Week 9 Flashcards
For innate immunity,
- Define innate immunity.
- What types of cells are involved?
- What immunue mediators are involved?
- Innate immunity
- First responder to infection, tissue damage, and inflammation
- Cells involved: include neutrophils, dendritic cells, macrophages, natural killer cells
- Immune mediators involved: interferons, cytokines, and chemokines
For adaptive immunity,
- Define adaptive immunity.
- What does it require?
- What cells are involved?
- What are the two types?
- Highly specific recognition of antigens
- Requires clonal expansion of memory cells
- Self-reactivity leading to autoimmune disease
- Cells involved: B-cells, T-cells, dendritic cells, and macrophages
- Types
- Humoral
- Cell-Mediated
What are the cells and their functions in:
- humoral immunity
- cell-mediated immunity
- Humoral
- B cells – creates antibodies (memory cell)
- Block infections and eliminate extracellular microbes
- Cell-mediated
- Cytotoxic T-cells – kills infected cells and eliminate reservoirs of infection (memory cell)
- Helper T-cells – eliminates phagocytosed microbes (memory cell)
What are the three major cell types?
- Lymphocytes
- Antigen-presenting cells
- Effector Cells
What two types of cells are called lymphocytes and how do they progress through their life cycle?
- Lymphocytes
- B-cells: humoral immunity
- T-cells: cell-mediated immunity
- Life Cycle: naïve cell → effector lymphocyte → memory lymphocyte
What cells types are in the subtype: antigen-presenting cells?
- What is the function of each cell type?
- Dendritic cells: initiation of T-cell response
- Macrophages: effector phase of cell-mediated immunity
- Follicular dendritic cells: initiation of B-cell response
What cells types are in the subtype: effector cells?
- What is the function of each cell type?
- T-cells: activation of phagocytes and killing of infected cells
- Macrophages: phagocytosis and killing of microbes
- Granulocytes: kills microbes
What are the four postulates in “The Clonal Selection Hypothesis”?
- Clonal Selection Hypothesis
- Each lymphocyte bears a single type of receptor with a unique specificity (by V(D)J recombination)
- Virus must bind to lymphocyte receptor for lymphocyte activation (selection)
- Daughter lymphocyte cells derived from an activated lymphocyte will bear receptors of identical specificity as the parental cell (clonal)
- Lymphocytes bearing receptors for endogenous molecules will be deleted at an early stage
Differentiate between primary and secondary immune responses.
- In primary immune response, response is slow because naïve B-cells must undergo V(D)J recombination in order to respond to first contact with an antigen → creates memory B-cells
- In secondary immune response, memory B-cells can respond quicker because of acquired specificity to antigen
Where do B-Cells and T-Cells mature?
- B-cells maturate in bone marrow
- T-cells maturate in thymus
What are some secondary homes for B-Cells and T-Cells?
- Within these tissues, where are B-cells and T-cells located?
- Secondary homes: B-cells peripherally, T-cells centrally
- Spleen
- Lymph nodes
- GALTs – gut-associated lymphoid tissues
- MALTs – mucosal-associated lymphoid tissues
What are the five phases of immune response in situ?
- “First responders” = innate immune cells
- Antigen presentation to naïve adaptive immune cells
- Clonal expansion; amplification of antibody and cytokines
- Pathogen elimination; contraction phase of the immune response
- Memory
What kind of cells can act as antigen presenting cells (APCs)?
- Antigens are captured by dendritic cells, macrophages, and B-Cells (pAPCs) in the epithelium
What is the process of antigen presentation leading to T-Cell
- Antigens are captured in the epithelium.
- Blood borne antigens are captured in the spleen
- Tissue resident APCs migrate to lymph nodes
- T-Cell activation
For Cytotoxic T-Cells, what is:
- the surface marker?
- the function?
- location of antigen source within a cell?
- MHC Class recognized?
- Surface Marker: CD8
- Function: Cell Killing
- Antigen Source: Cytosolic
- MHC Recognized: MHC Class I
For Helper T-Cells, what is:
- the surface marker?
- the function?
- location of antigen source within a cell?
- MHC Class recognized?
- Surface Marker: CD4
- Function: Promote macrophage activity and B-Cell function
- Antigen Source: endosomal
- MHC Recognized: MHC Class II
What is the structure of MHC Class I?
- How many alpha and beta chains?
- Expressed on what ells?
- Binds peptides of what size?
- MHC Class I
- 3 alpha chains and 1 beta chain
- Expressed on all somatic cells
- Binds short peptides (8 to 11 AAs)
What is the structure of MHC Class II?
- How many alpha and beta chains?
- Expressed on what ells?
- Binds peptides of what size?
- 2 alpha chains and 2 beta chains
- Expressed only on professional APCs (dendritic, B, and macrophage)
- Binds long peptides (11 to 30 AAs)
What facilitates the MHC binding proteins to bind peptides?
- How MHC Proteins bind peptides
- Binding site of MHC molecule only requires 2 to 3 AAs (anchor peptides)
- MHC molecules can bind large repertoire of peptides
What are the three important characterisitics of MHC proteins?
