Humoral Immune Response Flashcards
Components of mature naive B cell
BCR: IgM, IgD, Ig a & Igβ
Co-BCR: CD19, CD81 & CR2 (CD21)
HLA-Class II
CD40
CD20
Two Types of B-2 cells
Follicular B cells are re-circulating B cells: Majority
Marginal B cells reside in the spleen: blood-borne polysaccharide Ags
What signal allows for migration to the Primary Follicle
CXCR5
First Signal Activation
via mIgs
Must cross link 2 or more BCR
signaling occurs through Igα& Igβcytoplasmic tails
phosphorylation of Syk-B
activate PLCy
leads to inositol triphosphate and DAG
activate Ca2+ dependent enzymes and PKC
Also Activation of RAS and RAC lead to ERK and JNK
All three pathways promote Myc, NFAT, NFkB, and AP-1 which increase
protein synthesis
First signal helping activation signals
Ag bound with C3d binds CR2 and enhances signal 1000 fold. Occurs through: Igα& Igβ, CR2 & CD19 cytoplasmic tails (BCR co-receptor complex*)
also can be TLR signaling
Outcomes of First signal
- Increased survival and proliferation
- Interaction with helper T cells (increased B7 expression)
- Responsiveness to cytokines
- Migration from follicle to T cell area (expression of CCR7)
- Secretion of IgM
what are the two types of Second Signals
- T independent signal- would be the mitogen
- T dependent antigen would be the T helper cell and the CD40/CD40L interaction
Both signals cause the B cell to Proliferate and expand
Once activated by T helper cells B cells will begin to?
Change their chemokine receptor expression (class switch) and affinity maturation
Successful re-arrangements are selected/supported by TFH and follicular dendritic cells
What two things do cytokines released by Th cells promote
- induce H chain class switching
- Augument B cell differentiation and proliferation
Cytokine IL-4 causes activated Isotype switching in B cells to?
IgE
Immunity against Helminths and Mast cell degranulation
Cytokine TGF-beta, APRIL, BAFF causes activated Isotype switching in B cells to?
IgA
Mucosal Immunity
Cytokine IFN-y causes activated Isotype switching in B cells to?
IgG?
Opsonization of phagocytosis and complement activation
Switch Recombination occurs in what region of DNA and by what type of antigen
CD40: CD40L ligation and cytokines in T dependant AG binding (protein)
Occurs in a downstream C region, intervening DNA is deleted
Affinity Maturation
Introduction of Point Mutations in the Variable areas of Ig genes
AID converts C’s to U’s
UNG creates the abasic cites
Ape 1 Endonuclease generates nick ( double strand breaks in DNA)
Idea of Somatic Hypermutation,
Where do the majority of Mutations occur in Somatic Hypermutation
Heavy chain and Light chain V regions,
Mutations mainly occur in secondary and Teritary Antibodies
Characteristics of T follicular Helpers
CD4+ and low levels of CD25 expression
Have ICOS/ICOS-L essential for germinal center reaction
What do T follicular helper cells secrete?
IL-21 to facilitate differentiation to plasma blasts
also provide IFN-y and IL-4 cytokine for switching
What is the selection checkpoint?
Where T Follicular Helper cells and Follicular Dendritic Cells choose the B cell with the highest Affinity to the presented antigen for its necessary survival
Rest of cells Apoptosis
Plasma Cell components?
Terminally differentiated effector B cell
Decrease in CD19 and CD20 expression,
Increase in CD27 cell marker
only secrets its class dependent Antibody
Expansion of ER in Cytoplasm
What is the effector of the Humoral Immunity
Antibodies
What is the type of B cells that are T-Independant
B-1 cells respond to T- independent responses (non-protein) Ag in mucosal tissues
Marginal zone B cells (B-2) in spleen recognize blood-borne polysaccharides.
