Viral infections & Hypersensitivity reactions Flashcards
What are different ways new infection diseases can emerge in a population?
- Antibiotic resistance
- New clinical presentations
- Changes in geographic regions
- Novel zoonotic infections causing epidemics in human populations (viruses)
What is a virus? what are important features?
Small segments of nucleic acid with a protein or lipoprotein coat
- Some have a lipid bilayer envelope, some don’t
Obligate intracellular parasites → absolutely needs a host cell to undergo replication
Sub-microscopic, filterable → need EM to see it
Unaffected by antibiotics (which target bacteria)
What is Baltimore classification?
It is a viral classification based on genomes
Class I → dsDNA (ex: Herpes, small pox, adenovirus)
Class II → ssDNA (ex: parovirus)
Class III → dsRNA (ex: rotavirus)
Class IV → (+) ssRNA (ex: polio, yellow fever, corona virus)
Class V → (-) ssRNA (ex: rabies, ebola, influenza, LCMV)
Class VI → ssRNA-RT (ex: HIV)
Class VII → dsDNA-RT (ex: Hepatitis B virus)
*RT means they have RNA and convert it to DNA for replication and change it back to RNA or inversly
Which of the following was the first human virus identified:
a. Human immunodeficiency virus
b. Hemophilus influenzae
c. Rabies virus
d. Yellow fever virus
e. Tobacco mosaic virus
b. Hemophilus influenzae → not a virus, its a bacteria
d. Yellow fever virus → YES
e. Tobacco mosaic virus → infects plants, but 1st virus identified
What are important aspects/steps of viral replication and spreading?
- Entry into a susceptible host
- because obligate intracellular pathogens - Replication in cells (cell tropism)
- Tropism = the ability of a virus to infect specific cells but not in other types (need specific cell type)
- most virus use cell machinery for transcription and replication - Spread within host
- local replication (cell-to-cell)
- dissemination to lymph node
- viremia, transport to distal tissue sites (can detect the virus in the blood) - Shedding & transmission to new host: skin lesions, saliva, coughing, urine, feces, semen
What are 3 patterns of viral infections?
Give examples for each.
3 general categories based on levels of infectious virus detectable in organism at various times:
- Acute infection followed by viral clearance by the immune response
Ex: poli, influenza, LCMV Armstrong - Acute infection followed by latent infection and periodic reactivation
Ex: Herpes virus - Acute infection followed by chronic infection
- The immune system is not able to fully clear the virus and gets to an equilibrium with the virus
Ex: LCMV clone 13 (used in model models of chronic infections)
What are the kinetics of the different aspects of host defense against viruses?
- Type 1 IFN and other innate cytokines, NK cells → peak even before the peak of the infection
- Cytotoxic cells, Th1 cytokines, Th2 cytokines → peak a bit after the peak of infection
- Serum Ab → increases slowly and stays high in the blood even after clearance of the virus because of the long-lived cells in the bone marrow still producing Abs
Is it possible to be infected with a virus, but tets negative to it?
YES, different viral loads are seen in different sites/organs
- Nose swab
- Sputum
- Stool
How does Innate immune recognition of virus infection occur?
What does it depends on?
Innate immune receptors triggered depends on viral genome & replication intermediates
TLR9 recognized by + DNA
TLR7 recognized by + RNA
finish… slide 11 L19
Innate receptor leads to transcription of IFN alpha and beta → Type 1 IFN → autocrine signaling (to itself through release and receptor) + act on neighbouring cells
- Type 1 IFN has viral replication suppressive effect
What is Type 1 Interferons? What triggers its synthesis?
Induction of type I interferons: IFNa and IFNb so named because of their ability to interfere with viral replication
Synthesized by many cell types in response to activation of innate sensors: RIG-I, MDA-5 & cGAS/STING
IFNb induces cells to make IFNa, thus amplifying type 1 IFN response
binds to common cell surface receptor known as IFNAR, activating STAT1/STAT2 → production of many interferon stimulated genes (ISGs)
*Induction of antiviral states in neighbouring uninfected cells
What are 2 pathways by which type 1 IFN induce antiviral effects?
Both pathways are triggered by type 1 IFN + dsRNA + ssDNA
- Activated Protein Kinase PKR (ribosome-associated) → phosphorylates initiation factor of translation eIF-2a → preventing mRNA translation shuts down the replication cycle
- Activated Oligoadenylate Synthetase OAS
*Multiple forms: nuclear and cytoplasmic → activates 2’, 5’-Oligo adenylic Acid → activates RNase L → RNA degradation
What are plasmacytoid dendritic cells?
