B&L Unit 2 Flashcards
What does IFN-y do?
Chemotactic for monocytes
Classically activates macrophages
2 things classically activates macrophages secrete
TNF-alpha
IL-1
What 2 lymphokines do Th1 cells secrete?
IFN-y - chemotactic, activates macrophages
IL-2 - activates killer T cells
What are 5 things the Th0 cell can differentiate into?
TH1 THh17 Th2 Tfh Treg
3 things that alternatively activate macrophages
IL-4
IL-5
IL-13
What do alternatively activated macrophages do? (4)
Healing stuff
Debris removal
Scar formation
Walling off pathogens
Which cell classically activates macrophages and which one alternatively activates macrophages
Th1
Th2
Where to Tfh cells hang out?
Lymph node follicles, where the B cells are
What do Tfh cells do?
They help B cells that have recognized antigen activate and differentiate into plasma cells Get them to do class switching as well
What do Tregs do?
Suppress activation and function of other Th cells
What 3 things do Tregs make?
Foxp3 transcription factor
TGFbeta
IL-10
What are the two ways a killer T cell can induce apoptosis in its target cell?
Engagement of death receptor Fas with Fas ligant
Secrete lytic granules that contain granzymes and perforins
What 2 things do killer T cells require for activation?
Contact with antigen-bearing dendritic cell
IL-2 from Th1 cells
Which CD is on the surface of basically all T cells?
CD3
It is part of the TCR
Which CD identifies B cells?
CD20
Which CD identifies helper T cells?
CD4
Which CD identifies killer T cells?
CD8
T cells are _________-specific and _________-restricted
Antigen
MHC (major histocompatibility complex)
Do T cells see free antigen?
No. They see antigen only when it is complexed with cell-surface MHC molecules
What are the 2 TCR (T cell receptor for antigen) chains?
Alpha
Beta
What does CD3 do for the T cell?
Transduces TCR signals
Where are MHC class I products locate? Class II?
MHCI is on all nucleated cells
MHCII is on dendritic and macrophage cells
What is the gene structure for the T-cell receptor alpha chain? Beta chain?
V and J
V, D, and J
A different gene than the B cell one!
Killer T cells look at antigens with MHC class______ molecules and Th cells look at antigens with MHC class _____ olecules
I - because they look for infected cells
II
What is cross-presentation?
Dendritic cells (ONLY dendritic cells) can present antigens to class I and class II MHC at the same time
What is a mitogen?
An agent that stimulates T cell mitosis
Ligands for the ___________ receptor are unique to the thymus and guide T cell precursors
Notch
What other 2 unique things do double-negative cells express?
Rag-1 and Rag-2 DNA recombinases
Help rearrange TCR V(D)J genes
When are T cell precursors double negative? When are they double positive?
When they first get to teh thymus
Before selection. They turn off one or the other during selection.
What does a T cell recognize?
Antigenic peptide + self MHC
T cells are positively selected for ___________ affinity and negatively selected for ___________ affinity
Self MHC
Self other things
How do T cells get selected against for other body stuff when in the thymus? How do they encounter it?
AIRE (autoimune regulator) gene causes thymic stromal/epithelial cells to express a wide variety of peptides expressed elsewhere in the body
What happens to non-selected T cells?
If they have no MHC affinity and no self (non MHC) affinity, they are not stimulated through their TCRs. Apoptosis in 2-3 days
Which HLA loci do we care about? Which is most important for transplants?
HLA-A
B
D
DR
HLA expression is ___________ (like recessive, dominant, etc)
Codominant
What is the structure of MHC class I and II
Glycoproteins composed of two poplypeptide chains
Class I has a variable chain with a constant beta2-microglobulin chain
Class II has 2 variable chains (alpha and beta)
Do minor histocompatibility antigens cause acute or chronic rejection?
