Humoral and Cell-Mediated Immunity Flashcards
IgG traits
- Structure
- Abundance
- Response type
- Complement
- FcRs
Monomeric
Main antibody in tissues and blood due to low molecular weight
Important in secondary/memory responses
Can activate complement
Binds FcRs on phagocytes and NK cells
How is class switching used in primary and secondary response?
Why is IgM lower affinity?
IgM involved in primary response and class switched to higher affinity antibody like IgG in secondary response
Other classes tend to be higher affinity due to somatic hypermutation and affinity maturation
What is FcRn? (hint - newborns)
What does it do? (hint - protection)
Neonatal Receptor for IgG
Permits transfer of maternal IgG antibodies
Protects foetus and newborn by providing antibodies
What do naïve CD4/CD8 +ve T cells differentiate into?
Effector helper or effector cytotoxic T cells
What do naïve T cells require for survival and to avoid being “tolerised” (unresponsive)?
Give example
Co-stimulatory signals e.g. B7
What do cytokines produced by APCs do to activated T cells? (signal 3)
Influence the subset of effector CD4 +ve T cells generated
Which co-stimulatory molecule is expressed by dendritic cells, macrophages and B cells?
What does it interact with and what happens? (hint - IL-_, autocrine)
B7
Interacts with CD28 to induce expression of IL-2 and IL-2 receptor
IL-2 acts in autocrine fashion on CD4+ve T helper cells; Also required for CD8+ve cytotoxic T cell activation
Other cytokines direct T cell differentiation into different subsets of CD4+ve T effector cells (signal 3)
Signal 3 – Cytokines made by antigen presenting; Vary depending on the type of infection
What do different APC produced cytokines induce?
What differs between CD4+ve T cell subsets?
What does this ensure? (hint - appropriate)
Different cytokines induce activated “naïve” T helper cells to differentiate into various T cell effector subsets
These differ in cytokines produced and role in immune responses
- Ensures pathogen appropriate immunity
What is a TH0 cell?
Activated “naïve” T helper cells
What are the 5 main T cell subsets?
TH1
TH2
TH17
T-FH
T-Reg
What induces TH1 cell production?
What do they produce and what do they do? (hint - opson, inflamm)
What are they important for?
Production of these cells is induced by IL-12 and γ-interferon
These cells produce Il-2, γ-interferon and TNF
Activate macrophages –> Inflammation (classic cell-mediated immunity)
Induce B cells to make IgG1 and IgG3 (opsonising) antibodies
Important for the development of cytotoxic T cells
What induces TH2 cell production?
What do they produce?
What do they do? (hint - allergy)
Production of these cells is induced by IL-4
These cells produce IL-4,-5 and -13
Activate eosinophils and mast cells
Induce B cells to make IgE; Promotes mast cell degranulation (allergy)
What induces TH17 cell production?
What do they produce?
What do they activate?
These cells are pro-_?
Production of these cells is induced by TGF-β, IL-6
These cells produce IL-17 and IL-22
These cells activate epithelial cells and fibroblasts
They are proinflammatory, especially at mucosal surfaces
What induces T-FH cell (Follicular Helper T Cell) production?
Where are these cells found?
What do they do? (hint - somatic-, class)
What is meant by them being contact dependent?
Production of these cells is induced by IL-6
Found in lymphoid “follicles”
Help naïve B cells differentiate into plasma cells and memory cells
Promote somatic hypermutation and class switch
Contact-dependent - Requires interaction between co-stimulatory molecules CD154 and CD40, but also produce IL-21
What do T-Regulatory (reg) cells do?
T-Reg cells are heterogenous, meaning?
Suppress immune responses
There are 2 groups; Natural and induced
Traits of Natural T-Reg cells
- Where they develop
- Recognise?
- Suppression
- Target
- Role
Develop in thymus
Recognise MHC + Self-peptide
Suppress via contact dependent methods and IL-10 and TGF-beta
Target dendritic and effector T cells
Role is to suppress autoreactive T cells
How are T-Reg cells induced?
