The Immune

System
Cell Mediated Immunity
ADAPTIVE DEFENSES
 ADAPTIVE DEFENSES

 Innate & adaptive mechanisms work together in a

cohesive fashion
Adaptive Defenses: Characteristics
 Specificity: directed at specific targets

 Systemic: not restricted to initial site of infection /

invasion

 Memory: after initial exposure & activation, a

more rapid & more vigorous response is made to
subsequent exposures to pathogens
 (secondary response)
Adaptive Defenses: Components
 Humoral Immunity: (antibody mediated immunity)
provided by antibodies floating free in body fluids
 Cell mediated immunity:
 lymphocytes directly attack specific invaders by
lysis or indirect attack by initiating inflammation
and/or activating other lymphocytes &
macrophages
Adaptive Immune System: Cells
 Lymphocytes
 T-cells
 B-cells
 Antigen Presenting Cells (APCs)
 Immunocompetent B or T cells
Red Key: = Site of lymphocyte origin
bone marrow
= Site of development of immunocompetence
as B or T cells; primary lymphoid organs
= Site of antigen challenge & final
Immature differentiation to activated B & T cells
Circulation in lymphocytes
1
blood
1 1 Lymphocytes destined to become T
Thymus cells migrate to the thymus & develop
immunocompetence there. B cells
Bone
marrow develop immunocompetence in red
bone marrow.

2 2 After leaving the thymus or bone

Immunocompetent,
marrow as naive immunocompetent
but still naive, Lymph nodes,
spleen, & other cells, lymphocytes “seed” the lymph
lymphocyte
lymphoid tissues nodes, spleen, & other lymphoid
migrates via blood
tissues where the antigen challenge
occurs.

3 Mature (antigen-activated)
3 3 immunocompetent lymphocytes
circulate continuously in the
Activated bloodstream & lymph & throughout
immunocompetent the lymphoid organs of the body.
B & T cells
recirculate in blood
& lymph

Figure 21.8
Adaptive Immune System: Cells
 Immunocompetence: as T- or B-cells mature
they become immunocompetent, they display
receptors on their cell membrane for a specific
antigen.

 All of the receptors on one cell are identical;

immunity depends upon genetic coding for
appropriate receptors.
 Adaptive Immune System: Cells
 Lymphocytes: initially uncommitted
 T-cells: are sorted in the Thymus
 Positive selection: recognize MHC survive
 Negative selection: react against to self-antigens on MHC killed
 2% of initial T-cell precursors
 T-cells manage the immune response
 B-cells: are sorted in the marrow by an incompletely understood process

Figure 21.9
Cell Mediated Immune Response
 T-cell activation: involves recognition of PM
surface antigens only
 Antigen is combined with MHC & displayed on PM
 T-cell receptors: bind to the MHC & are stimulated by
the associated antigen
 The addition of a co-stimulator (cytokines,
interleukins, etc) prompts the T-cell to form a clone
 In the absence of a co-stimulator the T-cell becomes
tolerant to antigen (anergy)
Adaptive, Humoral response
 Humoral response (clonal selection)
 B-cells: Antigen challenge to naïve
immunocompetent B-cell
 Antigen binds to B-cell receptors & form cross-
links between receptors
 Cross linked antigen-receptor complex
undergoes endocytosis
 B-cell presents antigen to T-cell
 T cell prompt the B-cell to mature & form
antibody
Cell Mediated: MHC
 MHC occurs as two classes
 MHC I on virtually all tissue cells
 MHC II only on PM some immune system cells
 Interacts with two major types of T cells
 CD8 - Cytotoxic
 CD4 – Helper T cells
Cell Mediated:
MHC display properties

Figure 21.16a

 MHC I on virtually all tissue cells

 Display only proteins produced inside the cell
 Endogenous antigens = foreign proteins produced by
the cell (viral / cancer)
 Stimulate the CD8* cell population
 form cytotoxic T-cells (Killer T, TC)

