Flashcards in Ch6: Host Response to Infection Deck (106):
Primary immune response has a lag until when?
Before antibodies are detected
Which immunoglobulins are detected first by primary adaptive immune response?
Low affinity IgM
Germinal center reactions yields what?
Increased affinity and isotype switching (IgG)
The secondary response to an infection is different how from the first?
Stronger memory response
Vacciniation is defined how?
Attempt to induce a primary response to a pathogen so that natural exposure will induce, strong rapid clearance
What antibody is produced more at beginning first exposure?
What antibody is produced at far greater amounts upon repeat exposure?
Describe the 3 steps of primary response
1. Naive B cell binds pathogen
2. Activated B cell becomes anti-body producing plasma cell
3. Plasma cell produces low affinity IgM antibodies
Describe the 3 steps of secondary response in Naive B cells?
1. Binds pathogen coated with specific antibody
2. Negative signal given to naive B cell to prevent its activation
3. NO production of IgM
Describe the 3 steps of secondary response in memory B cells
1. Memory B cell binds pathogen coated with specific antibody
2. Memory B cell is activated and becomes an antibody-producing plasma cell
3. Production of high affinity- IgG, IgA, and IgE antibodies
How exactly does the negative signal to naive B cells occur?
When IgG antibodies toward a specific antigen simultaneously cross-link the B cell
receptor of a naïve B cell and the inhibiting Fc receptor (FcgRIIB1), activation of the naïve
B cell does not occur.
Memory B cells preferentially respond when?
Host has previously encountered antigen
What is the method efficiently recognizing antigenic epitopes?
You only respond to epitopes that you were exposed to last time. As new epitopes are involved, they aren't responded to until the cell has no choice.
Mucosal layers are found where? 8
1. lacrimal gland
2. salivary gland
3. mammary gland
5. urogenital tract
7. GI tract
8. Respiratory tract
Mucus contains what? 4
That act as what
proteoglycans, peptides, and enzymes
act as barriers to infection
The mucosal immune system is made up of what? (2)
Mucosal-associated lymphoid tissues and draining lymph nodes
What is secondary lymphoid organ of small intestine?
Peyer's patches contain a follicle of what type of cells?
What transports antigens across the epithelial layer in Peyer's patches?
Microfold (M) cells
Isolated lymphoid follicles in Peyer's patches are typically composed of what?
B cells beneath a single M cell
What is produced in intestine crypts for immune response
Explain how antigen elicts a response in mucosal sites?
1. M cells take up antigen by endocytosis and phagocytosis
2. Antigen is transported across M cell in vesicles and released at basal surface
3. Antigen is bound by dendritic cells
4. Dendritic cells activate T cells
What special skill do dendritic cells have in mucsal tissues?
Can extend process between two epithelial cells to capture antigen (independent of M cells)
In MALT, what cells exist right below epithelial surface? 6
CD8 T cells,
CD4 T cells, plasma cells, DCs,
macrophages, and mast cells
Mucsal surfaces are the sites for localized production of what immunoglobulin?
And the transport of these through what?
Are neutrophils found in mucosal sites?
What is different about macrophages and DC's in MALT?
do not express TLRs
don’t produce inflammatory cytokines
don't establish strong Th1-type immunity
Attraction of naive B and T cells to Peyer's patches involves what chemokines?
What receptor needs to be on naive lymphocytes?
Chemokines: CCL21 and CCL19
Naive lymphocytes enter Peyer's patches through what?
What happens to naive lymphocytes that do not find their antigen in MALT?
Leave and enter mesenteric lymph node
What happens to naive lymphocytes that don't find their antigen in MALT or lymph node?
Return to circulation via efferent lymph
What happens if cell interacts with antigen in Peyer's patch?
Proliferate and differentiate
Activated lymphocytes leaving Peyer's patches express what?
What is it looking for?
Through what interactions?
CCR9 chemokine receptor
CCL25:CCR9 chemotaxis back to mucosal sites
What is the name of cytotoxic T cells that intercalate into epithelial layer?
IEL's (intraepithelial lymphocytes
How do IEL's know where to position themselves?
use chemokine receptors and adhesion
molecules to position themselves between epithelial cells.
IEL's contain intracellular granules and can express which type of T cell receptor besides CD8?
Alpha:Beta OR gamma:delta T cell receptors
What are 5 ways IgA can interact with pathogens in epithelium?
