Immunology 4 & 5- Response to infections Flashcards
What do RNA Viruses rely on to evade the immune system?
Antigenic variation
What do DNA viruses rely on to evade the immune system?
Immunoregulatory genes and Antigenic variation
What are the Immunoregulatory genes allowing DNA viruses to evade the immune system?
-Proteins that block interferon signaling
- Proteins that interfere with MHC-1 associated Antigen presentation
- Evasions of NK cells
- Alterations in humoral immunity (non-neutralizing or slower neutralizing immunity)
What are the 5 pathogens?
- Virus
- Bacteria
-Protist - Helminth
- Fungus
What is homeostasis
balance between the pathogens and immune response
What happens if there is too much immune reponse?
Immune disease, hypersensitivity, autoimmunity
What happens when there is too much pathogen disease?
Infectious disease?
Location/size of viral infection
obligate intracellular
20-400 nm
Location/size of bacterial infection?
Intra or extracellular
0.2-12 um
Location/size of protist infection?
Intra or extracellular
1-50um
Location/size of helminth infection?
Extracellular
3-1000 mm
Location/size of fungus infection?
intra or extracellular
2-200 um
Pathogenesis of fungus infection?
- Enzyme production
- Direct cell/tissue damage
- Immunopathology
Pathogenesis of viral infection?
- Direct Cell damage
- DNA damage
- Immunopathology
Pathogenesis of bacterial infection?
- Direct cell Damage
- Toxin Production
- Immunopathology
Pathogenesis of protist infection?
- Direct cell damage
- Immunopathology
Pathogenesis of helminth infection?
- Competition for resources
- Direct tissue damage
- Immunopatholgy
What are the innate immune defenses?
- Epithelial barriers
- Secretions
- Endogenous microflora
- Resident phagocytes
- Pattern recognition receptors
What are some epithelial barriers?
Skin
respiratory epithelium
Enterocytes (gut epithelium)
What are secretions of the innate immunity?
Mucus
Sweat
Acid
Enzymes
defensins
polyreactive Antibodies
surfactant
What are the necessary innate immunity pattern recognition receptors
PAMPs
PRRs
What are PRRs?
Pattern recognition receptors
What are PAMPs?
Pathogen-associates molecular patterns- get recognized by the PRRs
Ex: what does TLR1 recognize?
Triacyl lipopeptide
Ex: what does TLR2 recognize?
Peptidoglycan
Lipoteichoid acid
lipoprotein
What are the TLRs that are in the endosome? why are they there?
TLR3, 7, and 9
- Because they recognize RNA/DNA patterns so they must be intracellular
- All recognize viruses
What are the adaptive immune responses?
-CMI
- Humoral immunity
What is CMI? What does it do and what type of pathogen does it respond to?
Cell-mediated immunity
- Mediates by Th1 to help cytotoxic t-cells respond
- important for intracellular pathogens
What does humoral immunity do? What type of pathogen does it respond to?
- Mediated Th2 response to activate B cells to produce antibodies
- Good at controlling extracellular pathogens
What are the steps of a virus infecting a cell?
- Bind to VAP
- Viron enters the cell (3 ways)
- Nucleic acid released into cytoplasm
- Replication
- Protein production
- Assembly
- Release
- Spread
What triggers the innate immunity response to a viral infection?
- Recognition of viral patterns by PRRs
- Cells damage
What PRRs recognize viral patterns?
- RIG-1
- MDA5
- TLR 3, 7, 8, 9
What PRRs recognize viral patterns in the cytoplasm?
- RIG-1
- MDA5
What PRRs recognize viral patterns in the endosome?
- TLR 3, 7, 8, 9
What is an interferon?
Glycoproteins
- Signaling proteins
- Regulate protein expression
What are the three types of interferons?
- Type 1
- type 2
- type 3
What are the type 1 INF and where are they produced? How quickly are they produced?
INF alpha- produced by dendritic cells
INF beta- produced by ANY virally infected cell
- Produced upon binding of TLR 3, 7, 8, 9, RIG-1, or MDA-5 and act on near by-cells
- Within hours (before antibodies)
What are the type 2 INF and where are they produced?
