3 Microbiology: Adaptive (Specific, Acquired) Immunity (not done) Flashcards
Adaptive immune responses are generated by what?
clonal selection of lymphocytes.
What is the adaptive immune response?
the response of antigen-specific lymphocytes to antigen, including the development of immunologic memory.
In the earliest stages of infection, innate responses do what?
predominate, but later the lymphocytes start to generate adaptive immune responses.
Adaptive immune responses display what four characteristic features?
Antigenic specificity
Diversity
Immunologic memory
Self/nonself recognition
Describe Antigenic specificity
Lymphocytes can distinguish subtle differences between two molecules that differ by only a single amino acid.
Describe Diversity
The immune system is capable of generating tremendous diversity in its recognition molecules, allowing it to specifically recognize billions of uniquely different structures on foreign antigens.
Describe Immunologic memory
Once a lymphocyte has recognized and responded to an antigen, it exhibits immunologic memory, ie, it also “remembers” the pathogen, and mounts a more effective and rapid response should the individual or animal become reinfected with the same pathogen at a later date.
Describe Self/nonself recognition
The immune system normally responds only to foreign antigens indicating that it is capable of self/nonself recognition.
What are antigens?
are substances capable of inducing a specific immune response.
An antigen is the initiator and driving force for all adaptive immune responses.
The immune system has evolved to do what?
to recognize antigens, destroy them and eliminate the source of their production—bacteria, virally infected cells, etc.
When antigen is eliminated, immune responses switch off.
Antigens are generally very large and complex, therefore they are not what?
they are not recognized in their entirety by lymphocytes.
Instead, both B and T lymphocytes recognize discrete sites on the antigen called antigenic determinants or epitopes.
What are Epitopes?
are the immunologically active regions on a complex antigen, the regions that actually bind to B cell receptors and antibodies or T cell receptors.
What is polyvalent?
A particular antigen can have several different epitopes
What is multivalent?
A particular antigen can have repeated epitopes
Why are Lymphocytes central to all adaptive immune responses?
they specifically recognize individual pathogens.
In addition to lymphocytes what also play an essential role in the adaptive immune response?
accessory cells such as antigen-presenting cells
Lymphocytes and accessory cells are localized and concentrated where?
in anatomically defined organs or tissues that constitute the lymphoid system.
Classification of Lymphoid Organs and Tissues is based on?
(1) the level to which they participate in the matu- ration of lymphocytes and
(2) provision of a suitable environment for the inter- action between foreign antigen and T and B lymphocytes.
Central [Primary] lymphoid organs regulate what?
regulate production and maturation of lymphocytes from lymphoid stem cells, ie, generate lymphocytes that are individually different to meet the threat posed to an animal by the large number of microbial pathogens, the concept being “one cell, one specificity.”
What are the Central [Primary] lymphoid organs of mammals?
Bone marrow, Thymus
What are the Central [Primary] lymphoid organs of avian?
Bursa of Fabricius, Thymus
Peripheral [Secondary] lymphoid organs provide what?
Provide the environment where ma- ture lymphocyte responses to foreign antigens are initiated and develop.
List the Peripheral [Secondary] lymphoid organs
Spleen
Lymph nodes
Mucosa-associated lymphoid tissue [MALT]
The spleen responds to what?
Responds to blood-borne antigens.
The lymph nodes respond to what?
Respond to lymph-borne antigens, ie, antigens entering the body via the skin and mucosa or from parenchymal organs and connective tissues.
Mucosa-associated lymphoid tissue [MALT] does what?
Includes all the lymphoid tissues associated with mucosae, eg, Peyer’s patches, tonsils, etc. Protects the mucosal surfaces.
What is the Major Histocompatibility Complex (MHC)?
is a complex of genes found in all mammals that encode cell- surface MHC molecules responsible for:
(1) the rapid rejection of grafts between individuals and
(2) antigen presentation to T cells.
What are Class I MHC molecules?
Expressed on the cell membranes of most nucleated cells except neurons, erythrocytes, and cells in early embryonic life.
Bind to pep- tides derived from cytosolic proteins [endogenous antigens] and present them to cytotoxic T cells.
What are Class II MHC molecules?
Expressed on the cell membranes of professional antigen presenting cells [macrophages, dendritic cells, and B cells].
Bind to pep- tides derived from endosomal antigens [exogenous antigens] and present them to helper T cells.
T lymphocytes arise from what?
arise from lymphoid stem cells in the bone marrow.
Unlike B lym- phocytes, which mature in the bone marrow, pre-T cells migrate to what to mature?
the thymus gland to mature.
During its maturation within the thymus, the T cell expresses a what?
a unique antigen-binding receptor on its membrane, called the T cell receptor.
The process of T cell maturation also involves what?
random rearrangements of a series of gene segments encoding the cell’s antigen receptor.
Each T lymphocyte expresses about how many receptors per cell?
10^5 receptors per cell, and all 10^5 receptors on a cell and its clonal progeny have identical specificity for antigen.
