Lecture #1 -- Innate and Adaptive Immunity Flashcards
Name some phagocytes.
Macrophages (Tissue Residents)
Neutrophils (Recruited from Blood)
Dendritic Cells (Tissue Residents)
What types of immune cells do peptides turn on?
ab-T cells and B cells
What types of immune cells do glycoproteins/carbohydrates turn on?
B cells, Macrophages/Neutrophils/DCs/Tissue Cells
What types of immune cells do glycolipids and phospholipids turn on?
B cells
NKT cells, gd-T cells
What types of immune cells do peptidoglycans/nucleic acids/flagella turn on?
B cells
Mac/Neu/DC/Tissue via TLRs
Name phagocyte cell surface receptors
Complement, Fc, MHC Class II, TLR
Name some chemotactic agents.
C5a, LTB4, Chemokines (IL-8, MIP, MCP)
Name some ways phagocytes can kill bacteria.
Metabolic Burst
Superoxide (via NADPH oxidase)
H2O2 (via Superoxide Dismutase)
Acid Hydrolases, Muramidase, Lysozyme, Defensins
Name the two types of receptors on a macrophage.
Phagocytic receptor and signaling receptor
Cytokines involved in inflammation?
Il-1, TNF-a, IL-6, CXCL8, IL-12
What does IL-1/TNF-a do?
Increase BV permeability
What does IL-6 do?
Increase fat/muscle metabolism –> Fever
What does CXCL8 do?
Recruits neutrophils
What does IL-12 do?
Recruits/Activates NKs, strengthen Mac response
What cytokine induces acute phase proteins? Where are they made? Name three.
IL-6
Liver
CRP, Fibrinogen, Mannose-binding Protein
What do acute phase proteins do?
Opsonization and Complement Activation
What is sepsis?
Systemic Inflammatory response due to Infection
What two parts does C3 split into? What do they do?
C3a – Recruits Phagocytes
C3b – Tags bacterium for destruction
How does C3b affect bacterium after binding?
Binds macrophage CR1, causing endocytosis
After endocytosis, eventually phagolysosome breaks up bac.
Receptors on Macrophages?
Complement receptor 3/4 (Mac-1)
LPS Receptor (CD14)
Toll Like Receptors
What are the components involved in LPS recognition?
CD14, TLR4, MD2, LPS
X2 (its a dimer)
What does TLR 2/6 recognize? Where is it located?
Lipoteichoic Acid/Zymosin
Plasma Membrane
What do TLR 4/4 homodimers recognize? Where are they located?
LPS
Plasma Membrane
What does TLR9 recognize? Where is it located?
Unmethylated CpG-rich DNA
Describe the molecular steps of TLR activation.
TLR–>TIR Domain–>MyD88–>IRAK4–>TRAF6–>IKK–>Degradation of IkB –> NFkB transcribes cytokines
What receptor is unique to neutrophils?
N-formyl methionine receptor
What are competitors used in bacterial destruction?
Lactoferrin and B-12 binding protein
How do defensins work? What makes defensins?
electrically attracted to lipid bilayer, make pores. Made by paneth cells.
What are the steps of Leukocyte adhesion?
Rolling Adhesion, Tight Binding, Diapedesis, Migration
What molecule facilitates rolling adhesion?
Selectins
What molecule facilitates tight binding?
Chemokines (like CXCL8)
What molecule facilitates diapedesis?
Integrins (like ICAM-1)
What molecule facilitates migration?
Chemokines
ID markers on NK cells?
CD14 and CD 56
What do NK cells secrete?
IFN-g, IL-1, CM-CSF, TNF-a
How do NK cells work in immune response?
Use perforin on MHC fuck ups or promote Ab-dependant cytotoxicity
Activating receptors for NK cells?
MIC-A,B, Fc
Inhibitory receptors for NK cells?
HLA Class I, HLA B,C
What cytokines turn on NK response?
IFNa, IFNb, TNFa, IL-12
What do interferons do?
Interfere with viral infection
- Induce resistance to viral replication
- Increase NK ligand expression and Activation
What happens in Antibody Dependant Cell-Mediated Cytotoxicity?
Fc receptors on NK cells recognize bound Ab, trigger kill response
What type of Ab do Fc’s usually respond to?
IgG
Who has FcR 1? CD#?
Macrophages, Monocytes
64
Who has FcR 2? CD#?