INF gamma- produced by activated Th1 cells
What are the type 3 INF and where are they produced?
Many places (primarily mucosal epithelial cells)
What does a Type 1 INF activate?
Activate JAK/STAT pathways
What is a JAK/STAT pathway cause?
- increased production of antiviral and immunoregulatory proteins
- Directly inhibit viral uptake, replication
- induction of apoptosis
How does the humoral immunity protect against viral infections?
- Antiviral antibodies against virus
- Antibody bind prevents viral infection
- ADCC targets infected cells for destruction
How does antibody binding prevents viral infection?
- Blocking viral invasion
- Stimulate phagocytosis
- triggering complement system
- Promoting viral clumping
- DOES NOT CAUSE DIRECT VIRAL DESTRUCTION
What cells are activated with the ADCC?
NK cells and cytotoxic t-cells
How does Cell-mediated immunity prevent viral infections?
- Cytotoxic T cells recognize infected cells prior to rupture
- Macrophages are activated by Th1 Cells
How do Cytotoxic T cells affect viruses?
- Recognize peptide-MHC-1 complexes and kills cells
– sensitized by type-1 INF
— Induce apoptosis
Macrophages are activated they do what?
Phagocytosis
What is antigenic variation?
- point MUTATION and poor editing
– Makes antigen unrecognizable by Tcells - Sporadic recombination of strains
EX: Antigenic variation of Influenza A
- Express envelope proteins (And will switch these up)
- Gradual variation in amino acid sequences
- Co- infection leads to new strains
All of these make the virus unrecognizable
How does a Bacterial cause disease?
- Presence of bacteria does not mean disease
- Disease development depends on:
– Bacterial virulence factors - Dose of bacteria
- Concurrent disease or compromise
- Normal flora
- Immune system function
What are the mechanism of bacterial
Opportunistic
Pathogenic: simple or complex
How does an opportunistic bacteria work?
Normal flora taking use of a host compromise (break in epithelium)
How does pathogenic bacteria work?
Simple: inducing phagocytosis
Complex: inject proteins into the host cell to create a receptor so bacteria can enter the cell
How does the innate immune system respond to bacteria?
- Bacteria are recognized by PRR
- Cytokines are released, complement activation, inflammation and phagocytosis
- They MUST sequestration of nutrients (iron and tryptophan) so by preventing this we can control the bacterial infection
What are the PRRs that recognize bacteria?
TLR 1, 2, 4, 5, 6, 9
The adaptive immune system uses both CMI and humoral immunity to work on bacterial infections. What types of bacteria do the CMI and humoral adaptive immune response work on?
Extracellular bacteria = humoral
Intracellular bacteria = cell mediated
What are the mechanisms of humoral immunity?
Act on extracellular bacteria:
- Neutralization of toxin
- opsonization by antibodies
- killing by classical compliment pathway phagocytosis by activated macrophages
What are the mechanisms of the CMI?
Act on intracellular bacteria
- Macrophage activation and phagocytosis
- Destruction by cytotoxic t cells
What is the mechanism of neutralization?
- Antibodies bind to toxin
- Prevent interaction with host receptors
What antibodies perform neutralization?
- IgG or IgA (mucosal surfaces)
What is the mechanism of opsonization and phagocytosis?
- Opsonization increases efficiency of phagocytosis
- Bacteria coated in the antibodies and complement fragments are primed for phagocytosis
What antibodies perform opsonization?
- IgG (good)
- IgM (Best)
What is the mechanism of activated macrophages?
This is when macrophages have the bacteria inside them
- Th1 Cells produce IFN gamma to activate macrophages
- Acidification of phagosomes and intracellular bacterial destruction
- NK and cytotoxic t cell can also kill cells infected with intracellular bacteria
How does bacteria evade the innate defenses?
- Interfere with TLR signaling (modify PAMPs and interfere with intracellular signaling)
- Resistance to antibacterial peptides
- Block phagocytosis
- Intracellular bacteria interfere with phagosomal maturation and escape phagosomes
How does bacteria evade the adaptive defenses?
