THE IMMUNE SYSTEM
OVERVIEW: RECONNAISSANCE, RECOGNITION AND RESPONSE
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Pathogens: infectious agents that cause disease
o An animal’s body offers nutrients, protection for growth and means of transportation
Immune system: defense that allow an animal to avoid/limit infections
Innate immunity: found in all animals
o Responses are active immediately upon infection and are the same whether or not the
pathogen has been encountered previously
o Includes barrier defenses (skin), defenses that combat pathogens after they enter the body
Acquired immunity: adaptive immunity
o Active after innate immune defenses take effect, develop more slowly
o Synthesis of proteins that inactive bacterial toxin, targeted killing of a virally infected body cell
43.1: INNATE IMMUNITY: RECOGNITION AND RESPONSE RELY ON SHARED
TRAITS OF PATHOGENS
INNATE IMMUNITY OF INVERTEBRATES
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Invertebrates rely only innate immunity
o Insects rely on their exoskeleton as defense against infection
 Lysozyme: enzyme that digest microbial cell walls
 Low pH
 Hemocyte: immune cells that circulate
within the hemolymph, carry out
 Phagocytosis: ingestion and
digestion of bacteria and
other foreign substances
 Trigger production of
chemicals that kill
microbes/entrap parasites
 Antimicrobial peptides:
inactivate/kill fungi and
bacteria by disrupting their
plasma membranes
o Insect immune cells secrete specialized
recognition proteins, which bind to the
macromolecules on invaders
INNATE IMMUNITY OF VERTEBRATES
BARRIER DEFENSES
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Mammals
o Epithelial tissues block entry of pathogens – skin + mucous membranes lining the digestive,
respiratory, urinary and reproductive tracts
 Mucus: viscous fluid that enhances defenses by trapping microbes
 Ciliated epithelial cells sweep mucus and microbes upward, preventing
infection of lungs
 Saliva, ears, mucous secretions
 Saliva contains lysozyme
CELLULAR INNATE DEFENSES
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Pathogens that get into the body encounter leukocytes (WBC)
Toll-like receptor (TLR): recognizes fragments of molecules characteristic of a set of pathogens
o Recognition triggers a series of defenses, starting with phagocytosis
 WBC engulfs the invading microbes, trapping them in a vacuole—fuses with a
lysosome
Neutrophils: most abundant phagocytic cells in the mammalian body; attracted by signals from
infected tissues
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Macrophages: seen in spleen, lymph nodes; really large and can trap larger microbes
Eosinophils: defend against multicellular invaders (parasitic worms); discharge destructive enzymes
that damage invader
Dendritic cells: populate tissues, stimulate development of acquired immunity against microbes
^The human lymphatic system
Made up of the lymphatic vessels, adenoids, tonsils, lymph nodes, spleen, Peyer’s patches and appendix
ANTIMICROBIAL PEPTIDES AND PROTEINS
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Interferons: proteins that provide innate defense against viral infections
o Virus-infected body cells secrete interferons, inducing uninfected cells to produce substances
that inhibit viral reproduction
o Limit cell-to-cell spread of viruses, controlling viral infections like colds/flu
Complement system: 30 proteins in blood plasma
o Circulate in an inactive state and are activated by substances on the surface of microbes
o Activation results in an influx of biochemical reactions leading to the lysis of invading cells
o Inflammation
INFLAMMATORY RESPONSES
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Inflammatory response: changes brought about by signaling molecules released upon injury
Histamine: inflammatory signally molecule, stored in mast cells, connective tissues cells that store
chemicals in granules fore secretion
o Histamine released by mast cells @ sites of damage triggers blood vessels to dilate and
become more permeable
o Macrophages discharge additional signally molecules that promote blood flow to the injured
site
o Increase in local blood supply causes redness and heat of inflammation
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Cycles of signaling and response transform the infection site
o Enhanced blood flow = antimicrobial proteins
o Activated complement proteins = release of histamine and help attract phagocytes
o Endothelial cells secrete signaling molecules = attract neutrophils and macrophages
o Pus: fluid rich in white blood cells, dead microbes and cell debris
Major damage may lead to a response that’s systemic (throughout the whole body) – increased
production of WBC
Fever: systemic inflammatory response
o Pyrogens: released by macrophages, reset body’s thermostat to higher temp
o Fevers accelerate tissue repair by speeding up chemical reactions?