B cells, Neutrophils, Macrophages, Monocytes
32
Who has FcR 3? CD#?
NK cells, Neutrophils, Macrophages
16
How are Mast cells activated?
Ig-E binds FcR 1
What five tasks are Fc Receptors important for?
Phagocytosis and Killing (FcRIII for NK, I/II for Phago) Mediator Release (FcRI on Mast Cells) Enhancement of Uptake B-cell negative feedback Complement Activation
Give examples of primary and secondary lymphoid tissues.
Primary – Bone Marrow/Fetal Liver, Thymus
Secondary – Lymph Nodes, Spleen, MALT
Describe a lymphoid cell working around the system starting in high endothelial venules.
High Endothelial venules –> efferent lymphatic vessels –> thoracic duct -> blood lymphocyte pool –> afferent lymphatic vessels
Where do CD3+ T cells become functional?
LN Cortex/Paracortex
Where do CD19+ B cells differentiate?
Germinal Centers
What are the roles of the white and red pulp of the spleen?
WP – Lymph Node
RP – Blood Filter
Name the lymphocytes.
B cell, T Cell, NK Cell
Name Antigen Presenting Cells
DC, Macrophage, B Cell
Name Effector Cells
T Cell, Macrophage, Granulocytes
How much faster is secondary immune response?
1.5-2 weeks
Role of CD4 T Cells?
Control of B cells and macrophages
Mechanical antimicrobial factors.
Mechanical barrier of skin
Mucous epithelial barrier
Ciliated epithelium
Normal Microflora
Name the innate immunity cells
Neutrophils Macrophages NK Mast Cells Eosinophils, Basophils Dendritic Cells
Name oxygen dependent antibacterial factors.
Superoxide (from NADPH oxidase)
Hydrogen Peroxide (Superoxide dismutase)
Hypochlorite (myeloperoxidase)
Name oxygen independent antimicrobials
Acid hydrolases Muramidase Lysozyme Lactoferrin Defensins
Major cytokines of Sepsis?
TNF-alpha, IL-1, IL-6
Two macrophage receptors that recognize microbial products.
TLR, LPS receptor
Two macrophage receptors that bind pathogens
Mannose Receptor
CR3
Glucan Receptor
Scavenger Receptor
When do you see neutrophils in tissue?
Only in infection/inflammation
Macrophage receptors used for identification in phagocytosis?
CTLD
Dectin-1
Complement Receptors
SR-A, SR-B
Basic methods used by phagolysosomes (6)
Acidification Toxic Oxygen Toxic NO Antimicrobial Peptides Enzymes Competitiors
How do defensins work?
Electrostatic attraction brings them to lipid bilayer
Defensins bind together to form pores
Loss of osmotic control = dead bacteria
T of F. Many neutrophils must be generated at the onset of an infection.
F. Large neut. reserves are stored in the marrow for rainy days
What happens to neutrophils in battle?
They engulf and kill bacteria
Die nobly in the tissue
Engulfed and degraded by macrophages
What percentage of circulating lymphocytes are NKs?
10-15%
What is the murder weapon of choice for NK cells?
Perforin
Significance of NKs in cancer?
NK cells attack tumor cells lacking MHC I
Significance of inhibitory and activating receptor activity in NK cell.
Inhib binds MHC Class 1
Activating binds activating ligands
Activation + No Inhib = Targeted Killing
Activation + Inhib = Depends on balance of signals
Receptor utilized in Antibody-dependent-cell-mediated toxicity?
CD16/Fc-gamma-RIII
Difference in T/B Cell Life cycle compared to neutrophil.
T/B can beome memory cells, be recycled through circulation many times.
Neutrophils are on a one way trip
Name the gut-associated lymphoid tissue.
Peyer’s Patches
Of the APCs, which is prone to prsent to T cells? B cells?
Dendritic Cells. Follicular Dendritic Cells.
Microbial primary target for B cell, CD4 helper, CD8 cytotoxic
B – Extracellular Microbes
CD4 – Phagocytosed Microbes
CD8 – Intracellular Microbes (like viruses)
Difference in peptide bonding of Antibody and TCRs?
Antibody recognizes whole proteins
TCRs recognize small peptide pieces presented by dendritics
Phases of a T cell response
Clonal Expansion
Differentiation
Cell Mediated Immunity
Apoptosis/Survival as Memory Cells