1. Export toxins and pathogens from lamina propria while being secreted into lumen
2. Bind and neutralize antigens in endosomes of epithelial cells
3. Secreted IgA can bind toxins/pathogens in lumen
4. Secreted IgA can bind pathogen on M cell surface and take it to lymphoid tissue
5. Secreted IgA can pick up antigen in endosomes of M cells and take it to lymphoid tissue
Process that IgA molecules go through to transport from basolateral side to apical surface?
What is relative health of someone with IgA deficiency?
Compensation from other isotypes at mucosal sites
What is most common immunodefciency?
Selective IgA deficiency
3 anatomical features of MALT?
1. Intimate interactions between mucosal epithelial and lymphoid tissues
2. Discrete compartments of diffuse lymphoid tissue and more organized structures such as Peyer's patches, isolated lymphoid follicles, and tonsils
3. Specialized antigen-uptake mechanisms provided by M cells
2 effector mechanism features of MALT?
1. Activated effector T cells predominate always
2. Plasma cells are in tissues where antibodies are needed
Streptococcus pneumoniae exists in many different what?
Based on what?
Capsular polysaccharide expression
Do antibodies recognize more than one serotype of Strep pneumoniae?
No, only one
What do antibodies recognize in influenza virus?
Hemagglutin surface protein
How does influenza continue to get past immune system?
RNA genome of influenza virus undergoes an error-prone replication process, and
changes in hemagglutinin allow for the generation of a new strain of influenza virus that antibodies don't recognize
Why are influenza vaccines updated annually?
What is antigenic shift?
phenomenon that occurs when reassortment of the
individual influenza virus RNA segments occurs
Describe antigenic shift using influenza
A secondary host (different animal) gets infected with human and avian strain of a virus. Recombination between these two viruses occur producing a virus with a diferrent hemagluttin.
Key characteristic of pandemic influenza virus?
What method do protozoans such as Trypanosoma brucei use to evade host immunity?
Alteration of surface antigens using gene rearrangements
Tryapnosome genomes encode how many genes for Variagle Surface Glycoproteins?
What prompts a trypanosome to switch its VSG?
When the dominant form is cleared by the immune system
Herpes virus remains latent where?
Why does the herpes virus select nerves to reside?
Neurons don't make enough CTL response
When does herpes virus emerge from latency?
When immune system is weakened.
How does human cytomegalovirus evade immunity?
Has 10 proteins that can interfere in different ways to prevent recognition by CTL's and NK cells
What does the HCMV protein UL142 do?
Downregulates the expression of MIC-A and MIC-B ligands for NKG2D
What do superantigens do?
Bind the alpha chain of class II MHC and Variable beta chain of the TcR without using binding cleft.
Superantigens can activate what percentage of T cells?
Superantigens have what effect?
Turn on T cells and create an inflammatory cytokine response that can lead to systemic shock.
3 main types of mechanisms of immune evasion?
1. Antigenic variation (viruses and bacteria)
2. Inhibition of complement activation (bacteria)
3. Resistance to phagocytosis (bacteria)
Epstein Barr virus has what mechanisms of evading host immunity? (2)
1. Inhibition of antigen presentation through inhibition of proteasomal activitiy
2. Production of IL-10 which inhibits macrophage and dendritic cell activation
Pox virus has what mechanism of evading host immunity?
Inhibition of effector cell activation by production of soluble cytokine receptor
How to measure B cell in vivo?
Serum Ig levels and specific antibody levels
Induced antibody production in response to antigen
How to measure T cells in vivo?
T-cell proliferation in response to tetanus toxoid
Why can antibodies be diagnostic tools?
Antigen binding site can be manipulated.
What is a polyclonal response?
Toward all epitopes of a protein through multiple B cell clones
What is a monoclonal response?
Toward a single epitope using ONE B cell clone
How are antibodies used to kill tumors? (3)
1. Tumor specific antibody binds to tumor cell and is recognized by NK cells with Fc receptors that will kill the tumor cells.
2. Tumor-specific antibody conjugated with toxin binds to tumor cell. Conjugates are internalized and kill the cell.
3. Tumor specific antibody conjugated to radio isotope binds to tumor cell. Radiation kills the tumor cell and the neighboring tumor cells
Antibodies can cause agglutination by their ability to do what?
What is equivalence?
The antibody:antigen ratio where there is optimal binding and cross-linking
What happens where there is too much antibody?
