Lecture 27 Flashcards
Normal defense mechanisms against pathogens
physical and chemical barriers such as skin, mucous membrane, tears, earwax, stomach, mucous, commensal bacteria
Innate/Adaptive immunity
Routes of infection: Skin
Normal defenses include: dense keratinized outer layer of skin, pH 5.5, content of fatty acids that inhibit microbial growth
Pathogens can enter through release of enzymes to break skin barrier
Through cuts, wounds, burns, and foot sores
Intravenous catheters in patients
Routes of Infection: Respiratory tract
Normal defenses include: mucus, swallowing, cilia, phagocytic killing by alveolar macrophages, secreted antibodies (IgA)
Pathogens can enter though express molecules to adhere to the respiratory tract (influenza virus)
Routes of infection: Intestinal tract
Normal defenses: acidic gastric pH, viscous mucous membrane, bile detergents, defensins, IgA, normal gut flora
Routes of infection: Urogenital tract
Normal defenses: frequent urination to remove pathogens, low pH in the vagina resulting from catabolism of glycogen in the normal epithelium by commensal lactobacilli
antibiotics can kill lactobacilli and make the vagina susceptible to infection
How are pathogens disseminated into various organs and tissues?
infection may be able to break through a cut in the skin and get into the lungs and from there they may get into the lymphatic system or blood system and spread to other parts of the body
when certain virus are in the bloodstream they can be spread through bug bites
4 mechanisms by which microbes can evade immune defense
- remaining inaccessible to the host immune system
- constantly changing antigenic repertoires
- inactivating antibodies or complement, resisting phagocytosis, or growing within phagocytes from ingestion
- suppressing the host adaptive immune response
Remaining inaccessible to the host immune system
bacterial propagate in the lumen of the intestine or gallbladder
viruses that shed from epithelial luminal surfaces
Constantly changing antigenic repertoires
influenza virus, rhinoviruses, HIV
Inactivating antibodies or complement, resisting phagocytosis, or growing within phagocytes from ingestion
various microbes can produce molecules which deal with innate immune defenses
Suppressing the host adaptive immune response
CMV and EBV can inhibit production of MHC class 1 proteins or alter their intracellular trafficking, impairing peptide presentation to CD8 T cells and preventing killing of infected cells
Mechanisms of viral entry to host cells
Host-cell receptors for a particular virus
HIV: gp120 binds to CD4 and to the chemokine receptors CXCR4 (T cells) or CCR5 (macrophages)
Rhinoviruses bind to ICAM-1
Cell-type specific transcription factors that recognize viral enhancer and promoter sequences
Physical barriers: enteroviruses replicate in the intestine
Rhinoviruses replicate only within the upper respiratory tract, because they survive in lower temperatures
Mechanism of viral injury
- lysis of host cell
- Immune cell-mediated killing
- Alteration of the apoptosis pathway
- homologues of the cellular BCL-2 that inhibit apoptosis allowing the cell to replicate and spread in the body - induction of cell proliferation and transformation resulting in cancer
- can alter host cell DNA, RNA, or protein synthesis
- Damage to the plasma membrane
- Damage to cells involved in antimicrobial defense, leading to secondary infections
Mechanisms of bacterial injury
They must adhere to cells, invade cells and tissue, and deliver toxins that will damage and allow the bacteria to invade further
Bacterial endotoxins - LPS a component of the gram-negative bacteria cell walls. It causes the production of effector cytokines. It helps the bacteria move through the body and invade further
How can diphtheria toxin inhibit proteins synthesis
Has 2 subunits (cysteine bond) that can exist in harsh environments and can bind to a host cell receptor and get engulfed once in the cell it breaks the disulfide bond
A subunit can catalyze an EF-2 reaction that is needed for protein synthesis and this change will inactivate and kill cells
