Midterm Flashcards
Which part of the adaptive immunity is induced by exposure to organism?
active
What part of the adaptive immunity is established by transferring immune components to a different animal?
passive
What cells are involved in the humoral adaptive system?
B cells and CD4 TH2 cells
What cells are involved in cellular adaptive immune system?
CD4 Th1 cells and CD8 cells
What are the soluble factors of adaptive immunity?
antibodies and cytokines
What happens during effector phase of adaptive immunity?
elimination of anigen through inflammation
What is the term for antibodies facilitating phagocytosis of an antigen?
opsonization
What 3 cells are made from the common lymphoid progenitor cell?
B cell, T cell, NK cell
What is an important effector function of NK cells?
ADCC = antibody dependent cell mediated cytotoxicity
B-cells are differentiated by T-cells based on what molecules on their cell suface?
Fc receptors and surface immunoglobulins
What are the 3 primary (central, generative) sites of lymphocyte development and initial maturation?
bone marrow, thymus, bursa of fabricious
What are the 4 secondary lymphoid organs?
lymph nodes, spleen, MALT, cutaneous
What is the order of immunogenicity for the following: Lipids, Nucleic Acids, Poteins, Polysacchardies?
Proteins>Polysaccharides>Lipids = Nucleic Acids
What are the 4 characteristics of antigens that lead to immunogenicity?
Foreignness, molecular size, chemical complexity (and heterogeneity) and degradability
What are the 4 characteristics of the host that influence immunogenicity?
genetics of animal, dose and route of exposure to immunogen, physiologic status of the host, adjuvant
What is the term for a antigen that has more than one determinant?
multivalent
What are the number of AA on proteins that a B-cell can recognize? Can it be linear or discontinuous?
15-22 AA
both linear and discontinuous
How many different types (constant region) of light chains are there?
2
How many different types (constant region) of heavy chains are there?
5
What part of the immunoglobulin molecule has variable regions?
amino termini of each light and heavy chain
How man folded domains does the H chain have? L chain?
H chain -3-4
L chain - 1 domain
What immunoglobulin fragment consists of a heavy and light chain?
Fab
What fragment of the Ig molecule contains just heavy chains?
Fc region
What are the 3 regions on the end of the Ig molecule that contain the most variability?
hypervariable regions/complementarity determining regions (CDR)
(on both heavy AND light chains)
What are the 2 basic functions of an antibody molecule?
Recognition and effector function
What is the dimer made of in secreted IgA?
2 mononumeric units + J chain
Which 2 Igs are best at neutralization?
IgG and IgA
What Ig class is best at opsonization?
IgG
What 2 Ig classes is best at activating complement?
IgM and IgG
What Ig class is the best at being transported across epithelium?
IgA (dimer)
What Ig class is best at crossing the placenta and diffusion into EV sites?
IgG
What part of the antibody molecule alters its ability of transport?
Fc region
How is IgA transported across basement membrane in intestine?
bound by poly-Ig R, then becomes dimer and binds to secretory piece
What Ig genes make up a light chain and are involved in somatic recombination?
C-region gene + V region gene segements (V, J)
What Ig genes make up the heavy chain in somatic recombination?
C regione genes + V region (V, D & J)
How are hyper variable regions completed for L chains in somatic recombination?
First 2 hypervariable regions are encoded in V segment, 3rd is created at juncture of a V and J region
How are hyper variable regions determined in H chains in somatic recombination?
first 2 hypervariable regions are encoded in V segment, 3rd is created at jucture of a D and J region
What is junctional diversity?
happening during somatic recombination, as V and J segments join, additional nucleotides are introduced
What is combinatorial diversity?
In different B cells, a single H chain can associate with a number of different L chains
Where does somatic hypermutation of a B cell occur?
in germinal centers in the cortex of the lymph node
What species uses gene conversion to develop more diversity in Ig?
chickens - in the bursa
What is the term for a b-cell to change which class of antibody it produces?
isotype switching
Where is complement made?
in the liver and by inflammatory cells
What type of molecules are active enzymes that trigger activation of next inactive molecule downstream in pathway?
zymogens
What complement activation pathway is the first to act and is activated by the local environment on a pathogen surface?
alternative pathway
What pathway is the second to act and is activated by mannose-binding lectin?
lectin pathway
What pathway is the third to act and is activated by a C-reactive protein or Ab that binds to antigen on pathogen surface?
classical pathway
What do all the complement pathways have in common?
lead to cleavage of C3 to C3a and C3b –> C3b covalently bonded to pathogen –>inflammation, opsonization, perforation
What is C5a?
anaphylotoxin –> establishes local sites of inflammation
What does C5b do?
forms membrane attack complex in late phase
What are the components of the alternative pathway?