T cell receptors can only recognize antigen that is associated with what?
cell membrane proteins called major histocompatibility complex [MHC] molecules.
What happens when a naïve T cell encounters antigen associated with an MHC molecule on a cell?
the T cell proliferates and differentiates into memory T cells or effector cells.
What are the two subpopulations of T cells?
T helper cells [TH] and cytotoxic T [Tc] cells.
TH cells express what?
CD4 membrane glycoproteins
Tc cells express what?
CD8 membrane glycoproteins.
Activation of both the humoral and cell-mediated branches of the adaptive im- mune system requires what?
cytokines secreted by TH cells
TH cells can only recognize what?
protein antigen that is displayed together with MHC class II molecules on the surface of antigen-presenting cells [APCs].
What are antigen-presenting cells [APCs]?
are specialized cells that are distinguished by two properties:
(1) they ex- press class II MHC molecules on their cell membrane and
(2) they are able to deliver a costimulatory signal that is necessary for TH cell activation.
The APC population is made up of what?
macrophages, B lymphocytes, and dendritic cells.
APCs first internalize antigen, either by what or what?
phagocytosis or by endocytosis, and then degrade the ingested exogenous antigen into peptide fragments within the endosome [phagosome].
The peptide fragments bind to class II MHC mo- lecules and the peptide- MHC complexes are exported to the cell surface, to be identified by what?
antigen-specific TH cell.
TH cell interacts with the peptide-MHC complex via the what?
antigen-binding T cell receptor and CD4 molecules on the TH cell membrane.
This interaction generates a signal that, together with a costimulatory signal, leads to
the synthesis of the cytokine interkeukin-2 [IL-2] and interleukin 2 receptors [IL-2Rs].
If the IL-2Rs are bound by IL-2 [T cell autocrine growth factor], the cell undergoes what?
clonal expansion and differentiation of the daughter cells mostly into effector cells and a small population of antigen-specific memory cells.
What do Effector TH cells do?
They secrete the cytokines that play an important role in activating B cells, Tc cells, macrophages, and various other cells that participate in the immune response.
What do Memory TH cells do?
They account for the increased and accelerated response on subsequent exposure to the same antigen.
What is Cell-Mediated Immunity (CMI)?
are host immune responses that are mediated by antigen-specific T cells and various nonspecific cells [macrophages and NK cells] of the immune system.
What serve as effector cells in cell-mediated immune reactions?
Both activated TH cells and Tc cells.
Transfer of primed [activated] T cells confers this type of immunity on the recipient.
CMI protects against what?
intracellular bacteria, viruses, and tumors and is responsible for graft rejection
Cytotoxic T cells (Cytolytic T Lymphocytes) express what on their membranes?
antigen-specific T cell receptors and CD8 molecules
Cytotoxic T cells (Cytolytic T Lymphocytes) respond to what?
to endogenous [cytosolic] antigens presented in association with class I MHC molecules.
Cytotoxic T cells (Cytolytic T Lymphocytes) destroy what?
destroy virus-infected cells, tumor cells, and cells of a foreign tissue graft.
What is a Cytosolic [Endogenous] antigen?
This is an antigen produced within the host cell itself, eg, viral proteins synthesized within virus-infected host cells and unique proteins synthesized by tumor cells.
Cytosolic [Endogenous] antigen are degraded into what?
degraded into peptide fragments that bind to class I MHC molecules within the endoplasmic reticulum. The peptide-class I MHC complex is then transported to the cell membrane.
What type of receptors recognize and bind to the peptide-class I MHC complex on the cell surface?
CTLs displaying CD8 and antigen-specific T cell receptors
Activation of antigen-specific naive CTL and its subsequent proliferation and differentiation into effector CTLs requires two signals: what are they?
signal1 [antigen recog- nition] and
signal 2 [provided by co-stimulators expressed on professional APCs or by cytokines produced by activated helper T cells].
Following contact with the target cell, effector CTL mediates target cell death by doing what?
releasing perforins and granzymes
Prior to cell death, the CTL dissociates itself from the what?
the target cell to find another target cell.
As the antigen is eliminated, many of the effector CTLs die by apoptosis.
What are Perforins?
Form pores on the membrane of the target cell.
What are Granzymes?
Activate the target cell’s endogenous apoptotic pathway.
A small fraction of daughter CTLs differentiate to become what?
memory CTLs.
A number of pathogens, including some bacteria, fungi, and protozoa, have developed strategies for surviving and proliferating within what?
normal macrophages; this may result in the killing of the macrophage.
What can activate macrophages to become highly microbicidal?
Interferon-y released by helper T cells.
thereby killing the otherwise resistant intracellular parasites.
B lymphocytes mature within what?
the bone marrow
B lymphocytes leave the bone marrow expressing a what?
a unique antigen-binding receptor on their cell membrane.
What type of molecule is The B cell receptor?
a membrane-bound immunoglobulin [antibody] molecule.
