1. Dendritic Cells
They respond to microbes by producing numerous cytokines
that initiate inflammation. They also serve as vehicle in
transporting the antigen(s) from the skin and mucosal sites to
lymph nodes where they present the antigen(s) to T cells.
Hence, dendritic cells serve as a bridge between innate and
acquired immunity.
2. ANTIGEN PRESENTATION
For induction of immune responses, recognition of antigens by T cells is
essential. T cells cannot recognize the native and free antigens, but they do so
only after the antigen is processed into smaller antigenic peptides containing
specific epitopes which are subsequently combined with MHC molecules (class I
or II)
Antigen-presenting Cells (APCs)
•Antigen presentation refers to presentation of antigenic peptide to both TH
(helper T cells) and TC (cytotoxic T cells) by complexing with MHC-II and I
respectively.
•However, antigen-presenting cells (APCs) in strict sense implies only to those
cells (e.g. dendritic cell, macrophage, etc.) that present the antigenic peptide
along with MHC class II to TH cells
3. Dendritic cells, macrophages and B cells are the major APCs and
are called professional APCs. There are some other non-
professional cells that can occasionally present antigens to helper
T cells.
4. Antigen Processing Pathways
For induction of immune response (both Cell-mediated Immune Response (CMI)
and Humoral or Antibody-mediated Immune Response (AMI), antigens must be
presented to TH cells. In addition, for CMI induction, antigen presentation to TC
cells is essential.
Two well defined pathways are used by the immune system for this purpose.
Cytosolic pathway: Here, the endogenous (intracellular) antigens such as viral
antigens and tumor antigens are processed and presented along with MHC class I
molecules to CD8 T cells.
2. Endocytic pathway: In this pathway, the exogenous antigens (extracellular
microbes and their products, e.g. toxins) are processed and complexed with MHC
class II molecules and presented to TH cells
6. Cell mediated immunity and their role
The term cell-mediated immune response (CMI) refers to destruction
of cells carrying intracellular microbes and other abnormal cells,
such as tumor cells by various specific and nonspecific cells of
immune system, of which the most important is cytotoxic T (TC) cells.
Role of CMI
Provides immunity against microbes residing in intracellular milieu:
„
. For obligate intracellular organisms, CMI remains the only
effective immune response. Examples include all viruses, some
bacteria (Mycobacterium, Chlamydia and Rickettsia), some parasites
(Plasmodium, Leishmania, Trypanosoma and Cryptosporidium)
and some fungi (Pneumocystis)
„
. For facultative intracellular organisms, humoral immunity is active
as long as the organism is extracellular. Once they come to
intracellular milieu, CMI takes the leading role. Examples include
Bacteria like Listeria, Salmonella and Yersinia and fungi such
as Histoplasma and Cryptococcus.
7. Provides immunity against tumor cells and other damaged and
altered cells
Mediates delayed hypersensitivity (type IV hypersensitivity)
™
Plays key role in transplantation immunity and graft versus- host
(GVH) reaction.
8. Effector Cells of CMI
CMI can be mediated by both antigen specific and nonspecific
effector cells. They perform their function by direct killing of the
target cells (e.g. virus infected cells or tumor cells). The
nonspecific effector cells use antibodies as receptors to recognize
the target cells for killing.
Cytotoxic T cell which is antigen specific
Macrophages, NK cells, neutrophils, and eosinophils (Non-
specific)
9. Cytotoxic T Lymphocytes
CD8 cytotoxic T lymphocytes (CTL or TC) are the principal
effector cells of CMI, involved in the destruction of target cells
such as virus infected host cells and tumor cells. Naïve TC cells
(or CTL precursors) respond to viral or tumor peptide antigens
which are processed by the target host cells (by cytosolic
pathway) and presented along with MHC class I molecules.
Activated TC in turn secretes cytotoxic enzymes that lyse the
target cells.
Perforins produce pores in the target cell membrane; through
which granzymes are released inside
Granzymes are serine proteases; they induce cell death by
apoptosis through caspase pathway.
11. Natural Killer (NK) Cells
Natural killer cells are large granular lymphocytes that constitute
10–15% of peripheral blood lymphocytes.
They are derived from a separate lymphoid lineage. NK cells are
cytotoxic, but antigen nonspecific™
.
They are part of innate immunity, act as first line of defense and
do not require prior contact with the antigen.
NK cells act against virus infected cells and tumor cells till the TC
cells are activated and take over the function.
14. Antibody-dependent Cell-mediated Cytotoxicity (ADCC)
(e.g. NK cells,macrophages, monocytes, neutrophils, and
eosinophils)
A number of nonspecific cytotoxic cells express receptors (FcR)
on their surface that can bind to the Fc region of any
immunoglobulin.
FcR bearing cells can bind to Fc portion of the antibody coated
on the target cells, and subsequently cause lysis of the target cell.
These cytotoxic cells are nonspecific for the antigen, the
specificity of the antibody directs them towards the specific target
cells. This type of cytotoxicity is referred to as antibody-
dependent cell-mediated cytotoxicity (ADCC).
16. HUMORAL/ANTIBODY-MEDIATED IMMUNE RESPONSE
Antibody-mediated immune response (AMI) provides protection to
the host by secreting antibodies; that prevent invasion of
microbes present on the surface of the host cells and in the
extracellular environment, but has no role against intracellular
microbes.
AMI occurs through the following three sequential steps:
•Activation of B cells following contact with the microbial antigen
(B cells act as APCs)
• Proliferation and differentiation of B cells into effector cells
(antibody producing plasma cells) and memory cells
•Effector function: Production of antibodies by plasma cells which
in turn counter act with the microbes in many ways, such as
neutralization, opsonization, complement activation, etc.
17. Activation of B Cells
Antigens that activate B cells fall into two categories.
1. Most antigens are thymus-dependent (TD); they activate B
cells indirectly via activation of T cells. TD antigens are
processed by APCs, presented to TH cells following which the
activated TH cells secrete cytokines that in turn activate the B
cells
2. The thymus independent (TI) antigens (e.g. bacterial capsule)
are not processed by APC. They can directly activate B cells
without the help of T cell induced cytokines
18. Proliferation and Differentiation of B Cells
Following the antigenic exposure, the naive B cells are
activated and then they proliferate™
. Eventually, the
primary lymphoid follicles transform into secondary
lymphoid follicles™
. Secondary lymphoid follicles bear a
germinal center which in turn has two areas; dark zone
and light zone.
Events occurring in the secondary lymphoid follicles are
as follows.
19.
20. Effector Functions of AMI
Antibodies secreted from plasma cells mediate a number of biological
functions through their Fc portions that bind to Fc receptors (FcRs) expressed
by many cell types.
•Promotes opsonization: FcRs present on phagocyte surface recognize
antibody coated microbes, bind to them and that leads to enhanced
phagocytosis.
•Transcytosis: Poly-Ig receptors are expressed on the inner (basolateral)
surface of epithelial cells (facing the blood). They bind to dimers of IgA and
multimers of IgM antibodies and transfer them through the cell to their apical
(outer) surface and into the lumen of an organ (e.g. the intestine). This is a
process referred to as transcytosis
•Mediates mucosal immunity: Transcytosis of IgA to gut lumen provides
mucosal immunity by neutralizing the microbes at local mucosal sites
•Activates complement-mediated inflammation and cytolysis
•Promotes ADCC
21. Opsonization of bacteria and phagocytosis
Transcytosis of dimeric IgA
Complement-mediated cytolysis.
