What are the two differentiations of B cells
- Plasma cells
- Produces low affenity antigen specific antiboides
2. Memory B cells
- produce high affinity antigen-specific antibodies
- These are long-lived plasma cells
What are the 5 main antibodies
- IgA
- IgG
- IgM
- IgD
- IgE
- Each have a specialised function - Classified according to their heavy chain
What is the dual biological function of Antibodies
- Varaible regions - Recognition function
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Binding of antigen is mediated by variable regions
2. Constant regions - Effector function
- Clearance mediated by constant region interacting with effector molecules
- Effector molecues = Complement and Fc receptors
Describe the structure and role of IgM
-
Monomer - Memebrane bound form serves as a B cell antigen recptor
- Function: B cell activation
2. Pentamer - present in plasma and scretory fluids
- first antibody produced during an immune responce
- Function: Agglutination and complement activation
Describe Agglutination
- When an antibody cross-links multiple antigens producing clumps of antigen
- Specific antigen binding to IgM and IgG
- Enhances clearance of pathogen by phagocytosis
How is the classical pathway of complement activated
- Initiated by specific antigens binding to IgG or IgM antibodies
- leads to conformation change in the heavy regions of the antibodies
-
Exposes multiple binding sites for C1 complement protein - which is the first component of the classical pathway
Describe the structure and function of IgG antibody
- Most abundant antibody in serum - 80%
-
This antibody is produced during a secondary/memory immune responce
- Functions
- •Agglutination
- •Complement system activation
- •Foetal immune protection
- •Neutralisation
- •Opsonisation
- •Natural Killer cell activation
How does IgG take part in foetal immune protection
Transport via placenta directly into foetal blood circualtion
Describe neutralisation by antibodies
- For specific antigen binding to antibody- protective mechanism
- IgG and dimeric IgA
- Function:
- Protects pathogen from infecting host
- Prevents pathogen toxins from disturbing normal cellular function
Describe opsonisation by antibodies
- Antibody coats spefici antigens
- Constant region of heavy chains Bind to Fc receptor on macrophage
- Enhance phagocytosis
How do antibodies enhance NK cell activity
- Infected host cells or apoptotic cells express
- IgG antibodies on surface
- Binds to Fcy receptor on Natural killer cells
- Leads to cell killing and release of IFNY which enhances phagocytes
Describe the structure and function og IGD antibodies
- Membrane bound form - B cell activation
- secreted form in low levels in plasma and function is not well understood
Describe the structure and function of IgA antibodies
- Second most abdundant
-
Monomeric form - in serum - B cell activation
-
Dimeric form - found in secratory fluids
- Secreted IgA:
- Neonatal defence
- Neutralisation
Describe the structure and function of IgE antibodies
- Tiggering allergic responces
- Asthma, allergy anaphylaxis
When are the different antibodies produced during the adaptive immune responce
-
IgM is the main produce early one in the reponces to antigen
-
IgG and others are produced later on
How are antibodies of the same specificity, but different Ig classes produced?
- During B cell activation, B cells can change the gene segments of heavy chain constant region
- process if induced by specific cytokines
What are the effector functions of activated CD4+ T cells
What are the different T effector cells and whats their function
How do T effector cells stimulate other Immune cells
How do Effector T cell help T cell responces?
They secrete Interleukin-2 (IL-2) – this a cytokine which stimulates proliferation and differentiation of antigen-activated T cells (and antigen-activate B cells)
How do effecto T cell stimulate macrophages
- Effector TH1 cells migrate from secondary lymphoid tissues into infected tissue sites.
- TH1 cells are re-activated by tissue-resident macrophages in an antigen-specific manner
- TH1 cells express co-stimulatory molecules (e.g. IFNy) that hyper-activate macrophages, enhancing their killing activities and pro-inflammatory cytokine production.
How do Effector T cells help B-cells
- Protein antigen bound to BCR is internalised by the B cell
- Antigen is degraded and peptides are presented on the B cell surface in complex with MHC-II
- Effector TFH cells move into B cell zone of the lymph node where they are re-stimulated by B cells in an antigen-specific manner and start to express co-stimulatory molecules
- Re-activated effector TFH cells stimulate the B cell to clonally proliferate
- •The re-activated Effector TFH cells secrete cytokines that further activate the B cell and stimulate the Germinal Centre response
What are the germinal center responces
- B cell proliferation
- Differentiation into plasma cells
- Differentiating into memory B cells
- Ig Heavy chain class switching
- Generation of high affinity antibodies
What are the effector functions of CD8+ T Cells
CD8+ cells → Cytotoxic T Lymphocytes (CTLs)
→ Kill infected host cells
How do CTLs kill infected hosts
Exit lymph nodes - enter site of infection - recognise and kill infected tissue cells in an antigen-specific manner
Describe the killing process by CTLS
- Release of lytic grangules containing
-
Perforin - forms a pore in target membrane
-
Granzyme - Serin proteases triggers Apoptosis
- Granulosin - Induces apoptosis
2. Fas-ligand mediated killing
Restoring immune system back to Homeostasis
