Memorization Flashcards
NK Cells uses what two things to kill cells?
Perforin proteins to deliver “suicide” enzymes ex. Granzyme B into a target cell
Interferon Gamma- mainly produced by what?
Helper T cells and NK cells
What are NK cells look for what in a cell?
MHC receptors
“dont kill” signal is conveyed if its present
“kill” signal is conveyed if it is not
The smallest antigenic determinant to which an antibody can be made is what?
3-6 AA or 5-6 sugar residues
An antigen has many different ______, in which an antibody or T cell response is made
Antigenic determinants
What is an immunogen?
an antigen that stimulates an immune response.
Can a hapten initiate an immune response?
No, it is too small. It can initiate an immune response if bound to a large carrier molecule
what is the difference in diversity of innate and adaptive?
Innate is germline encoded. Adaptive subject to somatic recombination of gene segments
What are the cells of the innate immune system?
Macrophages, Dendritic Cells, NK cells, Neutrophils,
What kind of information does the innate relay to the adaptive?
Evaluates the invader in the context of intracellular vs extracellular and then provides instructions.
What is a chemokine?
A subset of cytokine that regulates cell migration and movement
Each cell expresses a set of specific signaling receptors for what?
Cytokines
What is the function of a cytokine?
growth and differentiation of all immune cells, activation of effector functions of lymphocytes and phagocytes
What subset of adaptive immunity , is mediate by ab’s and is the principal defense mechanism against extracellular microbes?
Humoral Adaptive
Ehrlich is the father of?
Humoral Immunity
Elie Metchnikoff father of ?
Cell Mediated immunity
The function of cell mediated immunity is?
T helper lymphocytes activate macrophages to kill phagocytized microbes of cytotoxic T cell directly destroy infected cells
What is clonal selection?
Ag specific clones of lymhocytes develop before and independent of exposure to ag. A characteristic that maximizes the potential for recognizing diverse microbes
What is the diff. between active and passive and give an example of each
Active- conferred by a host response to a microbe or microbial antigens- displays memory- Immunizations
Passive- conferred by transfer of antibodies or T lymphocytes specific for a microbe- no memory- Ab’s transferred through breastfeeding
What are the two professional phagocytic cells in the innate immune system?
Neutrophils and Macrophages
Dendritic cells are also phagocytic cells
Neutrophils are stimulated by what cytokine?
Granulocyte colony stimulating factor
Neutrophils contain what?
Azurophilic granules-lysozymes that contain enzymes and other microbicidal substances
Neutrophils give off what cytokine?
TNF
How do neutrophils kill yeast and fungi?
Neutrophils bind to yeast and internalize them via phagocytosis, they fuse with azurophilic granules, the production of ROS and the release of enzumes such as elastase into the phagosome contribute to killing the organism
Fungi- when they encounter hyphae they can’t internalize them so the azurophilic granules are released and enter the nucleus where chromatin decondensation occurs and release of NET’s- Net’s contribute to the immobilization and killing of extracellular organisms but at the cost of some tissue damage
What are the functions of mast cells and where are they located?
Mast cells are located at sites that are exposed to the external environment such as skin near blood vessels.
They regulate vascular permeability and degranulate on invaders to cause effector cell recruitment. They release: Histamine, Heparin, Protease, Chondroitin Sulfate, TNF, and antimicrobial peptides
Cells of the macrophage arise from precursor cells where? They are stimulated by what factor?
Bone Marrow
M-CSF- monocyte/macrophage colony stimulating factor
Macrophages function in the activation of what cells and how?
Present antigens to T lymphocytes at the site of infection which leads to activation and production of cytokines that further activate the macrophage- This is important for microbes that have been ingested by phagocytes but resist killing
Inflammatory DC can arise from what in inflamed tissue?
Monocytes
Langerhans cells are what type of cell and originate when?
Tissue resident DC’s- arise from embryonic precursors
Naive lymphocytes are in what phase of the cell cycle?