Chronic
In graft rejection, Th1 cells recognize foreign ___________ on ___________ and ___________ cells
Killer T cells recognize ___________ and ___________ on ___________ cells
HLA-DR
Macrophages from graft
Dendritic cells from graft
HLA-A
HLA-B
All graft cells
People with ankylosing spondylitis often are HLA___________
B27
Why do blood vessels bypass the cortex in the thymus?
Ensures differentiating T cells don’t get exposed to blood antigens until they are fully differentiated
At what age does thymus involution begin?
Onset of puberty
Where are B cells in the lymph node? Where are T cells?
Cortex
Paracortex
Where do lymphocytes enter the lymph nodes? What is special about these tissues?
Postcapillary venules
High, cuboidal endothelial cells
What are Hassal’s corpuscles made of? Where are they?
Concentric layers of reticular cells
In thymus medulla
What is special about splenic blood flow?
Discontinuous endothelium so that an open circulation occurs
Where is most of the lyphoid tissue in the spleen?
Periarteriolar lymphoid sheath
Where are germinal centers in the spleen?
Periarteriolar lymphoid sheath
Lymphokines are a subfamily of ___________
cytokines
What 2 factors classically activate macrophages?
IFN-Y
IL-1
What 2 things does IL-4 do?
Alternatively activate macophages
Chemotactic for eosinophils
What is the extrinsic pathway (of idk T cell something)
APCs take in antigen, digest it, and put it on MCH class II
What is immune surveillance?
Body cells put things from inside them on their surface MHC receptors so that the immune system can decide if they are normal or not.
This makes sure body cells aren’t making foreign or mutated proteins
What is antien cross-presentation?
An APC puts antigen on class I and class II MHC
When Th1 looks at the antigen on class II, it makes IGN-Y and IL-2 IL-2 and the antigen on MHC I activates the killer T and then it goes around fucking shit up on other cells displaing this antigen
What is T-independent B cell activation?
For antigens whose epitopes are regular and joined, usually carbohydrates
This alone gives the B cell enough signal that it gets activated and makes antibody
It does not class switch, however
What is a cytokine storm? What causes it?
Lectins can stick to sugars on T cell receptors, fooling the T cell into thinking its binding antigen and activating
Mitogen! This stimulates all the T cells to get activated at the same time and make lots of cytokines
What are the fates of a pre-T cell?
No CDR binding -> no signal -> it dies because it doesn’t recognize the MHC
Complete CDR binding -> it is autoimmune -> dies or becomes a Treg
4 important environmental toxins
Polycyclic aromatic hydrocarbons
Aromatic amines
Nitrosamines
Aflatoxin
What is the MHC gene organization?
ClassII: DP/DQ/DR
Class III: C4/Bf/C2/TNF
Class I: B/C/A
Chromosome 6
Do HLA genes experience recombination?
No. Linkage disequilibrium occurs.
How does a mixed leukocyte reaction work?
Get blood monocytes from the donor by irradiating blood (kills lymphocytes)
Check if Th cells from the recipient recognize the monocytes form the donor
What is the Ames test? What information does it provide?
A screen to decide which chemicals should be tested for carcinogenic potential in animals.
Take Salonella typhimurium that are His- (require histidine). Put them in media w/o histidine and liver microsomal enzymes. If the chemical is mutagenic then His+ mutants will form
What are the 2 stages of cancer development with carcinogens?
- Initiation. Direct effect of a carcinogen and is irreversible.
- Promotion. Effect of a noncarcinogen. Is reversible and requires repeated application after initiation
Why does inflammation promote cancer? 2 reasons
Production of oxygen radicals are
Mutagenic
Promote cell proliferation
What does tumor invasion mean (of an epithelial cancer)?
Tumor cells have broken through the basement membrane that separates the epithelium from connective tissue stroma
What is a conjugate vaccine?
Antigen that is coupled to a protein ‘carrier’ to which Tfh cells can respond
This increases B cell activation in response to the antigen
What are vaccine adjuvants?
