Immunology 1 - The immune response to infection/ primary immune deficiencies part 1 Flashcards
Incomplete - excludes basics and material that is mentioned in subsequent lectures
How is pus formed?
What about abscess formation?
Following phagocytosis, neutrophils die
When they die, they release residual enzymes which causes the liquefication of closely adjacent material
This forms pus
*8abscess formation: if you get extensive localised formation of pus**
Recall 2 functions of CD4+ T lymphocytes
Provide help for development of:
- Full B cell response
- Some CD8+ T cell responses
Which type of plasma cell is dependent on CD4+ T cells for activation?
IgG
Which components of complement comprise the classical pathway?
C1 C2 C4
Which components of complement comprise the mannose binding lectin pathway?
c4 and c2
What is the role of the membrane attack complex formed at the end of the complement pathway?
Makes holes in membranes
What is the first class of immunoglobulin to be made in the adaptive immune response?
IgM
What is the difference between oxidative and non-oxidative killing?
Oxidative: uses NADPH and hydrochlorous acid
Non-oxidative: uses lysozyme and lactoferrin

Which form of HLA is recognised by CD4 cells?
HLA-2
Which form of HLA is recognised by CD8 cells?
HLA-1
Which cytokines induce development of CD4 T cells into Th1 cells?
IL12 and IFN gamma
What is the function of Th1 cells?
‘Help’ CD8 T cell and macropage responses
Which cytokines induce development of CD4 T cells into Th17 cells?
IL6 and TGF beta
What is the function of Th17 cells?
‘Help’ neutrophil recruitment and enhance generation of autoantibodies
Which cytokine induces development of CD4 T cells into Treg cells?
TGF beta
Which cytokine induces development of CD4 T cells into follicular T helper cells?
IL6
Which type of T cell produces CD25 and FOXP3?
T reg cells
By what mechanism do CD8 cells effect their cytotoxicity?
Injection of perforin, which enables granzyme entry
OR
Fas ligand expression
Which cytokines are secreted by CD8 T cells?
IFN gamma and TNF alpha
How do CD4 cells activate B cells?
Express CD40 ligand, which interacts with CD40 on immature B cell surface, causing the B cell to differentiate
**the ligand is what is needed to activate the recetor; T cell is what is needed to activate the B cell; ligand is on the T cell and the receptor is on the B cell**
Recall the 2 processes that B cells undergo to become mature
- Class switching
- Somatic hypermutation
Which part of an immunoglobulin determines its class?
Heavy chain
Which class of immunoglobin forms a pentamer?
IgM
Which class of immunoglobulin forms a dimer?
IgA
Which portion of an immunoglobulin mediates pathogen identification?
Fab portion
Which portion of an immunoglobulin mediates activation of complement/ NK cells?
Fc portion
Where is complement produced?
Liver
Neutrophils and macrophages:
a) site of production
b) mechanisms of action COMMON to both
a) produced in the bone marrow (macrophages - called macrophages once in tissue)
b) mechanism of action
- receptors for: pathogens themselves (via pattern recognition receptors), cytokines/chemokines (detect inflammation), immune complexes (via Fc receptor)
- phagocytic killing: oxidative and non-oxidative
How do neutrophils kill pathogens?
Oxidative and non-oxidatvie killing
Release:
- preformed myeloperoxidase
- neurtophil elastase
- defensins
Difference between monocytes and macrophages
Monocytes- produced in bone marrow
When they migrate to tissues they are called macrophages
What is the main difference in function between neutrophils and macrophages?
Macrophages can present antigen on their surface following phagocytosis, but neutrophils cannot
Which cell surface marker is associated with macrophages?
CD14
Recognises LPS on bacterial cell walls
Give two examples of pattern recognition receptor
Toll like receptor
Mannose receptor
Mode of action of NK cells
- inhibitory receptors: recognise self HLA/MHC I
- activatory receptors: recognise heparan sulfate proteoglycans
- Loss of inhibitory signals/increase in activatory signals–>activates NK cells
- NK cells kill altered self cells - ie virus infected or malignant
- They also secrete cytokines - regulates inflammation and promotes dendirtic cell activity
NB: NK cells are lymphocytes
What type of cell is a dendritic cell?
Describe the changes that occurs in dendritic cells following phagocytosis
Dendritic cells mediate the transition between innate and adaptive immunity.
After phagocytosis:
- Upregulate expression of HLA-1
- Express costimulatory molecules
- Migrate via lymphatics to lymph nodes (mediated by CCR7)
- Process non-self antigen and present it to T cells in lymph nodes to prime the adaptive immune response
What are the two types of dendritic cells?
Immature: detecting pathogens and phagocytosis
Mature: processing pathogens and presenting to T cells
How do antigens and lymphocytes reach the lymph nodes from respecive sites?
Antigens: reach lymph nodes via migration through lymphatics from the infected site
Lymphocytes: reach the lymph nodes via the blood
After this, lymphocytes and lymph return to the blood via the thoracic duct
What are the soluble components of the innate immune system?
- complement
- acute phase proteins
- ferritin
What are acute phase proteins?
Proteins secreted by the liver in response to infection
Examples:
- IL1/IL6 - pyrogenic
- CRP - binds to surface of infected cells–> activates the complement cascade via c1q
- ferritin
What is opsonisation?
Modification of a pathogen to attract it to a NK or phagocytic cell
May be mediated by antibodies, complement components or acute phase proteins
Enables phagocytosis
Summary: which cells of the immune system are phagocytic?
monocytes and macrophages
granulocytes
dendritic cells
i.e. NK cells are not phagocytic !!
Describe the process of T cell development: overview
- T cells start as stem cells in bone marrow
- Lymphoid progenesis
- Pre-T cells go out into circulation
- T cells mature in thymus
- T cells proliferate
- T cells undergo positive and negative selection within thymus
- Mature T cells exported to periphery, reside in secondary lymphoid organs
Describe the process of maturation of T cells once in Thymus
- TCR with intermediate affinity for HLA moelcules are selected, whilst those with too low or too high affinity are deleted
- These intermediate affinity T cells undergo further differentiation based on whether they have affinity for HLA class 2 or HLA class 1
- Those that bind to HLA class II differentiate into CD4 positvie T cells
- Those that bind to HLA class I differentiate into CD8 positive T ccells
CD8+ vs CD4+ T cells
-
CD8+ t cells: detect INTRACELLUAR peptides presented by MHC class I (on APC)
- particularly important for viral infections/malignancy
-
CD4+ t cells: detect EXTRACELLULAR peptides presented by MHC class II (on APC)
- variety of functions including activation of B cells and development of other T cells
Examples of HLA class I and HLA class II molecules
HLA class 1: HLA A, HLA B, HLA C
HLA Class II: HLA-DP, HLA-DQ, HLA-DR
**these are expressed on the APC
** they present processed peptide to T cells
Summary of different CD4+ T cell subsets

