4. Pathogenicity and the Host Response (Immunology) Flashcards
1
Q
What is complement?
A
- A part of innate immunity
- Collection of circulating serum proteins
- Many complement proteins are proteases that cleave one another to create a “complement cascade”
e. g. C3-covertase - Result of complement activation:
- Inflammation (C3a and C5a)
- Opsonisation of bacteria (C3b)
- Bacterial lysis
2
Q
What are the 3 pathways that activate complement?
A
- Alternate pathway:
- C3 is activated and binds directly to pathogen surface - Lectin pathway:
- C3 is activated by mannose binding lectin residues (glycoproteins that are found exclusively on the surface of microbes) - Classical pathway:
- C3 is activated by antibodies (IgM and IgG) that have bound pathogens
3
Q
How do innate immune cells e.g. macrophages recognise pathogens as foreign?
A
- Pattern recognition recepetors (PRRs) such as TOL receptors expressed by the immune cell recognise structures shared by many microbes called Pattern Associated Molecular Patterns (PAMPs)
- Therefore there is some limited specificity
4
Q
What is the inflammatory response?
What triggers it?
A
- Inflammation is a localised accumulation of fluid and white blood cells characterised by reddening, swelling, heat and pain
- When innate immune cells such as macrophages recognise PAMPs of bacteria with their PRRs it triggers the release of cytokines and chemokines
- These cytokines cause vasodilation and increased permeability of blood vessels (causing heat and swelling)
- The chemokines cause inflammatory cells (neutrophils) to migrate into tissues which release inflammatory mediators that cause pain
5
Q
What are cytokines?
A
- Proteins secreted by immune cells that function as mediators of immune and inflammatory reactions
- Act by binding to a specific cytokine receptor on the target cell which induces signal transduction and gene transcription
6
Q
What are the proinflammatory cytokines?
A
- IL-1B: activate endothelial cells and promote leukocyte recruitment
- TNFa: activate endothelial cells and promote leukocyte recruitment
- IL-6
- IL-12: promotes Th1 differentiation and cytotoxic activity in CTLs and NK cells
- CXCL8
- IFNy: activates macrophages
7
Q
How are leukocytes recruited to the site of infection?
A
- Resident macrophage in tissue will bind pathogen PAMPs with PRRs and release cytokines and chemokines
- These cytokines activate the local vascular endothelium
- Selectin molecules upregulated on the endothelial surface allow the leukocytes to loosely bind via their selectin ligand to roll over the endothelial surface
- As the leukocyte rolls it is activated by the chemokines bound on the endothelial wall which cause the integrin molecule on the leukocyte surface to go from low affinity to high affinity
- The high affinity integrin allows the leukocytes to stably adhere to the integrin ligand on the endothelial wall
- The leukocyte will them migrate out of the vasculature and flow a chemokine gradient towards the site of infection
8
Q
How does IFN-1 function?
A
- Type 1 interferon is a cytokine with a potent antiviral activity
- It is secreted when PRRs are triggered
- It allows virally infected cells to fight the virus by degrading viral RNA, inhibiting viral gene expression and inhibiting viral protein synthesis
- It also activtes NK cells and Dendritic cells
9
Q
What cells do NK cells kill?
A
- NK cells are innate immune cells that are activated by IFN-1
- These cells recognise stress ligands on infected cells via an activating receptor
- If the inhibitory receptor on the NK cell does not recognise self MHC I (which is often lost during infection) on the infected cell the NK cell will be activated and commence killing
10
Q
What are features of Toll Like Receptors?
A
- Membrane proteins that are expressed either at the cell surfce on in endosomes
- Recognise PAMPs from a diversity of pathogens (the innate immune system can therefore distinguish different peptides)
11
Q
What are Rig Like Helicases?
A
- A type of PRR
- Located in cytoplasm and recognise viral dsRNA
12
Q
What are Nod-like receptors?
A
- A family of cytoplasmic receptors that recognise a variety of microbial products
- Some of them are components of the inflammasome
13
Q
What is the inflammasome?
A
- The role of the inflammasome is to cleave and thus activate IL-1B
- Pro-IL-B is produced in response to pattern recognition from PRRs
- The inflammasome is assembled in response to the presence of intracellular factors (e.g. bacteria products, viral DNA etc)
- It is made up of NOD-like receptor, adaptor protein and caspase-1 which cleaves caspase-1 into its active form which will cleave pro-IL-1B into IL-1B which is then secreted from the cell
14
Q
What is the B cell receptor structure?
A
- Has 2 identical heavy chains and 2 identical light chains
- Has constant regions and variable regions
- Has 12 CDRs (3 per chain)
- Binds whole antigen epitope
- Can be secreted
15
Q
What is T cell receptor structure?
A
- Has one alpha (light chain) and one beta (heavy) chain
- Has constant regions and variable regions
- Has 6 CDRs (3 per chain)
- Binds antigen peptide presented in the groove of MHC
16
Q
Are antigen receptors germline encoded?
A
- No, antigen receptor genes in the germ line state are comprised of multiple gene segments
- During development these are randomly arranged via somatic recombination to generate unique receptors
17
Q
What are the key features of the adaptive immune system?
A
- Specificity:
- Immunity is antigen specific - Diversity:
- An extremely large number of lymphocyte clones- each with a particular antigen specificity (at least 10^9 antigen determinants can be recognised) - Discrimation between self and non-self:
- The adaptive immune system generally only responds to foreign antigens because of the self-tolerance developed - Clonal expansion: the antigen-specific lymphocytes are selected and undergo clonal expansion to increase in number
- Memory:
- Secondary immune responses are always greater in magnitude (memory T and B cells) - Self-regulation:
- Immune responses are self-limiting
18
Q
Why are adaptive immune responses only observed after around a week?
A
- Once the B/T lymphocyte with the antigen specific receptor is activated it undegoes clonal selection and proliferation
- It takes time for this proliferation to take place
- The clones must then differentiate
19
Q
Are B and T cells morphologically different?
A
- No
20
Q
What are two important features of T cells?
A
- The T cell receptor recognises antigen peptide presented in the groove of MHC (class 1 or 2)
- There are two major types of T-lymphocytes:
2/3 are CD4+ (once activated become T helper cells)
1/3 are CD8+ cytotoxic T cells (once activated become cytotoxic T cells)
21
Q
What is:
- CD4?
- CD8?
A
CD4:
- CD4 is a molecule expressed on the surface of CD4+ T cells
- It binds to MHC Class II in a peptide independent manner
- Upon activation the CD4+ T cell differentiates to become a T helper cell
CD8:
- CD8 is a molecule expressed on the surface of CD8+ T cells
- It binds to MHC Class I in a peptide independent manner
- Upon activation the CD8+ T cell differentiates to become a cytotoxic T cell
