EXAM II Flashcards
List the principal components of innate immunity:
- Physical & Chemical barriers
- Phagocytic Cells, DCs, NK Cells, etc.
- Blood proteins (complement system, APP, Cytokines, Chemokines, etc.)
What is the function the complement system?
Plasma proteins that complements the ability of Abs & Phagocytic cells to clear pathogens
Define cytokines
Define chemokines
Signaling molecules that aid cell-cell communication
Chemokines - subfamily of cytokines that induce chemotaxis
T/F; Innate Immunity is highly diverse
False; you are born with what you already have whereas in adaptive, it “adapts” to what the body is exposed to
Which immune response has reactivity to self?
Neither
List cells of innate immunity
Neutrophil Monocyte, MO NK cell Mast cell Eosinophil Basophil
State the main differences between cell-mediated and humoral adaptive immunity
Cell-Mediated: intracellular (i.e. viruses), ran by T-helper cells which activate MO & Cytotoxic T-cells
Humoral: extracellular, ran by B-lymphocytes, blood and mucosal secretions, use the help of CD4 T Cells
State the clonal selection hypothesis
Ag-specific clones of lymphocytes develop before and are independent of exposure to Ag
Happens twice? During maturation and after Ag exposure
Clone = a lymphocyte of one specificity & its progeny
Clonal Selection allows for a max potential of recognizing diverse microbes
Which disease was involved during the formation of vaccines?
Smallpox
List the cells of adaptive immunity
B Lymphocytes
T Helper cells
Cytotoxic T cells
T Regulatory cells - suppress and prevent immune responses
List the steps and cell types during B lymphocyte activation
Naive B lymphocytes, respond to soluble Ag in secondary organs
Helper T cells present peptide Ags
Stimulated B cells proliferate in germinal centers of LN & mature into plasma cells or memory cells
Plasma cells are terminally differentiated & produce & secrete large amounts of Abs (rarely found in blood)
B cells in spleen respond to polysaccharides
What are the two fates/types of cells in which naive T cells develop into once they are activated by Ag?
Memory T cells
Effector T cells
List the steps of T cell activation, what are the two fates of differentiation?
Naive T cells enter LN and differentiate into effector or memory T cells which migrate to periphery
Some remain in LN helping Ag-activated B cells
Classical vs. Plasmacytoid DCs
Follicular DCs (unrelated)
Inflammatory DCs
Classical - (skin, mucosa, organ parenchyma) once activated migrate to LN
Plasmacytoid - early responders to viral infections, recognize nucleic acids & produce soluble proteins type I interferons (IFN alpha/beta); antiviral activities
Follicular - display unprocessed Ags for B Cell recognition only. DOES NOT INTERNALIZE Ag
Inflammatory - via circulating monocytes
What is the major effect of inflammation?
Recruitment of leukocytes and plasma proteins from the blood to the site of infection or tissue injury
What occurs when damaged endothelial cells are activated by cytokines (secreted by resident immune cells)?
Adhesion molecules are expressed, causing an increased adhesiveness for myeloid leukocytes and effector and memory lymphocytes
Steps of leukocyte recruitment at damaged tissue sites
- Tethering - selectins & integrins w/ their ligands
- Rolling - chemokine interaction
- Adhesion - integrins & receptors
- Transmigration
List the four types of integrins, what cells are they located on?
- LFA-1; lymphocyte function-associated Ag 1 = Neu, Monocytes, T cells (naive, effector, memory), Naive B cells
- Mac-1; MO-1 Ag = MO, DC, Neu.
- VLA-4; very late Ag 4 = Monocytes, T cells (all 3)
- Alpha4-Beta7; Mono, T cells, B cells (gut homing)
What ligands are associated with each of the 4 integrins?
- LFA-1 = ICAM-1/CD54, ICAM-2/CD102; endothelium; cytokine induced
- Mac-4 = ICAM-1, ICAM-2; endothelium; cytokine induced
- VLA-4 = VCAM-1/CD106; endothelium; cytokine induced
- alpha4-beta7 = VCAM-1, MadCAM-1; endothelium in gut & gut-associated lymphoid tissues
Function of integrins?
Mediate adhesion of cells to other cells or ECM via specific ligands
Heterodimeric cell surface proteins w/ 2 noncovalently linked polypeptide chains
Activated in response to chemokine binding to chemokine receptors
“Inside-out signaling”
What is the basic mechanism in which innate immune cells recognize self vs. nonself?
What cell receptors recognize these?
Used by phagocytes and PMNs to initiate phagocytosis
PAMPs - pathogen associated molecular patterns
Recognized by PRRs - Pattern Recognition Receptors
What are the 3 receptors of PRR (pathogen recognition receptors)? These are encoded in germline (found in gamete producing cells of the host
Toll-like receptor - activate inflammation
N-formylmethionyl receptor (fMet) - found in proks only
Mannose receptor
What are the 5 TLRs that recognize extracellular pathogens?
TLR-1 = bacterial lipopeptides
TLR-2 = bacterial peptidoglycan = gram (+)
TLR-4 = LPS = gram (-)
TLR-5 = bacterial flagellin
TLR-6 = bacterial lipopeptides
What are the 4 TLRs that recognize ingested microbes in the endosomes?
TLR-3 = dsRNA
TLR-7 = ssRNA
TLR-8 = ssRNA
TLR-9 = CpG DNA
Define necrosis, what 3 DAMPs do they release which activate NF-kB?
A passive, catabolic cell death in response to external toxic factors
Damage-associated molecular patterns
- HSP
- UA
- HMGB1
Bind to DCs activating NF-kB pathway for inflammation
Define Cathelicidins, what produces them? In response to what?
Antimicrobial peptides; activate leukocytes, direct toxicity to microorganisms, bind and neutralize LPS
Produced by neutrophils and barrier epithelial cells in skin, GI, resp. tract
In response to cytokines and microbial products
Which component of complement system is the most abundant in the blood?
Strongest chemoattractant?
What is MAC attack?
Blood - C3
Chemoattractant - C5a
C5bC6-C9
What 2 Abs are involved in the activation of the classical pathway of the complement system?
IgM
IgG
Forms an Ab-Ag complex with C1q (binds Fc portion) and C1r, C1s
What three things activate each of the complement systems?
Classical = Ab
Alternative = microbe
Lectin = mannose binding lectin
What are the many functions of pulmonary surfactant proteins SP-A and SP-D?
- Act as opsonins
- Inhibit bacterial growth
- Directly activate MO
- contain lipophilic properties
What two components can activate the Lectin pathway of the complement system?
- MBL - mannose binding lectin
2. Ficolin (humoral plasma proteins) - binds N-acetylglucosamine
List the proteins that regulate complement, what are their functions?
- DAF or CRI - enhance dissociation of C4bC2a (classical & lectin C3 convertase)
- CRI and FI - cleave C4b and C3b
What are the products of papain and pepsin digestion of Ab?
Papain - cleaves above Hinge = 2 Fabs, Fc receptor w/ Fc fragment
Pepsin - cleaves below Hinge = single bivalent Ag-binding fragment (Fc portion is entirely cleaved)
Define Ab valency vs. Avidity
Valency - (1 Fab region = monovalent, bivalent (IgG), etc.) the max # of Ag determines that can react.
High valency = high affinity
Avidity - Ag-Ab complex strength; high avidity with high amount of binding sites (quantity) = IgM (low affinity)
What is the function of HLA-DM during MHC II development?
Ensures the presentation of only the most relevant Ags for eliciting an immune response
Causes dissociation of CLIP from peptide binding groove
Stabilizes and prevents degradation of the empty MHC II