What do T-independent cells secrete
IgM
Considered short lived plasma cells
Memory B cell components
Survive long time without AG
Express high levels of Bcl-2 (anti-apoptotic protein)
surface markers: CD27 and CD45R(O)
Secretory class Ig dependant
Capable of mounting rapid response to similar Ag: Secondary immune mresponse
Antibody feedback
Control mechanism triggered by IgG and when there are too many antibodies for an ending immune response
ITIM - activates SHIP which blocks B cell receptor signaling
what is the effector region of of an antibody and how is it triggered
Fc Region is the effector function but it is triggered by the binding of Ag to Fab(V) region
Aspects of the Primary Response
usually 5-10 days
peak is smaller
usually more IgM vs IgG
Lower affinity
Aspects of the Secondary Response
Usually 1-3 days
peak is larger
More IgG and even IgA or IgE
Higher average Affinity
Antibody Effector functions
Neutralize microbes and toxins
Opsonization and phagocytosis of microbes
Antibody dependent cellular cytotoxicity
Complement activation
- inflammation
- lysis of microbes
- Phagocytosis of microbes with complement fragments
What binds to Fc and what is Fc’s two main functions
FcR
Deliver antibody to inaccesible anatomical sites
link bound antigen to molecules/cells that effect destruction
FC receptor FcyRI (CD64)
High affinity for IgG
On
-Macrophages, neutrophils, eosinophils
Function: Phagocytosis
FcyRIIA (CD32)
low affinity
Macrophages and Neutrophils and eosinophils
Phagocytosis, and cell activation
FcyRIIB (CD32b)
Low affinity
B lymphocytes,DC, mast cells, and neutrophils
Feedback inhibition of B cells
attenuation of inflammation
FcyRIIIA (CD16)
Low affinity
NK cells
Antibody dependant cellular cytotoxicity
FceRI
High Affinity
mast cells and basophils and eosinophils
Activation/degranulation of mast cells and basophils
Neutralization via Ntibodies
Any Ab class can do this
Blocks penetration of microbe through epithelial barrier
Blocks binding of microbe and infection of cells
Blocks binding of toxin to cellular receptor
Waste Management
Clearance of immne complexes
CR1 on erythrocytes bind to C3b or C4b on IC floating through the blood
Take to spleen or liver to drop off IC
IC gets phagocytosed by local macrophage
ADCC anti viral state
NK binds to CD16/ FcR receptor on IgG that locates a surface antigen on host cell
NK kills the cell
IVIG
treats autoimmune/ inflammatory disesses
Ig engages the inhibitory FcR on B cells and DC
Natural Antibodies
IgM and some IgG
Produced by B-1 and marginal zone B cells
reacts with alloantigens (ABO blood type)
IgE mediated reactions
Binds FceR on Eosinophils and mast cells and cause them to degranulate to kill helminth
Mother provides what types of immunity for fetus and babies
Physical barrier for fetus
IgG during pregnancy
IgA through secreted breast milk
What receptor does IgG travel through in the placenta
FcRn due to the low pH causes the tight binding to prevent lysosome destruction
Why are babies at risk for disease after birth
IgG and IgA are just starting to be synthesized
IgM has started only a little bit
Passive Immunity
given antibodies
Prevent disease after known exposure
protect immunosuppressed patients
get rid of ongoing symptoms
Prevent the cause of the disease
ie snake bite
mother giving antibodies to child
Active Immunization
Delayed but more permanent
Produces immunological memory
ie natural exposure
vaccines
Criteria for an effective vaccine
safe
provide protection
cost effective
establish long term immunity
Problems with vaccines
Clinically important epitopes may not be intact in vaccine•
Individual genetics may effect efficacy•
Some individuals may be genetically predisposed to adverse events •
Often work poorly in very young infants or the elderly•
Many do not induce CMI; Ab may not be sufficient•
Allergies to vaccine components
Types of evasions of the Humoral immunity
Antigenic Variations
Inhibition of complement activation
Blocking by Hyaluronic Acid capsule