Specialized immune cells which can make 1000x more type I IFN that other cell types
How is type 1 interferons related to SARS-CoV-2 disease burden?
Early robust type 1 interferon response:
- Mild disease
- Viral clearance
- Lower viral load
- Normal T and B cell response
Delayed type 1 interferon response:
- Higher viral load / Severe disease
- Partial viral clearance
- T cell lymphopenia
- Robust B cell response (higher levels of Abs)
Type 1 interferon deficiency:
- Uncontrolled viral replication / Severe disease
- T cell lymphopenia
- Compensatory B cell response (very high Abs)
*T cell lymphopenia = low T cells (type 1 IFN = important survival signal)
What can cause Type 1 inteferon deficiency?
- Genetic mutation in type 1 interferon pathways
- Neutralizing antibodies to type 1 interferons
What are other immunomodulatory functions of IFNa/b?
– changes in cell distribution
– activation of NK cell cytotoxic activity
– regulation of cytokine/cytokineR expression, induction of MHCI to promote CD8 T cell responses
Depending on the context in which type I IFNs are being produced, they can be pro-inflammatory or anti-inflammatory
ex: in HIV, chronic production of type 1 IFN errods immune responses over time
What are important features of NK cells?
When do they come into play in immune responses?
What stimulates their activity?
2nd cell type to after IFN producing cells ~ day 2-5
Lymphoid cells that are a critical first line of defense against infection with intracellular pathogens
- Activity is stimulated by type I IFNs and IL-12
- Produce IFNg
- Express NKRs: NK receptors that can
be activating or inhibitory - They are Cytotoxic, but detection of MHCI leads to downregulation of NK activation
- Missing self model
What is the missing self model? What cell type does it relate to?
The missing self model of natural killer (NK) cells states that NK cells attack cells that lack or have altered MHC class I molecules. This model helps explain how NK cells are part of the immune system’s defense against viruses and tumors.
MHC-I acts as an inhibitor receptor for NK cells, without which NK cells kill their target cell
What are the key steps of a CD8 T cell response in the situation of a viral infection?
- Activation & priming
- Effector differentiation & clonal expansion
- Migration to infected tissue site to deliver effector function (
- Arrive similarly to neutrophils, by the blood, followed by chemokine signals
- Response is mediated by the amount of Ag present
Hi dose of Ag: Expansion → contraction → memory maintenance
Low dose of Ag: → small CD8 T cell response with less memory maintenance and less expansion
What are the 3 phases of CD8+ response?
- Expansion
- Contraction (after antigen clearance)
- Memory maintenance
What is the contraction phase of the CD8 T cell response?
After antigen clearance, we don’t want to keep all these effector CD8 T cells in our lymph nodes:
- Death of >95% of antigen-specific CD8 T cells by apoptosis
- Apoptotic cells are disposed of by specialized
macrophages (CX3CR1+) in the T cell zone
What assay is used to detect antigen-specific T cells? Study Activated CD8 T cells?
Phenotype: expression of cell surface proteins using flow cytometry
- Label different cell phenotype with Ab-florochrome → Flow cytometry
- can identify chainhes in % of cells - Golgi plug + Fix cells + permeabilization + intracellular stain → assess cytokine production by intracellular staining with specific (Anti-cytokine Abs)
Tetramer binding assay:
Tetramer = MHC-I-peptide bound by biotin → 4 of them bound by 1 fluorescetly labelled streptavidin
- requires knowing what is the peptideof interest and MHC allele of the animal model
- Tetramer bidns exclusively to the TCR specific for that antigen → can isolate Antigen=specific cells by FACS
What does the tetramer binding assay reveal on CD8 T cells in the case of Acute vs Chronic infections?
What is this: D^b GP276-286?
D = MHC-I, b = haplotype, 276-286 = specific peptide presented
Lots more tetramer positive cells in acute compared to chronic responses
T cells in acute are much more functional, higher IFNy production
What are TCR transgenic mice?
Mice that all have the same TCR specificity for a specific peptide
OT II CD4 T cells → have specificity for SMARTA peptide
OT I CD8 T cells → have specificity for P14 peptide
*Both from ovalbulmin protein
TCR transgenic mice are created by injecting DNA fragments into fertilized mouse eggs. The DNA fragments contain genes for T cell receptors (TCRs). The mice are then raised by foster mothers.