 *formerly T8 cells
Cell Mediated:
MHC display properties

Figure 21.16b

 MHC II found only on PM of B-cells, some T-cells & APCs

 Display proteins derived from a phagocytized target
 Exogenous antigen: foreign protein from outside the cell –
presented to PM surface
 Stimulates the CD4* cell population
 form Helper T-cells (T )
H
 *formerly T4 cells
Helper T cells
 Helper T cells are arguably the most important cells in adaptive
immunity, as they are required for almost all adaptive immune
responses.
 They help activate B cells to secrete antibodies and
macrophages to destroy ingested microbes, and they also help
activate cytotoxic T cells to kill infected target cells.
 Helper T cells themselves, however, can only function when
activated to become effector cells.
 They are activated on the surface of antigen-presenting cells,
which mature during the innate immune responses triggered by
an infection.
 The innate responses also dictate what kind of effector
cell a helper T cell will develop into and thereby determine the
nature of the adaptive immune response elicited.
Helper T cells
 When a an antigen-presenting cell activates a naïve helper T cell in a
peripheral lymphoid tissue, the T cell can differentiate into either a TH1 or
TH2 effector helper cell.
 These two types of functionally distinct subclasses of effector helper T
cells.
 TH1 cell
 will mainly defend the animal against intracellular pathogens.
 will activate macrophages to kill phagocytized microbes and activate cytotoxic T
cells to kill infected cells.
 TH2 cell
 will mainly defend the animal against extracellular pathogens.
 will stimulate B cells to make antibodies
T-cell roles: Cytotoxic T-cells
 Cytotoxic T-cells (TC, Killer T):
directly attack & kill cells with
Cytotoxic T-cell
specific antigen
 Activated TC cells are co-
stimulated by TH cells
 TC mechanism
Target
 TC binds to cell & releases perforin cell

& granzymes
 In the presence of Ca2+ perforin
forms pores in target cell PM
 Granzymes enter through pores &
degrade cellular contents
 TC then detaches & moves on
 Macrophages clean up
Adaptive Immune System: Cells
 Antigen Presenting Cells (APCs)
 APCs ingest foreign material, then present
antigenic fragments on their cell surface where
they are recognized by T-cells
 T-cells:
respond to antigen only if it is displayed on
plasma membrane.
 APCs: Macrophages & B lymphocytes
 Interactions between APCs & lymphocytes &
lymphocyte-lymphocyte interactions are critical
to immune response
Major Types of T Cells

Figure 21.14
Antigen Presentation - MHC Class I

Figure 21.16
Antigen Presentation - MHC Class II

Figure 21.17a
T-cell roles: Humoral Immunity
 Activated TH cells
interact with B-cells
displaying antigen &
produce cytokines that
prompt the B-cell to
mature & form antibody

Figure 21.18
T-cell roles: Cell Mediated Immunity
 TH cells also produce
cytokines that
promote TC cells
 TH cells recruit other
WBCs & amplify
innate defenses
(inflammatory)
 Subpopulations of TH
cells specialize in
specific sets of
activations Figure 21.18
Cell Mediated: T-cell roles

 Helper T-cells (TH) stimulate B-cells

& other T-cells to proliferate

Figure 21.18
Cell Mediated: T-cell roles
 Other T-cells
 *Regulatory T-cells (TReg): release inhibitory cytokines
that suppress B-cell & T-cell activity
 Help to prevent autoimmune events
 *formerly Suppressor T (TS)

 Gamma Delta T-cells (Tgd): live in the intestine.

Function in surveillance & are triggered much like NK
cells
Summary of the Primary Immune Response

Figure 21.19
Immunologic Disorders
 Primary immunodeficiency disorders (see Box 4-3)
 Mostly these are inherited single-gene disorders that present in infancy in
early childhood with the exception of common variable
immunodeficiency which usually occurs in adults.
 They are sometimes classified according to which component is faulty (T
cells, B cells, phagocytic cells or complement) or according to individual
clinical syndromes.
 The overall incidence of symptomatic primary immunodeficiency is
estimated to be 1/10,000.
 About 80% of patients are less than 20 years old when diagnosed, because
the majority of cases are inherited or congenital. 70% occur in males due to
X-linked inheritance in many syndromes.
 B-cell defects account for 50% of primary immunodeficiency.
 T-cell defects account for 30%, phagocytic deficiencies 18%
and complement deficiencies 2%.
Immunologic Disorders
 Secondary immunodeficiency disorders (See Box 4-4)
 Secondary immunodeficiencies, also known as acquired
immunodeficiencies, can result from various
immunosuppressive agents, for example:
 malnutrition

 aging

 medications (e.g. chemotherapy, disease-modifying

antirheumatic drugs, immunosuppressive drugs after

organ transplants, glucocorticoids).
 For medications, the term immunosuppression generally
refers to both beneficial and potential adverse effects of
decreasing the function of the immune system.