Immune system
General concepts
DR RAMADAS NAYAK
PROF & HOD PATHOLOGY
YENEPOYA MEDICAL COLLEGE
MANGALORE
 The normal immune system is essential for
protection against infection.
 Immune system is like a double-edged sword.
 Though it is protective in most of the situations,
sometimes a hyperactive immune system may cause
fatal diseases.
IMMUNITY
 Definition: Immunity is resistance (defense
mechanism) exhibited by host against invasion
by any foreign antigen, including
microorganisms.
 Types
 There are two types namely innate and adaptive
immunity.
Innate (Natural/Native) Immunity
General Features
 First line of defense present by birth.
 Provides immediate initial protection against an
invading pathogen.
 Does not depend on the prior contact with
foreign antigen or microbes.
 Lacks specificity, but highly effective. No
memory, and no self/non-self recognition.
 Triggers the adaptive immune response.
 No memory is seen.
 Major Components
 Innate immunity components:
 1. Physical barriers
 2. Phagocytic cells, NK cells
 3. Soluble plasma proteins (complements).
 1. Physical/anatomical barriers:
 It includes epithelium lining skin, gastrointestinal
and respiratory tracts which act as mechanical
barriers, produce antimicrobial molecules such as
defensins.
 2. Cells:
 a. Phagocytic cells:
 It consists of mainly monocytes (macrophages
in tissue) and neutrophils in the blood.
 Phagocytic cells use several receptors to sense
microbes and are called as “microbial sensors”
(pattern recognition receptors).
 2. Cells:
 a. Phagocytic cells
 i. Pathogen associated molecular patterns
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(PAMPs)
ii. Pattern recognition receptors (PRRs)
Toll-like receptors (TLRs)
Receptors for mannose residues
NOD (nucleotide-oligomerization domain
protein)-like receptors
Receptors for opsonins.
 b. Dendritic cells
 These cells function as antigen presenting cells
to T-cells.
 They produce type I interferons (IFN) (e.g. IFN-α),
which inhibit viral infection and replication.
 c. Natural killer (NK) cells
 They provide defense against many viral infections
and other intracellular pathogens
 3. Soluble molecules in the blood and tissues:
 Complement system
 Proteins that coat microbes and aid in phagocytosis,
e.g. mannose-binding lectin and C-reactive protein.
Functions of Innate Immune Response
 Inflammation and destruction of invading microbe
 Antiviral defense is mediated by dendritic cells
and NK cells.
Adaptive Immunity
 If the innate immune system fails to provide effective
protection against invading microbes, the adaptive
immune system is activated.
General Features
 Second line of defense acquired during life
 Capable of recognizing both microbial and
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nonmicrobial substances
Takes more time to develop and is more
powerful than innate immunity
Long-lasting protection
Prior exposure to antigen is present
Three characteristic features are: 1) specificity,
2) diversity and 3) memory.
Components
 1. Humoral immunity: B lymphocytes and their
soluble protein products called antibodies and helper
T-cells.
 2. Cellular immunity: T lymphocytes and their
soluble products called cytokines.
Functions of Adaptive Immune Response
 Antibodies: Protection against extracellular
microbes in the blood, mucosal secretions and
tissues.
 T lymphocytes:
 Defense against viruses, fungi and intracellular
bacteria either by direct killing of infected cells by
cytotoxic T lymphocytes or by activation of
phagocytes to kill the ingested microbes.
 Important immunoregulatory role, orchestrating and
regulating the responses of other components of the
immune system.
CELLS OF THE IMMUNE SYSTEM
 Cells of immune responses (lymphocytes and other
cells) migrate among lymphoid and other tissues and
the vascular and lymphatic circulations.
Naïve Lymphocytes
 These are mature lymphocytes which have not
encountered the antigen (immunologically
inexperienced).
 After the lymphocytes are activated by recognition of
antigens, they differentiate into:
 Effector cells: They perform the function of
eliminating microbes.
 Memory cells: They live in a state of heightened
awareness and are better able to combat the microbe
in case it infects again.
 T Lymphocytes
 Development: T (thymus-derived) lymphocytes
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develop from precursors in the thymus.
Distribution: Mature T-cells are found in:
Peripheral blood where it constitute 60–70% of
lymphocytes
T-cell zones of peripheral lymphoid organs namely
paracortical region of lymph node and periarteriolar
sheaths of spleen.