When activated they go into what phase?
G0,G1
Naive lymphocytes depend on signals generated by what to survive?
Antigens and BCR/TCR receptors
Is has been suggested that Ag receptor of naive B cells (BCR) generate a survival signal even in the absence of what?
Antigen
Naive TCR recongnize self ag’s weakly to generate survival signals but without triggering what?
Clonal expansion into effector cells
What is the most important cytokine for survival of naive T cells?
IL-7- promotes low level cycling of naive T cells
What is the most important cytokine ( in the TNF family) required for naive B cell survival?
BAFF- b cell activating factor
What cytokines play an important role in development of T cells?
B cells?
T - Cells, IL-1,2,6,7
B Cells, IL-1,6,7
B cell development begins when are where before birth and where after birth?
about the 14th week of development in the fetal liver and then in bone marrow
T cell interact with what type of cells in the thymus?
Macrophages, Dendritic Cells, Epithelial Cells
What happens to B and T cells during development that recognize self ag?
They are eliminated
What are the two types of T cells that are created?
Helper T that express CD4- provide help with b cell growth and differentiation
Cytotoxic T that expresses CD8- recognize and kill virus infected cells
What are the two types of B cells with different properties that develop?
B1 and B2
What is a plasma cell?
A mature B cell that is terminally differentiated and produces and secretes large amounts of antibodies.
Lymphocytes circulate continuously and reach all the parts of the body except
eye, brain and testicles
Lymphocytes reach the LN’s, Skin, and intestine via..?
HEV- high endothelial vessicles- they express high levels of adhesion molecules- adressins that serve as homing receptors for lymphocytes
Fully mature naive T cells and Immature naive B cells migrate where?
Secondary lymph organs such as spleen,LN . B cells complete their maturation.
Ab’s secreted by effector B cells in LN, Spleen and bone marrow go where?
enter blood and go to the site of infection
What is the first antibody expressed on a B cell followed by the coexpression of another antibody?
IGM-first then IGD- coexpression
Name the three APC’s and their function
Macrophages, B-Cells and Dendritic Cells.
DC- can activate virgin T cells in LN’s by traveling there and presenting a snapspot of the infection
Macrophages- don’t travel but they can stimulate experienced T cells to the site of infection
B-cells - only experienced b cells- can act as APC’s to T helper cells
Macrophages mainly present to T lymphocytes in what type of adaptive immune response
Cell Mediated
B cells function as APC to T cells is what type of adaptive immune response?
Humoral Immune response
Follicular DC does what?
Displays antigens to B cells during phases of the humoral immune response
Maturation of DC’s depends on what cytokine?
Flt3 ligand which binds to Flt3 tyrosine kinase receptor on precursor cells
Macrophages and Dendritic cells express receptors that recognize antigens made by what?
Microbes not by mammalian cells
Follicular DC reside where
LN’s, Spleen, and mucosal lymph tissue, they display protein ag’s on their surface for recognition by B lymphocytes- They can retain complement fixed ag’s on their cell surface for extended periods of time - Provide the antigenic stimulus that drives Ab affinity maturity
Classical DC reside where?
Skin , mucosa and parenchyma
Plasmacytoid DC do what?
What do they produce?
Cellular responders to viral infections
Produce soluble proteins- IFN-1 aka IFN alpha/beta- they have potent antiviral activities
What are the three functions of Innate Lymphoid Cells and whats an example of one?
- Provide early defense against pathogens
- Recognize stressed and damaged host cells and help eliminate them
- Influence the nature of the subsequent adaptive immune response
- -NK cells–
The Thymus is composed of what two sections and where do T lymphocytes develop?
Cortex and Medulla- T cells develop in the Medulla
The medulla has a characteristic Hassals corpuscle but function is not understood
The spleen contains white and red pulp, which do T and B cell zones make up?
White pulp
How do Naive T and B cells enter a LN and how do they exit?
How do DC enter?
