L5 Adaptive Immume Reksponse Flashcards
Helper T lymphocytes (CD4)
secrete cytokines that stimulate different mechanisms of immunity and inflammation.
Cytotoxic T lymphocytes (CD8)
kill any type of host cells (including nonphagocytic cells) that harbor infectious microbes, such as viruses in the cytoplasm
The class I MHC pathway converts proteins in the_____ into peptides that bind to MHC-I molecules for recognition by _____cells
cytosol
CD8 + cytotoxic T
The class II MHC pathway converts protein antigens that are_____ into vesicles of antigen-presenting cells into peptides that bind to MHC-II molecules for recognition by ____ cells
endocytosed
CD4 + helper T
T-cells will travel from where to develop the thymus
Bone marrow
Mature T-cells will leave the thymus to travel to the secondary ____
lymphoid tissues
Cell lineage of a T-cell
▪ T-cell precursors travel from the bone marrow to
develop in the thymus
▪ Mature T cells leave the thymus and travel to
secondary lymphoid tissues
T cells can be distinguished from other lymphocytes like B cells as the maturation and differentiation of T cells occurs where.
in the thymus
T cells are different from other lymphocytes as these have what on their surface
a T-cell receptor on the surface, which is absent in other lymphocytes.
Positive selection [T-cell]
In the positive selection, the CD4+ cells interact well with class MHC molecules, whereas the CD8+ cells interact well with class II MHC molecules.
What happens to T-cells that don’t. recognise MHC molecules
They don’t receive
survival signals and die by programmed cell death
Negative selection [T-cell]
- process where all T cells are screened to check for strong recognition of self-antigens.
- eliminates developing lymphocytes whose antigen receptors bind strongly to self antigens present in the lymphoid organs.
What happens to T-cells that react strongly to Self-antigens?
The cells that interact too strongly with the self-antigens receive an apoptotic signal resulting in cell death.
Avoiding that self-reactive T cells escape
to the periphery
True or False: every T-cell has a different T-cell receptor
True
What is self-tolerance
When the immune system can identify and won’t react to self-antigens.
Central tolerance Vs Peripheral tolerance
C:
* During lymphocyte development development (in thymus or bone marrow for T/B cells)
* Immune cells that bind to self antigen eliminated
* modifies number of naive lymphocytes circulating the periphery
P:
* After lymphocytes mature and go to lymph nodes
* prevent autoreactive immune cells from causing damage in the periphery
*
Immunologic tolerance
lack of response to antigens induced by exposure of lymphocytes to these antigens
What is the underlying cause of autoimmune disease?
Failure of self-tolerance
The principal mechanisms of central tolerance in T-cells
- Immature T-cell death (neg selection)
- Generation of CD4+ regulatory T-cells
When does peripheral tolerance lead to functional inactivation (anergy)/death/ suppression?
when the self-reactive lymphocytes are suppressed by regulatory T cells
Name the 2 types of TCR
αβ TCRs and γδ TCRs
What are the names of the antigen-recognising domains of receptors
Variable regions (V)
Constant regions (C)
Antigen receptor chains are associated with invariant membrane proteins whose function is to deliver intracellular signals following antigen recognition
Just a fact to learn
Invariant membrane proteins function
Deliver intracellular signals after antigen recognition
True or False: Each clone expresses the same TCR specificity
False
Each clone expresses a single TCR specificity
CD3 complex structure
Heterodimer with an alpha (α) and beta (β) polypeptide chain with each polypeptide containing a constant and a variable region.
All T-cells contain which cell marker CD_
CD3
How can T-cells be found within WBC
Via CD3 cell markers
APCs provide additional signals required for T cell
activation
Fact
First signal that APCs provide for T-cell activation
– presentation of the antigen by an APC (CD4 and CD8 co-receptors on T cells stabilise interaction of TCR and MHC/peptide)
2nd signal that APCs provide for T-cell activation
Dendritic cell presents B7 (CD80/CD83) to T cells (CD28 receptor)
3rd signal that APCs provide for T-cell activation
Release of cytokines by APC and T cells themselves (IL-2), driving T cell proliferation, survival and differentiation
DC pathway simple
- Antigen captured by DC
- Activation of DC
- Migration of DC
- Maturation of migrating DC
- Mature DC presents antigen to naive T-cell
What is enough for a Naive T-cell [simpleish]
- Naive T-cell
- Need TCR
- Signal CD28
- More cytokines Il2 and Il12 differentiate to helper T-cells
APCs for T-cell activation you need to look at slide 10 on L5
look at it
Adhesion molecules for T-cell activation
LFA-1 and ICAM-1
What provide additional signals required for T cell activation?
APCs
Several proteins that are homologous to B7 or CD28 function to stimulate or inhibit ____?
immune responses
What two molecules are needed to activate naive T-cells
B7 and CD28
What inhibits B7-CD28 interaction and how
CTLA-4 blocks and removes B7 molecules from the surface of APCs, reducing costimulation by CD28 and preventing the activation of T cells
After T-cells act they express what on the surface to increase preferential binding to B7 and suppress activation of T-cells
CTLA-4
Which molecules will inhibit kinase dependent activating signals from CD28 and the TCR complex?
