Immune System Introduction
Innate immunity
- Employed by every living organism (plants, animals, etc.)
- First line of defense and initiates within seconds to minutes of introduction of a microbe
- Non-specific, rapid response
- Employs 3 protective mechanisms
 Anatomical and chemical barriers
o Skin, mucous membranes, complement proteins, stomach acids (some examples)
 Effector cells
o Granulocytes release granules that help destroy certain types of pathogens (bacteria, parasites)
o Neutrophils
 Short-lived (a few hours in blood, ~1-4 days in tissue)
 Phagocytose and lyse bacteria and fungi
 Respond only to extracellular pathogens (ineffective at
killing intracellular pathogens)
 Neutrophilia (increased neutrophils)
- Indicative of bacterial, extracellular infection
 Organisms with neutrophil defects suffer from
recurrent chest infections and skin abscesses
Neutrophil
o Macrophages
 Differentiate from monocytes
 Long-lived (several months)
 Bean-shaped, single-lobed nucleus
 Phagocytose and lyse extracellular pathogens
 Type of professional antigen-presenting cell (APC)
- Present antigens to T cells
 Remove apoptotic/necrotic tissue and aged RBCs
 Secrete cytokines to stimulate inflammation
- Communicate messages among cells
- Play major role in initiating adaptive immune
Macrophage
response
o Dendritic cells
 Mononuclear
 Long membrane extensions that resemble neuronal dendrites
 Phagocytose and lyse pathogens
 Most effective professional APCs (main function)
 Produce cytokines that promote immune response
 Langerhans cells (dendritic cells of skin)
Dendritic cells
Basophil
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Phagocytosis (ingestion of foreign particles)
 Performed by neutrophils, macrophages, and dendritic cells
 After ingestion, foreign particles are entrapped in a phagocytic vacuole (phagosome)
that fuses with a lysosome to form a phagolysosome, which is degraded by enzymes
Basophils
 Lobes nucleus, heavily-granulated cytoplasm
 Recently-discovered as APCs
 In tissue, release pharmacologically-active substances (e.g. histamine) that cause
inflammation and allergic (immediate hypersensitivity) reactions
Eosinophil
Mast cells
Natural killer cell
Eosinophils
 Bi-lobed nucleus, granulated cytoplasm
 Effective against extracellular parasites
 Granules damage parasite membrane
 Granules can also cause allergic reactions
o Mast cells
 Single-lobed nucleus, most heavily-granulated cytoplasm
 Often at boundaries b/w outside world and internal milieu (skin, mucosa, conjunctiva)
 Like basophils, release pharmacologically-active substances (e.g. histamine) that
cause inflammation and allergic reactions
- Protect mucosal surfaces, skin, and other tissues by inducing inflammation
o Natural killer (NK) cells
 Only cell of innate immunity that can kill cancer cells and host cells infected with
intracellular pathogens (NOT phagocytic)
 Deliver antiviral activity by lysing virus-infected cells prior to assembly of virus
 Bind with cancer or infected host cells and secrete proteins
- Perforin facilitates entry of granzymes into the cell
- Granzymes induce apoptosis of cancer or infected host cell
 Inflammation (also involved in adaptive immunity)
o Typical signs of inflammation
 Rubor (redness due to vasodilation)
 Calor (heat due to increased blood flow)
 Tumor (swelling due to influx of fluids)
 Dolor (pain due to stimulation of nerve endings)
o Extravassation
 Leukocytes (particularly neutrophils) leak out of capillaries in order to reach a site of
tissue injury in order to remove injurious stimuli (pathogens, damages cells, irritants)
 Leukocytes only adhere to the endothelium of veins and do not leak out of arteries
Adaptive immunity
- Only employed by vertebrates
- Takes days to respond to a pathogen
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 A measurable response is usually detected after ~7 days of infection
Main characteristics
 Specificity
o T and B lymphocytes are the immune cells of adaptive immunity. Their surfaces express
specific antigen receptors (BCRs or TCRs) that can recognize and distinguish different
antigenic determinants (epitopes) expressed by pathogens