Septic shock: life-threatening condition: high fever, low blood flow, low BP
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NATURAL KILLER CELLS
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Natural Killer (NK) Cells: help recognize and eliminate certain diseased cells
o Patrol body, attach to sick cells and release chemicals that lead to cell death
INNATE IMMUNE SYSTEM EVASION BY PATHOGENS
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Pathogens have evolved in order to avoid destruction by phagocytic cells
o Aren’t recognized by , prevent destruction, resistance to breakdown within lysosomes
following phagocytosis (Tuberculosis)
43.2: ACQUIRED IMMUNITY: LYMPHOCYTE RECEPTORS PROVIDE PATHOGEN SPECIFIC RECOGNITION
BUNCH OF VOCAB
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Lymphocyte: B cells and T cells, types of WBC, critical for acquired immune defense
Thymus: an organ in the thoracic cavity above the heart that houses the T Cells
B Cells: mature in the bone marrow
B&T Cells recognize and inactivate foreign cells and molecules, contribute to
Immunological memory: enhanced response to foreign molecule encountered previously
o responsible for the protection we obtain against chicken pox
o B&T cells only function in acquired immunity, but the two systems aren’t independent
 Signally molecules of phagocytic cells set the stage for acquired immunity
 Cytokines: proteins secreted by phagocytic cells that help recruit and activate
lymphocytes
ACQUIRED IMMUNITY: AN OVERVIEW
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“Each B cell or T cell has on its surface many receptor proteins that can bind to particular foreign
molecule. The receptor proteins on a single lymphocyte are all the same, but there are millions of
lymphocytes in the body that differ in the foreign molecules that their receptors recognize. When an
animal is infected, B and T cells with receptors that can recognize the microbe are activated […] B and
T cells interact with fragments of microbes displayed on the surface of cells. Activated lymphocytes
undergo cell division […] Some T cells assist in activated other lymphocytes. Other T cells detect and
kill infected host cells. Specialized B cells secrete soluble receptor proteins that attack foreign
molecules and cells” (936).
ANTIGEN RECOGNITION BY LYMPHOCYTES
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Antigen: a foreign molecule that is specifically recognized by lymphocytes and elicits a response
o Most are large molecules, either proteins or polysaccharides
o Some are toxins secreted by bacteria
B and T cells recognize antigens using their antigen-specific receptors embedded in their plasma
membranes
A single B or T cell has about 100,000 antigen receptors on its surface
o Sometimes B cells give rise to plasma cells that secrete a soluble form of the antigen
receptor, the antibody or immunoglobulin (Ig).
