Chapter6 Diseases of the Immune response: OVERVIEW OF LYMPHOCYTE ACTIVATION AND IMMUNE RESPONSES Flashcards Preview

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Flashcards in Chapter6 Diseases of the Immune response: OVERVIEW OF LYMPHOCYTE ACTIVATION AND IMMUNE RESPONSES Deck (39):
1

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

2

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

3

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

4

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.

5

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).

6

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.

7

 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.

8

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

9

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

10

The best
defined subsets of differentiated CD4+ helper cells are the :

TH1 and TH2 subsets.

11

What does TH1 subset secrete?

 

 

Cells of the
TH1 subset secrete the cytokine IFN-γ, which is a potent macrophage activator. 

12

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

13

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.

14

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]

 

15

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.

16

TH1

 

  1. cytokines produced:
  2. Cytokines that induced this subset:
  3. Immunological reactions triggered:
  4. Host defense against:
  5. Role in disease:

  1.  IFN- y
  2. IFN-y and IL -12
  3. Macrophage activation and IgG stimulation
  4. Intracellular microbes
  5. Immune- mediated chronic inflammatory diseases ( often autoimmune)

17

TH2

  1. cytokines produced:
  2. Cytokines that induced this subset:
  3. Immunological reactions triggered:
  4. Host defense against:
  5. Role in disease:

  1. IL-4, IL-5, IL-13
  2. IL-4
  3. Stimulation of IgE production, Activation of mast cells and  Eosinophils
  4. Helminthic parasites
  5. Allergies

18

TH17

  1. cytokines produced:
  2. Cytokines that induced this subset:
  3. Immunological reactions triggered:
  4. Host defense against:
  5. Role in disease:

  1. IL-17, IL-22 and chemokines
  2. TGF- B, IL-6, IL-1, IL-23
  3. Recruitment of neutrophils, monocytes
  4. Extracellular fungi and bacteria
  5. Immune-medicated chronic diseases ( often autoimmune)

19

Activated CD8+ lymphocytes differentiate into_______________

 CTLs that kill cells harboring microbes in the
cytoplasm. By destroying the infected cells, CTLs eliminate the reservoirs of infection.

20

What happens in Humoral Immunity?

Humoral Immunity:

Activation of B Lymphocytes and Elimination of Extracellular Microbes

21

Upon activation,what happens to B lymphocytes _____________

 

proliferate and then differentiate into plasma cells that secrete
different classes of antibodies with distinct functions ( Fig. 6-12 ). 

22

What initiates the process of B-cell activation?

 

 

Typical
globular protein antigens are not able to bind to many antigen receptors, and the full response
of B cells to protein antigens requires help from CD4+ T cells. [24] B cells ingest protein
antigens into vesicles, degrade them, and display peptides bound to MHC molecules for
recognition by helper T cells. The helper T cells express CD40L and secrete cytokines, which
work together to activate the B cells.

Many polysaccharide and lipid
antigens have multiple identical antigenic determinants (epitopes) that are able to engage many antigen receptor molecules on each B cell and initiate the process of B-cell activation. 

23

Typical globular protein antigens are not able to bind to many antigen receptors, and the full response
of B cells to protein antigens requires help from __________. [24] 

CD4+ T cells

 

B cells ingest protein
antigens into vesicles, degrade them, and display peptides bound to MHC molecules for
recognition by helper T cells. The helper T cells express CD40L and secrete cytokines, which
work together to activate the B cells.

24

Each plasma cell secretes ____________

 

 

antibodies that have the same antigen binding site as the cell
surface antibodies (B-cell receptors) that first recognized the antigen. 

 

25

What stimulate secretion mainly of IgM antibody.?

 

Polysaccharides and
lipids stimulate secretion mainly of IgM antibody. 

26

What induce the production of antibodies of different classes or isotypes ( IgG, IgA, IgE)

 

 

Protein antigens, by virtue of CD40L- and
cytokine-mediated helper T-cell actions, induce the production of antibodies of different
classes, or isotypes (IgG, IgA, IgE). 

27

The humoral immune response combats microbes in many ways

  1. Neutralization of the microbes and toxins
  2. Opsonization and phagocytosis
  3. Ab dependent cytoxicity
  4. Complement Activation
    1. Lysis of microbes
    2. Phagocytosis
    3. Inflammation

28

Cytokines that induce isotype switching include I________

FN-γ and
IL-4.

29

What is affinity maturation?

Helper T cells also stimulate the production of antibodies with high affinities for the
antigen. This process, called affinity maturation, improves the quality of the humoral immune
response.

 

30

Isotype switching and affinity maturation occur mainly in ______________

germinal centers, which are
formed by proliferating B cells, especially in helper T cell-dependent responses to protein
antigens.

31

What happens in " neutralizing"?

Antibodies
bind to microbes and prevent them from infecting cells, thus “neutralizing” the microbes.

32

What does IgG do?

IgG
antibodies coat (“opsonize”) microbes and target them for phagocytosis, since phagocytes
(neutrophils and macrophages) express receptors for the Fc tails of IgG

33

What antibodies activate the complement system?

IgG and IgM activate
the complement system by the classical pathway, and complement products promote
phagocytosis and destruction of microbes.

The production of most opsonizing and complementfixing
IgG antibodies is stimulated by TH1 helper cells, which respond to many bacteria and
viruses; thus, the protective response to most bacteria and viruses is driven by TH1 cells.

Some
antibodies serve special roles at particular anatomic sites

34

What antibody is secreted from the mucosal epithelia and neutralizes microbes in the lumens of the respiratory tract?

IgA is secreted from mucosal
epithelia and neutralizes microbes in the lumens of the respiratory and gastrointestinal tracts
(and other mucosal tissues)

 

 

 

35

Which antibody is actively transported across the placenta and protects the
newborn until the immune system becomes mature.

IgG

 

G for Gestational

36

What does IgE do?

IgE and eosinophils cooperate to kill
parasites, mainly by release of eosinophil granule contents that are toxic to the worms.

As
mentioned above, TH2 cells secrete cytokines that stimulate the production of IgE and activate
eosinophils, and thus the response to helminths is orchestrated by TH2 cells

37

Most circulating IgG antibodies have half-lives of about ________.

 

3 weeks

 

Some antibody-secreting
plasma cells migrate to the bone marrow and live for years, continuing to produce low levels of
antibodies.

38

Discuss the decline of Immune Responses and Immunological Memory

The majority of effector lymphocytes induced by an infectious pathogen die by apoptosis after
the microbe is eliminated, thus returning the immune system to its basal resting state, called
homeostasis.

 

The initial activation of lymphocytes also generates long-lived memory cells,
which may survive for years after the infection. Memory cells are an expanded pool of antigenspecific
lymphocytes (more numerous than the naive cells specific for any antigen that are
present before encounter with that antigen), and that respond faster and more effectively when
re-exposed to the antigen than do naive cells. [25]

This is why the generation of memory cells is
an important goal of vaccination

 

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