EX2 Immunology 2 Flashcards
review: are cell players and protein player components of innate immune system present before or after the body encounters an invader?
BEFORE
cell players= neutrophils, macrophages, NK cells
protein players= cytokines, chemokines, complement system proteins
review: what responds to PAMPs and DAMPs and what do they do
macrophages and mast cells
they release mediators that increase blood vessel permeability
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.
(after macrohpages recognize PAMPs, DAMPs- release these cytokines)
describe process of leukocytes getting into tissue
- initla binding is slow so leukocytes roll along endothelium
- binding strengthens and leukocyte firmly attaches to endothelium
- migrates through endothelial cells and enter tissue
- follows chemoattractants in tissue ( like chemokines and C5a) that guide to the pathogens
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 needed for bacterial management?
*Neutrophils, *Macrophages (these are the 2 leukocytes needed) and Complements ( for ingestion and destruction)
what are phagosomes adn what do they become
neutrophils and macrophages that ingested pathogens into vesicles
become phagolysosomes then exocytose soluble debris
how and why do phagocytes make phagolysosomes?
phagosomes fuse with lysosomes
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( lymph nodes) , 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.
describe overview process of adaptive immunity
dendritic cells gather antigen from tissue
send to peripheral lymph nodes
dendritic cells present antigens to native T cells in LN
pathogen specific T cells are activated
1- effector CD4 t cell act and pathogen specific b cells are activated and differentiate into plasma cells and form antibody to go to infection
2- effector cytotoxic CD8 t cell go to 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. (2 types)
What is the difference between the two types of cell-mediated adaptive immunity?
(CD4) 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 (macrophage activation). eliminate phagocytosed microbes
CD8 T-cells defend against intracelullar microbes like viruses that replicate in host cells . Cytotoxic T cells cause apoptosis by releasing mediators.* kill infected cells and eliminate resevoirs of infection*
what is humoral adaptive immunity
defends against extracellular microbes like bacteria, their toxins, and large parasitic worms
mediated by secreted antibodies by B lymphocytes
*block infections and eliminate extracellular microbes
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
what is costimulation
Th2 cells producing cytokines and interact with B cell via receptor ligand interaction to activate the B cell
(process of Th2 and B cell working together)
What is the proliferation of B cells known as?
Clonal expansion, occurring after activation/costimulation (once activated)
what is isotype switching and what is it used for
producing different heavy chain antibody isotypes
used by most b cells to continue differentiating
What is affinity maturation? what cells undergo this?
It is the selection process that helps B cells create a stronger bond between their receptor and antigen.
( b cells that continue differentiating by isotype switching)
what do plasma cells do
secrete antibodies
What is the first antibody isotype made by any plasma (B) 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.
what do memory cells do
can lay dormant for years
when memory cells become activated they can mount a rapid response to subsequent exposure to a specific pathogen
(put it together)
describe the Naive B cell activation
- antigen specific Th2 and B cells recognize their specific antigen
- Th2 cells help B cells become fully activated
- some B cells immediately become plasma cells and secrete IgM antibody
-most continue the differentiation process
(isotyope switching)
how are immunoglobulins classified
based on their ROLE in humoral immunity
Describe the makeup of an immunoglobulin (antibody).
Imglob 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
what is the Fab fragment
what makes the Y shape of immunoglobulin- the identical light and heavy chain on ends that go out to the side
variable region
antigen binding site
What is the constant region of the immunoglobulin (antibody)
It is the sequences of amino acids that are the same among antibodies of that class of Ig
It determines the class/end function of the Ig antibody.
(bottom core and first half of Y endings)
what is the variable region of an Ig
amino acid sequences vary from antibody to antibody
contain the Fab fragment (antigen binding sites)
what allows recognition of epitope
the variable amino acids allow the Fab region of the antibody to recognize its epitope
What is the complementary antigen
epitope
B lymphocytes can divide forming ______ but ______ can occur during course of immune response
clones with identical antigen binding receptors, but class switching can occur
characteristics of IgG
75% total circulation
- ONLY Ig that can cross placenta
- displays antiviral, antitoxin, antibacterial properties
- provide newborn passive immunity
- activates complement and binds to macrophages
characteristics of IgA
15% total circulation
-predominant Ig in body secretions ( saliva, nasal, resp, breast milk)
- protects mucus membranes
- prevents viral and bacterial att. to epithelial cells
characteristics of IgM
10% total circulation
- forms natural antibodies (ABO blood antigens)
- found mostly in early immune responses
- activates complement
characteristics of IgD
0.2% total circulation
- found on B lymphocytes
- needed for B cell maturation
characteristics of IgE
0.004% of total circulation
- binds to Fc receptors on mast cells and basophils
- involved in parasitic infections, allergic, and hypersensitivity reactions
Name the five Isotyopes of Antibody (immunoglobulin) from greatest to smallest percent circulation
IgG (75)
IgA (15)
IgM (10)
IgD(0.2)
IgE(0.004)
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? and which Ig are responsible?
- Blocking entry of the microbe through the epithelial barriers.
- Blocking binding of the microbe and infection to a cell.