By having the gene direclty there instead of made by somatic recombination you increase your chances of having this TCR so much that you basically only have that one (allelic exclusion).
What is the role of follicular helper T cells in antibody responses?
T follicular helper cells specialize in promoting germinal center reactions that support: B cell proliferation, somatic hypermutation, class-switch
recombination → afinity maturation
Bi-directional signal exchange:
- TCR interacting with pMHC on B cell provides signal to T cell
- CD40 interacting with CD40L on T cell provides signals to B cell
What marker expression and TFs characterize follicular helper T cells in antibody responses?
TFH characterized by expression of CXCR5, ICOS, PD1
- CXCR5 is required to enter the germinal center, interacts with CXCL13
TFs: Bcl-6, IL-21 and IL-6R
What is the host-pathogen arms race
The adaptive immune system need to constantly adapt to highly changing antigens
What are the main characteristics of Influenza A virus/surface glycoproteins?
Spanish influenza (1918) caused by H1N1, ~40 million deaths
Surface glycoproteins:
- hemagglutinin (HA)
- neuraminidase (NA)
Antigenic drift → constant change in antigenicity of HA and NA owing to point mutations
What is antigenic shift in the case of influenza?
Slow shift in antigenicity of HA and NA owing to point mutations → leading to Abs not recognizing the antigen anymore (Abs/adaptative immune response needs to adapte)
Can also involve sudden emergence of a new subtype of influenza through reassortment of ssRNA strands
- Recombination in the reservoir host → big shift in virus → no longer recognized
What is an allergy?
Expression of harmful immune responses to antigens that are not derived from infectious pathogens (innocuous environmental antigens)
Allergies (immediate hypersensitivity reactions) are usually associated with generation of IgE
Includes diverse diseases
What are 4 classes of common SOURCES of allergens?
*All manifested at mucosal barriers
- Inhaled materials
- Plant pollen, feces of very small animals, mold spores, etc. - Injected materials
- Insect venoms, vaccines, drugs, therapeutic proteins - Ingested materials
- Food, orally administered drugs - Contacted materials
- Plant leaves, metals, synthetic chemicals in industrial products
What is the allergic atopic march?
The “allergic atopic march” refers to the progression of allergic diseases that typically starts in infancy with atopic dermatitis (eczema), often progressing to food allergies, and then potentially developing into allergic rhinitis (hay fever) and asthma later in childhood, essentially describing a natural sequence of allergic conditions as a person grows up; it’s also simply called the “atopic march” or “allergic march” because “atopic” refers to a genetic predisposition to allergies.
- Eczema (atopic dermatitis)
- Food allergy (~1 yo)
- Allergic rhinitis (hay fever ~ 3 yo)
- Asthma (~ 6yo)
What is causing the increase in allergies in western world?
- Suggests an environmental etiology
- Increasing evidence that early-life exposure to a biodiverse microbial environment is crucial for the proper development of the immune system
“Hygiene Hypothesis”: reduced early-life exposure to pathogens leads to increased atopy & risk for allergies
What is the “old friends” hypothesis? And how does it differ from the “Hygiene Hypothesis”?
“old friends” hypothesis: early life microbiota has an important role in the development of tolerogenic immune functions
“Hygiene Hypothesis”: reduced early-life exposure to pathogens leads to increased atopy & risk for allergies
Expanded version on the hygiene hypothesis which focuses on all aspects of microbiota, not just pathogens
What are key modulators of the microbiota in early life for allergic development?
- Breast milk
- mode of delivery (vaginal vs caesarian)
- Antibiotic use at early age
- Family size (more pathogen exposure)
- Interaction with farm animals, pets
*Microbiota includes the skin microbiome, nasopharynx microbiome, lung microbiome, gut microbiome
What is thought to increase vs decrease incidence of peanut allergy in early childhood?
Increase:
Peanut-containing oils put on kids with eczema → the peanut antigen is encountered in a context of inflammation and T cell response
Decrease:
Oral peanut consumption → lots of tolerance mechanisms in the gut
Why did allergic/Th2 responses responses evolve?
To fight these following factors:
1. Helminths
2. Venoms
3. Noxious compounds
4. Envrionmental irritants
Allergies are mis-directed responses → generation of Abs against non-pathogens
Are allergies simply misdirected anti-worm responses or do they serve a purpose?
Propose that type 2 responses are response to get you to remove yourself from noxious stimuli. They maybe served an evolutionnary purpose beyond expulsing parasites (weep and sweep version)
What are the 4 types of hypersensitivity?
