Lecture 5 Flashcards
Explain the process by which leukocytes are recruited into tissues.
Resident macrophages recognize PAMPs and DAMPs respond by producing cytokines, such as IL-1 and TNF.
What is “activating the endothelium”?
It is the stimulation of the endothelium at site of infection by IL-1 and TNF-alpha to express adhesion molecules, which bind leukocytes to the endothelium.
What are some chemoattractants involved in chemotaxis?
Chemokines and C5a
What are some of the effector functions of neutrophils and macrophages?
Phagocytosis, production of cytokines, and presentation of antigens to T cells (Macrophage only)
What 3 things are used in bacterial infection?
Neutrophils, Macrophages, and Complements
Why do phagocytes make phagolysosomes?
In order to use enzymes and toxic molecules to kill pathogens safely.
Describe the process of innate immunity vs. viruses
- Virus infects cell
- Resident macrophages and mast cells respond by releasing mediators that increase permeability of blood vessels.
- Allows NK cells to enter bloodstream.
- NK cells release chemical mediators to kill infected cells via apoptosis.
Describe the process of innate immunity vs. parasites
- Parasite infects host
- Macrophages and mast cells release chemical mediators that increase permeability of blood vessels.
- Eosinophils, mast cells, and some basophils enter tissue from the bloodstream.
- Eosinophil granules release toxic chemicals to kill the parasite.
Describe the process of innate to adaptive immunity
- Dendritic cells gather antigen from tissues
- Dendritic cells go through lymphatic vessels to peripheral lymphoid organs, where they present antigens to naive T cells.
- Pathogen-specific T cells are activated.
- Effector T helper cells and effector CD8 cytotoxic cells are made.
- T helper cells costimulate B-cells into plasma cells to release antibodies.
- CD8 T cells and antibodies fight the infection.
What are the types of adaptive immunity?
Humoral adaptive immunity modulated by B-cells.
Cell-mediated adaptive immunity, which is carried out by T cells.
What is the difference between the two types of cell-mediated adaptive immunity?
T helper cells are when there are intracellular microbes that cannot be killed by macrophages, such as bacteria and protozoa. T helper cells enhance phagocytosis.
CD8 T-cells are when there are intracelullar microbes like viruses. Cytotoxic T cells cause apoptosis.
Why do B cells require Th2 cells?
B cells on their own can recognize antigens, but need stimulation from a Th2 cell to become fully activated, which is known as costimulation. This involves a receptor-ligand interaction.
What is the proliferation of B cells known as?
Clonal expansion, occurring after activation/costimulation.
How do B cells differentiate with their antibodies?
They do isotype switching, by changing their heavy chain antibody isotypes.
What is affinity maturation?
It is the selection process that helps B cells create a stronger bond between their receptor and antigen.
What is the first antibody made by any plasma cell?
IgM
What happens to B cells that do not become plasma cells?
They become memory cells to fight off the infection faster in the future.
Describe the makeup of an antibody.
Antibodies are made of 4 polypeptide chains with at least 2 identical antigen binding sites on top.
They have a pair of identical light chains and heavy chains, which is the Fab fragment of the antibody. It is the Y ending and is variable.
What is the constant region of the antibody?
It is the sequences of amino acids that make up the bottom core of the antibody. It determines the class/end function of the Ig antibody.
What is the complementary antigen to a Fab fragment?
epitope
What is the most common Ig?
IgG
Which Ig is needed for B-cell maturation?
IgD
Which Ig activates complements?
IgM and sometimes IgG
Which Ig is found in bodily secretions?
IgA
Which Ig gives a newborn passive immunity?
IgG
Which Ig can cross the placenta?
IgG
Which Ig makes up our blood type antigens?
IgM
What is the rarest Ig?
IgE
What are the 4 ways antibodies can neutralize microbes and toxins?
- Blocking entry of the microbe through the epithelial barriers.
- Blocking binding of the microbe to a cell.