C3,5,6,7,8,9
factor B and D
properdin
What complement factor is involved in amplifying the cascade when classical and alternative pathways are both active?
C3
What are the 3 main complements involved in opsonization?
C3b, C4b and iC3b
What are the 5 effector functions of complement?
opsonins
anaphylatoxins
lysis of cells (MAC)
enchancement of B cell responses
remove immune complexes
remove dead and dying cells
Which receptor does complement enhance B-cell response?
mediated through CR2 receptor on B cells
How does complement remove immune complexes?
binding of C3b –> bind to RBC via CR1 –> circulation
Which T cell activates macrophages?
CD4 Th1 cell
What T cell helps B cells make antibody?
CD4 Th2 cell
What T cell kills tumor cells and virally infected cells via MHC-1 molecules?
CD8 cell
What is the structure of MHC class 1 molecules?
alpha chain with 3 domains plus B2 microglobulin
What is the structure of a class 2 MHC molecule?
alpha chain plus beta chain - each with 2 domains, both are polymorphic
What cells express MHC class 1 molecules? class 2?
class 1 - all nucleated cells
class 2 - immune APCs (dendritic, B cells, macrophages)
Where are the location of polymorphisms/peptide binding in MHC class 1? MHC class 2?
Class 1 = a1 and a2 domains
Class 2 = a1 and b1 domains
What is the name for the pathway of Class 1 MHC presenting to CD8 cells?
cytosolic pathway
What is the name for the pathway for class 2 MHC to present to CD4 cells?
endocytic pathway
What is the structure of a T cell receptor?
1 alpha chain and 1 beta chain, each has 3 hypervariable regions (CDR).
Also has a hydrophobic transmembrane region
What are the 2 main differences between a B-cell Ig receptor and T-cell receptor?
- TcR not produced in secreted form
- TcR does not perform effector fxns
What are the genes that make up the TCR?
alpha cains - VJC segments
beta chains - V, D, J, C segments
What are the 2 differences between the way B-cells generate diversity from T-cells?
- no additional diversity in T cells after Ag stimulation (all diversity occurs in thymus)
- no class switching
What is the function of the TCR complex and what is it made out of?
stabilization of alpha and beta on T cell surface, signal transduction needed to turn on gene expression
made of TCR + CD3 + gamma?
What is the difference between BCR and TCR in regards to the site of Ag binding?
BCR - bivalent
TCR - monovalent
What are the functions of the co-stimulatory molecules on a T cell?
upregulate or downregulates T cell
What is the function of the Fas ligand as a membrane effector molecule on T cells?
signal for apoptosis
What membrane effector molecule on T cells is involved in activation of B cells and macrophages?
CD40L
What are pro-t cells?
double negative thymocytes
How does a pro-t cell become pre-t cell?
expresses TcR beta chain on surface with a pre-T alpha chain and CD3/zeta
What is the goal of positive selection of T-cells?
retain ones that can recognize self MHC molecules
Where does positive selection of T-cells occur?
surface of cortical thymic epithelial cells
What is the goal of negative selection of T cells?
eliminate cells that have high affinity for MHC
Where does negative selection of T cells occur?
macrophages and dendritic cells in medulla
Where does T-cell response to pathogen occur?
secondary lymphoid tissue
How do T cells go from blood to lymph nodes?
high endothelial venules
What are the 4 adhesion molecules present on T-lymphocutes?
L-selectin (binds to endothelium)
Integrins, ICAM3, Ig Superfamily (bind to APCs)
What are the 2 adhesion molecules present on High Endothelial Venules?
Vascular addessins (bind to L-selectin)
ICAMS1, 2 (bind to integrins on T cell)
What are the 2 adhesion molecules present on APCs?
Integrins (bind to ICAM3 on t -cells)
ICAMs 1 +2 (bind to integrins)
What keeps an activated T-cell in the node for several days?
presence and upregulation of adhesion molecules LFA-1 and VLA-4
What kind of peptides do B-cells present to T-cells?
derived from soluble antigens
What co-stimulatory molecules are on a naive T cell? Which one is upregulate and downregulate?
CD28 (upregulatory)
CTLA-4 (downregulate)
What co-stimulatory molecule on an APC binds to CD28 or CTLA-4 on a naive T-cell?