What Antibodies are involved in each?
What antigens are involved in each?
What effector mechanism is involved in each?
Type I:
- IgE
- Soluble antigens
- Mast-cell activation
Type II:
- IgG
- Antigen = Cell- or matrix-associated antigen → complement, FcR+ cells
- Antigen = Cell-surface receptor → Abs alters signaling
Type III:
- IgG
- Soluble antigens
- Complement, phagocytes
Type IV:
T cell responses to soluble antigens (further elaboration in other flashcards)
What are characteristics of type I hypersensitivity reactions/allergies?
- Predisposition to become IgE-sensitized to environmental allergens (atopy)
- Prerequisite for type I hypersensitivity reaction is that the person makes IgE antibody when he/she first encounter the first Ag. (context of 21st encounter is important)
- IgE binds irreversibly to Fc receptors on mastcells (leading to degranulation), basophils and eosinophils.
- IgE antibody causes allergic reactions because of its exceptionally high affinity Fc receptor and cellular distribution of the receptor. (Fc ε RI).
*All IgE-mediated responses involve mast cell degranulation
What is atopy?
Predisposition to become IgE-sensitized to environmental allergens in type I hypersensitive reactions
What do the symptoms of type I hypersensitivity reactions/allergies depend on?
Symptoms vary depending on the site of encounter of the allergen → eaten vs injected
This will influence the site of mast cell degranulation
How does sensitization to an inhaled allergen occur? Full steps using Der p1 as an example.
Der p1is found in dust, it has its own enzymatic activity
- The enzyme Der p1 cleaves occludin in tight junctions and enters mucosa (in the lungs)
- Taken up by resident DCs for antigen presentation and Th2 priming (in lymph nodes)
- Th2 cells induce B-cell switch to IgE production
- Plasma cell travels back to mucosa and produces Der p1-specific IgE antibodies
- IgE binds to Fc eplisonR1 receptor on mast cells
- Der p1-specific IgE binds to mast cells; Der p1 triggers mast cell degranulation
- Mast-cell degranulation contents cause allergic symptoms
Where are mast cells mostly found?
What features of them makes them important for allergic responses?
Mast cells reside in nearly all tissues, mature locally
- found in connective tissues, often surrounding blood vessels or lymphatics
- can release mediators which impact vasculature as well as spreading to distal sites via the blood or lymph
Large cells found that have secretory granules containing inflammatory mediators
- Bind monomeric IgE (no degranulation, resting)
- In a second contact with the Ag, it cross-links 2 IgE bound molecules on the mast cell and triggers rapid degranulation and the release of histamine.
- Degraunlates very quickly (~20-30mins)
Mast cell activation in allery orchestrates a broad inflammatory cascade with pathophysiological consequences
Do mast cell have antigen specificity?
No, the antigen specificity is confered by IgE and the mast cells binds non-specifically to cross-linked IgE
Assay:
Take a mast cell → coat it with IgE and cross-link them in an non-antigen specific way → mast cell degranulates
What is the effect of mast cell activation in allergy?
Mast cell activation orchestrates a broad inflammatory cascade with pathophysiological consequences
- Downstream inflammatory cascades
- Cytokine production → epithelial mucous production + smooth muscle constriction
- Immune cell recruitment
- Release of histamine (→ endothelial vascular leakage), Proteases, Eicosanoids
etc.
Ex: runny nose is due to mast cell degranulation
What are different effects of mast cell ACTIVATION specific to different tissues?
- Gastrointestinal tract:
Increased fluid secretion, increased peristalsis
Leading to → Expulsion of gastrointestinal tract contents (diarrhea, vomiting) - Airways:
Decrease diameter, increased mucus secretion
Leading to → Congestion and blockage of airways + Swelling and mucus secretion in nasal passages - Blood vessels:
increased blood flow, increased permeability
Leading to → Increased fluid in tissues causing increased flow of lymph to lymph nodes, increased cells and proteins in tissues, increased effector response in tissues
What is the allergy inflammatory cascade?
What is the role of eosinphils?
IgE mediated mast cell activation → recruitment of basophils, eosinophils, Th2 CD4 T cells, B cells → amplify the response
Eosinphils:
- Granule release
- Synthesis of mediators such as prostaglandins, cytokines, leukotrienes
- Amplify mast cell/basophil activation
Th2 cell production of GM-CSF & IL-5 leads to greater production of eosinophils by the bone marrow (Amplification)
What is anaphylaxis?
