Chapter6 Diseases of the Immune response: OVERVIEW OF LYMPHOCYTE ACTIVATION AND IMMUNE RESPONSES Flashcards
All adaptive immune responses develop in steps, consisting of: _____________
,_______________________,
,_______________.
The major events in each step are summarized below; these general principles apply
to protective responses against microbes as well as pathologic responses that injure the host
- antigen recognition,
- activation of specific lymphocytes to proliferate differentiate into effector and memory cells,
- elimination of the antigen
- , and decline of the response, with memory cells being the long-lived survivors
What is clonal selection hypothesis?
Lymphocytes specific for a large number of antigens exist before exposure to the antigen, and
when an antigen enters, it selects the specific cells and activates them.
This fundamental
concept is called the clonal selection hypothesis.
According to this hypothesis, antigen-specific
clones of lymphocytes develop before and independent of exposure to antigen.
The cells
constituting each clone have identical antigen receptors, which are different from the receptors
on the cells of all other clones.
It is estimated that there are about 10 7 to 10 9 different
specificities in the total pool of about 10 12 lymphocytes in an adult, and therefore, at least this
many antigens can be recognized by the adaptive immune system.
It follows that the number of
lymphocytes specific for any one antigen is very small, probably less than 1 in 100,000 to 1 in 1
million cells. To permit a small number of lymphocytes to find antigen anywhere in the body, the
immune system has specialized mechanisms for capturing antigens and displaying them to
lymphocytes.
Microbes and their protein antigens are captured by dendritic cells that are
resident in epithelia and tissues. These cells carry their antigenic cargo to draining lymph
nodes ( Fig. 6-10 ). [19] Here the antigens are processed and displayed complexed with MHC
molecules on the cell surface
The Display and Recognition of Antigens
- Cell-Mediated Immunity: Activation of T Lymphocytes and Elimination of Intracellular Microbes
- Humoral Immunity: Activation of B Lymphocytes and Elimination of Extracellular Microbes
Describe what happens in Cell-mediated immunity.
Dendritic cells (DCs) capture microbial antigens from epithelia and tissues and transport the antigens to lymph nodes.
During this process, the
DCs mature, and express high levels of MHC molecules and costimulators.
- *Naive T cells**
- *recognize MHC-associated peptide antigens displayed** on DCs.
The T cells are activated to
proliferate and to differentiate into effector and memory cells, which migrate to sites of
infection and serve various functions in cell-mediated immunity.
CD4+ effector T cells of the
TH1 subset recognize the antigens of microbes ingested by phagocytes, and activate the
phagocytes to kill the microbes.
CD4+ T cells also induce inflammation. CD8+ cytotoxic Tlymphocytes (CTLs) kill infected cells harboring microbes in the cytoplasm.
Not shown are
TH2 cells, which are especially important in defense against helminthic infections. Some
activated T cells differentiate into long-lived memory cells. APC, antigen-presenting cell.
B lymphocytes use their antigen receptors (membrane-bound antibody molecules) to recognize
antigens of many different chemical types, including proteins, polysaccharides, and lipids.
At the same time as the antigens of a microbe are recognized by T and B lymphocytes, the microbe elicits an innate immune response; in the case of immunization with a protein antigen,
the innate response is induced by the adjuvant given with the antigen.
During this innate
response the microbe activates APCs to express molecules called costimulators and to secrete
cytokines that stimulate the proliferation and differentiation of T lymphocytes. The principal
costimulators for T cells are the B7 proteins (CD80 and CD86) that are expressed on APCs and
are recognized by the CD28 receptor on naive T cells. [20] Thus, antigen (“signal 1”) and
costimulatory molecules produced during innate immune responses to microbes (“signal 2”)
function cooperatively to activate antigen-specific lymphocytes (see Fig. 6-3 ).
The requirement
for microbetriggered signal 2 ensures that the adaptive immune response is induced by
microbes and not by harmless substances. In immune responses to tumors and transplants,
“signal 2” may be provided by substances released from necrotic cells (the “danger-associated
molecular patterns” mentioned earlier).
One of the earliest responses of CD4+ helper T cells is
secretion of the __________
cytokine IL-2 and expression of high-affinity receptors for IL-2.
What is IL 2?
IL-2 is a growth
factor that acts on these T lymphocytes and stimulates their proliferation, leading to an increase
in the number of antigen-specific lymphocytes.
The functions of helper T cells are mediated by
the combined actions of _________.
When CD4+ helper T cells
recognize antigens being displayed by macrophages or B lymphocytes, the T cells express
CD40L, which engages CD40 on the macrophages or B cells and activates these cells.
CD40-ligand (CD40L) and cytokines
What are effector cells?
Some of the progeny of the expanded T cells differentiate into effector cells that can secrete
different sets of cytokines, and thus perform different functions
The best
defined subsets of differentiated CD4+ helper cells are the :
TH1 and TH2 subsets.
What does TH1 subset secrete?
Cells of the
TH1 subset secrete the cytokine IFN-γ, which is a potent macrophage activator.
The
combination of CD40- and IFN-γ–mediated activation results in the ____________.
induction of microbicidal
substances in macrophages, leading to the destruction of ingested microbes
What does TH2 produce?
TH2 cells produce
- *IL-4**, which stimulates B cells to differentiate into IgE-secreting plasma cells, and IL-5, which
- *activates eosinophils**.
Eosinophils and mast cells bind to IgE-coated microbes such as
helminthic parasites, and function to eliminate helminths.
What is the third subset of CD4+ T cells?
A third subset of CD4+ T cells that has
been discovered recently is called the TH17 subset because the signature cytokine of these
cells is IL-17. [22,] [23]
What are TH17?
TH17 cells are powerful recruiters of neutrophils and monocytes, and
thus play major roles in several inflammatory diseases.
They may also be important for defense
- *against some bacterial and fungal infections** in which neutrophilic inflammation is a prominent
- *feature**.
We will return to the generation and functions of these subsets when we discuss
hypersensitivity reactions.
