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)
opsonization and phagocytosis
Opsonization increases efficiency of phagocytosis (natural ketchup)
Antibodies against surface antigens
Bacteria coated in antibodies and complement fragments are primed for phagocytosis
IgM is the most efficient antibody in opsonization
destruction by activated macrophages
Some bacteria can replicate inside macrophages
Th1 cells activate macrophages by secreting IFNg
Acidification of phagosomes
Intracellular bacterial destruction
NK and cytotoxic T cells can also kill cells infected with intracellular bacteria
destruction by activated macrophages
Some bacteria can replicate inside macrophages
Th1 cells activate macrophages by secreting IFNg
Acidification of phagosomes
Intracellular bacterial destruction
NK and cytotoxic T cells can also kill cells infected with intracellular bacteria
bacterial evasion of innate defenses
Interfere with TLR signaling
* Modify PAMPs (molecular patterns)
* Interfere with intracellular signaling
**Resistance to antibacterial peptides **
**Block phagocytosis **
Intracellular bacteria
* Interfere with phagosomal maturation
* Escape phagosome
bacterial evasion of adaptive defenses
Antigenic variation
Secrete proteases to destroy antibodies or cytokines
Survival within macrophages
Interference with macrophage polarization
TLRs that recognize viruses
3, 7, 8, 9 (9 is both)
parasites
Organism that lives in/on host and gets nutrients from the host or at the expense of the host
Three categories of eukaryotic parasites
* Protozoa – single-celled, intra- or extracellular
* Helminths – multicellular, extracellular
* Arthropods – multicellular, extracellular
Immune response to protozoa
Innate mechanisms similar to bacteria and viruses
Mutual adaptation and species-specific infection is important
* Toxoplasma in cats vs. other mammals
Stimulate both cell mediated and humoral response
* Humoral – antibodies opsonize parasites in blood and tissue
* Cell mediated is important for intracellular protozoa
extracellular protoza immune response
Similar response to bacteria
* Complement activation
* Activation of macrophages for phagocytosis
Th22 responses are important
* Macrophages produce IL-22
Recruitment of neutrophils
* Oxidative damage to pathogen
intracellular protozoa immune response
Intracellular location protects organisms from immune detection
Some actively penetrate cells
* Toxoplasma sp., Cryptosporidium sp.
Th1 responses are important
* Recruitment of cytotoxic T cells
immune evasion by protozoa
Parasite-induced immunosuppression
* Secondary infections and sepsis
Reduced antigenicity of encysted protozoan
Antigenic variation
Infections more common in immunosuppressed hosts
adverse consequences of immune reponse to protozoa
Immune response to protozoa may result in hypersensitivity
Type I: Trichomoniasis infection causes local irritation of genital tract
Type II: Parasite antigens bind to host erythrocytes
Type III: Immune complex formation in visceral leishmaniasis
immune reponse to helminths
Larvae and adults trigger Th2 adaptive response
* Attacked by eosinophils and basophils
Adult worms are expelled from mucosal surface by IgE binding
* Cell mediated immunity less important
* Innate immune cells and Th2 cells secrete IL-4, IL-5 and IL-13
* Increased production and recruitment of eosinophils
* Eosinophils have Fc receptors and bind to opsonized worms
Thick cuticles or tegument
* Complement and perforin (cytotoxic T cells) will not penetrate
* If outer covering is damaged, they can grow a new one
Eosinophils and macrophages release Th2 cytokines – cuticle damage
* important in destroying migrating larvae
Similar clinical signs to type I hypersensitivity: (Eosinophilia, Edema, Asthma, Urticaria)
helminth immune evasion
Migrating larvae are very good at immune evasion
Innate immunity
* Neutrophil inhibitors
* Surface antioxidants
* Interfere with complement
Adaptive immunity
* Reduced antigenicity over time
* Antigenic variation
* Interference with antigen processing
immunosuppression by parasites
Common feature of parasitized animals
Parasites produce immunosuppressive molecules
* ex: Fasciola hepatica proteases can destroy antibodies
Redirection of T cell response
* Produce IL-10 which is immunosuppressive
immune response to arthropods
Fleas, ticks, mosquitos, mites, lice
Inject saliva
* Digestive enzymes
* Immunomodulatory substances
Three types of response
* Th1 response
* Th2 response
* Cutaneous hypersensitivity
immune response to fungi
Innate immune response
* PRRs recognize fungal PAMPs
* Neutrophil recruitment – moderately effective
* Small spores may be ingested by macrophages
Adaptive response
* Th1 most important
* Activated macrophages
* Neutrophils
Enzyme Linked Immunosorbant Assay (ELISA)
- add serum that has antigen, binds to captured antibodies
- add labeled/detection antibodies
- add substrate
- signal detection
monoclonal antibodies
react to one antigen
polyclonal antibodies
Reacts to many antigens expressed by a certain pathogen
snap tests
- precoated capture antibodies on matrix
- add serum/conjugate, antigen binds to capture antibodies
- wash antibodies that are not bound
- substrate moves across matrix making color
immunohisochemistry
- primary antibody targets protein
- direct: enzyme on primary antibody
- indirect: secondary antibody binds to primary antibody
- gives off a color
agar gel diffusion assay
Test for antigen-specific antibody in test serum
Wells in a gelatinous matrix
Known antigen in middle well
Serum from control and possibly infected animals in peripheral wells
Look for lines of precipitation
COVID 19 rapid antigen test
Antigen binds to detection antibody
The complex migrates and is captured by antibody coated in the test band area
Control antibody only recognizes the detection antibody (not antigen)
