Basic Concepts in Immunology

ESRA YETİŞGİN, ASSIST. PROF.

05.03.2024
 The collection of cells, tissues, and molecules that mediate
these reactions is called the immune system.
 The coordinated response of these cells and molecules to
pathogens and other substances comprises an immune
response.
 The most important physiologic function of the
immune system is to prevent or eradicate infections.
 The immune system also plays a major role in the repair of
damaged tissues.
 Immunology is the study of immune responses in this broader
sense and of the cellular and molecular events that occur after an
organism encounters microbes and other foreign molecules.
 The importance of the immune system for health;

 Individuals with defective immune responses are susceptible to

serious, often life-threatening infections
 Vaccination is the most effective method for protecting
individuals against infections
 Worldwide eradication of smallpox
 The appearance of acquired immunodeficiency syndrome
(AIDS) in the 1980s
 Pathogens are agents that cause disease, such as bacteria,
viruses, fungi, or others
 Dedicated cells of the immune system enable animals to
avoid or limit many infections
 First lines of defense help prevent pathogens from gaining
entry to the body
 Within the body, two types of molecular recognition allow
detection of nonself molecules, particles, and cells
 Host defenses are grouped under innate and adaptive
immunity.
 Innate immunity provides immediate protection against
microbial invasion
 All animals have innate immunity
 Always present in healthy individuals
 Active defense immediately upon infection

 Adaptive immunity, which develops more slowly and

provides more specialized defense against infections.
 Activated after the innate response
 Someinnate defenses of mammals are barrier defenses,
phagocytosis, and antimicrobial peptides.

Barrier defenses include the skin and mucous membranes

of the respiratory, urinary, and reproductive tracts
 Mucus traps and allows for the removal of microbes
 Many body fluids including saliva, mucus, and tears are
used against many microbes
 The low pH of skin and the digestive system prevents
growth of many bacteria
 There are twomain types of phagocytic cells, which engulf
and destroy pathogens, in the mammalian body:
 Neutrophils circulate in the blood

 Macrophages migrate through the body or reside

permanently in organs and tissues
 develop from circulating monocytes
 live in tissues much longer than neutrophils do
 also help to repair damaged tissues.
 There aretwo additional types of phagocytic cells:
 Dendritic cells stimulate development of adaptive
immunity
 They have specialized function of capturing microbial
antigens and displaying them to T lymphocytes to initiate
adaptive immune responses and are therefore called
antigen-presenting cells (APCs).

 Eosinophils discharge destructive enzymes against

parasites
 Cellular innate defenses also involve natural killer cells
 These circulate through the body and detect abnormal
cells
 They release chemicals leading to cell death, inhibiting
the spread of virally infected or cancerous cells
 Many cellular innate defenses involve the lymphatic
system
 The inflammatory response, including heat and swelling,
is brought about by molecules released upon injury or
infection
 Mast cells, immune cells found in connective tissue,
discharge cytokines, signaling molecules that recruit
neutrophils to the site
 They also release histamine, which triggers blood vessels to
dilate and become more permeable
 The resulting increase in blood supply produces the
inflammatory response
 Pathogen recognition in mammals, triggers the production
and release of peptides that attack pathogens or impede
their reproduction
 Interferons are proteins that provide innate defense by
inhibiting the replication of viruses
 Some types of interferons help activate macrophages
 The complement system consists of about 30 proteins in
blood plasma
 These are activated by substances on the surface of many
pathogens
 A resulting cascade of reactions lead to lysis of the invading
cells
 The complement system also functions in the inflammatory
response and in adaptive defense
 Unlike innate immunity, the adaptive response is enhanced by
previous exposure to the pathogen
 The adaptive response relies on two types of lymphocytes, or
white blood cells
 Lymphocytes that mature in the thymus, above the heart, are
called T cells, and those that mature in bone marrow are called
B cells
 The cells and molecules of innate immunity recognize
structures shared by classes of microbes
 The lymphocytes of adaptive immunity express receptors
that specifically recognize a much wider variety of
molecules produced by microbes, as well as noninfectious
molecules.
 Any molecule that is specifically recognized by lymphocytes
or antibodies is called an antigen.
 Adaptive immune responses often use the cells and
molecules of the innate immune system to eliminate
microbes.
 For example, antibodies (a component of adaptive
immunity) bind to microbes, and these coated microbes
bind to and activate phagocytes (a component of innate
immunity), which ingest and destroy the microbes.
 The term immune response generally refers to adaptive
immunity.
 The two types of adaptive immunity

 Humoral immunity and cell-mediated

immunity,
 They are mediated by different cells and molecules
and provide defense against extracellular microbes
and intracellular microbes, respectively.
 Secreted antibodies enter the circulation,extracellular
tissue fluids, and the lumens of mucosal organs such as the
gastrointestinal and respiratory tracts.
 The antibodies defend against microbes present in these
locations by preventing them from invading tissue cells and
by neutralizing toxins made by the microbes.
 Defense against microbes that have already entered host
cells is called cell-mediated immunity because it is
mediated by cells, which are called T lymphocytes.
 Cell-mediated immunity is especially important to defend
against intracellular organisms that can survive and
replicate inside cells.
 Some T lymphocytes activate phagocytes to destroy microbes
that have been ingested and live within intracellular vesicles of
these phagocytes.
 Other T lymphocytes kill any type of host cells (including
non-phagocytic cells) that harbor infectious microbes in the
cytoplasm or nucleus.