They enter through HEV through an artery, they migrate to separate areas via chemokine gradients and exit through HEV through the efferent lymphatic vessels.
DC enter through the afferent Lymph vessels
Endothelial cells at the site of infection and tissue injury are activated by what?
Cytokines produced by macrophages and mast cells
P Selectin: Where is it located and what is the ligand?
Endothelium activated by Histamine or Thrombin
Ligand: Sialyl Lewis X on PSGL-1 and other glycoproteins, neutrophils, monocytes, T cell
E Selection: found where? what is the ligand?
Endothelial cells activated by cytokines TNF and IL-1
Ligand: Sialyl Lewis X CLA-1 on glycoproteins, neutrophils, monocytes, T cells
L-selectin where is it found and what is its ligand?
Found on Neutrophils, monocytes, T cells, and B cells-naive
Ligand- Sialyl Lewis X on GlyCAM-1, cd34, MadCAM-1, HEV
E selectin is expressed where?
P selectin is expressed where?
L selectin is expressed where?
E and P on endothelial cell
L on Leukocytes and Lymphocytes
E/P/L selectin are expressed in response to what two cytokines?
TNF and IL-1
E selectin is synthesized and expressed in response to the production of the cytokines in 1-2 hours
L selectin does what to naive T and B lymphocytes?
It causes homing into LN by interacting with HEV
L selectin ligand expressed on HEV is called what?
Peripheral node adressins (PNAd)
Where is the Integrin LFA-1 located and what is it’s ligand
located on neutrophils,monocytes,T-cells- effector,memory,naive-B cells-naive
Ligand- ICAM-1 and ICAM-2 on endothelium- cytokine induced
Where is Integrin Mac-1 located and what is it’s ligand
Neutrophils, monocytes, DC’s
ligand- ICAM-1 and ICAM-2 on endothelium- cytokine induced
Where is the VLA-4 integrin located and what is it’s ligand?
on monocytes, T cells- naive, effector, memory
Ligand- VCAM-1 cytokine induced
Where is integrin alpha 4 beta 7 located and what is its ligand
monocytes, T cells- gut homing, naive,effector,memory and B cells- gut homing
Ligand- VCAM-1 and MadCAM-1 endothelium in gut and gut assoc. lymphoid tissues
What do Integrins do?
Mediate adhesion of cells to other cells or ECM
and
Integrate signals triggered by extracellular ligands with cytoskeleton dependent motility,shape,change and phagocytic responses.
How does integrin activation in T lymphocytes occur?
when antigen binds to TCR
what is inside out signaling?
Integrins are normally in a low affinity state, when a rolling leukocytes chemokine receptor binds to a chemokine on the endothelium this leads to chemokine induced conformational changes in the extracellular domain of the Integrin that increases it’s affinity for it’s ligand- high affinity state
Neutrophils and monocytes are recruited into tissues of infection or injury without activation- how do they enter?
Through post-capillary venules except parenchymal tissues (liver,lungs, kidney) where all blood cells enter through capillaries
What cytokines are used in the transmigration of neutrophils
1.Chemokine IL-8 or CXCL8 ligand-
Receptor on neutrophil CXCR1 andCXCR2 - Neutrophil recruitment
2. Chemokine CCL2 or MCP-1 ligand
Receptor CCR- transmigration of monocytes
L selectin is expressed on naive T and B to help with what?
To help naive T and B lymphocytes enter the LN through the HEV- the HEV has L selectin ligrand called (PNAd) Peripheral node addressins
–If deficient the naive T and B are unable to enter the LN–
When L selectin binds to PNAd it causes naive T to home to the LN
HEV’s are present where?
ONLY in secondary lymph organd
What chemokines are displayed on the surface of HEV’s and what is their function and ligand
CCL19 aka MIP-3B
CCL21 aka SLC
Both share a ligand CCR7 and a function- to help naive T cells and DC migrate into parafollicular zones in LN’s
This chemokine binding activates integrins
CD44 is important for what?
What is it’s ligand?
