Infectious and Skin Diseases Flashcards
Clinical Presentation of Immune Response:
Clinically, histologically, impt mediator, etc
Clinically: redness, swelling, pain
Histologically: edema
Pyogenic: pus production
Granuloma: macrophages surrounded by T cells
Tumor necrosis factor (TNF): important mediator
When does the immune response end?
when phagocytes clear all antigen
Lack of T-cell stimulation results in apoptosis
Acute vs. Chronic Inflammation
Acute Inflammation
Dilaton of small blood vessels
Increased microvasculature permeability
Migration and activation of immune cells
More WBCs
Acute vs. Chronic Inflammation
Chronic Inflammation
Infiltration by macrophages, lymphocytes, plasma cells
Increased tissue destruciton
Attempts at healing
Meningitis - Infectious Disease
What are the 3 layers of the Meninges?
Meninges protects CNS
- Dura mater (tough mother)
- Arachnoid (and subarachnoid)
- Pia mater (tender mother)
Meningitis - Infectious Disease
Dura mater
Outermost covering
Dense CT
Meningitis - Infectious Disease
Arachnoid
Middle layer
Subarachnoid space is fluid filled with many projections
Large blood vessels
Meningitis - Infectious Disease
Pia mater
Innermost covering (immediately next to the nerve tissue)
Loose CT and small blood vessels
Meningitis - Infectious Disease
Meningitis
What is it? General Presentation?
Bacterial or viral infection
Acute onser fever
Headache
Stiff neck
Photophobia (light sensitiviy)
Confusion
Usually inflammation of subarachnoid space
Meningitis - Infectious Disease
How does Meningitis cause Neuronal Injury?
Inflammation in subarachnoid space
substantial infiltration bvy neutrophils
May breach blood-brain barrier and cause localized inflammation in neural tissue
Damage to blood vessels can cause hemorrhage into the brain
Most damage is due to increases pressure
Meningitis - Infectious Disease
Meningitis Pathogenesis
- Coloization of nasopharynx
- Evade Opsonization in the bloodstream
- CSF access through endothelium of Blood-brain barrier
Meningitis - Infectious Disease
Host Defense (Pathogen Strategy) against colonization or mucosal invasion (stage 1)
Secretory IgA (IgA protease secretion)
Ciliary Activity (Ciliostasis)
Mucosal Epithelium (Adhesive pili)
Meningitis - Infectious Disease
Host Defense (Pathogen Strategy) against intravascular survival (stage 2)
Complement (Evasion of alternative pathway by polysaccharide capsule)
Meningitis - Infectious Disease
Host Defense (Pathogen Strategy) against Crossing of blood brain barrier (stage 3)
Cerebral endothelium (adhesive pili)
Meningitis - Infectious Disease
Host Defense (Pathogen Strategy) against Survival within CSF (stage 4)
Poor opsonic activity (Bacterial replication)
Meningitis - Infectious Disease
Pathogen Strategy: Immunoglobulin A (IgA)
Where does it come from? What is it? What does it do?
Produce dby plasma cells associated with mucosa
First line of defense
Opsonization
Primarily acs through exclusion, bindng, and crosslinking
Extensive glycosylation to prevent degredation by proteases
Not an inflammatory Ig
Meningitis - Infectious Disease
Pathogen Strategy: Ciliostasis
Prevent movementof bacteria out of bronchial tubes
Attachment of bacteria to cilia impedes movements
Toxins - may damage axoneme or deplete ATP
Meningitis - Infectious Disease
Pathogen Strategy: Adhesive Pili
Pili bind non-ciliated mucosal cells allowing them to cross the epithelium and basement membrane
Infection occurs most easily in simple epithelia (Nasopharynx, intestines)
Meningitis - Infectious Disease
Pathogen Strategy: Bacterial Toxins: Exotoxins
Secreted by living bacteria
Highly antigenic (antitoxin neutralizes)
Highly Toxic (fatal in microgram quantities)
Usually do not induce fever
Usually bind to specific receptors
Meningitis - Infectious Disease
Pathogen Strategy: Bacterial Toxins: Endotoxins
Secreted when bacteria cells are killed
Weakly immunogenic
Toxic at 10-100s micrograms
Induce fever
no specific receptors
Part of cell wall then released
Parasitic Diseases
How do parasitic diseases cause damage?