 In both cases, the T cells recognize microbial antigens that

are displayed on host cell surfaces, which indicates there is a
microbe inside the cell.
 Immunity may be induced in an individual by infection or
vaccination (active immunity) or conferred on an individual
by transfer of antibodies or lymphocytes from an actively
immunized individual (passive immunity).
 In active immunity, an individual exposed to the antigens
of a microbe mounts a response to eradicate the infection
and develops resistance to later infection by that microbe.
 In passive immunity, a naive individual receives antibodies
or cells (e.g., lymphocytes) from another individual already
immune to an infection or protective antibodies that have
been synthesized using modern bioengineering techniques.
 Specificity and Diversity

 The adaptive immune system is capable of distinguishing

millions of different antigens or portions of antigens, a feature
that is referred to as specificity.
 Total collection of lymphocyte specificities, sometimes called the
lymphocyte repertoire, is extremely diverse.
 The total population of B and T lymphocytes consists of many
different clones.
 The clonal selection hypothesis, formulated in the 1950s

 Clones oflymphocytes specific for different antigens

develop before an encounter with these antigens, and each
antigen elicits an immune response by selecting and
activating the lymphocytes of a specific clone.
 Memory

 The adaptive immune system mounts faster, larger and

more effective responses to repeated exposure to the same
antigen.

 This feature ofadaptive immune responses implies that the

immune system remembers every encounter with antigen, and
this property of adaptive immunity is called immunologic
memory.
 Clonal expansion

 When naive or memory lymphocytes are activated by antigens,

they undergo proliferation, generating many thousands of
cells, all with the same antigen receptors and specificity.

 This process, called

clonal expansion, rapidly increases the
number of cells specific for antigen encountered and ensures
that adaptive immunity keeps pace with rapidly proliferating
microbes.
 Lymphocytes

 Lymphocytes are the only cells that produce clonally distributed

receptors specific for diverse antigens and are the key mediators
of adaptive immunity.
 Although all lymphocytes are morphologically similar and
rather unremarkable in appearance, they are heterogeneous in
lineage, function, and phenotype and are capable of complex
biologic responses and activities.
 These cells often are distinguished
by the expression of
surface proteins that may be identified using panels of
monoclonal antibodies.

 The standard nomenclature for these proteins is the CD (cluster

of differentiation) numeric designation, which is used to
delineate surface proteins that define a particular cell type or
stage of cell differentiation and that are recognized by a cluster
or group of antibodies.
 CD4+ helper T lymphocytes
 CD8+ cytotoxic T lymphocytes
 All lymphocytes arise from common lymphoid precursor cells
in the bone marrow.
 Lymphocytes mature in the bone marrow, and T
lymphocytes mature in an organ called the thymus.
 These sites in which mature lymphocytes are produced are called
the generative (or central) lymphoid organs.

 Mature lymphocytes leave the generative lymphoid organs and

enter the circulation and peripheral (secondary) lymphoid
organs, which are the major site of immune responses where
lymphocytes encounter antigens and are activated.
 When naive lymphocytes recognize microbial antigens and
also receive additional signals induced by microbes, the antigen-
specific lymphocytes proliferate and then differentiate into
effector cells and memory cells.
 Naive lymphocytes express receptors for antigens but do
not perform the functions that are required to eliminate
antigens.
 These cells reside in and circulate between peripheral lymphoid
organs and survive for several months up to a few years, waiting
to find and respond to antigen.
 If they are not activated by antigen, naive lymphocytes die by the
process of apoptosis.
 The differentiation ofnaive lymphocytes into effector cells and
memory cells is initiated by antigen recognition.

 Effector lymphocytes are the differentiated progeny of naive

cells that have the ability to produce molecules that function to
eliminate antigens.
 The effector cells in the B lymphocyte lineage are antibody-
secreting cells, called plasma cells.
 The common portals of entry for microbes—the skin and
gastrointestinal, respiratory, and genitourinary tracts—
contain specialized cells located in the epithelium that
capture antigens, transport them to peripheral lymphoid
tissues, and display (present) them to lymphocytes.

 These are the

first steps in the development of adaptive
immune responses against antigens.
 Thisfunction of antigen capture and presentation is best
understood for dendritic cells, the most specialized
antigen-presenting cells (APCs) in the immune system.

 Dendritic cells capture protein antigens ofmicrobes that

cross epithelial barriers and transport these antigens to
regional lymph nodes, where they display fragments of the
proteins for recognition by T lymphocytes.
 The generative lymphoid organs, in which T and B
lymphocytes mature and become competent to respond to
antigens
 The peripheral lymphoid organs, in which adaptive
immune responses to microbes are initiated.
 Most of the lymphocytes in a healthy human
are found in lymphoid organs and other tissues.
 Lymph nodes are encapsulated nodular aggregates of lymphoid
tissues located along lymphatic channels throughout the body.
 Fluid constantly leaks out of small blood vessels in all epithelia
and connective tissues and most parenchymal organs.
 This fluid, called lymph, is drained by lymphatic vessels from
the tissues to the lymph nodes and eventually back into the
blood circulation.
 The spleen is a highly vascularized abdominal organ that serves
the same role in immune responses to blood-borne antigens as
that of lymph nodes in responses to lymph-borne antigens.
 Blood entering the spleen flows through a network of channels
(sinusoids).
 Blood-borne antigens are captured and concentrated by
dendritic cells and macrophages in the spleen.
 The spleen contains abundant phagocytes that line the
sinusoids, which ingest and destroy microbes in the blood.
 These macrophages also ingest and destroy old red blood cells.