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Epitope: antigenic determinant, a small accessible portion of an antigen
All of the receptors on a single lymphocyte recognize the same epitope; each of the body’s
lymphocytes displays specificity for a particular epitope
ANTIGEN RECEPTORS OF B CELLS AND T CELLS
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B cell receptor for an antigen is a Y-shaped molecule consisting of four polypeptide chains
o Two identical heavy chains
o Two identical light chains
o With two disulfide bridges linking the chains together
o The light and heavy chains have a constant (C) region: amino acid sequences vary little among
the receptors, includes the cytoplasmic tail and transmembrane region of the heavy chain and
all the disulfide bridges
o Variable (V) region: two tips of the Y shape, amino acid sequence varies from one B cell to the
other
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Antibodies have the same overall recognition as B cell receptors except they lack the
transmembrane region and cytoplasmic tail
T cell receptor: consists of two different polypeptide chains: a chain and b chain, linked by disulfide
bridge
o Have as many features as the B cell receptors
o Tip of the molecule = V region: antigen binding site
o Rest of the molecule = C region
B cell receptors recognize and bind to an intact antigen whether it is free or bound to a pathogen ; T
cell receptors bind only to antigen fragments that are displayed on the surface of host cells
Major histocompatibility complex (MHC): genes in a group , produces a host cell protein that can
present an antigen fragment to a T cell receptor
THE ROLE OF THE MHC
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Antigen presentation: display of the antigen fragment on the cell surface
o By MHC proteins either activates immune responses against the antigen or target destruction
of the infected cell
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Class I MHC molecules:
o found in almost all cells of the body
o bind to peptide fragments of foreign antigens synthesized within cells
o recognized by cytotoxic T cells (kill by toxic gene products)
Class II MHC molecules: made by just a few cell types—dendritic cells, macrophages, B cells
o bind to antigen fragments derived from foreign materials that have internalized through
phagocytosis/endocytosis
o antigen-presenting cells: dendritic cells, macrophages and B cells because of their key role in
displaying internalized antigens
o recognized by cytotoxic T cells and helper T cells: a group of T cells that assist both B cells and
cytotoxic T cells
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LYMPHOCYTE DEVELOPMENT
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Major properties of acquired immune system
o Diversity of receptors ensures that new pathogens are recognized as foreign
o Ability to recognize vast numbers of foreign molecules coexist with a lack of reactivity against
body’s own molecules
o Response to antigen that has been encountered previously is stronger (immunological
memory)
GENERATION OF L YMPHOCYTE DIVERSITY BY GENE REARRANGEMENT
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Differences in amino acid sequences of V regions make antigen receptors extremely different
Each person has 1 million + different B cells and 10 million + different T cells
Understanding the origin of receptor diversity
o Immunoglobulin (Ig) gene that encodes the light chain of secreted antibodies and membranebound B cell receptors
 Joins randomly selected V and J gene segments
 Undergoes transcription, splicing and translation
ORIGIN OF SELF-TOLERANCE
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Lymphocytes mature in the bone marrow of thymus; tested for self-reactivity
o The ones that try to destroy the body’s own cell are destroyed by apoptosis or rendered
nonfunctional
o Body lacks mature lymphocytes that react against its own components
AMPLIFYING LYMPHOCYTES BY CLONAL SLECTION
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It is rare for an antigen to encounter a lymphocyte with a specific for that antigen; acquired immune
response is effective because of the changes in cell number and behavior triggered by the binding of
the antigen to the lymphocyte
Binding of an antigen receptor
o B cells or T cells amplify by dividing many times, forming two different types of clones
 Effector cells: short lived, attack antigen and any pathogens producing the antigen
 Memory cells: long lived, less numerous, bear receptors specific for the antigen
o Clonal selection: proliferation of a lymphocyte into a clone of cells in response to binding an
antigen
 The presentation of an antigen to specific receptors on a lymphocyte leads to
repeated rounds of cell division
 Result? Clonal population of thousands of cells, specific to that antigen
Primary immune response: first exposure to an antigen, peaks about 10-17 days after initial exposure
o B cells generate plasma cells, antibody secreting effector cells
o T cells activated to their effector forms (helper cells and cytotoxic cells)