How is it treated?
Introduction of allergen directly into bloodstream can cause a systemic reaction called anaphylaxis
Causes can be: drugs (penicillin), food (peanuts), insect stings
Symptoms range from urticaria (hives) to fatal anaphylactic shock
Anaphylactic shock = reduction in blood pressure → inadequate supply of blood to organs → organs shutting down
Treated with Epinephrine
What is the effect of Epinephrine in the case of an anaphylactic shock?
Epinephrine is used to treat anaphylactic shock:
- Stimulates the re-formation of tight junctions between epithelial cells
- Relaxes constricted bronchial smooth muscle
- Stimulates the heart
*Preventing organ shut down
Slide 22 comeback L20
How is type 1 hypersensitivity detected?
Assessed by skin testing
- Introduction of potential allergens
- Mast cells degranulation and release of histamine → Development of a wheal and flare withing minutes
What are the main features of type II hypersensitivity reactions?
Antibody-mediated cytotoxic hypersensitivity, Immune reactant = IgG
Antibodies to foreign antigens on cells leads to destruction of cells
- Cell death is via activation of complement or via phagocytosis of the cells recognized by Fc receptors
Ex: Transfusion reactions, hemolytic disease of the newborn
Can be side-effects seen after the administration of certain drugs (eg. penicillin): hemolytic anemia
What is the mechanism behind drug-induced hemolytic anemia?
*Type II hypersensitivity response
1. Red cells that have been covalently bonded to complement-coated penicillin are phagocytosed by macrophages
2. Macrophages process the penicillin-modified protein and present peptide to specific CD4+ T cells
3. CD4 T cells stimulate penicillin-specific B cells to secrete Abs
4. Abs bind to RBCs
Responses:
1. Binding of Ab to penicillin-modified red cells makes them susceptible to complement lysis (Ag- Ab complex).
- Phagocytosis via Fc receptors and complement receptors
What are characteristics of type III hypersensitivity reactions?
What is the pathology due to? What determines the pathogenic potential?
These types of reactions are caused by immune complexes formed by IgG and soluble Ags
Ex: Serum sickness
Pathology is due to the deposition of these antigen:antibody aggregates and initiation of an inflammatory response
The pathogenic potential of immune complexes is determined by their size, the amount and isotype of antibody
How do immune complexes vary in size?
Early response → little Ab and excess antigen → small immune complexes are formed that do not fix complement and are not cleared from circulation
*The smaller complexes are less efficient to fix complement, they circulate in the blood and become deposited in blood vessel walls
Intermediate stages in the response → similar amounts of Ab and Ags → large immune complexes are formed that can fix complement and are cleared from the circulation
Late in the response → large amounts of Abs and little Ag → Immune complexes of intermediate size are formed that can fix complement and are cleared from circulation
*complexes when Ab is in excess are easily eliminated by complement and macrophages
What are local vs systemic type III hypersensitivity reactions?
Disease caused by type III hypersensitivity depends on the route of delivery and the site of immune complex deposition
- Local hypersensitivity reaction in the skin triggered by subcutaneous injection is called an Arthus reaction
- Local hypersensitivity reaction in the lung is called farmer’s lung
- Systemic hypersensitivity reaction can be triggered by injection of large quantities of a poorly catabolized foreign antigen and is called serum sickness
What is an Arthus reaction?
local type III hypersensitivity reaction in the skin triggered by subcutaneous injection is called an Arthus reaction
What is serum sickness?
systemic type III hypersensitivity reaction that can be triggered by injection of large quantities of a poorly catabolized foreign antigen
Involves formation of Ag:Ab complexes
Can lead to uticarial rashes
What could be a possible side effect of rituximab therapy?
Systemic type III hypersensitivity reaction → rashes, low blood pressure, flu-like symptoms
Rituximab is a monoclonal Ab therapy used to treat lymphoma (anti-CD20)
- Chimeric Ab made of murine variable sequence + human constant region
Binding of antibody to CD20 results in lysis of B cells via complement, or phagocytosis
What are the type IV hypersensitivity reactions?