PD-1 is expressed on T cells after antigen stimulation, and acts by inhibiting kinase dependent activating signals from CD28 and the TCR complex
What is an example for application for blocking T-cell activation
Therapeutic application in cancer immunotherapy (checkpoint blockade, immune checkpoint inhibitors)
IL12 differentiate into what
Helper T-cell 1
IL4 differentiates into
Helper T-cell 2
T lymphocytes activated by
antigen and costimulation begin to what
proliferate
When are memory cells formed and how long do they last?
During primary adaptive immune response and can persist for extended periods in the absence of the og antigen.
▪ Memory T cells undergo metabolic reprogramming to
survive long-term
▪ More sensitive to restimulation by antigen than naïve T cells
▪ Memory T cells proliferate more rapidly and robustly compared to their naive precursors
Memory cells
▪ Formed during primary adaptive immune response
▪ Memory T cells undergo metabolic reprogramming to survive long-term
▪ More sensitive to restimulation by antigen than naïve T cells
▪ Memory T cells proliferate more rapidly and robustly compared to their naive precursors
T-helper 1 cells function
Further activate macrophages (boost them)
T-helper 2 cells funtion
Respond to helminth infection (parasites in gut) will secrete more
1. mucus
2. Peristalsis
3. Contractility
T-helper 17 function
In mucosal sites to fight antifungal infections and activate phagocytosis of yeast (and extracellular bacteria)
T follicular helper cells (T-FH)
Affects all microbes
T-reg
Regulates activated T-cells
Th0 and IL4 pathway to helper cell
T-H0
↓
IL4
↓
T-H2
↓ activate
IL-4, IL-5, IL-13 (6 as well) (cytokynes)
↓
Activates B-cell
TH0 and Il-12 and INF-gamma to Helper
TH0
↓
TH1
↓ activate
IL-2 and INF-gamma
↓
Activates CD8 and macrophages
Cytokines that are produced by DCs during immune synapsis and trigger the differentiation of naïve T cells (Th0)
IL-4
IL-12
IL-any number
Th17 cells develop in response to [what] and induces [what]?
extracellular bacterial and fungal infections and induce inflammatory reactions that destroy these organisms
Regulatory T cells main function
Regulatory T cells main function is to suppress immune response
CD4+ helper T cells – Th1
- DCs produce INF-gamma & IL-12 which TH0 differentiates to TH1.
- Th1, acting through CD40 ligand and IFN- γ , increase the ability of macrophages to kill phagocytosed
microbes
T cells mediate protection against Mycobacterium tuberculosis
▪ IFN-γ is produced by Th1 cells,
▪ IFN-Y contribute to the recruitment of monocytes and granulocytes and activate the antimicrobial activity of macrophages - phagosome maturation, production of reactive nitrogen intermediates and antigen presentation
▪ T cells participate in granuloma formation, the pathologic hallmark of tuberculosis
HiV on TB
CD4 T cells deficiency (e.g., HIV+) dramatically increases susceptibility to both primary and reactivation tuberculosis
CD4+ Helper T cells – Th2
▪ DCs produce IL-4 = Th0 → Th2 cells
▪ Th2, secrete IL-4, IL-5 and IL-13, to stimulate antibody responses and defend
against helminth parasites
▪ Th2 cytokines inhibit activation of classical macrophages (microbicidal and proinflammatory), and stimulate alternative pathway of macrophage activation - important in tissue repair and fibrosis
Th2 cells are involved in allergic reactions to environmental antigens . What do repeat exposure to allergens trigger?
Triggers mast cell and eosinophil activation
CD4+ Helper T cells – Th2 picture look at it
SLIDE 21 on L5
CD8+ T cells
- Activated upon binding to non-self antigen presented by DC in the context of MHC-I
- CD8 + T lymphocytes recognise peptides on infected cells and tumor cells expressed in MHC-I molecules
- Cytotoxic T lymphocytes (CTL) uses perforin and granzymes to destroy infected cells
- look at slide
Cytotoxic T cells effector functions
▪ Perforin disrupts integrity of target cell plasma membrane and endosomal membranes - facilitates the delivery of granzymes into cytosol
▪ Granzymes activate enzymes caspases that are present in cytosol of target cells and whose major function = induce apoptosis
Cooperation between CD4+ and CD8+ T cells
▪ In a macrophage infected by an intracellular bacterium, some bacteria are sequestered in vesicles (phagosomes), and others may escape into the cytosol
▪ CD4 + T cells recognise antigens derived from vesicular microbes and activate macrophages to kill microbes in vesicles
▪ CD8 + T cells recognise antigens derived from cytosolic bacteria and are needed to kill infected cell -> eliminating reservoir of infection.
IL-4 pathway simple - hel,inth parasites
IL-4 produced by DCs lead to the differentiation of naïve CD4+ T cells into Th2 cells. Th2, acting through IL-4, IL-5 and IL-13, stimulate antibody responses and defend against helminth parasites
INF-γ and IL-12 pathway to kill microbes
INF-γ and IL-12 produced by DCs lead to the differentiation of naïve CD4+ T cells into Th1 cells. Th1 cells increase the ability of macrophages to kill phagocytosed microbes via CD40 ligand and IFN- γ
After the antigen is eliminated, contraction occurs (homeostasis/ equilibrium). However, some T cells differentiate into memory T cells, which are long-lived cells with an enhanced ability to react against the antigen
Read and understand
CD4 + helper T cells express molecules that recruit and activate other leukocytes to phagocytose and destroy microbe. CD4+ T cells include ???
Th1, Th2, Th17 and T-regs
