DLA24, L39, L41- Cell-Mediated Immunity Flashcards
the main cells that important in eliminating viral infections are….
- NK cells (Ag dependent cell mediated cytotoxicity - opsonization)
- Tc cells (MHC-I)
list the components of humoral immunity in relation to eliminating viral infections (include their effects)
- Igs: opsonizing elements
- IFN-α/β: produced by virally infected cells to inhibit transcription/translation of neighboring cells
- IFN-γ: activates macrophages, NK cells, enhances upregulation of MHC-I
describe the fate of a viral antigen
Cytosolic Pathway
1) endogenous Ag in cytosol
2) Ag ubiquinated, destroyed by proteosome
3) peptides of Ag into ER via TAP 1/2
4) peptides bind MHC-I
5) MHC-I to golgi then plasma membrane (Ag presentation)
list some viral strategies used to avoid immunity (hint- 6)
- antigenic shift/drift: antigenic variation
- polymorphism: avoid memory thru different immunological targets
- latent virus (HSV, VZV)
- modulation of MHC expression
- infection of lymphocytes (=> their death)
- prevention of complement activation
(1) cells are responsible for killing extracellular bacteria. (2) cells are required for Ab response and (3) cells recognize protein/non-protein Ags
1- phagocytes
2- Th cells (Th2)
3- B cells
extra cellular bacteria activate complement directly through (1) and (2) pathways where (3) is an opsonin, (4) and (5) recruit leukocytes, and (6) destroy outer membrane of Gram- bacteria
1- lectin 2- alternative 3- C3b 4/5- C3a, C5a (anaphylaxins) 6- MAC (perforates membrane)
_____ is a natural antibacterial of humoral mediated immunity that attacks NAG / NAM links of peptidoglycan => bacterial lysis
lysozyme
(1) is the principal defense against extracellular bacteria via (2), (3), (4) mechanisms
1- Abs
2- neutralization
3- activation of complement
4- opsonization
(1) and (2) cells are critical to process of cell-mediated immunity of extracellular bacteria
1- APCs (Ag presenting cells): macrophages, dendritic cells
2- Th cells (Th1) via MHC-II
describe the fate of a extracellular bacteria antigen
Endocytic Pathway
1) exogenous Ags endo-/phago-cytosis into endocytic compartments
2) Ags –> peptides w/in endosome
3) endosome fuses with ER or vesicle with MHC-II
4) Ag replaces CLIP in MHC-II and vesicle goes to surface
describe the role of humoral immunity in regards to intracellular bacteria
- it can bind intracellular bacteria while in transit, before it becomes intracellular
- ineffective once its intracellular
the main cells that important in eliminating intracellular bacterial infections are….
- NK cells (Ag dependent cell mediated cytotoxicity - opsonization)
- Tc cells (MHC-I)
list some bacterial strategies used to avoid immunity (hint- 4)
- prevent phagocytosis: destroy phagocytes via toxins, neutralize opsonization
- survives w/in phagocytes
- prevent complement activation
- avoid recognition by immune system via Polymorphism
describe the role of humoral immunity in regards to protozoal infections
- complement / Igs useful during extracellular stage of infection
- opsonization of protozoa => lysis
the main cells that important in eliminating protozoal infections are….
- NK cells
- Tc cells
(somewhat phagocytes, Th cells)
list some protozoal strategies used to avoid immunity (hint- 3)
- escape into cytoplasm following phagocytosis
- prevent complementation
- gene switching => Ag variation
the most important attack mechanisms against extracellular parasitic worms / helminths is…
IgE and complement activation (+ eosinophilic activation)
describe IgE role in helminth parasitic infections
activation of granulation of Basophils and Mast cells
(T/F) fungal infections are controlled by innate and adaptive immune systems
kinda both: T- few can have Abs, F- vast majority can only be controlled via innate immune system
describe the role of the innate immune system to control fungal infections
- Neutrophilic phagocytosis
- activation of complement (via fungal cell wall components) via alternative and lectin pathways
____ cells have been considered to have a role in elmination fungal infections as a link between their defectiveness and increased fungal infections has been made
Th-17 cells (adaptive immunity)- produces IL-17
TCR rearrangement occurs in….
