Parasitic protozoa
-single celled eukaryotes that replicate intracellularly (e.g. in RBCs) or extracellularity (e.g. in urine)
How microbes cause tissue damage
- direct invasion of cells resulting in cell death
- release of toxins that “kill at a distance” or enzymes that degrade tissue
- inducing host immune responses that cause tissue damage
Exotoxins secreted by bacteria
- enzymes (proteases, hyaluronidases)
- toxins that alter intracellular signally
- neurotoxins
- superantigens that stimulate large numbers of T cells, leading to massive cytokine release which can lead to shock
How can microbes evade the immune system?
- growth in niches that are inaccessible to the immune system (e.g. luminal intestine for C diff)
- antigenic variation (low fidelity of viral RNA polymerases such as in HIV; viral genome reassortment as in influenza)
- resistance to innate defenses (e.g. escaping phagocytosis; carbohydrate capsule on bacteria causing pneumonia shields antigens and presvents phagocytosis; some bacteria produce toxins that kill phagocytes or prevent their micration; neisseria etc secrete proteases that degrade antiobodies; some viruses produce proteins that block complement activation, e.g. herpes)
- impairment of effective T cell antimicrobial responses by specific or nonspecific immunosuppression (e.g. some DNA viruses bind to or alter localization of MHC class I proteins, impairing peptide presentation to CD8 cells)
Different inflammatory responses to infections
- purulent inflammation
- mononuclear infiltrates including granulomatous responses
- cytopathic/proliferation reactions (e.g. in viruses)
- tissue necrosis (e.g. c. perfringens)
- chronic inflammation and scarring
Histologic features of EBV
- striking paracortical area expansion by activated T cells (immunoblasts)
- minor population of infected B cells expressing EBNA2 and LMP1
- sometimes, EBV infected B cells resemble Reed-Sternberg cells
- sometimes, mild B cell follicular hyperplasia
- often, difficult to distinguish massive paracortical expansion from lymphoma
Examples of Staph virulence factors
- surface receptors for fibrinogen and other molecules to help it bridge to endothelial cells
- lipases to degrade lipids on skin surface
- alpha and beta toxins, that damage cell membranes
- A and B toxins which cause exfoliation resulting in a loss of barrier function
- superantigens that result in TSS (also found in strep pyogenes); these cause stimulation of T cells resulting in release of large amounts of cytokines that can result in shock
Examples of strep virulence factors
- capsules that resist phagocytosis
- M surface protein that prevents phagocytosis (probably antibodies to this result in rheumatic fever)
- S pyogenes secretes an exotoin that causes fever and rash
Anthrax morphology
-large, boxcar shaped gram positive extracellular bacteria in chains
Nocardia morphology
- filamentous gram positive bacteria that often have a beaded appearance due to irregular staining
- positive by Fite (modified acid fast) stain, unlike actinomyces
Donovan bodies
-Klebsiella granulomatis (Granuloma inguinale) in Giemsa smears; minute, encapsulated coccobacilli in macrophages; also positive with silver stain
Forms of leprosy
- tuberculoid: scaly skin lesions with decreased sensation (granulomas without bacilli)
- lepromatous: symmetric skin thickening and nodules with invasion into Schwann cells and macrophages with damage of peripheral nerves (granulomas with lots of bacilli in macrophages)
- good Th1 response results in tuberculoid form, while weak Th1 response, sometimes with a relatively increased Th2 response results in lepromatous form
What cells does CMV infect latently?
Monocytes and their bone marrow precursors
What genes does EBV express during latent infectino?
- EBNA1: binds EBV genome to chromosomes, permitting episomal persistence
- LMP2
Methods for diagnosing TB?
- conventional culture: takes 10 weeks but allows sensitivity testing for drugs
- liquid cultures: 2 weeks
- PCR: most rapid method
Three features of P. falciparum that make is more pathogenic than other subtypes?
- stimulates production of cytokines
- binds to RBCs of any age
- causes RBCs to clump together, resulting in ischemia
