FMS Week 8 Flashcards
Immunology
What are T regulatory cells?
suppress Th1 and Th2 and have an anti-inflammatory effect
What is the general result of deficiency in classical pathway components?
autoimmune disease
What is IL-4?
the major Th2 cytokine; activates Th2/suppresses Th1 production; promotes IgE production (parasites)
What additional binding is required for B-cell class switching in T-cell dependent activation?
CD40 (B-cells) to CD40 Ligand (T-Cells)
What does CRP bind to?
CRP joins the C1 complex to Bacterial polysaccharides
Describe the classical complement pathway
The C1 complex binds to CRP; the attaching of 2 adjacent Fc complexes removes C1-inh, activating C1r & C1s (proteases); C4 and C2 are cleaved; C4b and C2b create a C3 convertase; C3 convertase generates C3b
What proteins make up the membrane-attack complex?
C5b, C6, C7, C8, C9
what are interleukins?
cytokines that travel between leukocytes
Which antibodies are dimers?
IgA
what are cytokines?
cell signalling proteins that stimulate inflammatory response
What are the 3 key functions of macrophages?
phagocytosis, cytokine production, antigen presentation
What are the functions of antibodies?
opsonization, neutralization, activating complement
What are kupffer cells?
macrophages of the liver
What is DAF?
decay accelerating factor (CD55); disrupts C3b attachment in formation of C5 convertase; protects host cells from late complement pathway
What is the secretory component?
the bridge that links IgA monomers as they pass through epithelial cells creating a dimer in secretions
What are the key roles of Natural Killer Cells?
Kill virus-infected cells; produce INF-γ to activate macrophages
what cells are agranulocytes?
Lymphocytes (NKC, T & B) and monocytes (macrophages)
What are the properties of C5a?
Anaphylatoxin and neutrophil chemotaxis
What types of molecules do T-cells recognize?
only peptides presented by APCs
what is the difference between mast cells and basophils?
basophils are found in the blood stream, and mast cells are in the tissue
What is IL-1?
a cytokine released by macrophages; increases synthesis of endothelial adhesion molecules allowing neutrophils to enter inflamed tissue; acts as an endogenous pyrogen by acting on the hypothalamus
What are PAMPs?
pathogen-associated molecular patterns; present on many microbes but not human cells, used by the immune system to recognize pathogens
Describe the alternative complement pathway
Spontaneous conversion of C3 to C3b; stabilized by amino and hydroxyl groups on bacterial surfaces; stabilized C3b binds to Factor B (C3bB); Factor D clips Factor B to make C3bBb (C3 convertase); C3 convertase can make more C3b leading to rapid accumulation on surfaces
How do nucleic acids act as PAMPs?
DS-RNA and Unmethylated DNA are characteristic of pathogens and recognized by the innate immune system
What is the LPS pathway:
LPS binds LPS-binding protein of plasma; complex binds CD14 on macrophages, triggers TLR4 which produces cytokines (IL-1, IL-6, IL-8, TNF)
what are chemokines?
cytokines that attract immune cells (chemotaxis)
What is the structure of MHC class I?
One heavy chain (alpha) and one microglobulin (beta)
Which antibodies are pentamers?
IgM
What are the components of the c1 complex?
C1q, C1r, C1s, and C1-inh
What is Factor H?
Plasma glycoprotein that protects host cells from alternative compliment pathway: accelerates decay of C3 convertase, inactivates C3b; some pathogens/cancers have developed the ability to use endogenous Factor H for evasion
What are the unique characteristics of the adaptive immune system?
Slow acting (days), highly specific, memory, requires antigen presentation
What are Th1 cells?
CD4 T-cells that drive “cell-mediated” immunity and promote specific IgG subclasses
How does mannose act as a PAMP?
Binds MBL (mannose-binding lectin) from the liver and activates the lectin pathway of complement
What is IL-10?
a Th2 cytokine; inhibits Th1 production; anti-inflammatory
Describe T-cell maturation
immature T-cells migrate from bone marrow to thymus; express TCR, bind to self MHCs; only “ideal” TCR cells survive (positive selection in cortex, negative in medulla)
Why is IgM the best activator of compliment?
the C1 proteins of the Fc regions are positioned closer together
How does ADCC work in Eosinophils?