Function of TH17 cells
- Fungal and bacterial infections
- Helps neutrophil recruitment
- Enhance generation of autoantibodies
Function of Treg cells
- Secrete IL-10
- → inhibit the immune response
- T regs express CTLA-4 on cell surface
- → directly inhibit T cell activation
Function of Follicular helper T cells
- Promotes germinal centre reactions
- stimulates differentiation of B cells → IgG (memory B cells) and IgA secreting plasma cells
Explain the process of B cell maturation
Early IgM response
- they are produced in the bone marrow
- they leave the bone marrow as PRO B CELLS or PRE B CELLS
- once they are in the peirpheries they become IgM B cells
- so when they recognise antigen they are in the IgM state
- once they recognise antigen, they differentiate into IgM secreting plasma cells
Germinal centre reaction: Somatic hypermutation and istotype switching
- IgM secreting plasma cells migrate from the peripheries to the lymph nodes
- Here they encounter CD4+ helper T cells that have previously been primed (in the peripheries) by dendirtic cells (by detection of the SAME antigen)
- This interaction requires CD40L (T cell) - CD40 (B cell) interaction
- IgM producing B cells undergo SOMATIC HYPERMUTATION (the receptor mutates to become high affinity) and class switching (IgM switches to IgG, IgE or IgA)
- Now you have HIGH AFFINITY, IgG/IgA/IgG secreting plasma cells and memory cells leaving the lymph nodes to enter the circulation
Structure of antibodies
- two heavy chains
- two light chains
- FaB portion: light chain + variable region of heavy chain
- Fc portion: cosntant region of heavy chain
Fab: recognises antigen
Fc: effector function; interacts with other components of immune system (complement, phagocytes, NK cells)
Function of IgA
- protection of mucosal surfaces via salivary, respiratory, gastrointestinal and lacrimal secretions
- blocks pathogenic ligands from binding to epithelial cell surface receptors
- IgA is also present in breast milk
- providing passive immunity in neonates
Which antibody is present in breast milk?
IgA
*think it’s SECRETORY
FUnction of IgD
- found on the cell surface of immature B cells
- IgD provide role in lymphocyte activation
Function of IgG
- the most abundant/ common antibody
- and occurs in monomer form in the circulation
- Subclasses of IgG perform different functions,
- IgG2- fighting encapsulated bacteria
- IgG also has a role in activating complement proteins
**crosses the placenta
Function of IgM
- occurs as a pentamer
- and has a role in the primary response against pathogens
Function of IgE
- is produced in response to parasitic infections,
- as well as during type I hypersensitivity reactions
- where it is involved in mast cell activation.
Difference in B cells between primary and secondary immune response
Primary immune response: early IgM response
Secondary immune response: high affinity IgG and memory cell response
Main difference between IgM and IgG plasma cells
IgM plasma cells: not dependent on T cell help for generation
IgG: dependent on T cell help
Is the complement system part of innae or adaptive immune response?
Neither - it just complements the two systems
Explain the process of complement activation

