Exam 3 - Objectives Flashcards
(78 cards)
List the major differences between mucosal immunity and systemic immunity (in the skin, for example)
Mucosal:
Many active immune cells present
No inflammation - inflammation can be a sign of an autoimmune disease
Systemic:
Not many immune cells present
Inflammation can occur - helps to bring immune cells to the infection
Describe the basic structure and chemical features of mucin that allow it to protect mucosal tissue
Huge glycoproteins composed of subunits disulfide-bonded together
Has sialic acid as a glycan (sugar)
Polyanionic surface that can bind positively-charged defensins, antimicrobial peptides, and secretory IgA
Have N-terminal globular domains -allows them to disulfide bond together.
Describe the organization of Peyer’s patches, being sure to identify abundant cell types within them and the function of the M cells
Peyer’s patches are found only in the small intestine.
They vary in size and contain between 5 and 200 lymphoid follicles with germinal centers, interspersed with T cell areas that also include dendritic cells.
M cells within the Peyer’s patch brings in antigen from the gut.
There are efferent lymphatics that take the antigens taken in to the mesenteric lymph nodes.
Peyer’s patch release CCL21 and CCL19 that bind to CCR7 expressed on naive T and B cells causing them to leave the lymph vessel and enter secondary lymphoid tissue.
Associate intraepithelial lymphocytes (IEL) with the gut, and describe what their characteristics are and how abundant they are
IEL are dispersed in the epithelial layer of the gut. They are a type of CD8+ cytotoxic T cells that are activated by antigen and loaded with granules. There is a mix of alpha beta and gamma delta TCR with limited specificity. They express CCR9 and alphaE:beta7 integrin that allows them to bind to E-cadherins of the intestinal epithelial cells. There is one IEL for every 7-10 epithelial cells.
Identify chemokine and intgrin receptors expressed differentially on IEL, lamina propria lymphocytes, and skin lymphocytes that are responsible for these cells homing to the correct body site
IEL’s express the chemokine receptor CCR9 and alphaE:beta7 integrin that allows them to bind to E-cadherins of the intestinal epithelial cells.
Lamina propria lymphocytes (B and T cells) press CCR9 and alpha4:beta7 inegrin that binds to MAdCAM-1 mucosal addressin.
Skin homing lymphocytes express CCR4 and alpha4beta1 integrin
List the four known cytokines that cause plasma cells located in the gut to isotype switch to IgA production
TGF-beta drives isotype-switching to IgA (Treg and TFH).
TGF-beta cooperates with BAFF and IL-10 which are produced by dendritic cells scattered throughout the lamina propria (IgA1).
APRIL, a proliferation-inducing ligand, produced by colon epithelial cells (IgA2) and dendritic cells.
Identify the two main functions of dimeric IgA in the mucosa
Neutralization and transport of toxins
Describe how the immune system seems to compensate for a lack of IgA in “selective IgA deficiency”
Imune system compensates by over-producing IgM and exporting IgM across mucosa (J-chain via poly-Ig receptor)
Describe how Th2 responses in mucosal tissues are specifically effective at ridding the body of helminth infections, including the specific functions of Th2 cytokines Il-4, Il-5, and Il-13
Naive CD4 T cells activated during helminth infection differentiate to become Th1 or Th2 effector cells.
Th2 cells produce IL-13, which increases production of epithelial cells in the infected tissue - increase number of goblet cells produces more mucus and the increase in enterocytes increases their rate of turnover in the epithelium.
Th2 cells produce IL-5 which recruits eosinophils to the infected tissue and activates them - activated eosinophils acquire granules containing MBP and parasite-specific IgE bound to FceRI - this degranulation kills helminths.
Th2 cells produce IL-9 which recruits mast cells to the infected tissue. Mast cells bind parasite-specific Ige - degranulation causes muscle spasms and diarrhea that expels helminths.
Define primary immunity and secondary immunity
Primary immune response is the adaptive immune response that follows a first exposure to antigen. This can be slow, but it leads to the generation of memory cells with high specificity to the antigen for future attacks.
Secondary immune response is the adaptive response that occurs the second time a antigen is encountered. This response is quicker because it causes reactivation of memory cells. B and T cells are involved.
Describe the timeline of an adaptive immune response, including the amounts of effector T cells and antibody. Also be able to include the relative timing of first infections, aborted infections, and secondary infections
1 to 2 weeks after first infection, effector T cells and antibody are made. This was able to terminate the first infection. Effector T cells were soon inactive, but antibody remained to protect against further exposure (aborted infections). After about a year, antibody has decreased and an infection could occur again. If a second exposure occurs, the response will be much quicker as the memory cells will quickly respond and produce antibody.
Explain three ways that memory is maintained (antibody, T memory, B memory cells) and the cytokines needed for each
Antibody is maintained by plasma cells in bone marrow nursed by stromal cells secreting IL-6.
Memory CD4+ and CD8+ T lymphocytes rely on IL-7 and IL-15 for maintenance.
Memory B cells have isotype-switched high-affinity BCR and express CD27 which distinguishes them from naive and effector B cells.