IgE binds to pathogens, Eosinophils bind IgE (Fc), release toxic enzymes onto parasite
What is the significance of protein A?
part of some bacterial cell walls (Staph Aureus); binds Fc portion of IgG (preventing opsonization and compliment activation)
What is IFN-γ?
a cytokine from Th1 that increases MHC expression: activates Th1/suppresses Th2 production; activates macrophages
What is the role of neutrophils?
“back up” called in by macrophages; extra phagocytosis
what is the role of CD8 T-cells?
cytotoxic (Tc); kills virus-infected and tumor cells
How does tuberculosis block phagocytosis?
modifies phagosome so it cannot fuse with lysosome, leading to proliferation inside macrophages and protection from antibodies
What are TLRs?
toll-like receptors; a class of pattern recognition receptors on Macrophages, dendritic cells, and mast cells that recognize PAMPs and then secrete cytokines
What is CD59?
MAC inhibitory protein; disrupts formation of the MAC; protects host cells from late complement pathway
describe the co-stimulation of CD8 Tc?
TCR binds to antigen (on MHCI) and CD8 binds to MHCI; also IL-2 from Th cells
How are eosinophils stimulated?
IL-5 from Th2 cells
What is IL-2?
cytokines mostly from Th1 cells that are T-cell growth factors and lymphocyte activators
What is Chediak-Higashi Syndrome?
immune deficiency where lysosomes cannot fuse with phagosomes leading to recurrent bacterial infections
What is the purpose of multiple C genes in antibodies?
different C genes encode alternative antibody classes
What is LPS?
endotoxin; a PAMP; binds LPS-binding protein of plasma
What are the anaphylatoxins (inflammatory proteins) of the complement system and their relative potency?
C5a>C3a>C4a
Why is IgM always the default?
First C gene in the sequence; change requires alternative splicing
Describe neutrophil “rolling”:
selectin ligands on neutrophils bond to E-selectin or P-selectin of endothelial cells (stimulated by IL-1 and TNF during inflammation) and slow down
By what means does C3b lead to attack of bacteria?
Directly by opsonization; indirectly by activation of late pathway via C5 convertase
What is IgA protease?
bacterial enzymes that cleave the secretory component and allow colonization of mucosal surfaces
Why is IgM a weak opsonin?
Receptors cannot access Fc regions
What is somatic hypermutation?
Following mutations in V,D,J genes: B-cell receptors with stronger antigen binding proliferate more
What is required for T-cell dependent activation of B-cells?
receptor crosslinking; T cell binding
What is the most common manifestation of deficiency in DAF or CD59?
hemolysis of RBCs
What antibodies can cross the placental barrier?
only IgG
Describe neutrophil “crawling”:
the integrins of neutrophils (stimulated by LPS and C5a) bind ICAM on endothelial cells
What is ADCC?
antibody-dependent cellular cytotoxicity
What is the CD3 complex?
complex surrounding the alpha and beta chains of T-cell receptor that transmits “bound” signal into the cell
Why is CRP considered an “acute phase reactant”?
It activates the early classical pathway(C1-C4), but does not activate the late pathway (C5-C9)
What is the major antibody of secondary response?
IgG
What are Th2 cells?
CD4 T-cells that drive “humoral” immunity and activate B-cells to produce IgE/IgA antibodies
What happens to human cells with reduced MHC I?
killed by NKCs
What is inside the lysosomes of macrophages?
reactive oxygen species and nitrogen intermediates produced by NADPH Oxidase (respiratory burst); digestive enzymes
What genes make up the B-cell receptor?
Variable portion:V,D,J
Constant portion: C
What are the 2 types of activated B-cells?
plasma (antibody making) and memory (only in T-cell dependent)
What are Th17 cells?
Subset of CD4 that produces IL-17 to recruit neutrophils and macrophages; protect against GI bacteria and autoimmunity
What is the role of CD4 T-cells?
helper (Th); produces cytokines to stimulate B-cells, CD8 Tc, and macrophages
What are microglia?
macrophages of the CNS
What antibody is the most abundant in plasma?