As a B cell matures in the bone marrow, its specificity is generated by what?
by random rearrangements of a series of gene segments encoding the antibody molecule.
As a B cell matures in the bone marrow, its specificity is generated by random rearrangements of a series of gene segments encoding the antibody molecule.
WHAT IS A RESULT OF THIS?
each mature B cell possesses a single functional gene encoding the antibody heavy chain and a single functional gene encoding the antibody light chain; the cell therefore synthesizes and displays antibody with one specificity on its cell membrane.
About 10^5 antibody molecules are present on a single B cell.
How is a Mature B Cell antigenically committed?
All 10^5 antibody molecules on a given B cell have identical specificity, giving each B lymphocyte, and the clone of daughter cells to which it gives rise, a distinct specificity for antigen.
What does Humoral mean?
is derived from the Latin humor, meaning “body fluid”
Humoral immunity refers to what?
immunity that can be conferred on a nonimmune individual by administration of serum antibodies from an immune individual.
What do B cells combat and how?
extracellular pathogens and their toxins by releasing antibodies.
Interaction of the mature B cell in a peripheral lymphoid organ [eg, spleen, tonsils, lymph node, etc] and the antigen, triggers what?
internalization of the antigen by receptor-mediated endocytosis.
What happens after the B cell processes the antigen?
the B cell presents the resulting antigenic peptides together with a class II MHC molecule on its membrane. A TH cell specific for the processed antigen-MHC complex then binds to the complex; as a result of this interaction, the TH cell secretes a number of cytokines that stimulate various stages of B cell division and differentiation.
The activated B cell undergoes a series of cell divisions, differentiating into a population off what?
antibody-secreting plasma cells and memory cells.
What cells do not express membrane-bound antibody?
Plasma cells.
instead they produce antibody in a form that can be secreted. Although plasma cells live for only a few days [less than a week], they secrete enormous amounts of antibody during this time.
It has been estimated that a single plasma cell can secrete more than 2,000 molecules of antibody per second.
Memory B cells express what?
express membrane-bound antibody with the same specificity as the original parent naïve B cell, but have a longer life span than the naive lymphocytes from which they arise.
What are antibodies?
are plasma proteins secreted by plasma cells in response to antigenic stimulation of naive B cells.
The basic structure of the antibody molecule consists of what?
two identical heavy polypeptide chains and two identical light polypeptide chains.
The chains are held together by disulfide bonds.
What on the antibody form a cleft within which antigen binds?
The amino terminal ends of each pair of heavy and light chains [called variable regions]
What determines the antibody class?
The sequence of amino acids of the constant region of the heavy chain
A normal healthy individual or animal produces what five antibody classes?
IgA IgG IgM IgE IgD
Describe IgM
is made during the first exposure to an antigen.
It is also the first antibody made by newborns.
Because of its large size [pentameric IgM], it is mostly confined to the bloodstream. Monomeric IgM and IgD function as antigen receptors [B cell receptors] on naive B cells.
Describe IgG
is made when the animal has been exposed to an antigen for a long time or when the animal is exposed to the antigen for the second time.
Describe IgA
is the predominant antibody in secretions.
It plays an important role in preventing diseases caused by organisms that may enter the body through mucosal surfaces [eg, respiratory and gastrointestinal tracts].
Describe IgE
is associated with anaphylactic reactions and immunity to parasites.
Describe IgD
Functions as B cell receptor [BCR] on naive B cell.
How does an antibody function?
as the effector molecule of the humoral immune response by binding to antigen and neutralizing it or facilitating its elimination.
When an antigen is coated with antibody, it can be eliminated in what several ways?
Antibody can cross-link the antigen forming clusters that are more readily ingested by phagocytic cells.
Binding of antibody to antigen on a microbe can activate the complement system, resulting in the lysis of the foreign organism.
Antibody can neutralize bacterial toxins or viral particles by coating them and preventing their subsequent binding to host cells.
The initial encounter of a naive immunocompetent B lymphocyte with its antigen induces what?
a primary response
a second contact with the same antigen will induce a more rapid and stronger secondary response.
The initial primary response has a lag of what (how long) before antibody levels start to rise?
~ 5-7 days.
This lag is the time required for activation of naive B cells by antigen and TH cells and for the subsequent proliferation and differentiation of the activated B cells into plasma cells.
Antibody levels peak in the primary response at about what day?
day 14 and then begin to drop off as the plasma cells begin to die.
In the secondary response [booster, anamnestic, memory], the lag is how long?
is much shorter [1- 3 days] and antibody levels are much higher and are sustained for a much longer time.
The secondary response reflects the response of the clonally expanded population of what?
memory B cells.
memory B cells respond to the antigen How compared to the naive B cells?
more rapidly than the naive B cells; in addition, because there are many more memory cells than naive B cells, larger numbers of plasma cells are generated during the secondary response and antibody levels are consequently 100-fold to 1000-fold higher.
