L2b_APC lymphocytes innate lymphoid cells.ppt

lymphocytes innate lymphoid cells

1. Antigen-Presenting Cells
Lymphocytes
Innate lymphoid cells

2. Antigen-Presenting Cells (APCs)
•Cells that capture microbial and other
antigens, display them to
lymphocytes, provide signals that
stimulate proliferation and
differentiation of lymphocytes.
•Also known as cells that displays
antigen to T lymphocytes
•Recognise and respond to microbes
during innate immune reactions
•Link innate immune reactions to
responses of the adaptive immune
system.

3. Dendritic Cells- the most important APCs
•Major type of APC that is involved in
initiating T-cell responses.
•Functions
-Activating naïve T cells
-Major roles in innate responses to infections
-Linking innate and adaptive immune
responses
•Found in: lymphoid tissues, mucosal
epithelium, organ parenchyma
-Most are part of the myeloid lineage of
hematopoietic cells.
-Maturation depends on cytokine called Plt3
ligand, which binds to the Flt3 tyrosine
kinase receptor on the precursor cells.
Long membranous projections & has phagocytic
capabilities

4. FIGURE 2-4 Maturation of dendritic cells. Dendritic cells arise from a common precursor cell of the myeloid
lineage in the bone marrow and further differentiate into subsets, the major ones being classical dendritic cells and
plasmacytoid dendritic cells. Inflammatory dendritic cells may arise from monocytes in inflamed tissues, and some
tissue-resident dendritic cells, such as Langerhans cells in the skin, may develop from embryonic precursors.

5. Other Antigen-Presenting Cells
Macrophages
B-lymphocytes
important APCs to CD4
+
helper T cells
Macrophages present
antigens to helper T
lymphocytes
helper T cell activation
and molecules that
activate macrophage
leads to

7. Cytotoxic T Lymphocytes (CTLs)
•effector CD8+ T cells
•recognise antigens on any type of nucleated cell
•activated to kill cells

8. Follicular Dendritic Cells
•cells with membranous projections
•found intermingled in collections of activated B cells
•in the lymphoid follicles of lymph nodes, spleen and mucosal
lymphoid tissues
FDCs bind and display
protein antigen on
surface
recognition by B
lymphocytes that express
antibodies

9. Lymphocytes
•A subtype of leukocytes.
•In healthy adult is about five hundred billion.
•The only cells that express clonally distributed
antigen receptors, each specific for different
antigen determinant.
•Have specific receptors for antigens
•Express the antigen receptors with single
specificity.
•Genes encoding the antigen receptors of
lymphocytes are formed by recombination of
DNA segments during the maturation of these
cells.

10. Subsets of lymphocytes
•B-lymphocytes (bone marrow derived lymphocytes)
: produce antibodies
: matured in bone marrow
•T-lymphocytes (thymus derived lymphocytes)
: mediators of cellular immunity
- originated from haematopoietic stem cells in the bone marrow.
- migrate and and mature in thymus

11. B-lymphocytes
antibodies with very limited diversity
•Follicular B cells
oProduce highly diverse antibodies.
oclonally distributed sets of antibodies that serve as cell surface antigen
receptors.
othe key secreted effector molecules of adaptive humoral immunity
•Marginal zone B cells
•B-1 cells

12. T-lymphocytes
•CD4
+
helper T lymphocytes

•CD8
+
CTLs
•CD4
+
regulatory T cells - expressing αβ receptors
-function : to inhibit immune responses
•NKT cells
•γδ T cells
•express antigen receptors called αβ T cell
receptors (TCRs)
•function as the mediators of cellular
immunity
•express TCRs with limited diversity
•analogous to the antibodies made by B-1 cells.

13. How to distinguish distinct populations of
lymphocytes
•Use membrane protein
•most helper T cells express a surface protein called CD4.
•most CTLs express a different surface protein called CD8.

16. Development of Lymphocytes
•Lymphocytes arise from the stem cells in the bone marrow
•The origin of lymphocytes from bone marrow was first demonstrated
by experiments with radiation-induced bone marrow chimeras
•Lymphocytes are radiosensitive, killed by high doses of γ-irradiation
•They go through complex maturation stages during which they
express antigen receptors and acquire the functional and phenotypic
characteristics of mature cells
•Lymphoid organs : anatomic sites where the major steps in
lymphocyte development take place. (i.e bone marrow & the thymus)
•Naive lymphocytes : mature B and T cells

17. Figure 2-5. Maturation of lymphocytes. Lymphocytes develop from bone marrow stem cells, mature in the generative
lymphoid organs (bone marrow and thymus for B and T cells, respectively), and then circulate through the blood to secondary
lymphoid organs (lymph nodes, spleen, regional lymphoid tissues such as mucosa-associated lymphoid tissues). Fully mature T
cells leave the thymus, but immature B cells leave the bone marrow and complete their maturation in secondary lymphoid
organs. Naive lymphocytes may respond to foreign antigens in these secondary lymphoid tissues or return by lymphatic
drainage to the blood and recirculate through other secondary lymphoid organs.

