Transcript Adaptive immunity

IMMUNOPATHOLOGY
DR.HAMEED N.MOUSA
FICMS PATHOLOGY
HEAD OF DEPATMENT
. Learning objectives
At the end of the chapter, the student is expected to:
1. Learn mechanisms and examples of hypersensitivity reaction
2. Understand etiologic factors in autoimmune diseases
3. Have bird’s eye view concept on immunodeficiency states
Introduction:
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Immunity = protection against infections,
immune system : is the collection of cells and
molecules that are responsible for defending us against
the countless pathogenic microbes in our environment.
Deficiencies in immune defenses: result in an
increased susceptibility to infections, which can be
life-threatening if the deficits are not corrected.
 On the other hand, the immune system is itself capable
of causing great harm and is cause of some of the most
vexing and intractable diseases of the modern world.
 Thus, diseases of immunity range from those caused by
"too little" to those caused by "too much or
inappropriate" immune activity
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Defense against microbes consists of two types of
reactions : Innate immunity & Adaptive immunity
Innate immunity (also called natural, or
native, immunity) is mediated by cells and
proteins that are always present and poised to
fight against microbes and are called into action
immediately in response to infection.
The major components of innate immunity are:
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epithelial barriers of the skin, gastrointestinal
tract, and respiratory tract, which prevent
microbe entry
phagocytic leukocytes (neutrophils and
macrophages);
natural killer (NK) cell; a specialized cell type
complement system :circulating plasma proteins
The major components of
innate immunity are:
Epithelial barriers of
the skin, gastrointestinal
tract, and respiratory
tract, which prevent
microbe entry
2- phagocytic leukocytes
(neutrophils and
macrophages);
3- natural killer (NK) cell; a
specialized cell type
4- complement system :
circulating plasma
proteins
1.
Adaptive immunity
(Also known as Acquired or Specific immunity, Immune
system, & Immune response ).
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Adaptive immunity is normally silent and responds (or "adapts")
to the presence of infectious microbes by becoming active,
expanding, and generating potent mechanisms for neutralizing
and eliminating the microbes.
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The components of the adaptive immune system are lymphocytes and their
products.
The components of the adaptive
immune system are lymphocytes
and their products
There are two types of adaptive immune responses:
 humoral immunity, mediated by soluble antibody
proteins that are produced by B lymphocytes (B
cells) (Antibodies provide protection against
extracellular microbes in the blood, mucosal
secretions, and tissues.)
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, and cell-mediated (or cellular) immunity,
mediated by T lymphocytes (also called T cells)
T lymphocytes are important in defense against
intracellular microbes. They work by either:
* -directly killing infected cells (accomplished by
cytotoxic T lymphocytes)
*-or by activating phagocytes to kill ingested
microbes, via the production of soluble protein
mediators called cytokines (made by helper T
cells).
1.T-LYMPHOCYTES (THYMUS DERIVED ) T (THYMUSDERIVED) LYMPHOCYTES EXPRESS ANTIGEN RECEPTORS
CALLED T CELL RECEPTORS (TCRS) THAT RECOGNIZE
PEPTIDE FRAGMENTS OF PROTEIN ANTIGENS THAT ARE
DISPLAYED BY MHC MOLECULES ON THE SURFACE OF
ANTIGEN-PRESENTING CELLS.
CONSTITUTE 60 -70 % OF PERIPHERAL LYMPHOCYTES
CD4 HELPER ,INDUCER
60 % OF T CELLS.
CD8 CYTOTOXIC ,SUPPRESSOR
30 % OF T CELLS.
CD4 :CD8
2:1 IN NORMAL HEALTHY PERSON
CD4 
CLASS II MHC.
CD8 
CLASS I MHC.
EFFECTOR CD4 (TH1)  SECRET IL-2 &IFN-8.
(TH2 )  SECRET IL-4 ,IL-5 &IL-10.
CELLULAR IMMUNITY
2. B- lymphocytes (Bone marrow derived ) express
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membrane-bound antibodies that recognize
a wide variety of antigens.
They constitute 10-20 % of peripheral
lymphocytes
On antigenic stimulation B-cells
differentiated to
plasma cell
secrete immunoglobulin
humoral immunity
5 types of Ig (IgG ,IgM ,IgA ,IgE & IgD)
3.Macrophages (express class II MHC)
4.Dendritic cells ( antigen presenting cell “APC”)
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interdigitating D.C.
Langerhan’s Cell (skin).
Follicular D.C.
5.Natural killer (NK) cells
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kill cells that are infected by some
microbes, or are damaged beyond repair.
NK cells express inhibitory receptors that
recognize MHC molecules that are
normally expressed on healthy cells, and
are thus prevented from killing normal cells
Constitute 10-15% of peripheral blood
lymphocytes
Soluble mediators of the immune system
1.Cytokines that mediate natural immunity
(IL-1, TNF-α, type I –IFN & IL-8 ).
2.Cytokines that regulate lymphocytes growth
activation & differentiation.
