Karteikarten
Adaptive immunity
Karten in diesem Stapel (69)
- 1What is the humoral response?Based on B cell production of Abs
Deals with extracellular pathogens - 2What is the cell-mediated response?Based on T-cells (esp. Tcyt)
Deals with intracellular pathogens (esp. viruses) - 3What are the 3 main characteristics of adaptive immunity?1) Specificity
2) Memory
3) Tolerance - 4How does adaptive immunity show specificity?A response which confers protection from 1 disease will not protect against another
Based on the structures of immunoglobulins, TCRs and clonal selection of B/T cells - 5How does the adaptive immune system show memory?Re-exposure to a previously encountered disease > greatly enhanced response
Based on formation of memory cells and clonal selection of B/T cells - 6How does the adaptive immune system show tolerance?A healthy individual's immune sys can discriminate between self and non-self - if this doesn't occur > autoimmune disease
Based on elimination of self-reactive cells in the bone marrow and thymus - 7What cells and tissues are involved in the adaptive immune system?B lymphocytes: plasma cells, memory cells
T lymphocytes: memory cells and effectors: *CD8+ T cytotoxic cells
*CD4+ T helpers (subsets 1,2,17)
*T regulatory cells (ignore these)
APCs: DCs, macrophages, B cells
Lymphoid organs: 1ary (bone marrow, Thymus), 2ndary (lymph nodes, spleen) - 8What are the major features of an IgG molecule?* 2 identical heavy, 2 identical light chains
* Held together by disulphide bonds
* Variable regions and constant regions
* Fab - frag. Ag binding
* Fc - frag crystalyzable - binds to FcRs on macrophages and neutrophils - 9What are the major features of the TCR? Where is TCR found?* 2 TM Ps, α and β - non identical
* Held together by disulphide bonds
* Have variable and constant regions
Found on the surface of T lymphocytes - 10What are major histocompatability complex glycoproteins?* Discovered for the role in transplant rejection/acceptance
* Cell surface mols, involved in presentation of Ag to TCRs
Class I - present of all cells (-RBCs). 1 TM
Class II - B cells, DCs, Ms. 2 TM doms
Polymorphic (vary between individuals) - 11How do APCs present Ag to T cells via MHC glycoprotein?* Th TCR binds processed Ag presented assoc with MHC class II on professional APCs
* Tcyt TCR binds processed Ag presented assoc with MHC class I - can be on any cell - 12What are CD4 and CD8?Co-Rs that consolidate adhesion between T cells and presenting MHC on opposing cells
CD4 - on Th cells, binds MHC cII
CD8 - on Tcyt, binds MHC cI
Do NOT bind Ag directly! Just to MHC mols - 13Note: What are antigens?= 'antibody generating' molecules
Proteins/ polysaccharides/ glycoproteins/ glycolipids
3-6 AA residues = antigenic determining sequence, AKA epitope
1 molecule will have many epitopes - 14What is the immunoglobulin superfamily?* Large group of cell surface/soluble Ps involved in recognition/ binding/ adhesion
* Most involved in imm sys, some in N.sys/elsewhere
* Evolved from a single prototype mol!
* All possess Ig domains/ folds - 2 β-sheets back to back with disulphide bridges - 15What are "immature" lymphocytes?Haven't fully developed Ag-specific Rs
Found in bone marrow/ thymus - 16What are "naïve" lymphocytes?Have Ag Rs, BUT haven't yet encountered the Ag they are specific for
- 17What are "activated" lymphocytes?Have bound Ag and received the necessary accessory signals from other cells (e.g. cytokines) to proliferate to form a clone of activated B/T cells, ready to differentiate
- 18What are "effector" lymphocytes?Derived from activated lymphocytes, have effector functions - produce cytokines/ Abs, can kill infected cells
- 19What are "memory" lymphocytes?Long-lived descendants of activated lymphocytes. Dormant. Encountering same Ag again > quick change back to active lymphocyte able to differentiate to effector and further memory cells
- 20What 3 signals are required from DCs to activate a naïve T cell?1) Ag presentation via MHC cII
2) CD80 and CD86 (AKA B7.1/.2) -
co-stimulatory mols, bind CD28 - a
co-stimulatory R on the naïve T cell
3) Cytokines - 21DC's role in Ag presentation* DCs bind Ags at TLRs/ other PRRs in periphery (particularly lungs) > Activation (after phagocytosis) > Migrate to 2ary lymphoid organs and express CD80/86 on the way
* Present Ags to naïve Th/ Tcyt cells in the 2ary lymphoid organs (L.nodes, spleen) - 22B cells and macrophages as APCs* Activated B cells that have bound Ag express CD80/86
* M's activated by microbial products/ cytokines also express CD80/86
B cells and Ms can ∴ expand an ongoing response by stimulating/activating CD4 Ths - 23How do langerhans cells (DC cells in the skin) induce an adaptive immune response to pathogen invasion at the skin?* LCs phagocytose pathogens, broken down > products activate the cell
* LCs migrate through the lymphatic system to lymph nodes/ other 2ary L-tissue
* Mature LCs can transfer some Ags to other resident DCs in lymph node
*CD80/86 (B7)-positive DCs stimulate naïve T cells (triple signal) - 24What cell types can activated CD4+ T cells differentiate into?Th1, Th2, Th17
All involved in helping other immune cells to do things - 25What are the functions of Th1 cells?* Activate Tcyt cells and Ms
* Help B cells
* Viral and IC pathogen clearance - 26What are the functions of Th2 cells?* Help B cells to produce Abs, especially IgE responses
* Control parasitic infections
* Eosinophil activation - 27What are the functions of Th17 cells?* Involved in recruitment of neutrophils
* Regulation of inflammatory reactions - 28What cytokines do Th1 cells secrete?IL-2, INF-γ
- 29What cytokines do Th2 cells secrete?IL-4, IL-5, (6, 9, 10, 13?)
