TOPIC
I2
ADAPTIVE: T-CELL MEDIATED IMMUNITY
ADAPTIVE (SPECIFIC) IMMUNE SYSTEM
Highly specialized mechanisms of the immune system that once activated by innated immune system has the ability to
recognize and remember specific pathogens and mount stronger attacks each time the pathogen is encountered
– Stimulated by exposure to infectious agent
– May be either humoral immunity OR Cell-Mediated depending on the microbe
– The interaction of antigens with antigen receptors induces lymphocytes to acquire effector and generating
immunological memory.
Humoral Immunity (B CELLS) Cell-Mediated Immunity (T CELLS)
Immunity can be transferred from one individual to Immunity can be transferred from one individual to
another via serum another via effector cells
The immunity is due to the formation of antibodies Due to formation of activated cells
Important functions of antibodies is to neutralize Important function of the activated cells is to destroy
toxins and infectious organisms infected or foreign cells
– Involves mainly lymphocytes (B and T) and dendritic cells
– Takes more time to mobilize than innate system
– 5 Features:
o >It is specific: recognizes pathogens and antigens
o >it is systemic: immunity isn’t restricted to initial infection site
o >it has memory: adaptive responses are called action as ‘reinforcements’
o >self-limitation: immune response wanes off following elimination of antigens
o >self-tolerance: immune system non-reactive to self-antigens
3 Phases:
1. Recognition Phase: TLRs & PRRs on Macrophages & Dendritic Cells recognize PAMPs on the Antigens, & engulf
them via Phagocytosis. The Antigen is processed, and bits of it are displayed on their cell surfaces to be
‘presented’ to T-Lymphocytes. Activated Macrophages & damaged epithelia
secrete pro-inflammatory cytokines to attract more immune cells.
2. Activation Phase: Activated Dendritic Cells migrate to Lymph Nodes, where they activate Naive T Cells à Which
activate Naive B-Cellsà secrete Antibodies.
3. Effector Phase: Active T-Cells, as well as the secreted Antibodies, leave the Lymph Node and head back to fight
the infection via the LymphàBlood.
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– Roles
o Tremendously amplifies the inflammatory response
o Attack specific foreign substances- incl. antigens and abnormal body cells
o Mounts stronger attacks on previous encountered pathogens
Antigen-Presenting Cells:
(The link between the Innate & the Adaptive Immune Systems) - Cells that engulf & process antigens, and then present
fragments of them, like signal flags, on their own surfaces where they are recognized by T-Cells (Helper & Cytotoxic). NB:
T-Cells are unable to independently recognize Antigens, & hence require Antigen Presentation). Such APCs include:
- #1 Dendritic Cell: The most efficient APC. Upon recognition of an infectious particle, it ingests & processes the antigen,
and displays it on its cell surface, bound to either MHC-I or MHC-II. (NB: because Dendritic Cells present via MHC-I & -II,
they can present antigens to both Helper-T-Cells AND Cytotoxic-T-Cells.) The Dendritic Cell then migrates to the nearest
Lymph Node and activates ‘Naive’ T-Cells, which then leave the lymph nodes & travel to the site of infection.
#2 Macrophages: Part of the Innate Response. They possess various TLRs (Toll-like Receptors) that recognize patterns
(PAMPs) on foreign organisms, which when activated, causes processing & presentation of the antigen via MHC-II, as
well as Cytokine Secretion. pMHC-II then allows T-helper-Cells to bind to & further activate the Macrophage à More
Phagocytic.
-#3 B-Lymphocytes: The least efficient APC. Each recognizes a specific antigen via its immunoglobulin-based surface
receptors. Once ingested, the antigen is presented via MHC-II to T-Helper-Cells. The T-Helper Cell
then Activates the B-Cell à Differentiates into a Plasma Cell à Secretes Antibodies.
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CELL MEDIATED IMMUNITY
CD8/CD4 T CELLS
T CELLS
– T-cells develop in thymus and then enter the bloodstream
– Once they reach a secondary lymphoid organ, they leave the blood stream and migrate through lymphoid tissue,
returning via lymphatics to blood
– Mature circulating T cells who have not encountered antigen are called naïve T cells
– Once they encounter antigen with MHC, they proliferate and differentiate into cells called effector T cells
– Adaptive immune responses are initiated in the secondary lymphoid organs:
1. Spleen
2. lymph nodes
3. MALTs (Peyer’s patch in gut)
– T and B cells are partitioned into distinct regions of secondary lymphoid tissues by the actions of chemokines.
Antigen from lumen via Microfold
Antigen via arterioles which
(M) cells to dendritic cells in sub-
Antigen free or as cargo in dendritic branch from central arteriole
epithelial region
cells. to marginal sinus
Delivered to B-cell/T-cell zones In marginal zone antigen is
Under M cells dendritic cells
B/T cells enter from HEV: high taken by APC to Tcell zones
sitting there to detect B or T cell
endothelial venules or B cell follicles
T and B cells are partitioned into distinct regions of secondary lymphoid tissues by the actions of chemokines
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STEPS FOR MOVEMENT OF DENDRITIC CELLS TO T CELL/B CELL :
1. Circulating B and T cells come to secondary organs by common route. Then they move into distinct regions under
control of chemokines
2. Stromal cells and Bone marrow derived cells in B-T cell zones produce cytokines. Produce CCL21
3. CCL21 (LIGAND) binds to CCR7 ( RECEPTOR) on T-cells, Bcells and dendritic cells
4. Dendritic cells migrate. Secrete CCL19, attract T cells
5. B cells also follow path
TYPES OF DENDRITIC CELLS
Arise from myeloid progenitor cells within bone marrow. Migrate via blood to tissues throughout the body or directly to
secondary lymphoid organs.