- The mobilization of effector T cells in sites of infection and inflammation- at these sites endothelial cells secrete cytokines and express E/P selectin and HA
- HA- natural ligand or E-selectin
Which TLR’s are found extracellular?
1,2,4,5,6
Which TLR’s are found intracellular
3,7,8,9
TLR’s 1,2,5,6 use the adaptor protein _______ to stimulate what two transcription factors?
TLR 2 can also engage what protein?
MyD88
NF-KB and AP-1
TIRAP
TLR3 uses the adaptor protein _____ and activates what two transcription factors?
TRIF to activate IRF3 and IRF7
TLR 4 uses which transcription factors? through what protein?
TLR 4 can also engage what proteins?
It can use both pathways to use either NF-KB & AP-1 or IRF3 & IRF7
Through the protein Myd88
and also TRAM
TLR’s 7 & 9 activate which transcription factors?
NF-KB adn IRF7
Transcription factor NF-kb does what?
activates actue inflammation and stimulation of acute phase proteins
IRF transcription factor does what?
Stimulates the antiviral state
Activation of TLR’s can do what ?
Trigger antimicrobial pathways that directly kill the pathogen but at the expense of the host it can contribute to tissue damage and septic shock
Caspase -1 cleaves a zymogen to form what two homologous cytokines in the inflammasome?
IL-1B and IL-18- inflammatory cytokines
NLRP is a NOD like receptor that responds to _____ and ______ by forming a _________.
Pamps and Damps by forming an inflammasome
Scavenger receptors mediate the uptake of what type of cells?
Oxidized lipoproteins into cells
What two scavenger receptors are expressed on Macrophages and mediate the recognition/phagocytosis of microorganisms?
SR-A and CD36
CD36 functions as a coreceptor in __________ recognition and response to LTA
TLR2/6
Scavenger receptors bind bacterial constituents based on what type of charge?
Negative- such as LPS, LTA, nucleic acids
Mannose receptors recognize what on the microbial organism?
Do they recognize human carbohydrate domains?
Mannose, N-acetylglucosamine and B-Glucans
NO
The _____ receptor is involved in phagocytosis of microbes?
Mannose
Defensins are produced by what cell types?
Epithelial cells of mucosal surfaces, and by granulocyte containing leukocytes- neutrophils, NK cells and CTL
Synthesis of Defensins is stimulated by what?
Cytokines and microbial products
What two types of defensins are produced?
Alpha and beta
What do defensins do?
Direct toxicity to microbes, fungi, and enveloped viruses, they kill microbes by inserting into and disrupting functions of the membrane, and regulate activation of cells involved in inflammatory response to microbes
What is the function of Cathelicidins?
Direct toxicity to microbes, stimulate activation of leukoctes,
Cathelicidans are produced by what cell types?
Epithelial cells in the skin, GI and Respiratory tract.
Cathelicidins have a c terminal fragment LL-37 that does what?
Can bind and neutralize LPS and plays an antiinflammatory role by binding to DNA and blocking AIM-2 of the inflammasome activation
Classical DC reside where?
Skin, mucosa and organ parenchyma
Plasmacytoid DC produce what ?
Interferon 1 aka IFN alpha and beta
Innate Lymphoid cells develop with the help of what transcription factor?
Id2
Group 1 ILC produce what?
IFN gamma and TNF and provide defense against viruses- NK cells are in this group
NK cells function to do what?
NK cells kill infected or injured cells.
NK cells responds to IL-12 produced by macrophages and secretes what?
This secretion mediates what?
IFN-gamma
Activated macrophages to kill phagocytized microbes
NK cell activating receptors are called what?
KIR’s killer cell immunoglobulin like receptors
NK cells look for what in a cell?
MHC type 1
What happens what NK cells recognize an MHC1 molecule on a cell?
They activate protein tyrosine phosphatases and inhibit the activation signal that would kill the cell.
Thus NK cells do not harm cells that have an MHC-1 molecule