IgG
What composes MHC class II?
alpha and beta chains; invariant chain in ER; peptide antigens on the surface
How do neutrophils “transmigrate”?
tightly bound (crawling) neutrophils bind PECAM-1 between endothelial cells
What are phagocytes?
immune system cells that directly eat pathogens which enter the body; macrophages and neutrophils
What is the most abundant complement protein?
C3
What do NOD receptors do?
NOD receptors bind peptidoglycans of bacterial cell walls when they enter a cell, then secrete cytokines
What factors contribute to genetic variation of B-cell receptors?
V,D,J genes on chromosome 14 of heavy chain; V/J gene rearrangements on the light chain
What cleaves C5 into C5a and C5b?
C3b
How are CD4 Th activated?
MHC Class II of APCs binds CD4
What opsonins are associated with neutrophils?
only IgG
What are the steps of neutrophil blood stream exit?
rolling, crawling, transmigration, migration to site of inflammation (chemokines)
What disease is associated with C1-inh defects?
hereditary angioedema
What is TNF?
tumor necrosis factor; cytokine that causes tumor death
Which antibodies are monomers?
IgD, IgE, IgG
What is IL-5?
a Th2 cytokine; activates eosinophils; promotes IgA production (GI bacteria)
What are band forms?
immature neutrophils seen in bacterial infections due to extra active bone marrow production; referred to as “left shift”
What are Natural Killer Cells?
the lymphocytes of the innate immune system
How does ADCC work in NKCs?
CD16s are crosslinked by binding to IgGs (Fc) of antibody covered infected cells, leading to degranulation into a lytic synapse
Describe T-cell independent activation of B-cells
Requires very strong antigen crosslinking; important for non protein antigens; weaker response (mostly IgM, no memory)
Where do complement proteins bind the B cell receptor?
CH2 region of heavy chain
What disease is associated with DAF or CD59 defects?
paroxysmal nocturnal hemoglobinuria
What is the difference between macrophages and monocytes?
monocytes circulate in the blood, are referred to as macrophages if they enter the tissue
What surface proteins are important for B-cells?
CD40, MHC Class II, B7 (binding with T-cells)
CD19 (all), CD20 (most, not plasma), CD21 (compliment, EBV)
What is IL-12?
cytokine from macrophages that stimulates Th1 production
What chemotaxins are associated with neutrophils?
IL-8 from macrophages and C5a from complement
What is the key difference between MHC classes I and II?
MHC I is found on all cells (presents to CD8s); MCH II is only on APCs (presents to CD4s)
How are macrophages activated?
PAMPs via surface TLRs, IFN-γ from T-cells & NKCs, C5a from complement
What are interferons?
cytokines that interfere with viral replication
What is TNF-α?
a cytokine released by macrophages; can cause vascular leak (septic shock); inhibits lipoprotein lipase (cachexia); kills tumors via intravascular coagulation of tumor cells
What cells are antigen presenting cells?
dendritic cells, macrophages, and B-cells
How do CD8 Tc kill virus infected cells?
insert perforins (form channels in cell membrane); insert granzymes (degrade cell contents and activate caspases); insert granulysin (lyses bacteria); produces Fas ligand (extrinsic apoptosis)
Describe the Lectin Pathway
Circulating MBL and MASPs bind to the mannose-containing surfaces of microbes; complement proteins C2 and C4 come in and are cleaved into C2b and C4b which bond to create a C3 convertase (C4b2b); C3 convertase creates C3b
Neutrophil small granules vs larger granules
Small granules are secondary and are found in both lysosomes and extracellular space; larger granules are only in lysosomes
What disease is associated with defects in factor H?
age-related mascular degeneration and atypical hemolytic uremic syndrome
What cells are granulocytes?
neutrophils, eosinophils, basophils, and mast cells
Characteristics of IgE
defense against parasites (eosinophils and mast cells); low plasma concentration; no complement
What are dendritic cells?
antigen presenter cells of the skin and mucosal membranes; migrate to the lymph nodes to activate T-cells
Describe CD4 T-cell co-stimulation:
TCR binds antigen (on MHCII); CD4 binds MHCII; CD28 binds B7 protein of APC
what cells are activated by Th1s?
CD8 Tc and macrophages
Characteristics of IgA
Does not fix complement (no inflammation); secreted in mucous; coats pathogens so they cannot invade
What stimulates production of CRP?
IL-6 from macrophages