- 30What cytokines do Th17 cells secrete?IL17
- 31What cytokines do DCs have have to secrete to induce the differentiation of Th1 cells?IL-12
- 32What cytokines induce the differentiation of Th2 cells?IL-4
Can be from DCs, and other cells: Sokol et al (2008) showed that basophils may play a role in IL-4 production in response to Th2-inducing allergens - 33What cytokines do DCs have have to secrete to induce the differentiation of Th17 cells?IL-6, IL-23
Secreted in response to EC pathogens - 34What determines the cytokines DC cells produce?The antigens they have taken up by endocytosis trigger the production of different cytokines
- 35How are B cells activated?* Occurs in the 2ary lymphoid organs
* Ag must bind BCR - can be free-floating or bound to an APC (P, glycoP, polysac, whole virus particles/ bac cells)
* Activation is enhanced by the B cell co-receptor complex - 36What is the B cell co-receptor complex?CD21 on surface of B cells, associated with CD19 and CD81.
When BCR binds Ag tagged with C3, CD21 binds the C3 frag then coligates with bound BCR - signals are transduced through CD19 and CD81 that lower the activation threshold of the cell - 37What's the difference between Thymus-dependent (TD) and thymus-independent (TI) Ags?TD antigens require the help of Th cells (specific for the same Ag) to activate B cells. Takes several days but the Abs produced have higher affinity and are more functionally versatile.
TI antigens don't require Th cells - rapid response, but Abs have low affinity/vers - 38What are the 4 major classes of pathogen the adaptive immune system deals with?1) EC bac, fungi, parasites
2) IC bac, parasites
3) Viruses (IC)
4) Parasitic worms (EC) - 39What are the main functions of Th1 cells?* Activate Ms, enable them to kill IC pathogens (e.g. mycobac that cause TB + leprosy) more effectively
* Activate B cells > stronly opsonising Abs (IgG1/3 in humans, IgG2a/2b in mice)
* Help Tcyt to activate and proliferate - 40What are the main functions of Th2 cells?* Involved in B cell production of IgM (primary response)
* Class switching to IgE/A (2ary resp)
*Defense against parasitic helminths (worms) - 41Clonal expansion of naïve T cells depends upon production of which cytokine? How does this cytokine act?IL-2. Also requires upregulation of IL-2 Rs. Produced by all CD4+ T cells following Ag stimulation, but only Th1 after subtype differentiation. Tcyt also secrete it.
IL-2 actis in an auto-/paracrine manner to drive proliferation/ differentiation - 42IC paths can grow in M phagosomes and can inactivate the M. Which Th cells help re-activate the M? How do they do this?* Effector Th1 (specific for particular Ag) bind M presenting the same Ag
* Th1 secrete INF-γ and express CD40 ligand - these bind to M inducing activation
CD40L is induced on Th1/2, delivers activating signals to B cells/M via CD40 (R) - 43How does activation of the M lead to formation of the phagolysosome and pathogen destruction?* Activated M secrete TNF-α and express TNF-α Rs (autocrine +ve feedback loop)
* This, along with INF-γ > ↑ NO and O2-, and fusion of phago- and lysosomes - 44How do activated macrophages contribute to the activation of further Th cells?Upregulate B7 (CD80/86) and MHC class 2
- 45What is Ab class switching?Whereby the variable domain of an Ab is associated with the C-region of another isotype.
CD40-CD40L interractions key to this process! - 46What class switching does IL-4 trigger?IgM to IgG1 and IgE
- 47What class switching does TGF-β induce?IgM to IgG2b or IgA
- 48Where does IL-4 or TGF-β come from?Th2 cells!