Reactions mediated by antigen-specific effector T-cells (Th1 CD4 T cells and CD8 T cells) → release of type 1 IFN
Also known as delayed-type hypersensitivity reactions (DTH) because they occur 1 to 3 days after contact with Ag
- This time course contrasts with those of antibody-mediated hypersensitivity, which appear after few minutes
The amount of Ag required to elicit type IV hypersensitivity reaction is 100 to 1,000 greater than that required for antibody-mediated sensitivity
What is a classical example of delayed-type hypersensitivity reaction? (type IV)
Mantoux test, standard tuberculin test
Intradermal injection of 0.1 mL
Intrduration measured 48-72 hrs later
- Ag is injected into subcutaneous tusse and processed by local APCs
- TH1 effector cells recognize antigen and releases cytokines which acts on vascular endothelium
- Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion
*The presence of these antigen-specific T cells suggest you are infected with tuberculin or that you have been vaccinated recently
What are 4 downstream effects of activation of TH1 cells in type IV hypersensitivity reactions?
Antigen is processed by tissue macrophages → stimulates TH1 cells
*AMPLIFICATION of the local reaction
1. Chemokines → macrophage recruitment to site of antigen
2. IFN-y → Activates macrophages increasing release of inflammaotry mediators
3. TNF-a and LT → local tissue destruction, increased expression of adhesion molecules on local blood vessels
4. IL-3/GM-CSF → Monocyte production by bone marrow stem cells
What are features of allergic contact dermatitis (contact hypersensitivity)?
*Type IV
Give a common example.
- Occurs by direct skin contact
- Caused by small, highly reactive molecules that can penetrate the skin (cross barrier to get access to immune cells) and react with self-proteins
- Bind covalently as haptens to skin proteins which become antigenic, are taken up by APCs, processed, and haptenated peptides can be presented by MHC-II
→ Leads to Th1 cell activation (sensitization and then elicitation)
Common example in USA is poison ivy → contains lipid soluble pentadecacatechols in its urushiol oil that can cross cell membranes → Formation of vesicles, influx of monocytes, macrophages & lymphocytes, erythema
Other examples: nickel sensitization (nickel metal ions act as haptens)
How is Celiac disease a type iV hypersensitivity reaction?
Chronic condition of the upper small intestine cause by a CD4 T cell response directed against gluten (complex of proteins present in wheat, oats and barley)
Elimination of gluten from diet restores normal gut function but must continue throughout life
- Strong genetic predisposition (HLA-DQ2 allele, tells you it is CD4-related)
*Also has properties of autoimmunity
What is the process of a Celiac reaction like?
- Peptides naturally produced from gluten do not bind to MHC-II molecules (normally)
- An enzyme, tissue transglutaminase (tTG) modifies the gluten peptide (through deamination) so they now can bind to the MHC-II molecule
- TG is also generating auto-Abs (can screen for these anti-TG Abs to check for celiac disease) - The bound peptide activates gluten-sepcific CD4 T cells
- The activated T cells can kill mucosal epithelial cells by binding Fas
- Also secrete IFN-y which activates the epithelial cells - Local immune response destroys the villi in the intestinal epithelium, leading to loss of epithelial cells that cover the villi and normally absorb nutrients
- Intense inflammatory infiltrate in the lamina propria
**Autoimmune feature: autoantibodies against tissue transglutaminase
gluten-specific helper T cells → help activate glutentTG complex-specific B cells → anti-tTG Ab production
What are 3 sub-types of Type IV sensitivity reactions?
TH1 cells react to soluble antigens → macrophage activation (IFN-y) → chemokines, cytokines, cytotoxins
Ex: Contact dermatitis, Tuberculin reaction
TH2 cells react to soluble antigens → IgE production, eosinophil activation, mastocytosis (through IL-4, IL-5) → cytotoxins, inflammatory mediators
Ex: Chronic asthma, chronic alleric rhinitis
Cytotoxic T Lymphocytes → Cell-associated antigens → Cytotoxicity
Ex: Graft rejection
What does to mean for a virus to have these different classes of Genome in the Baltimore Classification?
Group I - dsDNA → use their dsDNA genome to directly transcribe mRNA.
Group II - ssDNA → convert their ssDNA genome into a dsDNA intermediate before mRNA production.
Group II dsRNA → one strand of their dsRNA genome is used as a template for mRNA synthesis by a viral RNA-dependent RNA polymerase.
Group IV - ssRNA+ → where their ssRNA genome can directly serve as mRNA.
Group V - ssRNA- → requiring a viral RNA-dependent RNA polymerase to transcribe their ssRNA genome into mRNA.
Group VI - ssRNA-RT → use reverse transcriptase to convert their ssRNA genome into a DNA intermediate (provirus) before integrating into the host genome and producing mRNA.