thymus- absent when T cell precursor leaves bone marrow
list the APCs
- Dendritic cells (most effective, MHC-II constitutively expressed)
- Macrophages (activation via phagocytosis before MHC-II expression)
- B-Cells (MHC-II constitutively expressed)
ALL EXPRESS MHC-II
T cell-mediated immunity only deals with (1) pathogens via expression in (2) or (3) cells and are presented on (4) receptor
1- intracellular
2- phagocytic cells (survive w/in phagolysosome / escape into cytosol)
3- non-phagocytic cells (live in nucleus / cytosol)
4- MHC-II
Ags must present to (1) T cells (2) times via APCs before they are activated into (3) T cells
1- naive T cells
2- 3 times
3- CD4+/Th or CD8+/Tc cells
list the 4 phases of T cell response to Ags (include the possible resulting cells)
1) Ag recognition
2) lymphocyte activation
3) clonal expansion
4) differentiation
Effector Functions: effector Th cell, memory Th cell, effector Tc cell (CTL), memory Tc cell
CD4+ effector T cells function to (1)
CD8+ effector T cells function to (2)
1- activation of macrophages, B cells, other cells + inflammation
2- killing infected target cells + macrophage activation
___ is an important CK responsible for advancing a activated lymphocyte into the clonal expansion phase
IL-2 (autocrine signaling)
(1) on T cells recognizes peptide shown on APC and (2) recognizes the MHC; (3) is the signal transduction element
1- T cell receptors (TCRs)
2- CD4/CD8 (co-receptors)
3- CD3
(1) are important in strengthening the binding of T cells to APCs and (2) from APCs are critical to completely stimulating T cell
1- adhesion molecules
2- second signals (co-stimulators)
list the co-stimulators in T cell activation
T cell: CD28, CTLA-4, PD-1
APCs: B7-1/2, PD-L1/2
list the adhesion molecules in T cell activation
T cell: LFA-1
APCs: ICAM-1
list the 3 polyclonal activators (non-specific)
- Abs for TCR, CD3
- Carbohydrate-binding proteins
- superantigens
Superantigens are (non-/specific) molecules that cause pathology through (2) by cross-linking (3) and (4); they also include (5) which stimulates cell proliferation
1- non-specific 2- toxic shock syndrome / massive load of CKs 3- MHC-II (APC) 4- VβTCR domain (T cell) 5- T cell mitogens
the most important adhesion molecule on T cells is (1) which is apart of the (2) group and binds to (3) on APCs
1- LFA-1 (leukocyte function associated antigen)
2- integrins
3- ICAM-1
CD28 on (1) cells is a critical co-stimulator that binds to (2) on (3) cells. (4) is present on (1) and (3) cells and is critical in upregulating (2)
1- T cells
2- B7
3- APCs
4- CD40L (T cells), CD40 (APCs) [L = ligand]
list the members of the B7 family
on APCs: B7-1/2, ICOS-L, PD-L1/2
list the members of the CD28 family (indicate activators and inhibitors)
on T cells:
- activators: CD28, ICOS
- inhibitors: CTLA-4, PD-1
(1) and (2) molecules on T cells are involved in terminating immune response
1- CTLA-4 (binds B7-1/2, opposite effect of CD28)
2- PD-1 (binds PDL-1/2)
agents that block B7-CD28 are used in ______ treatment
rheumatoid arthritis
Abs to CD40-CD40L interaction are being tested for…..
graft rejection
Abs that block CTLA-4 or PD-1 are used for….
enhancing immune response in cancer patients
______ interaction is involved in upregulation of B7
CD40 (APCs) – CD40L (T cell)
describe the role and use for adjuvant in T cell activation
binds PRR (protein recognition receptor) on the innate and activate APCs to enhance T cell activation –used in vaccines (which fail to elicit T-cell dependent immune response)
after presentation of Ag to Naive T cell, (1) is used to anchor T cell in lymph node, (2) activates T cell into effector T cells which express (3) that is necessary for enhancing 2nd signaling and then finally (4) that is necessary for controlling response
1- CD69
2- IL-2 (autocrine signalling)
3- CD40L
4- CTLA-4, PD-1
SCID (X-linked) is the result of a the following defect….