B7
How is ZAP-70 activated in a t-cell?
PTK phosphorylates tyrosine on ITAMS close to CD4 or CD8 –>ZAP70 –> signal transduction
What are the 3 seperate transcription factor families that ZAP 70 can activate in a T cell? What do they all lead to?
NF-AT
NF-kB (via protein kinase C)
AP-1
All turn on cytokines (IL-2)
What does IL2 do to T-cells?
growth factor –> proliferation and differentiation
What cytokines does a Th1 cell produce?
IL-2, IFN-y = macrophage and B-cell activation
(also TNFa)
What cytokines does Th2 cells produce? What do they help with?
IL-4 and IL5 –> activation of B cells to make Ab
What are the 3 factors that influence which type of effector T-cell a naive T-cell will become?
- cytokines present
- nature of Ag
- affinity of TCR for peptide
What type of effector T cells will migrate via blood to area of insult?
CD8 and Th1 CD4 cells
What effector T-cell tends to remain in secondary lymph tissue?
TH2 CD4
What is the MOA of autocrine cytokines?
acts on same type of cell that produces the CK
What is the MOA of paracrine cytokines?
acts on other types of cells nearby
What cytokines does a cytotoxic T cell produce?
IFNg
What are the 2 ways CD8 cells can induce apoptosis?
perforin/granzyme
Fas/Fas ligand
What are the fxns of IFNgamma when produced by CD8 cell?
inhibit viral replication
increases presentation of Ag by MHC
activates macrophages
How do CD4 Th1 cells activate macrophages and increase their phagocytic activity?
Increased production of IFNg + CD40L –>increased expression of CD40 on macrophages
How do CD4 TH1 cells aid in the destruction of intravesicular pathogens?
kils macrophages that cant be activated
secrets IL3 and GM-CSF with induce macrophage and PMN production
secretes TNFa, b and MCP with aid other cells
What effect does IL-4 production by TH2 cells lead to in B cells?
increase in B cell proliferation
What effect does IL-5 production by TH2 cells have on B cells?
differentiate into plasma cells
How does signal transduction happen in a B -cell?
PTKs phosphorylate ITAMS of Iga and Igb –> PTK Syk is activated –>transduction
What transcription factors are ultimately produced by signal transduction in a b-cell?
NFAT, NFkB and AP-1
What are the 4 changes in gene expression after a B-cell is activated?
CK receptors
Chemokine receptors
increase in MHC class 2
increase in co-stimulatory molecules
What does complement receptor CR2 of the B-cell receptor bind to?
C3d on microbes or Ag/Ab complex
What part of the B-cell receptor is involved in transmembrane signal transduction?
CD19
What is the difference between TD and TI antigens?
TD = all proteins, memory is generated
TI = polysacchardies, no memory
What is formed when a T-cell recognizes a MHC/Ag complex on B-cell?
conjugate pair: CD40/CD40 L is formed
What does the interaction of CD40/CD40L lead to?
B cell proliferation and differentiation
What 3 events occur in the germinal center of LN?
somatic hypermutation
Ig Class switch
formation of plasma and memory cells
What class of Ab is produced when B cells are acctivated by TI antigens?
IgM
What does plasma protein C-reactive protein do in the innate immune response?
binds to bacterial cell wall –> opsonin and triggers classical complement cascade
What do protease inhibitors do in the innate immune system?
inactivation of bacterial proteases
Where are PRRS located?
on macrophages and neutrophils
What are 4 examples of PRRS?
f-met-Leu-Phe receptor
complement receptor
mannose recceptor
LPS receptor
What is a toll receptor?
special category of PRRS –> activation of signal transduction in phagocytic cell
What is the final outcome of Toll like receptors inducing signal transduction in phagocytic cells?
NFkB transcription factor –> pro inflammatory genes (interferons and cytokines)
What is produced by virally infected cells and how does it initiate a response?
Type 1 interferon –> decrease viral replication, increase NK receptors, activate NKs
What 2 molecules lead to CD4Th1 cells and CD8 cells in innate response by macrophage?
IL-12 and IFNg
What replaces L-selectin on naive T cells when they migrate and turn into effector T cells?
VLA-4 on effector T-cells
Where do B cells go after they become activated?
some to medullary cords in LN or become plasma ccells
What are the main differences between memory T cells and naive T cells?
increase in precursor frequency
changes in cell surface markers
activation requirements ant timing
trafficking patterns
ck production pattern
