Immunophysiology

Dr: Omer Eltahir

Registrar of pathology
• Immunity refers to protection against infections.

• immune system is responsible for defending the body

against microbes

• Immune deficiency result in an increased

susceptibility to infections, which can be life-
threatening

• the immune system is itself capable of causing

great harm ( auto immune diseases & HSRs)
 Lymphoid Tissues
1- (primary) organs:
• Synthesis & maturation
• the thymus and bone marrow
2- peripheral (secondary) lymphoid organs:
• adaptive immune responses develop.
• lymph nodes, spleen, and mucosal and cutaneous
lymphoid tissues.
INNATE AND
ADAPTIVE
IMMUNITY
 Defense against microbes consists of two
types of reactions

Innate immunity
(natural immunity)
mediated by:
1. cells
2. proteins
3. Mechanical barriers

.
 Examples of components of innate
immunity
1. epithelial barriers of the skin, gastrointestinal
tract, and respiratory tract, which prevent microbe
entry;

2. phagocytic leukocytes (neutrophils macrophages,

natural killer (NK) cell;

3. several circulating plasma proteins, mainly

complement system
 adaptive immunity
(acquired or specific immunity)

• normally silent

• Start to function after failure of the innate

immunity

• Components:
• 1- lymphocytes
• 2- antibodies
 Arms of Adaptive immunity
1. humoral immunity, mediated by antibodies:
• defense against extracellular microbes

2. cell-mediated immunity, mediated by T cells:

• defense against intracellular microbes . Either by :
1. directly killing infected cells by cytotoxic T
lymphocytes
2. activating phagocytes to kill ingested microbes, via
the production of cytokines (made by helper T
cells).
CELLS AND TISSUES
OF THE
IMMUNE SYSTEM
 Cells of the immune system
1. T cells recognize antigens and mount adaptive
immune responses;

2. antigen-presenting cells (APCs), which capture

and display microbial and other antigens to the
lymphocytes;

3. various effector cells, whose function is to

eliminate microbes
 Lymphocytes
• present in the circulation and lymphoid
organs.
• T lymphocytes mature in the thymus
• B lymphocytes mature in the bone
marrow.
• Each T or B lymphocyte expresses
receptors for antigens
 T Lymphocytes
• the effector cells of cellular immunity

• 70% of the lymphocytes in peripheral blood

• the major lymphocyte population in splenic periarteriolar sheaths

and lymph node interfollicular zones.

• T cells function by:

1. kill infected cells

2. activate phagocytes or B lymphocytes
• T cells do not detect free or circulating antigens.

• T cells recognize only peptide fragments of protein

antigens bound to the major histocompatibility
complex (MHC). (MHC restriction)

• Peptide antigens presented by self MHC molecules

are recognized by the T cell receptor (TCR),
• CD4+T cells are “helper” T cells because they
secrete soluble molecules (cytokines) that:
1. help B cells to produce antibodies
2. help macrophages to destroy phagocytosed
microbes.
3. Activate CD8+ T cells which kills virus-infected or
tumor cells, and hence are called “cytotoxic” T
lymphocytes (CTLs)
 B Lymphocytes

• Bone marrow derived

• produce antibodies (the effector cells of humoral immunity.)
• 10% to 20% of the circulating peripheral lymphocyte
• present in:
1. bone marrow
2. in the follicles of peripheral lymphoid tissues (lymph nodes,
spleen, tonsils, and other mucosal tissues).

• recognize antigen by means of membrane-bound antibody of the

(IgM) class, expressed on the surface together with signaling
molecules to form the B cell receptor (BCR) complex
• B cells can recognize and respond to :
1. soluble or cell-associated proteins,
2. lipids,
3. polysaccharides,
4. nucleic acids, and
5. small chemicals;

• CD21 which recognizes a complement breakdown

product that frequently is deposited on microbes and
promotes B cell responses to microbial antigens.
• After stimulation, B cells differentiate into plasma cells

• plasma cells secrete antibodies,

• IgG , IgM, and IgA constitute 95% of circulating antibodies.

• IgA is the major isotype in mucosal secretions;

• IgE is present in the circulation at very low

concentrations and also is found attached to the surfaces of
tissue mast cells

• IgD is expressed on the surfaces of B cells but is not

secreted.
 Natural Killer Cells
• Are lymphocytes That participate in innate immunity

• viral infections and stress are associated with reduced

expression of class I MHC molecules,

• thus releasing the NK cells from inhibition.

• The net result is that the NK cells are activated and the
infected or stressed cells are killed and eliminated
 Effector Cells
1. Many different types of leukocytes perform the ultimate task of
the immune response, which is to eliminate infections.

2. NK cells are front-line effector cells in that they can rapidly react
against “stressed” cells.

3. Antibody-secreting plasma cells are the effector cells of humoral

immunity.

4. T lymphocytes, both CD4+helper T cells and CD8+CTLs, are effector

cells of cell-mediated immunity.
5. Macrophages, bind microbes that are coated with
antibodies or complement and then phagocytose and
destroy these microbes, thus serving as effector cells
of humoral immunity.