defect in common γ chain of IL-2R receptor
describe briefly how IL-2 works
- Ag stimulated Naive T cell activation
- IL-2 secreted (autocrine fashion)
- IL-2Rβγc complex (low affinity) –> IL-2Rαβγc complex (high affinity)
- => IL-2 induced T cell proliferation
HIV is responsible for destroying (1) cells which leads to the inactivation of (2) cells (or the prevention of activation of (2) cells)
1- Th CD4+ cells
2- Tc CD8+ cells
(1) cells usually require super APCs for activation where (2) do not
1- Naive T cells
2- memory T cells (CTLs)
list the primary events in CTL-mediated death
- conjugated formation
- membrane attack
- CTL dissociation
- target cell destruction
describe the steps of conjugate formation of CTL and a target cell
- Cell Adhesion: LFA-1 (CTL) binds ICAM (target cell)
- Recognition of MHC-I w/ Ag (target cell) via CD8 (CTL)
in the Membrane Attack phase on CTLs, granules release (1) first in order to (2) and then (3) is released to act as (4)
1- perforins (monomers –> polymer)
2- perforate or put pores in target cell membrane
3- granzymes
4- nucleases
CTL cells interact with target cells for (1) and then dissociate (able to conjugate with other target cells) while the target cell dies, which takes (2)
1- 5 mins
2- several hrs
NK cells defend against the following….
viruses, other intracellular pathogens, and tumors
NK cells recognize….
glycolipid and CD1d
activation of NKs is based on (1)
they don’t have the ability to recognize MHCs but can recognize (2)
1- balance between activating and inhibitory receptors
2- downregulation MHC receptors (since some viruses can do this) + other alterations in cell surface
NK cells can use (1) to induce apoptosis, activate (2) to kill target cells, or respond to (3) surrounding tumor cells
1- cytotoxic granules (perforins, granzymes, α-defensins)
2- macrophages (IL-12 –> NK cells –> IFN-γ –> macrophages)
3- Abs (Ab dependent cell mediated toxicity)
(1) is an adhesion molecule found on effector Th cells in order to bind to secondary lymphoid tissue. (2) is a chemokine that assists in this process, it also has functions to bring T cell to (3).
1- L-selectin
2- CCR7
3- maintain place in paracortex of lymph node (once CCR7 is gone, T cell may migrate ou of paracortex)
effector T cells have a (1) role in cell mediated immunity and a (2) role in humoral mediated immunity; it performs this through the expression of (3) on the surface and secretion of (4)
1- activate phagocytes (macrophages, neutrophils)
2- activate B cells
3- CDL40
4- CKs
Intracellular microbes are presented via (1) or (2) cells to naive T cells. (1) will secreted (3) and (2) secreted (4) for activation to occur, and the naive T cell will mature into (5). This is considered (cell/humoral) mediated immunity.
1/3- dendritic cell, IL-12
2/4- NK cell, IFN-γ
5- Th1 cell
6- cell mediated immunity
list the products and functions of Th1 secretions
- IFN-γ: macrophage activation, O2-dep./indep. mechs, respiratory burst, NO
- IL-12: O2-indep. mechs
- IL-2: Th1 target
- TNF-α: inflammation
Helminths are presented via (1) cells to naive T cells and secretes (2) for activation to occur. The naive T cell will mature into (3). This is considered (cell/humoral) mediated immunity.
1- mast cells / eosinophils (mainly, could be dendritic cells)
2- IL-4
3- Th2 cell
4- humoral mediated immunity
list the products and functions of Th2 secretions
- IL-4: IgE production, basophil/mast cell activation
- IL-5: eosinophil activation
- IL-10: inhibit Th1
- IL-25: activate the above CKs
Extracellular bacteria and fungi are presented via (1) cells to naive T cells and secrete the following, (2), to activate and mature the T cell into (3), which secretes the following CKs, (4).
1- dendritic cells
2- IL-1, IL-6, IL-23, TGF-β
3- Th17 cells
4- IL-17, IL-21, IL-22
Treg cells secrete (1) and (2) for the function to (3)
1- TGF-β
2- IL-10
3- immunoregulation (suppresor)
Tfh, aka (1), secretes (2) and other CKs in order to (3)
1- T follicular helper cell
2- IL-21
3- activate B cells
IFN-γ stimulates phagocytic mediated ingestion through (1) and (2). To promote phagocytosis it stimulates the expression of (3). To amplify T cell response it stimulates (4). It also activates macrophages to produce (5) in order to (6).