Traits of Induced T-Reg cells
- Where they develop
- Recognise?
- Suppression
- Target
- Role
Induced by TGF-beta (signal 3)
Develop in periphery
Recognise MHC + non-self peptide
Suppress via IL10 and TGF-beta
Target effector T cells
Role is to downregulate mucosal immunity and inflammatory responses
What do cytotoxic CD8 +ve T cells do once activated?
How? (hint - granzymes, fas)
Fas pathway importance? (hint - downregulation)
Bind specifically to infected target cells and induce target cell to undergo apoptosis
Proteases (granzymes) from cytotoxic T cell enter target cell via perforin channel
Fas ligand induces clustering of fas (death receptor) on target cell
Fas pathway may be important in downregulating immune responses
Traits of killing via cytotoxic T cell? (3 traits)
Specific - Only infected cells bearing antigen are killed
Efficient - Granzymes are pre-formed; Single cytotoxic T cell can kill 100s of infected
Clean – Enzymes formed during apoptosis degrade viral DNA and destroy non-viral pathogen; Apoptotic cells are taken up by phagocytes
What is allergy?
What the hypotheses for allergy increase in developing countries?
Disease following an immune response to innocuous antigen (allergen); Mostly IgE-mediated
Hygiene hypothesis
Counter regulation hypothesis
What is the hygiene hypothesis?
Children brought up on farms, or from large families, are less prone to develop allergy due to early repeated childhood infections; May be protective
Insufficient exposure to certain types of infection (“dirt”) skews TH1/TH2 balance towards TH2?
What is the counter regulation hypothesis?
Childhood infection protects against allergy by promoting IL-10 production (T-Reg ↑, TH1 ↓ and TH2↓); Imbalance of subsets
Infection with microbes or larger parasites plays a critical role in driving immunoregulation e.g. Promotes formation of Treg, IL-10
Human immune system and “Old Friends” co-evolved
May also explain rise in autoimmune disease (TH1/TH17-driven)
1-5% of T cells are Gamma-Delta T cells. What is the role of these cells?
- Location
- Diversity and recognition
- Processing by MHC?
- Cytokines
- Type of infection
- Innate and adaptive
Often found at mucosal epithelium
Less diverse, recognising a broader range of antigens (including lipids, phosphorylated antigens, DAMPs e.g. heat shock proteins)
Do not appear to require processing or presentation by MHCI/II
Can make cytokines e.g. IL-17, IFN-γ, TNF but also cytotoxic; Can act as antigen presenting cells to αβ T cells
Role in various bacterial, viral and parasitic infections (mycobacteria, flu, HIV, malaria) and also in cancer
May “bridge” innate and adaptive immunity
Once an infection is cleared, 99% of activated and effector cells die. How is an immune response terminated? (hint - CTLA-4 and B7)
Mechanisms of down-regulation via T-Regs and cytotoxic T cells
Inhibitory “immune checkpoints” expressed on lymphocytes e.g. CTLA-4 binds with high avidity to B7
1 CTLA-4 dimer binds 2 B7 dimers, preventing them from binding CD28 and inhibiting T cell activation
Why is it important that the immune system is switched back off?
Give example of KO CTLA4 mice
Avoid inflammation and tissue damage and conserve resources
KO CTLA4 mice die from uncontrolled T cell activation
PD-1 has an immunoreceptor tyrosine inhibitory motif (ITIM). What is PD-1?
What does it do?
PD-1 (programmed death) is a receptor on activated B and T lymphocytes – Interacts with widely expressed PD-ligand
Reduced T cell activation and limits damage, at expense of pathogen clearance
Fc gamma R IIb has an immunoreceptor tyrosine inhibitory motif (ITIM). What is Fc gamma R II?
Where is it expressed?
Binds FcR on naïve B cells and when co-ligated by antigen prevents activation of naïve cells
Expressed on B cells