- Antigenic variation
- Secrete proteases to destroy antibodies and cytokines
- Survival within macrophages
- Interference with macrophage polarization
Define parasites
organisms that live in/on host and gets nutrients from the host at the expense of the host
What are the three categories of eukaryotic parasites?
protozoa
helminths
arthropods
Explain the immune response to protozoa
stimulate both cell mediated and humoral response
humoral - antibodies opsonize parasites in blood and tissue
cell mediated - cell mediated for intracellular
What is the difference in the immune response to extracellular vs intracellular protozoa?
in extracellular, there will be Th22 responsible and recruitment of neutrophils
in intracellular, there will be a Th1 response and recruitment of cytotoxic T cells
Who are infections more common in?
immunocompromised hosts
What can result from parasite induced immunosuppression?
secondary infections and sepsis
What is an adverse consequence resulting from immune response to protozoa?
Hypersensitivity
Explain the immune response to Helminths
mostly Th2 adaptive response
What does the effectiveness of the immune response to helminths depend on?
genetic susceptibility
host age, gender, overall health
site of infection
parasite burden
helminth species
What do Helminth larvae and adults trigger?
Th2 response and attack by eosinophils
How are adult Helminth worms expelled from mucosal lining?
by IgE binding
Why is the cuticle important to Helminths and how can the immune response combat this?
thick cuticle protects the Helminth so eosinophils and macrophages release Th2 cytokines to destroy migrating larvae
T/F: Basophils are very important in immune response to Helminths
FALSE - eosinophils are important
How can eosinophils mount an immunologic response to Helminths?
Fc receptors on eosinophils and bind to opsonized worms
Which immunoglobulin is important for larval response?
IgE
Explain how migrating larvae are able to evade the immune system
evade innate immunity by neutrophil inhibitors, surface antioxidants, interfere with complement
evade adaptive immunity by reducing antigenicity over time, antigenic variation, and interference with antigen processing
How can parasites cause immunosuppression in an animal?
producing immunosuppressive molecules to destroy antibodies or by redirecting T cell response by producing IL-10
Which interleukin is immunosuppressive?
IL-10
What is an arthropod?
fleas, ticks, mosquitoes, mites, lice
How do arthropods cause infection?
by injecting saliva which has digestive enzymes and immunomodulatory substances
What are the 3 types of immunological responses to arthropods?
Th1 and Th2 response and cutaneous hypersensitivity
Explain the innate vs adaptive immune response to fungi
innate immune responses are
PRR recognize fungi PAMPs
Neutrophil recruitment
small spores may be ingested by macrophages
adaptive immune response is
Th1
and activated macrophages and neutrophils
What are some ways of using immune system components to diagnose infections?
ELISA
agglutination tests
Gel immunodiffusion tests
immunofluorescence assay
Complement fixation tests
immuhnocytochemistry
immunohistochemistry
Explain how ELISA works
sandwich
two antibodies sandwich antigen
plate coated with capture antibodies and add antigen which will bind and then add detection antibody which will bind to antigen
add substrate of detection antibody and it will react with enzyme and give up signal (color change)
Explain how the snap test works
detection antibody with a conjugated enzyme and mix with serum and antigen will bind the antibody
wash step removes unspecific unbound conjugate and blood sample components from background matrix
the substrate then moves across cleared matrix and the substrate reacts with conjugate to amplify presence of antigen for increased sensitivity and an unmistakable clear blue
Explain how an agar gel diffusion assay works
tests for antigen-specific antibody test in serum
wells in a gelatinous matrix with known antigen in middle well
serum from control and possibly infected animals in peripheral wells
look for lines of precipitation
Explain how immunocytochemistry works
have target protein and use primary antibody which will bind to protein of interest
add secondary antibody with fluorophone labeled which will bind the Fc receptor and will be able to see localization of different proteins
Explain how a COVID-19 Rapid Antigen Test works
antigen binds to detection antibody
complex migrates and is captured by antibody coated in the test band area
control antibody only recognizes the detection antibody