1- expression of lysosomal proteases
2- synthesis of ROS and NO (deal with organisms that escape phagosome)
3- Ab production
4- MHC-II and B7 expression on APCs
5- IL-12
6- drive Th1 cell production (amplification)
describe the 3 signals in a Th1 cell - macrophage interaction
1) CD4 (T cell) + MHC / co-stimulators (macrophages)
2) CD40L (T cell) + CD40 (macrophage)
3) IFN-γ (T cell) + IFN-γ Receptor (macrophage)
Th1 cell activation leads to the following three responses from macrophages
- killing phagocytosed bacteria (via ROS + NO)
- increased MHC + co-stimulator (B7) expression
- CK secretion: TNF-α, IL-1, IL-12
Th2 cells produce IL-4 for (1) production, where (1) coats (2) so (3) cells can kill them through release of granules enzymes. IL-5 is produced in order to (4).
1- IgE
2- parasites
3- eosinophils / mast cells
4- activate eosinophil
Th2 cell produce these three CKs, (1), to have alternative (2) activation in order to (3) and (4).
1- IL-4, IL-10, IL-13
2- macrophage (M2) [IL-10]
3- synthesis of extracellular proteins for repair
4- inhibit microbicidal activity of macrophages (suppress Th1)
classically activated macrophages (M1) are stimulated by (1) and have (2) and (3) as functions
alternatively activated macrophages (M2) are stimulated by (4) with (5) as its function
1- IFN-γ, TLR-ligands
2- microbicidal actions: phagocytosis / killing of bacteria/fungi
3- inflammation
4- IL-4, IL-13
5- antiinflammatory effects, wound repair, fibrosis
high Th1 has the internal threat of (1) and low Th1 has the internal threat of (2)
1- autoimmune issue (immune over-reaction)
2- cancer (immune under-reaction)
high Th2 has the external threat of (1) and low Th2 has the external threat of (2)
1- allergic reaction (immune over-reaction
2- infection (immune under-reaction)
mycobacterium leprae infections can have a dominant Th1 reaction leading to (1) or dominant Th2 reaction (or defective Th1) leading to (2)
1- tuberculoid leprosy (less severe)
2- lepromatous leprosy (more severe
Th17 cells function to destroy (1) and it defect would lead to (2)
1- fungal and extracellular bacteria
2- bacterial abscess, chronic mucocutaneous candidiasis (many fungal infections)
Th17 cells induce (1) and stimulates production of (2) antimicrobial. There most important CKs are (3) and (4) [include function of CKs]
1- inflammation
2- defensins
3- IL-17 –> recruits leukocytes / neutrophils (–> inflammation + antimicrobial peptides)
4- IL-22 –> maintains epithelial barrier integrity (+ antimicrobial peptides)
memory T cells found in lymphoid organs are called (1) and if found in peripheral tissue are called (2)
1- central memory T cells, rapid clonal expansion
2- (mucosa/skin) effector memory T cells, rapid effector cell
memory T cells (effector or central) are in the (1) phase of the cell cycle, require (2) to stay alive, have a (3) life-span compared to effector T cells, and are responsible for (4)
1- Go (quiescent) stage
2- IL-7
3- mos-yrs vs days-wks
4- secondary response to pathogens
describe the result of cell production after an acute viral infection vs a chronic infection
Acute- memory T cells, protective response to virus
Chronic- exhausted T cells, unable to respond to virus due to PD-1, CTLA-4 inhibition
define T cell anergy and its causes
Clonal Anergy:
- inability of cells to proliferate in response to MHC-peptide complex
- caused by absence of costimulatory signal OR presence of CTLA-4, PD-1 (inhibitory signals)
list 5 ways for microbes to resist cell-mediated immunity
- inhibit fusion of phagosomes and lysosomes
- inhibit Ag / MHC-I expression
- inhibit macrophage activation
- inhibit CK activation of T cells (neutralize CKs someway)
- directly infect T cells (ex. HIV)