6. Macrophages also respond to signals from helper T cells,

which improves their ability to destroy phagocytosed
microbes, thus serving as effector cells of cellular
immunity.

7. T lymphocytes secrete cytokines that recruit and

activate other leukocytes, such as neutrophils and
eosinophils, and together these cell types function in
defense against various pathogens
 OVERVIEW OF
NORMAL
IMMUNE RESPONSES
 The Innate Immune Response to
Microbes
• The principal barriers between hosts and their
environment are the epithelia of the skin and the
gastrointestinal and respiratory tracts.

• epithelia serve as physical barriers to infections and

eliminate microbes through production of peptide antibiotics
and the actions of intraepithelial lymphocytes.

• If microbes are able to survive and traverse these epithelia,

they encounter phagocytes, including neutrophils, which
are rapidly recruited from the blood into tissues, and
macrophages, which live in tissues under epithelia.
• phagocytic cells ingest microbes and destroy

• NK cells kill virus infected cells and produce IFN-γ.

• If the microbes enter the blood, the complement

system, recognize the microbes and are activated,
and their products kill microbes and coat (opsonize)
the microbes for phagocytosis.

• In addition to combating infections, innate immune

responses stimulate subsequent adaptive immunity,
 The Capture and Display of Microbial
Antigens
• Microbes that enter through epithelia, are captured by DCs that are resident
in and under these epithelia.

• Antigen-bearing DCs then migrate to draining lymph nodes

• Protein antigens are proteolytically digested in the APCs to generate peptides

that are displayed on the surface of the APCs bound to MHC molecules.

• Antigens that are ingested from the extracellular environment are

processed in endosomal and lysosomal vesicles and then are displayed bound
to class II MHC molecules.

• Because CD4 binds to class II MHC molecules, CD4+helper T cells recognize

class II–associated peptides.
• antigens in the cytoplasm are displayed by
class I MHC molecules and are recognized by
CD8+ cytotoxic T cells, because CD8 binds to
class I MHC.

• Protein antigens, as well as polysaccharides and

other nonprotein antigens, can also be
recognized directly by B lymphocytes in the
lymphoid follicles of the peripheral lymphoid
organs
 Cell-Mediated Immunity: Activation of
T Lymphocytes and Elimination of
Cell-Associated Microbes
• Upon activation, T lymphocytes secrete soluble
proteins called cytokines, which function as:
1. growth and differentiation factors for
lymphocytes and other cells, and
2. mediate communications between leukocytes.
 Cytokines: Messenger Molecules of the
Immune System
• Cytokines are polypeptide products of many
cell types (but principally activated
lymphocytes and macrophages)

• Function in:
• 1- inflammation
• 2- immunity
• Cytokines are synthesized and secreted in response to
external stimuli, which may be:
1. microbial products,
2. antigen recognition, or
3. other cytokines.

• The actions of cytokines may be :

1. autocrine(on the cell that produces the cytokine),
2. paracrine (on adjacent cells),
3. and, less commonly, endocrine(at a distance from the
site of production)
• The effects of cytokines tend to be
1. pleiotropic (one cytokine can have diverse
biologic activities, often on many cell types) and
2. redundant (multiple cytokines may have the
same activity).

• The most important cytokines are called

interleukins
 Cytokines may be grouped
into several classes on the
basis of their biologic activities
and functions.
1- Cytokines involved in innate immunity and inflammation,

1. TNF
2. (IL-1) and
3. chemokines.
4. IL-12, IFN-γ, IL-6, IL-23
 2- Cytokines that regulate lymphocyte responses
and effector functions in adaptive immunity

1. IL-2,
2. IL-4:
3. IFN-γ, which activates macrophages;
4. IL-5, which activates eosinophils).

• The major sources of these cytokines are

CD4+helper T lymphocytes
 Cytokines that stimulate hematopoiesis

• are called colony-stimulating factors.

• They increase the output of leukocytes from

the bone marrow and to thus replenish
leukocytes that are consumed during immune
and inflammatory reaction
 Effector Functions of T Lymphocytes

• CD4+helper T cells:
• is secretion of the cytokine 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.
• The subsets of CD4+helper cells are :
• TH₁, TH₂, and TH₁₇
• TH1 cells produce the cytokine IFN-γ, which:
1. activates macrophages
2. and stimulates B cells to produce antibodies

• TH2 cells :
1. produce IL-4, which stimulates B cells to differentiate into IgE-
secreting plasma cells;
2. IL-5, which activates eosinophils; and
3. IL-13, which activates mucosal epithelial cells to secrete mucus
and expel microbes, and activates macrophages to secrete growth
factors important for tissue repair.

• TH17 cells
1. produce the cytokine IL-17, which recruits neutrophils and thus
promotes inflammation;
2. TH17 cells play an important role in some T cell–mediated
inflammatory disorders
 Activated CD8+ lymphocytes differentiate into CTLs,

• which kill cells harboring microbes in the

cytoplasm.
• These microbes may be:
1. viruses that infect many cell types, or
2. Intracellular bacteria