18. Populations of Lymphocytes Distinguished by
History of Antigen Exposure
•Mature lymphocytes that arise from the bone marrow or thymus migrate
into peripheral lymphoid organs, where they are activated by antigens to
proliferate and differentiate into effector and memory cells, which some
of them migrate into tissues.
•Steps in activation of lymphocytes :
•Syntesis of new protein – cytokine receptor & cytokine
•Proliferation
•Differentiation into effector and memory cells
•Mixtures of naive, effector, and memory lymphocytes are always present
throughout the body, and these populations can be distinguished by
several functional and phenotypic criteria.

20. NAÏVE LYMPHOCYTES

21. What are NAÏVE LYMPHOCYTES?
•Mature T or B cells found in the peripheral lymphoid organs
and circulation and NEVER encountered foreign antigens
•The term naïve refer these cells are immunologically
inexperienced in encountering antigen
•These cells will die after 1 – 3 months if they do not
recognize antigen

22. How do they function?
•Before antigenic stimulation, Naïve lymphocytes are in Go (resting stage)
•In response to stimulation, they will enter the G1 stage before going on to
divide

23. How do they survive?
•Depends in signals generated by antigen receptors and cytokines
•Postulated : Antigen receptor of naïve B cells generates signals in the absence of
antigen, while naïve T lymphocytes recognize various self antigens weakly but
enough to generate survival signals without triggering initiate clonal expansion
•Cytokines are also essential in survival of naïve lymphocytes
•The most important cytokines  Interleukin-7 (IL-7) promotes survival and low-
level cycling of naïve T-cells
•B cell-activating factor (BAFF); cytokine belonging to TNF family, required for
naïve B cell survival

24. •When spontaneous death and production of new cells (generative
lymphoid organs), (pool of naïve cell is maintained)  STEADY STATE
•Any loss of lymphocytes leads to compensatory proliferation of the
remaining and increased output from the generative cell
•Homeostatic proliferation  ability of lymphocyte to fill the available
space

25. EFFECTOR LYMPHOCYTES

26. What are Effector Lymphocytes?
•After naïve cell are activated  LARGER and PROLIFERATE
EFFECTOR LYMPHOCYTES
•Ability to produce molecules that are capable of eliminating foreign
antigens
•Effector T lymphocytes: helper T cells and CTLs
•Effector B Lymphocytes: antibody-secreting cells
differentiate

27. •Helper T cells (CD4+) express surface molecule such as CD40 and secrete
cytokines that bind to receptors on macrophage and B lymphocytes
leading to their activation
•CTLs (cytoplasmic granules  proteins) when release kill the cells that are
recognized by CTLs
•Many antibody-secreting B cells are morphologically identifiable as
plasma cells
•Plasmablasts, which are circulating precursors of long-lived tissue plasma
cells and can be found in low numbers in blood

28. MEMORY LYMPHOCYTES
•Both B-lymphocytes and T-lymphocytes can form memory cells after encountering
pathogen in the body.
•Function: Allow the body to ‘remember’ the pathogens that it has already
encountered and hence, produce a much faster immune response to them during
a second exposure.
•Memory cells appear to be heterogeneous
Second exposure triggers more
antibodies to be produced in a
shorter period of time

29. MEMORY T CELLS: BASIC
PROPERTIES
•Memory T cells exhibit rapid effector cytokine production within
hours of stimulation, whereas naive T cells require days of sustained
activation to differentiate into effector cytokine producers.
•This “rapid recall” response is the defining feature of memory CD4
and CD8 T cells ; express high level of IL-7 receptor.
• Memory T cells differ from naive T cells in their elevated expression
of adhesion markers CD45RO (A exon RNA has been spliced out)
•Express surface molecules that promote their migration into sites of
infection anywhere in the body.

30. Memory B- cells
•Express certain classes of isotopes of membranes Ig as a
result of isotope switching.
IgG-promotes opsorization
IgE-responsible for intermediate reaction
IgA-prevent attachment of pathogen to epithelium
•Memory B cells proliferate and differentiate rapidly into
plasma cell to produce more antibody
•Antibody tend to have greater affinity for antigen
•The immunity is long lasting

31. INNATE LYMPHOID CELLS (ILCs)
•A group of innate immune cells that belong to the lymphoid
lineage (lymphocytes) but do not respond in an antigen-
specific manner because lack of B/T cell receptor.
•Roles :
Provide early defense against infectious pathogens
Regulating tissues of homeostasis and inflammation
•ILCs can be divided based on the cytokines that they can
produce and the transcription factor that regulate their
development and function.

32. Group 1 ILCs Group 2 ILCs Group 3 ILCs
1.Nature Killer (NK) cells
Secrete Cytokine IFN-γ
Killed infected and
damaged cells
Typically associated with
tumor surveillance,
inflammation, and
immunity against viruses
and intracellular
pathogens
1.Lack T and B cells
vital for anti-helminth
responses and allergic lung
inflammation
1.LTi (lymphoid tissue
inducer) cells are a
subset of group 3 ILCs
primarily involved with
secondary lymphoid
organ formation during
embryogenesis.
2.They are capable of
making
IL-17A and IL-22 after
stimulation