Chapter 11: Integrated Dynamics of Innate and Adaptive Immunity Flashcards
What are the stages of immune response?
Primary
- Adaptive immune response that follows first exposure of a particular antigen
Secondary
- The immune response that follows second exposure to a particular antigen
What happens when someone experiences severe COVID-19?
- Their viral load continues to rise as does the innate immunity to try to compensate, T cell levels will remain low
- For asymptomatic, the innate immunity rises and falls quickly as does the viral load
Outline the steps involved in a infection penetrating epithelium resulting in the activation of the adaptive immune system.
- Pathogens will enter the epithelium which Induces antimicrobial peptides, phagocytes, and complement to destroy invaders
- COmplement activation occurs. Dendritic cell will capture antigens and travel to lymph node. NK cells are activated. Phagocytic action occurs, and Cytokines and chemokines are produced.
- Once antigen is trapped in lymphoid tissue, adaptive immunity is initiated by dendritic cells
- Infection will be cleared by specific antibody, T cell dependent macrophage activation and/or CD8 cytotoxic cells
How do ILCs and T cells differentiate? What are the cytokines and their isotypes?
Effector Modules, NK cells, naive CD8
What are the main antibody isotypes found on innate effector cells?
- IgG1, IgG3, IgA, IgE
What are MAMPs?
- Microbial-associated molecular patterns are expressed by different types of pathogens which stimulated distinct Cytokine responses from innate sensor cells
- Dendritic cells, macrophages, epithelial cells, specialized tuft cells
- Subset of ILCs are early responders of immune response
What are cytotoxic ILCs? Group 1? Group 2? Group 3?
- IL-12,15
- IL-12,18
- TSLP, IL-25,33
- IL-23,1beta
What do CD4 T cells do to effector functions?
- Augment the effector functions of innate immune cells
What do TH1 cells do to host response? Why must TH1 activation of macrophages be regulated?
- TH1 cells coordinate and amplify host response to intracellular pathogens through classical activation
- Intracellular bact that cannot be killed by macrophages. Various mechanisms such as inhibiting fusion of phagosome with lysosome. Activation will enhance intracellular killing. Induction of key lysosomal enzymes will occur
- Activation of macrophages by TH1 cells must be regulated to avoid tissue damage
- Through orientation and secretory machinery towards macrophage
- Targeting only cells with antigen presentation on MHC II
What are the ways in which TH1 effector cells can function against infections by intracellular bacteria?
How is tuberculosis dealt with by T cell immunity?
- Tb taken up by macrophage is dealt with by TNF, IL-1, Vita D or C and if this fails CD8 T cell kills phagocyte and a no uninfected macrophage tires again
What happens if there is chronic activation of macrophages due to intracellular pathogens not being cleared?
- Ganulomas form
- Core includes multinucleated giant cells which are fused macrophages
- Surrounded by large macrophages often called epithelioid cells - In granulomas caused by mycobacteria the core usually becomes necrotic (caseous necrosis) because of a cheese like consistency of material that accumulates in the necrotic centers
What do TH2 cells do?
- Coordinate type 2 responses to expel intestinal helminths and repair tissue injury
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What do TH17 cells do?
- Coordinate type 3 responses to enhance the clearance of extracellular bacteria and fungi
(IMAGE 15 16)
How can effector T cells be activated ?
- Effector T cells can be activated to release Cytokines independently of antigen recognition
- T cells can be activated by pairs of Cytokines, independently of antigen recognition by T cell receptor
- Same pair of Cytokines that activate the ILC of the same subset
- Acquire innate-like functional properties that allow T cells to amplify different types of immune responses without the requirement for antigen recognition
How are CD4 T cells able to adapt during antipathogenic responses?
- Effector CD4 T cells demonstrate plasticity and cooperatively
- T cells can transition into different Cytokines producing cells based on local inflammatory environments or as a result of cooperatively bt different T cell subsets
What happens when your body encounters salmonella?
- As Salmonella enters, Macrophages capture them and mucus layer thickens and more antimicrobial peptides are produced. Neutrophils are recruited and the bacteria is cleared as the mucus is expelled from the body resulting in diarrhea
How long does immunity last after infection or vaccination?
- Long lasting
- Memory is sustained by long-lived, antigen specific lymphocytes that were induced by original exposure and persists until second encounter
Compare naive T cells to memory T cells. How does secondary immune response work?
- Persist at numbers 10-100 times greater than memory T cells
- More sensitive to antigens
- Faster proliferation, and more robust response when same dose of antigen
- More rapidly displayed heightened effector response
- Have a greater range of surveillance capabilities
- When second exposure, APCs activate memory T cells and memory helper T cells and memory B cells resulting in a faster response
How is the development of memory T cells related to the development of effector T cells?
- They’re parallel
- Linear model of memory cell development
- Memory T cells arise from effector T cells
- Branching (or asymmetrical division) model of memory cell development
- An antigen activated naive T cell gives rise to daughter cells that preferentially commit to either the effector or memory path
What are the three classes of memory T cells?
- Memory T cells are heterogeneous
Central memory T cells: TCM - Recirculate between blood, T cell zone of secondary lymphoid tissue, and lymph
Effector memory T cells: TEF - Recirculate bt nonlymphoidal tissue, lymph, lymph nodes, and blood
- May not enter T cell zone in lymph node
Tissue resident memory T cells: TRM
- May not enter T cell zone in lymph node
- Confined to a single tissue
What proteins can be found in TCM, TEM, and TRM?