- Blocking binding of a microbe from infecting a neighboring cell.
- Blocking toxins from binding to a cellular receptor.
What is required for a T cell to fully activate?
Costimulation, provided by an APC via receptor-ligand expression. Can also be done by cytokines!
What is the most common APC?
Dendritic cells
What cytokine triggers clonal expansion in T cells?
IL-2
Where do T cells go once they are fully differentiated?
They leave the thymus and go to the secondary lymphoid organs.
What is the first cytokine released by T helper cells?
IL-2
What are all the functions of IL-2?
Needed for clonal expansion of T helper cells, and the function of helper T cells, cytotoxic T cells, B cells, and NK cells.
What cells are the master regulators of adaptive immunity?
T helper cells
What are the two types of T helper cells and their pathways?
TH1: IL-12 secreted by macrophage and DC leads to TH1 differentiation.
TH2: IL-4 secreted by mast cells and T-cells leads to TH2 differentiation.
What is the function of TH1 cells?
TH1 cells produce IFN-gamma and IL-2, which target intracellular microbes via phagocytosis and stimulate IgG production.
What is the function of TH2 cells?
TH2 cells produce IL-4 and IL-5, which stimulate the production of IgE following an allergic/hypersensitivity reaction. Also activates eosinophils in response to helminth infections.
How are regulatory T cells made and what is their function?
CD4 T cells with strong recognition of self antigens can become regulatory T cells.
Function: Inhibit the activation of harmful T cells from differentiating into effector T cells. Harmful naive T cells are ones that have antigenic specificity to self antigens but were not eliminated in the thymus.
Where do T cells carry out their function?
In the peripheral lymphoid tissues.
Why do CD8 cells not attack all host cells?
They can recognize infected cells with MHC Class I separately from host cells with MHC Class I molecules.
What are the two organisms that CD8 cells stop?
Replicating viruses and intracellular bacteria.
What will dysfunction of CD8 cells result in?
An inappropriate immune response or autoimmune disease.
What are the enzymes released by CD8 cells?
Perforin and granzymes
How long does it take for most effector lymphocytes to clear out?
2 weeks
At what time do we typically see the most circulating lymphocytes relative to an immune response?
Around 1 week.
What does it mean if I have high IgM in my primary immune response?
First-time seeing that pathogen
What does it mean if I have high IgG in my primary immune response?
Not the first time seeing the specific pathogen.
When does hematopoeisis begin and where?
5-6 weeks gestation in the fetal liver.
When does the thymus begin developing in a fetus?
5-6 weeks
When do lymphoid cells begin migrating to the thymus?
7-9 weeks gestation
When do secondary lymphoid organs rapidly mature?
Postnatal period
How long does it take for a thymus to fully mature?
1 year
Why is it important for mothers to get vaccinated before and during pregnancy?
Offers babies passive immunity. Mothers should only get Tdap and Flu during pregnancy.
Why are premature babies more susceptible to infection?
The largest amount of IgG crosses the placenta in the last few weeks, which is the source of passive immunity.
What is colostrum and why is it significant?
Colostrum is the first milk produced by mothers postpartum and contains high concentrations of IgA antibodies, which offers GI protection to a baby once ingested.
When are Ig levels lowest in a newborn?
3-6 months
When is IgM at its peak in a newborn?
1 year
When does IgG from a mother expire?
9 months, mostly gone by 6 months.
What is involution?
The process by which thymus tissue begins being infiltrated by fatty tissue soon after birth.
When does our thymus begin losing function?
Soon after birth.
Is T-cell mediated immunity affected heavily by aging?
Not until around 50 years of age.
What causes altered immune response in elderly patients?
Reduced thymus function
Decreased leukocyte count in peripheral lymphoid tissues. Mainly a slightly greater decrease in T cells.
Why are CD4 T cells most affected by aging?
Decrease in cytokine production, which is required for lymphocyte proliferation and receptor expression.
What can occur to mutated lymphocytes?
They can have altered responses
