Adaptive Immune Response to Intracellular and Extracellular pathogens Flashcards
Cells associated with the innate immune response have an important role in the
early phase of infection.
Activation of NK cells leads to
degranulation: the degranulation kills the infected cell
Antigen specific cytotoxic T cells (i.e., CD8+ T cells) are involved with
eradicating intracellular pathogens
Naïve T cells come into contact with APC in
lymph nodes. Interactions with APC are necessary to activate the T cells.
CD4+ T Cells can Provide Co-stimulation to Activate
CD8+ T Cells
Professional APC’s phagocytose microbe infected cell (often apoptotic)
Microbial antigen is presented in context of MHCI and/or MHCII
CD4+ helper T cells provide co-stimulation needed for activation of naïve CD8+ T cells
CD4+ T Cells Help APC Activate
CD8+ T Cells
Professional APC’s phagocytose microbe infected cell (often apoptotic)
Microbial antigen is presented in context of MHCII
CD40L on the CD4+ T cell binds to CD40, which increases the ability of the APC to present Ag and activate CD8+ T cells.
Upon activation, naïve CD8+ T cells “differentiate” into
cytotoxic T lymphocytes (CTL).
Develop membrane bound granules that contain perforin and granzyme
Ability to secrete cytokines, such as IFN-γ and TNF-α
Activated T cells (now referred to as CTLs) must migrate to site of infection and be retained so that they can express their
effector functions and eradicate microbe- infected cells
CTLs kill targets that express the same
class I-associated antigen that triggered the proliferation and differentiation of naïve CD8+ T cells to become CTLs
MHCI/peptide complex
Accessory molecules: CD8 and LFA-1
Two important components of the granule,
perforin and granzyme.
Perforin helps
granzyme get into the cell.
Granzyme induces
apoptosis in the target cell by activating apoptotic pathways.
How do Fas:FasL interactions eradicate cells infected with an intracellular pathogen?
FasL will activate Fas on a microbe infected cell.
Fas will activate apoptotic pathways in the infected cell.
Are CD4+ T Cells Important?
- They produce IFN-γ to activate Macrophages
Are CD4+ T Cells Important?
- They produce cytokines to provide co-stimulation for CD8+ T cell activation
- They produce cytokines to enhance the activity of APC’s.
Some T cells will be retained as
long-lived memory cells.
The Humoral Immune Response Involves
Antibody Production
B Lymphocytes Produce
Antibodies
But, in order for B cells to produce antibody, they must become
activated. Naïve B cells can NOT produce antibodies.
Soluble antigen is also capable of
activating B cells
Involves crosslinking of immunoglobulin receptor (primarily IgM)
Typically involves antigens with long repeating epitopes (e.g., LPS), but not proteins
Primarily results in the production of IgM
Isotype (i.e., Class) Switching is Dependent Upon
Interactions with T Cells And Cytokines
What is the most prevalent antibody isotype in the mouth?
IgA
IgA Must be Secreted Onto
Mucosal Surfaces
Long lived antibody producing plasma cells and memory B cells take up residence in
bone marrow and secondary lymph nodes (respectively)
Antibodies can opsonize
microbes to facilitate phagocytosis.
Active immunization is know as vaccination.
It induces adaptive immunity, immunological memory and protection.
It involves “live” or killed (inactivated) vaccines.
A wide range of antigenic preparations are in use.
Passive immunization is accomplished by the
passive injection of preformed antibodies.
Live attenuated organisms - Organisms whose virulence has been
artificially reduced. Replication of the vaccine strain in the host reproduces many of the features of wild type infection, without causing clinical disease. Most successful viral vaccines belong to this group.
- Heterologous vaccines
- Closely related organism of lesser virulence, which shares many antigens with the virulent organism. Both cowpox virus and vaccinia virus are closely related to variola virus, the causative agent of smallpox. Widespread use of vaccinia virus as a vaccine has lead to the world-wide eradication of smallpox.
- Live recombinant vaccines –
Using genetic engineering, a gene coding for an immunogenic protein from one organism is placed in the genome of another (such as vaccinia virus). The organism expressing a foreign gene is called a recombinant.
- Live recombinant vaccines –
Using genetic engineering, a gene coding for an immunogenic protein from one organism is placed in the genome of another (such as vaccinia virus). The organism expressing a foreign gene is called a recombinant.
Attributes - live vaccines
Good immune response – induces CMI and antibody, and immunity is long lived. Usually a single dose is all that is required.
Safety - Danger of reversion to virulence. Can’t be used in immunocomprised patients.
Stability - Organisms in the vaccine must remain viable in order to infect and replicate in the host. Sensitive to storage conditions. Maintenance of the cold chain is very important.
Expense – Inexpensive to prepare
Potential drawbacks to these vaccines include: the danger of reversion to virulence and the possibility of causing extensive disease in immunocompromised individuals.
Killed (inactivated) vaccines
Killed vaccines are made when safe live vaccines have not been developed or when reversion to the wild type is common. The organism inactivated with either beta-propiolactone or formaldehyde. These vaccines are not infectious and are therefore relatively safe.
Subcellular fractions - It may be possible to use a purified preparation of a microbial protein as a vaccine. The protein is purified from the culture suspension. These vaccines are safe and fewer local reactions occur at the injection site.
Recombinant proteins - Immunogenic proteins of virulent organisms may be synthesized artificially by introducing the gene coding for the protein into an expression vector, such as E-coli or yeasts. The protein can be extracted from lysates of the expression vector, then concentrated and purified for use as a vaccine. The only example in current use is the hepatitis B vaccine.
Attributes - Killed vaccines
Immune response
poor; primarily an antibody response
- little cell mediated immunity.
response is short-lived and multiple doses are needed.
may be enhanced by the incorporation of adjuvants into vaccine
1. Safety
Inactivated, therefore cannot replicate in the host and cause disease.
Local reactions at the site of injection may occur.
2. Stability
Efficacy of the vaccine does not rely on the viability of the organisms.
These vaccines tend to withstand more adverse storage conditions.
3. Expense
Expensive to prepare.