L18 B lymphocytes and Antibodies Flashcards
What are the 4 classes of cytokines
- Innate immunity ones:
- Interferons and early pro-inflam cytokines - Adaptive cytokines:
- help with T and B cell differentiation and activation of cells - Chemokines:
- neutrophil migration (a) and allergic inflammation (B)
4.Haematopoietic:
CSFs + others which help proliferation of bone marrow lineages
What is the basic structure of antibody (Y-shaped glycoprotein when active, T when unbound)
Bound internally by disulphide bonds
2 x light chains + 2x heavy chains.
Both chains have a hypervariable region at the tip (50% for LC, 25% for HC)
Both chains have constant region as the remainder, with the HC constant region forming
- hinge region for flexing of the arms
- complement binding region for activating complement
- base: Fc region for binding to receptors on macrophages
Describe the process of B cell clonal activation
- In 2ndary lymphoid organs naive b-cells that have committed to a specific and individual shape of surface immunoglobulin interacts with antigen presented
- The b cell with the most affinity binds to it, phagocytoses and processes peptide then goes to present it to the helper CD4 T cell on class 2
- T cell sends activating cytokines and costimulation of b cell CD40 with T cell CD40L
- proliferation and differentiation into
a) Plasma cells which create soluble antibodies to circulate in the blood stream
b) Memory cells which are longer lived and populate the 2ndary lymphoid organs
What are the main effects of antibodies and how (5)
- Blocking and neutralising
- attachment and entry sites for viruses and parasites
- site of action for toxins eg. tetanus and diptheria
- bacterial flagella to immobilise and decrease viability
2. Agglutination: clumping antigen/pathogen together to assist phagocytosis = size dependent on ratio of antibody to antigen with larger clumps associated with complications
3. Opsonisation of pathogens for enhancement of phagocytosis (Fcgamma receptor on macrophage)
4. Antibody dependent cellular cytotoxicity: Large granular leukocytes can bind to antigen coated tumour/infected cell and kill them via short range toxins
5. Complement activation through classical pathway through exposure of complement binding site when antibody is activated
How does interferon IFN-a and IFN-B inhibit viral infections
It is released by virus infected cells to
1) tell nearby cells to impair ribosome transcription of viral proteins to produce transient viral resistance
2.tells natural killer cells to actively recognise and kill infected cells
Describe the classical pathway of complement (3)
- Antigen-antibody complex results in the formation of the C3-convertase from early complement components
- this leads to enzymatic cleavage of C3 to
a) C3a which is involved in vasodilation (via stimulating degranulation of mast cells) and chemotaxis
b) C3b which is involved in opsonisation - also receptors on macrophages - C3b can also form a focus for assembly of late complement components into membrane attack complex which causes cell lysis
What does class switching of antibodies in early life mean
It means that the first time you meet an antigen, the primary response has a equal peak of IgM then IgG.
However secondary response of memory cells leads to the dominant IgG peak and little IgM so there is a class switch from IgM to IgG
What is the heavy chain, size, location and function of IgM
- mu HC, in blood and lymphatics because its the largest (pentamer)
Function: defence against blood borne spread of infectious organisms. eg. bacteria
- first in primary response
- effective agglutinator
- efficient complement activator
What is the heavy chain, size, location and function of IgG
70-75%
- Gamma, in blood, extravascular spaces, placenta, small monomer
Function:
- secondary response
- good complement activator
- good antitoxin and virus binding
- high affinity for macrophages in opsonisation
What is the heavy chain, location and function of IgA
15-20%
- Alpha, predominant in sero-mucus secretions
Function: Protection of external body, gut, respiratory and GU tracts
What is the heavy chain, location and function of IgD
Trace amounts
- Delta: (found on surface naive B cells)
Function: receptor for antigen binding to activate naive B cells
What is the heavy chain, size, location and function of IgE
trace amounts
- Epsilon: FcE receptor bound strongly to mast cells (differentiated basophils) found in tissues
Function: Parasitic infections and allergies.
Allergens binding to mast cell- associated IgE activates processes that lead to symptoms of allergy or asthma.