What activates the classical complement pathway?
Immune complexes
Hence it requires activation of the adaptive immune response
So it does not occur early
*C1 activates C4 and C2

What activates the MBL 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)
- This is NOT dependent on the adaptive immune response

How does the alternative pathway of complement activation work?
This is directly triggered by binding of C3 to bacterial cell wall components
E.g. lipopolysaccharide of Gram-negative bacteria
E.g. teichoic acid of Gram-positive bacteria

What are the main regulatory factors for the alternative pathway?
Factor H
C1 inhibitor
–> prevent the alternative pathway from going into overdrive
What is the main amplification step of final common pathway?
Activation of C3 convertase
Triggers formation of Membrane attack complex via C5-c9

Function of MAC
- attacks membranes
- makes holes in membranes
- and lyses them
- → cell death
Functions of the complement system
- Increase vascular permeability and cell trafficking to sites of inflammation
- Opsonisation of immune complexes keeps them soluble
- Opsonisation of pathogens to promote phagocytosis
- pathogens are chemically modified
- Activation of phagocytes
- Promotes mast cells/ basophil degranulation
- Punches holes in bacterial membranes
Examples of chemokines
CCL19 and CCL21 are ligands for CCR7 on dendritic cells
important in directing dendritic cell trafficking to lymph nodes
What is VDJ recombination
VDJ recombination is the process by which T cells and B cells:
- randomly assemble different gene segments
- and nucleic acids are randomly deleted/ added at the sites of rearrangement
Consequence of VDJ recombination:
- Potential to create vast array of specificities (10^11- 10^12 receptors)
- Generates unique antigen receptors that can collectively recognise many different types of molecule
- Auto-reactive cells are likely to be generated
- Mechanisms must exist to delete or tolerise these autoreactive cells
Primary and secondary lymphoid organs
Primary:
Bone marrow
Thymus
Secondary
SIte of interaction between naive lmphocytes and microorganisms
Examples: spleen, lymph nodes, MALT
What are the constitutive barriers to infection?

What markers are expressed by T memory cells vs naive T cells?
Naive T cells: CD45 RA
Memory T cells: CD45 RO
What is the difference between central and effector memory T cells?

Describe B cell memory