These cells/molecules will recognize the specific antigen that they were created for quickly and be able to get rid of it before it causes a huge infection.
Explain how pre-existing antibody prevents naive B cell activation
In a primary response, antigen will activate a B cell and it will become an antibody-producing plasma cell creating low-affinity IgM antibodies.
In a secondary response, the antigen receptor and the inhibitory Fc receptor FcgRIIIB1 on a naive B cell can be cross-linked by a pathogen coated in IgG that delivers a negative signal that prevents the activation of the cell.
Memory B cells do not express the Fc inhibitory molecule, so they will become activated and make IgG.
Explain “original antigenic sin”
An occurrence in which the body will only respond to the original antigens of a pathogen, and has no response mechanism (sinning) to antigens that are rapidly changing. The memory response is to a mutated version of the antigen that no longer exists within the environment due to the pathogen rapidly changing.
Describe how RhoGAM protects agains hemolytic disease of the fetus and newborn
When the father is RhD+ and the mother is RhD-, the baby can be born with hemolytic disease.
In a first pregnancy, RhD+ erythrocytes can cross the placenta and stimulate the mother’s immune system to create anti-RhD antibodies. These will cause little harm to the fetus as they will be IgM and can’t cross the placenta.
In a secondary pregnancy, IgG antibody can be created and transported across the placenta by FcRn and can cause disease in the fetus.
If the mother had not begun created the IgG antibody in the secondary pregnancy, she could get infusions of RhoGAM. This coats fetal erythrocytes with IgG and prevents the mother from making her own that will attack the erythrocytes.
Identify the 4 general requirements necessary for a “good” antigen (an antigen that will be immunogenic)
- Must have a high molecular weight (at least 100,000 daltons)
- Should have high molecular complexity (like proteins of 20 or more amino acids)
- Foreignness = taxonomically distant from the host
- Inflammatory: inducing inflammation by possessing TLR ligand or some other sort of ligand that a pattern recognition receptor in our body induces or also by inducing cell stress that would give a danger signal to our immune system
Identify 4 mechanisms that may be responsible for the ability of adjuvants to enhance the immune response to vaccination
- Complex with the antigen to increase its size
- Trap the antigen in material that allows it to be relatively indigestible
- Lipid emulsion - antigen slowly leaks out (causes adaptive immune response rather than innate)
- Hyper-activate the innate immune cells (like macrophages that will initiate inflammation that will cause adaptive immune cells to be activated)
Identify the types of vaccines that are currently in use to immunize individuals against viral infections and bacterial infections
Virus:
Killed/inactivated virus
Live-attenuated virus
Subunit vaccine
Bacteria:
Live-attenuated bacterial vaccines
Subunit (toxoid and purified capsular polysaccharide from different bacterial organisms)
Combination vaccine
Describe the process of creating/inducing live-attenuated viral vaccines
- The pathogenic virus is isolated from a patient and grown in human cultured cells
- The cultured virus is used to infect monkey cells
- The virus acquires a variety of mutations that allows it to grow well in monkey cells
- The virus is not longer grows well in human cells (it is attenuated) and can be used as a vaccine
In general, identify how 𝛄δ T cells, NK cells and NKT differ from classic αβ T cells in their antigen recognition
ab T cells recognize peptide in MHC class I or II and use Cd1a,b, and c. gd T cells recognize a variety of antigens without classical class I or II. Use class-1 like, but can recognize without presentation. NK cells activating or inhibitory ligands. Lack of MHC class I will cause them to kill. NKT cells can recognize class-1 like molecules such as CD1d. These present lipids.
Specifically identify the antigen that V𝛄9:Vδ2 T cells bind, where these T cell populations are located in the body, and what their general effects function is once activated
V𝛄9:Vδ2 T cells: dominants adult human blood 𝛄δ T cells.
Contain the same V gene segments and variable D and J gene segments
Respond to a range of pathogens
Antigen recognized is NOT peptides, but phosphoantigen
Most (80%) can’t enter secondary lymphoid tissues and instead home to inflamed/infected site by using CCR5
Act as cytotoxic T cells to kill infected cells
Highly activated:
Capable of antigen presentation
Begin expressing MHC class II, B7, and CD40L
Increase MHC class I expression
Gain CCR7 expression to allow migration to lymph nodes and there present antigen to alpha beta T cells
Identify the CD protein expressed on the surface of all human NK cells
Mononuclear cells that lack CD3, but express CD16 and CD56 on their cell surface
Some will lack CD16, but all will have CD56
Compare and contrast NK and Tc target cell recognition and killing mechanisms
NK and Tc cells kill in a similar manner.
NK cells use inhibitory and activating receptors to find target infected cells or tumor cells that need to be killed. They lack CD3 and TCR proteins. They are an innate immune cell. They detect the loss of MHC class I on the infected cell. Can kill by signaling through activating receptors that detect stress ligands. All NK cells express NKG2D and CD56.
Describe the “ligand” for NK cell receptors (in general) and how the signals through these receptors are interpreted by the NK cell
HLA-E inhibitory ligand whose presence depends upon HLA-A,B, and C. "Self-MHC class I"