 Epitopes are parts of antigens specifically recognized by individual lymphocytes
- Linear epitopes
- Discontinuous epitopes
 Diversity
o Lymphocytes of an individual can recognize billions of unique epitopes of foreign antigens
o Only one lymphocyte clone can recognize only one unique epitope of an antigen
o Lymphocyte repertoire
 Total number of antigenic specificities of the lymphocytes in an individual
 Memory
o Immune system mounts larger and more effective responses following repeated exposure
 Primary immune response
- Response to the first exposure to the antigen
- Mediated by naïve lymphocytes
 Secondary immune response
- Responses to second and subsequent exposures
- Result from activation of memory lymphocytes
 Long-lived cells that were induced during the 1° response
 More rapid and vigorous response to antigen challenge than naïve cells
 Self/non-self recognition
o Tolerance (immunologic unresponsiveness to self)
o Abnormalities in maintaining tolerance to self-antigens results in autoimmune disease
Two types of adaptive immunity
 Humoral immunity (B cells)
o Within body fluids (humors), mediated by B cells that express antigen receptors
o B cell receptors (BCRs)
 Antibodies (immunoglobulins) on B cell surfaces that act as antigen receptors
 Each B cell expresses about 105 identical copies of a single type of BCR molecule with
a unique epitope-binding specificity
o BCRs recognize antigens by directly binding to them in the native forms of antigens
 Can recognize all types of antigens (protein, carbohydrate, lipid)
o Antigen binding
 Binding to specific epitope causes activation of B cell (it is no longer naïve), which
results in differentiation (clonal expansion)
- Divides into plasma cells (effector B cells)
 Secrete antibodies with same antigen specificity as parent, naïve B cell
 Involved in 1° immune response
 After antigen elimination, effector cells die by apoptosis (not needed)
- Divides into memory B cells
 Differentiate into plasma cells during 2° immune response
o Why are antibodies important?
 Bind to pathogens that are present in extracellular environment (outside host cells),
neutralize them, and facilitate their removal from the body
 Can neutralize virus particles if present in extracellular space
 Cell-mediated immunity (T cells)
o Mediated by T cells, which express antigen receptors (TCRs) that recognize antigens
o T cells bear ~105 identical TCRs that are expressed on the T cell surface (but never secreted)
o TCRs on T cells recognize antigens only when antigens are presented by APCs
 T cells bind to small peptides of protein antigens
- Peptides on major histocompatibility complex (MHC) molecules of APCs
Antigen binding
 Binding of TCRs of naïve T cell with peptide-antigen/MHC complexes leads to
activation of T cell, which results in T cell division
- Divides into effector T cells
 Involved in 1° immune response
 After antigen elimination, effector cells die by apoptosis (not needed)
- Divides into memory T cells
 Involved in 2° immune response
o 2 main types of T lymphocytes
 Helper T cells (Th)
- Helper function is mediated by cytokines that they produce
 Cytokines of Th cells are potent activators of macrophages and help
macrophages to become more efficient pathogen killers
- Express surface protein CD4 (but not CD8)
 CD4+ CD8 Cytotoxic T cells (Tc)
- Kill host cells that are infected by intracellular pathogens
 Employs perforin and granzymes
- Express surface protein CD8 (but not CD4)
 CD8+ CD4o Lymphocytes express other types of surface proteins beyond TCRs
 CD (“cluster of differentiation”)
- May be specific to cell type or group of cell types
o Why are T cells important?
 Protect against intracellular pathogens that are inaccessible by antibodies
Active immunity
 Immune system plays an active role in responding to a pathogen and developing immunity against it
 Induced in a naïve individual by infection or vaccination
Passive immunity
 Naïve individual plays no role in generating immunity, but receives immunity by transfer
 Induces in a naïve individual by transfer of antibodies or lymphocytes from an immune individual
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