Immunology Flashcards
Innate immune defenses
Epithelial barrier: Skin, respiratory epithelium, enterocytes
Secretions: Mucus, sweat, sebum, cerumen, acid, enzymes, defensins, polyreactive antibodies, surfactant
Endogenous microflora
Resident phagocytes
Pattern recognition receptors (PRR)
cell mediated immune response
Mediated by Th1 cells
Most important for intracellular pathogens
humoral immune response
Mediated by Th2 cells
Most important for extracellular pathogens
How viruses infect cells
- Bind to cell receptor (adsorption)
- Virions enter cell
- Nucleic acid released into cytoplasm
- Replication
- Protein production
- Assembly
- Release
- Spread
What triggers the innate immune response to viral infection?
Recognition of viral patterns by PRRs
RIG-I, MDA5 (cytoplasmic)
**TLR3, 7, 8, 9 **(endosomal)
Cell damage
interferons
Glycoproteins, Regulate protein expression
Three types
* Type I
IFNa – dendritic cells
IFNb – any virally infected cell
* Type II
IFNg – activated Th1 cells
* Type III
Various - mucosal epithelial cells
type 1 interferons
IFNa – dendritic cells
IFNb – any virally infected cell
Produced upon recognition of TLR7 or TLR9 ligands
Activate JAK/STAT pathways
* Increased production of antiviral and immunoregulatory proteins
* Directly inhibit viral uptake, replication
* Induce apoptosis
Produced within hours (before antibodies), part of innate immune system
humoral immunity in viral infections
Antiviral antibodies against viral proteins
Antibody binding prevents viral infection by
* Blocking viral invasion
* Stimulating phagocytosis
* Triggering complement-mediated virolysis
* Promoting viral clumping
* NOT by direct virus destruction
ADCC targets infected cells for destruction
* NK cells and cytotoxic T cells
cell mediated immunity in viral infections
Cytotoxic T cells recognize infected cells prior to rupture
* Induce apoptosis
* Recognize peptide-MHC-I complexes and kill cells
* Sensitized by type I interferons
Macrophages are activated by Th1 cells
* Phagocytosis
immune evasion by viruses
RNA viruses rely on antigenic variation
DNA viruses – immunoregulatory genes
* Proteins that block IFN signaling
* Proteins that interfere with MHC-I associated antigen presentation
* Evasion of NK cells
* Alterations in humoral immunity: Non-neutralizing or slowly neutralizing antibodies
* Antigenic variation
antigenic variation
Point mutations + poor editing
Sporadic recombination of strains
ex: Influenza A
* Express envelope proteins: Hemagglutinins (HA), Neuraminidases (N)
* Gradual variation in amino acid sequence leads to new antigens
* Co-infection leads to new strains
* No longer recognized by adaptive immune system
innate response to bacteria
Bacteria are recognized through PRRs (TLR1, 2, 4, 5, 6, 9)
Cytokine release,** complement** activation, inflammation, phagocytosis
Sequestration of nutrients (iron, tryptophan)
PRRs for bacteria
TLR1, 2, 4, 5, 6, 9 (9 is both)
adaptive immune response to bacterial infections
Extracellular bacteria = humoral immunity
* Neutralization of toxin
* Opsonization by antibodies
* Killing by classical complement pathway
* Phagocytosis by activated macrophages
Intracellular bacteria = cell mediated immunity
* Macrophage activation and killing
* Destruction by cytotoxic T cells
adaptive immune response to bacterial infections
Extracellular bacteria = humoral immunity
* Neutralization of toxin
* Opsonization by antibodies
* Killing by classical complement pathway
* Phagocytosis by activated macrophages
Intracellular bacteria = cell mediated immunity
* Macrophage activation and killing
* Destruction by cytotoxic T cells
neutralization
Important for toxogenic bacteria
Antibodies generated against toxins:
* Bind
* Prevent interaction with receptor
* Can be IgG or IgA (mucosal surfaces)