Immunology Flashcards
What are the order of events in the innate immune response?
(1) Pathogen Recognition;
(2) Complement system activation;
(3) Cytokine and chemokine production;
(4) Recruitment of neutrophil
How does the life span and location vary among Neutrophils and Macrophages?
Neutrophils: Short lived, blood stream
Macrophages: Long lived, tissues
Neutrophil life span is 6hrs - few days and the travel throughout the blood stream
Macrophages life span is Months to Years! And they stay resident in the tissues
How does the first step of the innate immune response occur?
Pathogen Recognition - through the interaction of PAMPs and TLRs (PRRs)
TLRs are on the surface of cells: Macrophages/Dendritic/fibroblast..
PAMPs: Pathogen associated molecular patterns
TLRs: Toll Like Receptors
PRRs: Pattern Recognition Receptors
What happens when PAMPs interact with TLRs
TLR:PAMP binding causes a signal cascade that induces an innate immune response and production of pro-inflammatory cytokines
Which TLRs are associated with periodontal disease? What do they recognize specifically?
Upregulartion of TLR 2 (Lipoteichoic acid) and 4 (LPS) on Fibroblasts is associated with periodontal disease (Sarah 2003, Wang 2006)
How does P Gingivalis interact with TLRs?
Its Lipid A Moity is a potent inhibitor of TLR 4 when in high iron environments.
How can the compliment cascade be activated?
Classical pathway (antigen-antibody)
Lectin Pathway (Lectin binds Mannose on pathogens)
Alternative pathway (Pathogens, injured tissues)
Where do the various pathways of the complement cascade converge? What does this result in?
C3 convertase - creates C3a and C3b (C3b is used for opsinization)
What does C3b do?
It coats pathogens for recognition (opsinization)
What is the final result of the complement cascade?
Formation of a membrane attack complex via C5b, C6, C7, C8, and C9 (C5b-9)
How does P. Gingivalis interact with the complement system?
It blocks ALL pathways of the complement system via Gingipains
Degrades C5b (no MAC) but keeps C5a (tissue degredation)
What is Autocrine, Paracrine, and Endocrine in relation to cytokines
Where the cytokine takes action
Autocrine - on cells that produce them
Paracrine - on nearby cells
Endocrine - on cells at distant sites
What are the functions of cytokines?
4 Rs
Recognition
Recruitment
Removal - either kill the pathogen directly or induce destructive enzymes
Repair - Anti-inflammatory cytokines
What are examples of ANTI inflammatory cytokines?
IL-4, IL-10, IL-1ra, TGFb
Examples of pro-inflammatory cytokines?
IL-1, IL-6, IL-8, TNFa, INFg, IL-17
Main effector of Cell Mediated Immunity?
T Cells
Main effector of Humoral Immunity?
B cell
Explain the process of Tcell activation
Pathogen phagocytosed by Antigen Presenting Cells
APCs present antigen via Major Histocompatibility Complexes (MHC I or MHC II)
MHCs present antigen to naive T cells
Which MHCs interact with which Tcells? What is the result of each?
MHC1 : CD4+ = Thelper cells
MHC2 : CD8+ = cytotoxic T cells - kills infected cells
Describe the basic design of an antibody
2 heavy chains
2 light chains
Fab - Vatiable antigen binding site
Fc - constant
What are the different classes of antibodies?
IgM, IgG, IgA, IgD, IgE
Where is MHC1 expressed?
All nucleated cells
Where is MHCII presented?
All Antigen Presenting Cells
Explain T-Cell INDEPENDENT B-cell activation
B-Cells have membrane bound antibodies that are Class IgM
Activation of IgM causes release of IgM antibodies
First Immunoglobulin to be released - not very specific
Explain T-Cell DEPENDENT B-Cell Activation
B-Cell recognizes antigen with membrane bound antibody
Internalizes antigen
Presents antigen via MHCII (as a mature B-cell)
T-Helper Cell recognizes presented antigen on MHCII
ThCell releases cytokines
Cytokines cause transformation of B-cell to Plasma cell
Plasma cell releases various Ig’s (IgG, IgA, IgM, IgE, IgD)
Also creates memory B cells
Which immunoglobulins are MONOMERS?
ALL CELL SURFACE IMMUNOGLOBULINS
Which immunoglobulins are NOT monomers? What are they?
Secretory IgM - Pentamer
Secretory IgA - Dimer
What do periodontal disease related plasma cells produce?
IgA, IgG, and RANKL
What cytokines do Th-17 cells produce? What are they involved in
IL-17
Up regulation of RANKL
What cytokines induce the production of Th-17s?
IL-12, IL-23
What cytokines do T-regs produce? What are they involved in?
IL-10, TGF-β
Anti-inflammation
(Give Citation) What Th Cells are involved in periodontal disease? How is it involved?
Cheng 2014
Th-17
Produces IL-17 which promotes osteoblasts, T-cells, and B-cells to produce RANKL
(Give Citation) How is IL-17 involved in periodontal disease?
IL-17 upregulates production of RANKL
ALSO upregulates production of MMPs by fibroblasts (Miossec 2012)
What are the stages of neutrophil recruitment? What is this process called?
Called Diapedesis
Tethering - Rolling - Adhesion - Crawling - Transmigration
How do neutrophils adhere to endothelial cells?
LFA-1 and Mac-1 on surface of neutrophil
Attach to ICAM 1 and 2 on Endothelial cells
What is Leukocyte Adhesion Deficiency type 1? What does it result in? (Pathogenesis)
Gene mutation: defect in LFA-1/Mac-1 : ICAM interaction
Neutrophils cannot migrate to cite of infection
What happens if neutrophils can