Can be caused by single celled and multicellular organisms
Damage can be caused by consumption by parasite (parasite is consuming something the host organism needs)
Damage may actually result from immune response to parasite
Parasitic Diseases: Trichinosis
Trichinosis
What causes it? What does it do?
Obtained by ingestion of undercooked meat, usually pork
Infects skeletal muscle
Parasitic Diseases: Trichinosis
Symptoms of Trichinosis
Fever
Myalgia (muscle pain)
Periorbital edema
Parasitic Diseases: Trichinosis
Life Cycle of Trichinella spiralis
- Adult in intestines produce larva
- Larva infiltrate blood
- Exit blood vessels in skeletal muscle
- Adults die and muscle fiber calcifies
Parasitic Diseases: Trichinosis
Enteric Phase of Trichinosis
Strong immune response to larvae: T helper cells produce cytokines, Eosinophil and Mast cell activation
Increases intestinal mobility: T helper cytokines, mast cell granules, expel larvae from gut in animal models
Inflammatory response to larvae elsewhere can cause widespread destruction
Parasitic Diseases: Trichinosis
Muscle Phase of Trichinosis
Muscle cell is co-opted as a nurse
Disruption of myofibrils
Enlarged/central nuclei
Collagen capsule formation
Parasitic Diseases: Trichinosis
Clinical Presentation of the Enteric Stage
Typical of enteric disease
Diarrhea and nausea
Vomiting, pain, low grade fever (immune response)
Parasitic Diseases: Trichinosis
Clinical Presentation of Muscle Stage
Typical of infection/muscle damage
Myalgia and paralysis
Fever, headache, skin rash
Edema and conjuctivitis
Integumentary Disorders
What are the two types of disorders of the skin?
Growths: Cyst, Malformation, Begnin/malignant neoplasm
Dermatitis (rashes): non-neoplastic
Integumentary Disorders: Psoriasis
Psoriasis
Inflammatory skin disease
Scaling skin condition
Reddness, swelling, edema
Integumentary Disorders: Psoriasis
Pathology of Psoriasis
Thickened epidermis (elngated rete ridges)
Neutrophil infiltration
Excessive epidermal proliferation (shortned cell cycle, 2X peoliferative population)
Accmulation of nucleated cells in the stratum corneum (parakeratosis)
Endothelial cell proliferation
Integumentary Disorders: Psoriasis
Pathogenesis of Psoriasis
Immunologic abnormalities:
* T helper lymphocytes (MHCs)
* cytokine overexpression (TNF, IFNy, IL-2)
* Presence of unique dendritic cells
* Genetic link to HLA-C
* Sensitized T cells accumulate in epidermis (IFNy)
* Can be induced by localized trauma
Integumentary Disorders: Psoriasis
What is the relationship between Angiogenesis and Psoriasis
Angiogenic facors can be found in psoriatic lesions
TNFa
TGFb
IL8
VEGF
Integumentary Disorders: Psoriasis
VEGF
Released from keratinocutes
Stimulate epidermal hyperplasia, vascular growth, leukocyte infiltration
Regulates psoriatic keratinocyte activity
Integumentary Disorders: Verrucae
Verrucae (warts)
What causes it? What does it do?
Squamoproliferative
Caused by HPV
Generally regress (self limited)
Virus transmitted by contact
Viral typing can confirm if problematic infection (poor prognosis -> cancer)
Integumentary Disorders: Verruca
Verruca Pathology
Epidermal hyperplasia is uneven
Cytoplasmic vacuolization (halos)
Increased keratohyalin granules
Eosinophilic keratin aggregates in cells
Integumentary Disorders: Verruca
Verruca Development
HPV viral proteisn in keratinocytes
E6 of HPV may interfere with maturation
Integumentary Disorders: Pemphigus
Blisters
What are they
Acantholysis
Dissolution of intercellular bridges
Which ones determine where blister forms
Integumentary Disorders: Pemphigus
What are the three types of blisters?
Subcorneal:
Suprabasal:
Subepidermal:
Integumentary Disorders: Pemphigus
Pemphigus
Autoimmune formation of blisters
Autoantibodies attack the intracellular junctions: inepidermis or mucosa
Integumentary Disorders: Pemphigus
Types of pemphigus
Foliaceus: subcornal lesion
Vulgaris: suprabasal lesion
Bullous Pemphigoid: subepidermial, nonacantholytic lesion
Eosinophils, lymphocytes, and sometimes neutrophils seen in lesion
