Humoral Immune Response 1 Flashcards
Humoral Adaptive Immune Responses-
- extracellular
- meditated by antibodies
- produced by B lymphocytes
- Principal defense mechanism against microbes with capsules rich in polysaccharides and lipids
Thymus-independent antigens (TI): Non- protein antigens
• Noisotype-switching
• No affinity maturation
-mainly IgM
-responders-marginal zone B cells and and B-1 cells
-These antigens activate B cells by pattern recognition receptors
Thymus-dependent antigens (TD): Protein antigens processed in APCs
-recognized by helper T cells • help B cell activation • heavy chain isotope switching • affinity maturation • Protein antigens with no helper T cell: weak or no antibody response -• B cell required direct contact with TH cell • Majority responders: follicular B- cells (B2 cells)
pattern recognition receptors
✓Type I (TI-1) – lipopolysaccharide
✓Type 2 (TI-2) – highly repetitious molecules (bacterial flagella)
Immunoglobulins with Thymus independent antigens
IgM
Thymus dependent immunoglobulins
IgM ,IgA,IgE,IgG
Role of the innate immune system in B cell activation (TI)
-Microbes become coated with C3d
▪ B-cell have C3d receptor CR2 or CD21
▪ Engagement enhances antigen-dependent activation of B cells
▪ B cells also express Toll- like receptors
B cell Activation (TD): signal 1
Membrane bound antibody have short cytoplasmic tails
▪ Membrane Ig must be associated with B-cell receptor
• Ig-α/Ig-β
▪ B cell co-receptor
- CD19: cytoplasmic tail for signal transduction • CR2: receptor for C3d (from complement)
- TAPA-1: transmembrane molecule
▪ Inhibitory co-receptor
- CD22: cytoplasmic tail for signal transduction
* Contains ITIM (Immunoreceptor tyrosine-based inhibitory motif)
ITIM (immunoreceptor tyrosine inhibitory motif)
- Associated with CD22
- Functionsto deactivate B cells – negative regulation
- Importantin preventing autoimmunity
TD-B cell activation: Tfh cells
- depend on costimulatory ICOS
- ▪ Secrete IL-21
In germinal center: class switching and affinity maturation
IL-21
antibody production
proliferation
ICOS-L (CD275)
- Activation
- follicular helper T cells in antibiotic responses
• 3 events in germinal centers
-arise within 7-10 days after initial exposure to thymus-dependent antigen in lymph node
❖Affinity maturation
✓Result of somatic hypermutation ❖Class switching
❖Formation of plasma and memory B cells
Affinity Maturation
- increases with prolonged or repeated exposure
- Result of somatic hypermutation of Ig genes
- Enzyme activation-induced cytidine deaminase (AID) is required
Class Switching (TD)
▪ Enzyme AID is required ▪ Dependent on cytokines to switch from IgM to other isotypes • Thymus-dependentantigens • Interaction of CD40 on B cell and CD40L on T cell
▪ X-linked hyper-M syndrome:
• TH cells don’t express CD40L, patients only produce IgM
✓No memory cell populations, no germinal centers
Humoral response primary
- lasts 5-10 days
- smaller response peak
- IgM > IgG
- lower avg affinity , more variable
- TD or TI antigen
Humoral response - secondary
-1-3 days long lag after immunization
-larger peak response
-increase in IgG
-Affinity maturation
TD antigen only
Humoral regulation
▪ Antibody feedback
▪ Antigen-antibody complex forms
▪ Fc tail binds to FcgRIIB receptors on B cells
Follicular B cells (B-2 cell) -
- Most common type of B cell. Found mainly in the lymphoid follicles of secondary lymphoid organs (SLOs) and circulating in blood. They are responsible for generating the majority of high-affinity antibodies during an infection
Marginal zone B cells
Found mainly in the marginal zone of the spleen and serves as a first line of defense against blood-borne pathogens. They undergo mainly T cell- independent activation
B-1 cells
Predominantly populate the peritoneal and pleural cavities. Generate natural antibodies (produced without infection) against mucosal pathogens. T cell- independent activation.
