncle

• A small, purulent skin lesion

• Sometimes called a boil

• Progression of folliculitis

Carbuncle

Abscess containing a large, deep, purulent skin lesion

Streptococcus pyogenes

• Bacterial skin infection

• Necrotizing Fasciitis: A serious infection, also known as flesh-eating disease, that leads to rapid destruction of tissue through the action of exotoxin A

  • Exposure: Fascia

  • Virulence: Adhesins, invasins, proteases, M protein, streptolysins, exotoxins

  • Infection: Skin death

  • Treatments: Skin removal, amputation

Pseudomonas aeruginosa

• Bacterial skin infection

• Exposure: Opportunistic (wounds, burns)

• Virulence: 2-aminoacetophenone (odor), pyocyanin, pyoverdine, etc.

• Infection: Hot tub rash, swimmer’s ear

• Treatments: Resistant to most antibiotics, polymyxin B, fluoroquinolones, topical ointments and ear drops

Cutibacterium acnes

• Bacterial skin infection

• Exposure: Opportunistic invasion of follicles

• Virulence: Lipases, chemokines

• Infection: Several types of skin lesions, acne

• Treatment: Depends on grade (salicylic acid, antibiotics, creams, strong medicines)

Acne

A skin disease in which hair follicles or pores become clogged, leading to the formation of comedones and infected lesions

Comedones

Blackhead or whitehead pimples

Haemophilus influenzae

• Bacterial eye infection

• Exposure: Respiratory droplets

• Virulence: Attachment pili, IgA proteases, LOS

• Infection: Bacterial conjunctivitis, green/white/yellow discharge

• Treatments: Broad-spectrum topical antibiotics

Conjunctivitis

Inflammation of the conjunctiva, the mucous membrane covering the eye and inside of the eyelid

Papillomavirus (HPV)

• Viral skin infection

• Exposure: Direct skin-to-skin contact, broken skin

• Virulence: Provirus, E6 and E7

• Infection: Warts (plantar, flat, filiform, genital)

• Treatments: Typically required, liquid nitrogen and salicylic acid but many treatments

Oral herpes (HSV-1)

• Viral skin infection

• Exposure: Direct oral contact, any mucous membrane, highly contagious

• Virulence: Basal keratinocytes

• Infection: Cold sores, fever blisters, latency in neurons

• Treatments: No cure, acyclovir, topical meds

Adenoviruses

• Viral eye infection

• Exposure: Very contagious secretions, seen with common cold

• Virulence: Fiber proteins

• Infection: Viral conjunctivitis, watery discharge

• Treatments: No effective treatment

Dermatophytes

• Cutaneous fungal skin infection

• Trichophyton, Epidermophyton, Microsporum

• Exposure: Direct contact

• Virulence and Infection: Keratinases, lipases, proteases

• Diseases: Tineas/ringworm, athlete’s foot, barber’s itch, jock itch

• Treatments: Diagnose with wood lamp and microscopy, treat with antifungal topical and oral treatments

Tinea

Any cutaneous fungal infection caused by dermatophytes, such as tinea corporis, tinea capitis, tinea cruris, and tinea pedis

Sporothrix schenkii (rose gardener’s disease)

• Subcutaneous fungal skin infection

• Exposure: Soil, plants, timber, wound

• Virulence: Melanin, thermotolerance

• Infection: Skin (ulcers) to lymph system and beyond

• Treatments: Avoid by wearing appropriate PPE, identify via culturing and microscopy, treat with itraconazole

Acanthamoeba

• Protozoan infection

• Exposure: Soil, unchlorinated fresh water

• Virulence: Proteases, phospholipases

• Infection: Skin (ulcers, nodules, abscesses) and eye (Acanthamoeba keratitis)

• Treatments: Difficult, intensive early application of topical antiseptics

Acanthamoeba keratitis

A condition characterized by damage to the cornea and possible blindness caused by parasitic infection of the protozoan Acanthamoeba