- Blocking binding of a microbe from infecting a neighboring cell.
- Blocking toxins from binding to a cellular receptor.
IgG and IgA
what is the mucosal immune system
plasma cells activate IgA and release through mucosal epithelium into lumen of intestine
first line of defense against microbial and dietary antigens
describe the two settings T cells defend against intracellularly
1- pathogens that survive adn sometimes replicate into the vesicles (phagolysosomes) after being ingested by macrophages
- CD4 activate infected macrog=phages to kill pathogen
-helper t’s further differentiate into type 1 or type 2 t helper cells
2- a virus that binds to receptors on non phagocytic cells and infects and replicates in the cells cytoplasm
- CD8 cytotoxic T cells, aka CTLs, kill cell infected with viruses and intracellular bacteria
look at ppt slide 33
what are CTLs
CD8 cytotoxic T cells
What is required for a T cell to fully activate?
Costimulation, provided by an APC via receptor-ligand expression. Cytokines also help fully activate naive T cell
What is the most common APC?
Dendritic cells
what do naive T cells recognize
MHC peptide antigens on APC, which is typically the dendritic cell
what class of MHC proteins do CD4 and CD8 recognie
CD4 recognized class II MHC
CD8 recognizes class I MHC
What cytokine triggers clonal expansion in T cells?
IL-2
Where do T cells go once they are fully differentiated? and what do they do?
They leave the thymus and go to the secondary lymphoid organs to travel to infection to carry out effector function.
once fully activated, T cells (CD4>CD8) makes IL-2, responds to this Il-2 and proliferates(clonal expansion)
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 function of T helper cells, cytotoxic T cells, B cells, and NK cells.
What cells are the master regulators of adaptive immunity and why?
T helper cells-CD4
initiate humoral and cell mediated immunity
what does CD4 do once activated
secrete cytokines that activate and regulate B cells, cytotoxic T lymphocytes, NK cells, macrophages, and others
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?
CD4 T cells with strong recognition of self antigens can become regulatory T cells.
Regulatory T cells will then leave the thymus to circulate in the body
what do regulatory T cells do
Inhibit the activation of harmful naive T cells from differentiating into effector T cells.
this process occurs in peripheral lymphoid tissue
what are harmful naive T cells
cells that were not eliminated in the thymus despite having antigenic specificity to self antigens
Where do T cells carry out their function?
In the peripheral lymphoid tissues.
what are the CD8 effector functions
monitor ALL cells in the body and destroy any that threaten homeostasis
Why do CD8 cells not attack all host cells?
They can recognize infected cells with MHC Class I separately from solitary class 1 MHC molecules on uninfected host cells- preventing destruction of self
how do CD8 cells destroy
via cytolytic enzymes and triggering intracellular apoptosis
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 and what do they do?
Perforin and granzymes
perforin facilitates granzymes entry into cytosol and granzymes activate apoptosis
review check-
innate and adaptive immunity used for bacteria
phagocytosis- neutrophila nd macrophages-complement activated
antibody- IgM, IgG, and IgA (on mucosal surfaces)
review check-
how do innate and adaptive immunity protect against viruses
natural killer cells
neutralization of free virus- IgM, IgG, IgA(mucosal surfaces),
antibody dependent cellular cytotoxicity: IgG
CD8 cytotoxic T cell
review check-
how do innate and adaptive immunity work against large parasites (worms)
eosinophils and mast cells
antibody- IgE when bound to receptors on eosinophils and mast cells
what happens after antigen is eliminated
- immune response declines
- effector lymphocytes die by apoptosis
- homeostasis restored
- antigen specific cells that survive are responsible for memory
(these memory cells are effector cells that respond quicker than naive lymphocyte when sub. infec. occur)
How long does it take for most effector lymphocytes to clear out?
2 weeks (apoptosis occurs around here-homeostasis restored)
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 antigen for 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
after lymphoid migration to thymus in weeks 7-9 development starts and these organs are fianlly developed at birth but are small for these first several weeks and mature rapidly once exposed to microbesin 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 (via IgG) .
This protection continues for first few months of life as newborn works to develop own immune system
mothers should only get tdap and flu vaccine 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 local immunity to infants GI tract once ingested.
When are IgG levels lowest in a newborn?
3-6 months
IgA levels in newborn and child
starts very low, becomes newly synthesized but very low through 1 year- keeps increasing through about age ~8
(my interpretation of graph)
When is IgM at its peak in a newborn?
1 year (plateaus)
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.
less new T cells produced by the thymus as we age
Is T-cell mediated immunity affected heavily by aging?
Not grossly impaired until around 50 years of age.
What causes altered immune response in elderly patients?
Multifactorial response:
- Reduced thymus function
- Decreased leukocyte count in peripheral lymphoid tissues.
- Slight decrease in number of T cells in proportion to other lymphocytes
- Decrease in CD4 and CD8 cells
Why are CD4 T cells most affected by aging?
Decrease in cytokine production that helps stimulate lymphocyte proliferation and receptor expression needed to interact with cytokines.
What can occur to lymphocytes in elderly?
They can have altered responses to antigen stimulation
they can be unresponsive to activation