- MHC genes are polygenic (multiple genes code for single phenotype)
- MHC genes are polymorphic (high number of mutations)
- MHC gene expression is codominant (mom and dad alleles of MHC class proteins are equally expressed → 6 class I molecules can be expressed)
What are the three functions of the polymorphic nature of MHC genes?
- MHC genes are polymorphic (high number of mutations)
- Allows for diversity of peptides to bind
- Alters contact with T Cell Receptor
- Each T Cell Receptor can only recognize a single peptide/MHC combo
What are the three functions of the invariant chain?
- Binds newly formed MHCII in ER
- Blocks peptide binding groove
- Targets complex to endosome (Ii is degraded in endosome → CLIP (peptide of invariant chain) is unloaded from MHCII by HLA-DM)
In which pathway can cross presentation occur (MHC I or MHC II)?
- Professional APCs can activate both MHC I and II presenting pathways without being infected
- Normally, MHC I pathway happens in infected cells
What causes Type I Bare Lymphocyte Syndrome?
- Type I – loss of MHC class I expression
- Mutations in TAP
What causes Type II Bare Lymphocyte Syndrome?
- Type II – loss of MHC class II expression
- Reduced number of T helper cells
- Much more detrimental
What causes Type III Bare Lymphocyte Syndrome?
- Type III – loss of both I and II
- Similar to type II
What viruses inhbiit the Class I MHC pathway and at what step?
- Viruses that inhibit MHC Class I pathway
- Herpes simplex – blocks peptide binding to TAP
- Adenovirus – retention of class I in the ER
- Cytomegalovirus – targets class I to cytosol
What pathogens escape the MHC Class II pathway and therefore require cytotoxic T-Cells?
- Pathogens that escape the MHC Class II pathway and require cytotoxic T Cells (MHC I pathway)
- Listeria monocytogenes – escape lysosome into cytosol
- Salmonella typhimurium – sequesters antigen from class II pathway
- Epstein Bar virus – suppresses class II expression
What are the two pathways of antigen presentation for MHC Class I and Class II (picture)?
Differentiate the characteristics of innate and adaptive immunity.
- Speed of Response
- Innate is immediate (actually means always present)
- Adaptive is delayed
- Immunological Memory
- Innate response is always the same response
- Adaptive memory response is faster and stronger with greater specificity after each encounter with antigen
Describe how innate immunity is triggered.
Two main triggers
Infection
Tissue damage
What are Pattern Recognition Receptors (PRRs)?
Trigger innate response by binding repetitive structures
What are types of PRR ligands?
- Ligands
- PAMPS (Pathogen-Associated Molecular Patterns): pathogen-induced
- RNA, DNA, polysaccharides, flaggelin
- DAMPS (Damage-Associated Molecular Pattern): autoimmune
- uric acid, cholesterol crystals, DNA, chaperone proteins
- PAMPS (Pathogen-Associated Molecular Patterns): pathogen-induced
What are PRRs located? Why?
- Locations – important because infections/viruses can arise in all three compartments
- Extracellular
- Cytosolic
- Endosomal
What are PRRs classes?
- Toll-Like Receptor (TLRs) at plasma membrane and in endosomes
- C-type lectin receptors (CLRs): recognize carbohydrates at plasma membrane
- Retinoic acid-inducible gene (RIG) Like Receptors (RLRs): recognize viral RNA in cytoplasm
- DNA Sensors: recognize viral DNA in cytoplasm
- NOD-like receptors (NLRs): recognize NLRP-3 domain and peptidoglycans in cytoplasm
How do Toll-Like Receptors Promote Inflammation?
(2) Pathways
- Activation of NF-kB (cytokines) – acute inflammation
- Activation of IFNs (interferons) – resistance to viral infection
- Plasmacytoid dendritic cells produce type I IFNs → expression of interferon stimulated genes → inhibition of viral RNA replication and activation of immune response
- Act in an autocrine and paracrine manner to protect uninfected cells
Describe the NLRP-3 Inflammasome Pathway?
- Phagocytosis by macrophages → recognition of PAMPS/DAMPS → NLRP-3 trimerization with adaptor protein and caspase-1 → cleavage and activation of caspase-1 → caspase-1 cleaves pro-IL-1B → active IL-1B → secretion → fever/acute inflammation
- Can cause auto-inflammatory syndromes, kidney diseases, and gout (by urate crystals)
What are the 2 barriers of the innate immune system?
- First Barrier – epithelium and mucous
- Second Barrier
- Intraepithelial lymphocytes (IELs) patrol epithelial layers
- Have low specificity and thus attack anything foreign
- Produce peptide antibiotics (defensins cathelicidins)
- Intraepithelial lymphocytes (IELs) patrol epithelial layers
What are Neutrophils (multi-lobed)?
- Rapid turnover (short half-life)
- First responders
What are Monocytes?
Explain respitory burst?
- Monocytes (differentiate into Macrophages once in tissues (horse-shoe lobbed))
- Ingest microbes with actin
- Long half-life in healthy tissues
- Macrophage phagocytosis can act with respiratory burst by activation via cytokines (among other pathways to kill)
- Cytokine receptor binds cytokine → NADPH → NADP+ via NADPH oxidase → produces ROS → ROS kills microbes