Substances added to vaccines to make them more immunogenic
They produce an innate immune response, leading to a better adaptive response
What 2 things cause cavities?
- Bacteria and stuff
2. Immune response
How long does it take to make a neutrophil under regular conditions? What about stressed conditions?
How long does it stay in the blood?
10-14 days
5 days
6 hours
How many neutrophils does a neutropenic adult have?
How many neutrophils does an adult have who has neutrophilia?
> 7500 / uL
How long does the monocyte stay in the marrow? The intravascular compartments? Tissues?
7 days
3-5 days
days-months
What does the monocyte nucleus look like?
Kidney-shaped
Which cytokine induces eosinophil production?
IL-5
What does the eosinophil nucleus look like?
Bi-lobed
What are the 5 mechanisms by which infection-associated neutropenia can occur?
- Increased utilization
- Complement-mediated margination
- Marrow suppression/failure
- Cytokine/chemokine induced margination
- Anti-neutrophil antibody production
What is left shift of a differential?
Increase in neutrophils (segs and bands) on the differential
3 cells that aren’t B cells in the germinal center
Tingible body macrophages
follicular dendritic cell
T helper cells
Whee do macrophages hang out in lymph nodes?
In the subcapular space
What is a syngenic graft/isograft?
A transplant between identical twins
What are the ‘arms’ of the phagocyte in opsonization?
Pseudopods
What are the 4 main reactive oxygen species?
Superoxide O2*
Hydrogen peroxide H2O2*
Hypochlorous acid HClO*
Hydroxyl radical *OH
What is the molecular defect and inheritance pattern of leukocyte adhesion deficiency I?
CD18 -> lack of expression of CD11b/CD18
Autosomal recessive
What is the functional defect in leukocyte adhesion deficiency I?
Neutrophilia (so like more in the blood)
Decreased adherence to the endothelial surface, so the neutrophils can’t get to where they need to go
What 3 things happen clinically in leukocyte adhesion deficiency I?
Recurrent soft tissue infections
Delayed separation of umbilical cord
Poor wound healing
What is the molecular defect and inheritance pattern of chronic granulomatous disease?
Defects in one of the 4 oxidase components
Recessive (autosomal or X-linked)
What is the functional defect in chronic granulomatous disease?
Neutrophila, but they can get to where they need to go just fine
Defect in the oxidase enzyme system
What is the molecular defect and inheritance pattern of Chediak-Higashi syndrome?
Alterations in membrane fusion -> giant, leaky granules
Problems w/ utubule assebly
Autosomal recessive
What is the functional defect in Chediak-Higashi syndrome?
Neutropenia
Giant granules in all luekocytes
Abnormal degranulation
Decreased degranulation, microbicidal activity
Movement defects (of muscles or intercellularly?
What 3 things happen clinically in Chediak-Higashi syndrome?
Albinism Nystagmus photophobia Recurrent infections by bacteria Lymphoproliferative disease with stuff Neurodegenerative syndrome
What is the molecular defect and inheritance pattern of myeloperoxidase deficiency?
Post-translational modification defect in processing the protein
Autosomal recessive
What is the functional defect in myeloperoxidase deficiency?
Partial or complete loss of myeloperoxidase
Mid defect in killing bacteria
Significant defect in killing candida
What 1 thing happens clnically in myeloperoxidase deficiency?
Increased fungal infections when diabetes present
What happens in C3 (complement) deficiency?
Inefficient opsonization of bacteria -> recurrent bacterial infections
What happens in C5-C9 deficiencies?
Increased risk for Neisseria bacterial infections
What happens in 1q, C4, and C2 deficiencies?
Increased risk of systemic lupus or other autoimmue/inflammatory vascular diseases
What compound results in neutrophil proliferation?
G-CSF
What infections are more common with chronic granulomatous disease?
Catalase-positive organisms