T-cell receptor: T-cell recognizes a specific cell-bound
antigen by means of an antigen specific T-cell receptor
(TCR).
Subsets of T lymphocytes
 Naïve T-cells can differentiate into two subtypes,
namely CD4 and CD8.
 Both subtypes serve as “coreceptors” in T-cell
activation. They are called as coreceptors because
they work with the antigen receptor in responses to
antigen.
CD4+ T-cell:
 These subset of T-cells have CD4 molecule and are
called as helper T-cells.
 They constitute about 60% of mature T-cells.
 The CD4 cells function as cytokine-secreting helper
cells that help macrophages and B lymphocytes to
combat infections.
 They are subcategorized as TH1, TH2 and TH17
CD4+ T-cells.
CD8+ T-cell:
 These subset of T-cells have CD8 molecule and are
called as cytotoxic/killer T-cells.
 They constitute about 30% of T-cells. CD8+ T-cells
function as cytotoxic (killer) T lymphocytes (CTLs) to
destroy host cells harboring microbes and tumor
cells.
B Lymphocytes
 Development: B (bone marrow-derived)
lymphocytes develop from precursors in the bone
marrow.
 Distribution:
 Peripheral blood: Mature B-cells constitute 10–
20% of the circulating peripheral lymphocyte
population.
 Peripheral lymphoid tissues: Lymph nodes
(cortex), spleen (white pulp), and mucosa-associated
lymphoid tissues (pharyngeal tonsils and Peyer's
patches of GIT).
Functions of B-cells
 Production of antibodies:
Dendritic Cells
 As the name suggests these cells have numerous fine
cytoplasmic processes that resemble dendrites.
 These are important antigen presenting cells in the
body and can be functionally of the following types:
 Interdigitating dendritic cells (IDC): They are
the most important APCs for initiating primary
T-cell responses against protein antigens.
Dendritic Cells
 Location:
 1) Common location is below the epithelial
lining: Immature dendritic cells within the
epidermis are known as Langerhans cells.
 2) Interstitia of all tissues
 Follicular dendritic cell:
 Location:
 It is present in the germinal centers of
lymphoid follicles in the spleen and lymph
nodes (hence named as follicular dendritic
cell).
Macrophage and its function
 Macrophages are a part of the mononuclear
phagocyte system.
 Role in adaptive immune responses:
 Processing of antigen
 Effector cell in immunityincluding
phagocytosis
Natural Killer Cells
 Non-phagocytic large (little larger than small
lymphocytes) granular (numerous cytoplasmic
azurophilic granules) lymphocytes.
 Comprise about 5–15% of human peripheral
lymphoid cells.
Function of NK cells
 Natural killer (NK) cells provide defense against
many viral infections and other intracellular
pathogens and also has antitumor activity,
CYTOKINES
 Immune responses involve multiple interactions among
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many cells.
These include lymphocytes, dendritic cells, macrophages,
other inflammatory cells (e.g. neutrophils), and
endothelial cells.
Some of these interactions are cell-to-cell contact.
However, many interactions and effector functions of
leukocytes are mediated by short-acting soluble
proteins called cytokines.
These cytokines represent the messenger molecules
of the immune system and mediate communications
between leukocytes and are called interleukins.
MAJOR HISTOCOMPATIBILITY
COMPLEX MOLECULES
 All human cells have a series of molecules on their
surfaces that are recognized by other individuals as
foreign antigens.
 Major histocompatibility complex (MHC)
molecules were discovered as products of genes
that evoke rejection of transplanted organs
and responsible for tissue compatibility between
individuals.
MAJOR HISTOCOMPATIBILITY
COMPLEX MOLECULES
 The human MHC are commonly called the human
leukocyte antigen (HLA) complex is the name
of the loci of genes densely packed (clustered) on a
small segment on chromosome 6 (6p21.3).
 They were named HLA because in humans MHCencoded proteins were initially detected on
leukocytes by the binding of antibodies.
MAJOR HISTOCOMPATIBILITY
COMPLEX MOLECULES
 Classification
 MHC gene product is classified based on their
structure, cellular distribution, and function into
three groups
 MHC class I and class II gene products are critical
for immunologic specificity and transplantation
histocompatibility, and they play a major role in
susceptibility to a number of autoimmune diseases.
MAJOR HISTOCOMPATIBILITY
COMPLEX MOLECULES
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