3.Cytokines that activate inflammatory cells.
4.Cytokines i.e. stimulate haematopoiesis (CSF ,
GM-CSF.)
5.Cytokines therapy of cancer (immunotherapy).
6.Chemokines:
induce their effect
autocrine.
paracrine.
endocrine.
It is the antigens responsible for the rejection of
transplanted organs.
Based on their chemical structure ,tissue distribution
& function . MHC gene products fall in to 3
categories :
1. Class I MHC [HLA-A,HLA-B,HLA-C]
CD8 +T-cell
 class I MHC
2. Class II MHC [HLA-D [ DP,DQ,DR]
CD4+T-cell
 class II MHC
3. Class III molecules [complement C2,C3&BF] they
don't act as histocompatibility (transplantation).
Figure 5-3 Lymphocyte antigen receptors .A ,The T-cell receptor (TCR) complex and other
molecules involved in T-cell activation. The TCRα and TCRβ chains recognize antigen (in the
form of peptide-MHC complexes expressed on antigen-presenting cells), & the linked CD3
complex initiates activating signals. CD4 and CD28 are also involved in T-cell activation. (Note
that some T cells express CD8 and not CD4; these molecules serve analogous roles).
B ,The B-cell receptor complex is composed of membrane IgM (or IgD,) & the associated
signaling proteins Igα and Igβ. CD21 is a receptor for a complement component that promotes
B-cell activation.
organ transplantation.
induction & regulation of immune response especially
HLA Class II .
paternity test.
HLA & Disease Association
e.g.ankylosing spondylitis HLA-B27
Adaptive immune responses consist of sequential phases: recognition of antigen by specific lymphocytes,
activation of lymphocytes (consisting of their proliferation & differentiation into effector cells), & the effector phase
(elimination of antigen).
The response declines as antigen is eliminated, & most of the antigen-stimulated lymphocytes die by apoptosis.
The antigen-specific cells that survive are responsible for memory.
The duration of each phase may vary in different immune responses.
These principles apply to humoral immunity (mediated by B lymphocytes) and cell-mediated immunity (mediated by
T lymphocytes
Cell-mediated immunity. Naive T cells recognize MHC-associated peptide antigens displayed on
dendritic cells in lymph nodes. The T cells are activated to proliferate (under the influence of the cytokine IL2) and to differentiate into effector and memory cells, which migrate to sites of infection and serve various
functions in cell-mediated immunity. Effector CD4+ T cells of the TH1 subset recognize the antigens of
microbes ingested by phagocytes and activate the phagocytes to kill the microbes and induce inflammation.
CD8+ 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 longlived memory cells. APC, antigen-presenting cell.
Humoral immunity. Naive B lymphocytes recognize antigens, and under
the influence of helper T cells), the B cells are activated to proliferate
and to differentiate into antibody-secreting plasma cells. Some of the
activated B cells undergo heavy-chain class switching and affinity
maturation, and some become long-lived memory cells. Antibodies of
different heavy-chain isotypes (classes) perform different effector
functions, shown on the right .
SUMMARY
Overview of Normal Immune Responses
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The physiologic function of the immune system is defense
against infectious microbes.
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The early reaction to microbes is mediated by the mechanisms
of innate immunity ,which are ready to respond to microbes.
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These mechanisms include epithelial barriers, phagocytes, NK
cells, and plasma proteins, e.g., of the complement system.
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The reaction of innate immunity is often manifested as
inflammation.
SUMMARY :Overview of Normal Immune Responses ( cont’d )
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The defense reactions of adaptive immunity
develop slowly, but are more potent & specialized.
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Microbes & other foreign antigens are captured by
dendritic cells & transported to lymph nodes, where
the antigens are recognized by naïve lymphocytes.
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The lymphocytes are activated to proliferate &
differentiate into effector & memory cells.
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Cell-mediated immunity is the reaction of T
lymphocytes, designed to combat cell-associated
microbes (e.g., phagocytosed microbes & microbes
in the cytoplasm of infected cells.
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SUMMARY :Overview of Normal Immune
Responses
Humoral immunity is mediated by antibodies & is
effective against extracellular microbes (in the
circulation and mucosal lumens).
 CD4+ helper T cells help B cells to make antibodies,
activate macrophages to destroy ingested microbes, &
regulate all immune responses to protein antigens.
 The functions of CD4+ T cells are mediated by
secreted proteins called cytokines.
 CD8+ cytotoxic T lymphocytes kill cells that express
antigens in the cytoplasm that are seen as foreign
(e.g. virus-infected and tumor cells).
 Antibodies secreted by plasma cells neutralize
microbes and block their infectivity, & promote the
phagocytosis & destruction of pathogens.
 Antibodies also confer passive immunity to neonates .
These may result from:
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Excessive immune responses (hypersensitivity
reactions)
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Unwanted or inappropriate immunes response (
Autoimmune diseases )
3.
Inadequate immune responses
(immunodeficiency disease