What signaling is involved in recruiting CD4 TRM into the epidermis?
- Activated CD4 and CD8 T cells enter dermis and other peripheral tissue
- CD69 induction reduces S1PR1 expression and retains TRM in dermis
- Alpha e Beta 7 is induced on TRM cells by TGF-beta for retention in epidermis
WHat trait is aquired for a T cell to undergo metabolic reprogramming to survive for longer?
- Heightened sensitivity to IL-7 and/or IL-15 allows for metabolic reprogramming = longer life
- Memory T cells require IL-7 and a subset of CD8 T cells also require IL-15
What metabolic pathways are involved in Naive T cells activation, Effector T cell activation, and Memory T cell formation? How long do they take to respond and how long do they last?
How do memory B cells responses compare to the response by naive B cells?
- Memory B cells respond more rapidly and with higher affinity than naive B cells
- Memory B cells can reenter germinal centers and undergo additional somatic hyper mutation and affinity maturation during the secondary immune response
What does the immune response rely on for secondary and subsequent responses?
- Relies mainly on memory lymphocytes
- Naive cell responses are suppressed after primary response
How would someones immunity respond as time passes and the virus changes its Epitopes?
- Shortly after infection all Epitopes would be recognized
- After a longer time and exposure to a mutated virus, the previously recognized Epitopes can still be recognized
What are six components of a vaccine?
- Active ingredient to activate immune system
- Adjuvants to boost immune response to vaccine
- Antibiotics prevent contamination by bacteria during vaccine manufacturing process
- Stabilizers for stable storage
- Preservatives to prevent bacterial and fungal growth
- Trace components are residual inactivating components
What are the types of vaccines?
- Whole cell virus or component based
- Alive(attenuated) or not alive (inactivated)
What are live attenuated vaccines?
- Use pathogens that have reduced virulence and don’t cause disease
- Attenuated is most common
- Grow poorly in human host but illicits full immune response
- Attenuation is achieved by serial passage of virus through non human cells
- Tissue culture, live animals, embryonic eggs
- The virus adapts to the non-human cells
What are pros and cons of live attenuated vaccines?
- Ex. Measles, mumps, rubella, varicella, smallpox
Pros: - More potent as they activate cell mediated immune response
- Long lasting and may even be life long
- Requires 1-2 immunizations for max immunity
Cons: - A immunocompromised person may have sever disease or even death
- Cannot be given to pregnant women
- Attenuated virus can return to its pathogenic form (oral polio virus)
- Stability is very temperature sensitive
How is genetic engineered Attenuation different from liver stage development?
- Genetically attenuated parasite can provoke an immune response but infection does not progress further. Liver stage results in the death of the host
What are inactivated vaccines?
- Composed of a killed pathogen that cannot replicate and cause disease
- Inactivation can occur chemically or physically
- Chemical - formaldehyde is most common agent. Is not a high amount and does not cause a disturbance. biochemical modification may result in some epitope loss
- Physical - Heat, ultraviolet light, gamma radiation, pH. Influenza uses formaldehyde and UV
What are pros and cons of inactivated vaccines?
- Ex. Polio, Influenza, Rabies
Pros: - Generally safer for people especially with weak immune system
- Less adverse reaction
- Easier to transport
Cons: - Do not activate cellular immune response
- Little to no cellular immunity, mostly antibody production
- Require three or more doses for max immunity
- Protection (antibody titers) fades over time
- Boosters needed
What is a subunit vaccine?
- Composed of specific antigens from the pathogen
- Recombinant protein/ peptide vaccine
- Various expression systems. Bacterial, yeast, insect cells
- Ex. Covid, acellular Pertussis
What are conjugated vaccines?
- Polysaccharides from bacterial capsules covalently attached to a protein antigen
- Polysaccharides alone cannot be processed and displayed on MHC unless attached to a protein
- Instead interact with a special set of B cells called marginal B cells
- Takes 1-2 years to develop therefore infants cannot mount immune response
- Ex. PCV, Haemophilus influenza
What are toxoid vaccines?
- Chemically inactivated bacterial toxins
- Formaldehyde most common
- Specific aa are altered with slight conformational change
- Overall struct is maintained as well as immunogenicity
Ex. Diphtheria, tetanus, DTaP
What is an mRNA vaccine?
- Synthetic mRNA in which ribosomes in the host recognize and translate the antigen (spike protein)
- mRNA is delivered in lipid nanoparticles (LNPs)
- Fuses with endosome to release mRNA into cytosol
- Consist of ionizable lipid, helper lipid, cholesterol, and PEGylated lipid
What are the pros and cons of an mRNA vaccine?
Pros:
- Effective at inducing cell mediated response
- Safe
- Can be quickly modified
Cons:
- Stability, must be kept frozen
- New
What are the other components of a vaccine?
ADJUVANTS: Enhance immunogenicity of vaccines
- Required in inactive vaccines, subunit, and other non living vaccines
- Triggered the innate receptors to stimulate an immune response
Antibiotics: Prevent contamination during manufacturing
- Antibiotics have rare change to cause allergic reaction
- Found in trace amounts
- Neomycin, Polymycin, streptomycin, gentamicin
Preservatives: Prevent microbial growth
- Used only in vials that contain multiple doses
- Thimerosal (only flu vaccine) no evidence of harm
Stabilizers: Protect active ingredient during manufacturing, storage, and transport
- Gelatin