Th2 also produce IL-5 which stimulates plasma cells already producing IgA - 49What class switching event can Th1 cells contribute towards?Th1 secrete INF-γ, induces switching of IgM to IgG2a and IgG3
- 50How is activation of B cells controlled?Cytokine secretion from Th cells is highly polarised, confined to the space directly between the T and B cell (immunological synapse)
- 51How is infection with Trichuris trichiura (whipworm) dealt with?* Worms secrete factors, taken up by DCs
* DCs present worm Ags to Th2 cells
* Th2 produce cytokines > ↑ IgE production by B cells, recruitment of eosinophils and mast cells to intestinal walls and activates their production of proteases etc to kill the worms - 52What are the cytokines that stimulate these effector mechanisms?IL-4 and -13 stimulate B cell IgE production
IL-5 recruits Eosinophils - 53Where were Th17 cells identified and when are they induced (what is their role)?Identified in autoimmune disease
Induced early in response to EC bacterial/ fungal infection - 54What cytokine do Th17 cells produce and what are its major effects?IL-17 - induces local epithelial/ stromal cells to produce chemokines that recruit Ns to sites of infection
IL-17 can induce expression of AMPs - e.g. β-defensins from the keratinocytes of the epidermis - 55What do Th17 cells achieve overall?Th17 cells increase the accute inflammatory response of the innate immune system at the site of infection:
They bring Ns to site of infection to phagocytose + kill the bac/ fungi - 56What other Th cell can the actions of Th17 induce?IL-17 can stimulate epithelial cells to produce chemokines that attract Th1 to site of infection
E.g. Mycobac TB - early response of Th17 cells > recruitment of Th1 to activate Ms - 57How does Candida albicans induce the production of Th cells?CA = dimorphic fungus, normally commensal but can become pathogenic
* Yeast form induces seretion of IL-12 from DCs > Th1 formation
* Hyphae induce IL-23 production - involved in late stages of Th17 prolif/diff (Early stages induced by IL-6 + TGF-β) - 58What do Tcyt cells do? AKA CTL (cytotoxic T lymphocyte)* Recognise viral Ags presented in assoc with MHC class I
* CD8 binds MHC class I to stabilise the interraction
* T cyt releases effector Ps > programs target cell for death (very specific - adjacent uninfected cells are unharmed
* CTL - 59What are the 3 classes of effector Ps released by Tcyt cells?1) Perforins - helps deliver contents of granules into cytoplasm of target cell
2) Granzymes - serine proteases - activate apoptosis once in target cell cytoplasm
3) Granulysin - antimicrobial actions, can induce apoptosis - 60What is apoptosis?Form of programmed cell death (autophagy)
Characteristics: nuclear blebbing, shedding of memb-bound vesicles (debris), DNA frag
Apop can > degradation of viral DNA in infected cells (nucleases also act on them) - 61How do the Tcyt effector proteins induce apoptosis?* Perforin and granzymes form complex with serglycin (a proteoglyc) which acts as a scaffold
* Granzymes activate caspases (cystein-proteases, cut after aspartic acid) > caspase cascade which activates cytoplasmic CAD (caspase-activated deoxyribonuclease) > DNA frag - 62How is the highly-polarised release of Tcyt effector Ps achieved?TCR:pMHC interaction - release only occurs right next to this cell-cell interraction
- 63Tcyt cells also release INF-γ. What are the effects of this on the target cell?1) Inhibition of viral replication
2) Increase in MHC class I expression ∴ ↑ presentation to Tcyt
3) Activation of Ms - 64Note: NKCs - part of innate imm sys (myeloid derived) BUT have a very similar function to Tcyt cells. What do they do and how?* Mediate early protection against viruses
* Kill cancer cells
* Rid body of Ab-coated cells
* Mechanism of killing - same as Tcyt
However, they don't express 1 Ag-specific R type - rely on many PRRs for specificity
* Activate in resp to interferons and M-derived cytokines. Secrete cyts - INF-γ - 65What is Ab-dependent cell-mediated cytotoxicity (ADCC)?* Ab binds Ag on surface of target cells
* FcR on NKCs recognize bound Ab (Fc)
* Cross-linking of FcRs signals to the NKC to kill the target cell > targeted secretion of effector Ps > apoptosis - 66What are the 3 main ways Abs participate in host defence?1) Neutralisation of toxins
2) Opsonisation of bac
3) Complement activation - 67How do Abs neutralise toxins?Ab binds toxin, prevents it interacting with Rs. M's ingest clumps of toxin-bound Abs
- 68How do Abs opsonise pathogens?Abs bind to bac, M's have FcR which bind the Fc portion of the Abs > phagocytosis
- 69How do Abs promote destruciton of pathogens through activation of the complement system?Bound Ab acts as R for the 1st P of comp sys > formation of P complex on bac > kills cell directly by formation of pore/lysis OR promotes phagocytosis
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- UG degree Immunology (Prof Green's material) Karteikarten am Adaptive immunity, erstellt von Tom McFarlane am 19/04/2016.
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- Tom McFarlane
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