Lecture 9: Host Defense I Flashcards
Innate response
Functions in normal host without prior exposure to invading microbes
Adaptive response consists of what responses
Antibody response (humoral) and lymphocyte mediated response (cell-mediated) response - tailored to particular microbial infection and characterized by memory
Adaptive immunity
adaptive, specific immune responses are induced by exposure to an antigen, the response is specific for the inducing antigens and immunologic memory is generated
5 factors of innate immunity
- Constitutional factors
- Natural barriers and normal flora
- Cytokines/Interferons
- Phagocytosis
- Complement
Constitutional factors
Making one species innately susceptible and another resistant to certain infections
Examples of constitutional factors
- Genetic: between species
- Age: young more susceptible
- Metabolic factors: hypoadrenal and hypothyroid states
- Neuroendocrine factors
- Environment - malnutrition, poor living conditions, overcrowding
Normal flora =
Colonization resistance, competition for attachment sites and for essential nutrients
Major functions of Type I Interferons (IFN)
- Induce resistance to viral replication in all cells
- Increase MHC class I expression and antigen presentation in all cells
- Activate NK cells to kill virus-infected cells
IFN is demonstrated in
animal models
Defective IFN response
- Reduced ability to contain infection
- Increased illness and death
Abrogation of IFN - a/b
- Global increase in susceptibility
- IFN - y -modest effect
Phagocytosis
Engulfment and digestion of infectious agents or other foreign bodies by phagocytic cells
Phagocytic cells
- Phagocytes
- Neutrophil
5 steps of phagocytosis
- Bacterium becomes attached to membrane
- Bacterium is ingested, forming phagosome
- Phagosome fuses with lysosome
- Lysosomal enzymes digest captured material
- Digestion products are released from the cell
Receptors of innate immune system
- Pattern recognition receptors
- Missing/altered self receptors (NK cells)
3 types of pattern recognition cells
- Toll like receptors (TLRs)
- Rig like receptors (RLR)
- Complement
Adaptive immune system
- Antigen presentation (MHC)
- Antibodies
- T cell receptors
PRR (toll like receptors) recognizes
Pathogen-associated molecular patterns
Mediators of antimicrobial and cytotoxic activity of macrophages and neutrophils
Oxygen-independent killing
- Defensins
- Tumor necrosis factor alpha (macrophage only)
- Lysozome
- Hydrolytic enzymes (acid hydrolases)
Neutrophils
Primarily function to phagocytize and kill extracellular bacterial and yeast pathogens in acute inflammation
Neutrophils live
Only 1 day in the tissues
Dead neutrophils are cleaned up by
macrophages
Leukocytosis
Granulocytosis involving neutrophils = bacterial infections
Typical scenario for acute inflammatory response involving neutrophils
- Large reserves of neutrophils are stored within the bone marrow and are released when they’re needed to fight infection
- Neutrophils travel to and enter the infected tissue, where they engulf and kill bacteria.
- The neutrophils die in the tissue and are engulfed and degraded by macrophages
Eosinophils are 1-3%
WBC but #’s increase in parasite infections and patients with type I hypersensitivities
Eosinophils are important against the defense against
helminths
Abundant lymphocytes- ___% of circulating
2
Large, granular lymphocytes lack
antigen-specific receptors found on T and B cells
Number of natural killer cells increases rapidly after
viral infection
They’re stimulated to divide by IFN produced by infected cells and dendritic cells
On binding, lymphocytes release
a mix of cytokines (IFN y and TNF a)
How do natural killer cells kill cells?
Releasing perforins and granzymes - perforate membranes and trigger caspase - mediated cell death
How do NK cells recognize infected cells?
Detection of altered self