Precipitation does not occur causing prozone effect
Radial immunodiffusion uses what two things to detect amount of antibody or antigen in a sample?
1. Agglutination technology
In RID, what forms at the point of equivalence?
What is immunoelectrophoresis?
Inoculation of serum from a patient and serum from a normal control onto a gel matrix and poured into a glass slide. The slide is exposed to electric field and the proteins migrate based on their charge. After this is complete, anti-sera specific for all human antibody isotypes is inoculated into a trough set up between the two sera samples
What are agglutination tests used for?
Rapidly dianogse pneumococcus and meningococcus infections and identify the specific strain of the isolate.
Speed and difficulty of agglutination tests?
For blood typing, what happens?
Red blood cells from a patient are mixed with anti-sera against the A or B antigens.
The antibody that agglutinates the red blood cell indicates the antigen expressed by that blood cell.
Anti-A and Anti-B antibodies are what isotype?
What is hemolytic disease of the newborn?
Maternal IgG binds fetal red blood cells and newborn can suffer from reticulocytosis, anemia, and hydrops fetalis
What test is performed to determine whether maternal antibodies have bound fetal red blood cells?
Direct Coombs test
What test is performed to determine whether maternal serum contains antibody against Rh antigen?
Indirect Coombs test
Both Coombs tests require what?
Antibodies against the human antibodies to agglutinate the RBC's.
What is administered to Rh- mothers carrying a potentially Rh+ fetus?
Rhogam (anti-D antigen sera)
How can antibodies be labeled for inspection?
Antibodies against defined molecules can be used to detect what?
Specific antigens and antibodies within sera.
Two ways to detect specific antigens/antibodies in sera?
What type of label does each do?
1. RIA: Radioactive label
2. ELISA: Enzyme label
What makes a Western blot different from ELISA?
Can determine size of the proteins that the serum antibodies recognize.
Pregnancy tests detect what?
hCG in urine
hCG pregnancy tests use what types of antibodies? (2)
1. Polyclonal antibodies against hCG
2. Monoclonal antibodies against hCG with an attached enzyme.
White blood cells can be separated out of whole blood using what?
Ficoll density gradient
Describe the steps of WBC's in flow cytometry? 3
1. White blood cells are incubated with monoclonal antibodies that are dye-labeled.
2. Individual cells are taken up into a stream and exposed to a laser that excites the fluorescent label to emit light at a specific wavelength.
3. Emitted light is collected by a photomultiplier tube and quantitated to define the strength of fluorescence and number/percentage of cells expressing the desired cell marker.
Flow cytometry separates cells how?
Based on proteins expressed on their surface (CD4 vs. CD8).
What are the molecules used to stimulate lymphocytes without antigen?
Clinical use of mitogens?
Can determine global deficiencies in B or T cell populations
How can the responses of T cells to certain antigens be measured?
Using APC's loaded with a specific peptide and mixing them with T Cells. If the antigen-specific T cell exists, then that line will proliferate which can be measured using radioactively labelled thymidine.
How does one actually measure the antigen-specific T cells in a lab test?
Limiting dilution assay
What is a limiting dilution assay.
The assay is set up so that when 37% of wells are negative, there is one specific T in each well at beginning of culture period. APC's that have been in contact with the specific antigen are then added. After awhile these cells are irradiated. T cells are then added and incubated for 24-72 hours before reading the results.
What are steps of ELISpot test? 5
1. Cytokine-specific monoclonal antibodies are added to a filter on a plate
2. T cells form the patient are cultured in wells
3. T cells are activated through mitogens or APC's with antigens.
4. Cytokines are secreted from T cell bind to monoclonal antibodies on the plate
5. These antibodies are labeled so that the number of cytokine producing cells can be detected.
What are the steps of intracellular cytokine staining
1. Activated T cells are treated with inhibitor that blocks cytokine release
2. Cell is fixed and permeabilized with detergents
3. Cytokine-specific antibodies are added and penetrate the cell to bind the cytokines.
Detection of microbial antigens can be done through what? (3)
1. Agglutination tests
3. Western Blot
What are two conditions where you can distinguish current infection from previous infection in blood? 1
1. IgM and IgG antibodies are distinguished
2. 4X rise in IgG antibody titer between acute and convalescent phase of infection
Common bacteriologic serologic tests include? (2)
1. ASO test
How does ASO work?
Antibody against streptolysin O prevents RBC lysis and indicates exposure to S. pyogenes