Immuno: Immune response to infection Pt.2 Flashcards
What are the key features of cells of the adaptive immune response?
- Wide repertoir of antigen receptors (NOTE: not entirely genetically encoded because of VDJ recombination)
- Highly specific
- Clonal expansion
- Immunological memory
Outline T cell maturation
- T cells arise from hematopoietic stem cells
- Exported as immature T cells to the thymus where they undergo positive and negative selection
- Cells with low and high affinity for HLA are deleted
- Cells with intermediate affinity will survive (10%)
- Mature T lymphocytes enter the circulation and reside in secondary lymphoid organs
How do T cells recognise HLA/peptide complex?
- T cells express CD3 and T cell receptor
- T cell receptor recognises peptides presented by HLA molecule on APC
Which class of HLA do CD4 and CD8 cells recognise?
CD4 - HLA-II
CD8 - HLA-I
Outline the functions of CD4+ T helper cells.
- Recognise peptides derived from extracellular proteins
- These peptides are presented on HLA-II (HLA-DP, DQ and DR)
- Provide help for the development of a full B cell response
- Provide help for the development of some CD8+ T cell responses
List the subsets of CD4+ T cell.
- Th1
- Th2
- Th17
- Follicular T cell
- Treg
For each of the following subsets of CD4+ T cell, list their polarising factors and effector factors.
- Th1
- Th2
- Th17
- Follicular T cell
- Treg
Th1
- Polarising
- IL-12
- IFN-gamma
- Effector
- IL-2
- IL-10
- IFN-gamma
- TNF-alpha
Th2
- Polarising
- IL-4
- IL-6
- Effector
- IL-4
- IL-5
- IL-10
- IL-13
Th17
- Polarising
- IL-6
- TGF-beta
- Effector
- IL-17
- IL-21
- IL-22
Follicular T cell
- Polarising
- IL-6
- IL-1b
- TNF-alpha
- Effector
- IL-2
- IL-10
- IL-21
Treg
- Polarising
- TGF-beta
- Effector
- IL-10
- Foxp3
- CD25
Describe the function of CD8+ T cells.
- Specialised cytotoxic cells
- Recognise peptides derived from intracellular proteins presented on HLA class I (A, B and C)
- Kills cell directly via perforin and granzyme or expression of Fas ligand
- Perforin destablises cell membrane and also allows granzyme to enter cell
- Granzyme is a serine protease that activate caspases to trigger apoptosis
NOTE: particularly important against viral infections and tumours
In what form are B cells found in the periphery?
IgM B cells
What is the early IgM response of B cells?
If the B cell in the periphery engages an antigen it can cause an early IgM response where the cell differentiates into an IgM secreting plasma cell.
What is a germinal centre reaction?
- Dendritic cells present an antigen, thereby priming the CD4+ T helper cells
- CD4+ T helper cells provide help for B cell differentiation via CD40L: CD40 interaction
- This causes B cell proliferation
- They undergo somatic hypermutation and isotype switching (from IgM to IgG/A/E)
- They will become plasma cells and produce antibodies
NOTE: this process is dependent on CD4+ T helper cells
Which part of an antibody detects antigen and which part is responsible for its effector function?
- Antigen is recognised by the antigen binding region (Fab) which is made up of the variable region of both heavy and light chains
- Effector function is determined by the constant region (Fc) of the heavy chain
Outline the function of antibodies.
- Identification of pathogens and toxins (Fab-mediated)
- Interact with other components (complement, phagocytes, NK cells) of immune responses to remove pathogens (Fc-mediated_
NOTE: antibodies are particularly important against bacteria
How is a secondary response to T-dependent antigens different from the primary response?
- Lag time between antigen-exposure and antibody production is decreased (to 2-3 days)
- Titres of antibody produced is increased
- Response is dominated by IgG antibodies with high affinity
- The response is independent of help from CD4+ cells
Describe B cell maturation
Stem cells in BM > lymphoid progenitors > Pro B cells > Pre B cells > IgM B cells in periphery
Describe the central tolerance of B cells
- No recognition of self-antigens = survive
- Recognition of self-antigens in BM = negative selection to avoid autoreactivity
What is complement?
- 20 tightly regulated, linked proteins
- Produced by liver
- When triggered, enzymatically activate other molecules in a biological cascade
- Results in rapid, highly amplified response
In what form are complement proteins present in the circulation?
Inactive molecules
Draw a schematic of the complement pathway.
Outline the classical pathway of complement activation.
- Activated by immune complexes
- Formation of antibody-antigen complexes results in a conformational change exposing a binding site for C1 on the antibody
- This binding results in activation of the cascade (this = formation of C3 convertase)
NOTE: this is dependent on antibodies, therefore it requires prior activation of the adaptive immune response (i.e. it does NOT occur very early in the immune response)
Outline the mannose binding lectin pathway of complement activation.
- Activated by the direct binding of MBL to microbial cell surface carbohydrates
- This directly stimulates the classical pathway involving C4 and C2 (but NOT C1)
NOTE: this is NOT dependent on the adaptive immune response
Outline the alternative pathway of complement activation.
- Directly triggered by the binding of C3 to bacterial cell wall components
- This is NOT dependent on the adaptive immune response (continuously active at low levels)
- Involves factors B, D and P
State an example of bacterial cell wall components that can activate complement in Gram-positive and Gram-negative organisms.
Gram-negative: lipopolysaccharide
Gram-positive: teichoic acid
What is the major amplification step of the complement cascade?
C3 convertase
What are the effects of complement fragments that are released during complement activation?
- MAC
- Opsonisation
- Chemotaxis
- Increase vascular permeability (anaphylatoxin)
What are the ligands for the CCR7 receptors on dendritic cells?
- CCL19
- CCL21
- This interaction is important in directing dendritic cells towards lymph nodes