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Secondary immune response: repeated exposure to the same antigen, faster response and of greater
magnitude
o Relies on the reservoir of T and B memory cells generated after the initial exposure
 Long-lived cells = provide immunological memory that can span many decades
43.3: ACQUIRED IMMUNITY DEFENDS AGAINST INFECTION OF BODY CELLS AND
FLUIDS
OVERVIEW
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Humoral immune response: activation and clonal selection of effector B cells- which secrete
antibodies that circulate in the blood and lymph
Cell-mediated immune response: activation and clonal selection of cytotoxic T cells- which identify and
destroy target cells
HELPER T CELLS: RESPONSE TO NEARLY ALL ANTIGENS
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Helper T cells are activated by encounters with antigen-presenting cells
Cell proliferates after interacting with antigen fragments displayed by antigen-presenting cells
Activated helper T cells secrete cytokines that stimulate activation of nearby B cells and cytotoxic T
cells
CD4: protein found on the surface of most helper T cells, binds to class II MHC molecule
o Keep the helper T cell and antigen-presenting cell joined
Dendritic cells are particularly important in triggering primary immune response
o Serve as messengers, capture antigens, migrate to the lymphoid tissues
CYTOTOXIC T CELLS: RESPONSE TO INFECTED CELLS
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Effector cells in cell-mediated immune response
Require signaling from helper T cells to become active, as well as interaction with an anti-gen
presenting cell
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CD8: protein found on most cytotoxic T cells, enhances interaction between target cell and T cell
Destruction involves the secretion of proteins that cause cell rupture and cell death
o Exposes pathogen to circulating antibodies
Dendritic cell can present fragments from a wide variety of protein antigens, whereas B cells only
present only to the antigen to which it binds
ANTIBODY CLASSES
 Monoclonal antibodies: prepared
from a single clone of B cells grown in
culture – identical and specific for the
same epitope on an antigen – useful for
tagging specific molecules
THE ROLE OF ANTIBODIES IN IMMUNITY
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Neutralization: antibodies bind to the surface proteins of a virus or bacterium, blocking the
pathogen’s ability to infect a host cell
Opsonization: antibodies bound to antigens present readily recognized structure for macrophages
and increase phagocytosis
Complement: proteins increase the effectiveness of antibody directed attacks on bacteria
Membrane attack complex: forms a pore in the membrane of the foreign cell, water and ions rusin
into the cell- lyses
Phagocytosis: eating of pathogen
PASSIVE AND ACTIVE IMMUNIZATION
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Active immunity: clones of memory cells form in response to an infection
Passive immunity: antibodies provided by the mother guard against microbes, persists only for a short
time
Immunization: introduction of antigens into the body to develop active immunity
o Vaccination: weakened forms of the pathogen to develop immunological memory
IMMUNE REJECTION
BLOOD GROUPS
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Type A blood would react with the type B antigen, shit would go down
TISSUE AND ORGAN TRANSPLANTS
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MHC molecules stimulate immune response that leads to organ/tissue rejection
43.4: DISRUPTIONS IN IMMUNE SYSTEM FUNCTION CAN ELICIT OR
EXACERBATE DISEASE
EXAGGERATED, SELF-DIRECTED, AND DIMINISHED IMMUNE RESPONSES
ALLERGIES
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Allergens: antigens that elicit an exaggerated response- mostly often involve IgE class antibodies
Degranulation: interaction with the large pollen grains cross-links adjacent IgE molecules, inducing
mast cell to release histamine
Vascular changes: sneezes, runny noses, tearing eyes, difficulty breathing (antihistamines diminish
allergy symptoms)
Anaphylactic shock: develops when widespread mast cell degranulation triggers abrupt dilation of
peripheral blood vessels, causing a precipitous drop in blood pressure (epinephrine, counters allergic
responses)
AUTOIMMUNE DISEASES
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Autoimmune disease: immune system turns against particular molecules of the body
o Lupus: immune system generates antibodies against histones and DNA released by the
normal breakdown of body cells
o Rheumatoid arthritis: leads to painful inflammation of the cartilage and bone of joints
o Type 1 diabetes mellitus: cytotoxic T cells destroy insulin-producing beta cells of the pancreas
o Multiple sclerosis: T cells infiltrate central nervous system and destroy the myelin sheath that
surrounds parts of many neurons
EXERTION, STRESS, AND THE IMMUNE SYSTEM
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Stress weakens the immune system, so does exhaustive exercise
Disrupt immune regulation by altering interplay of hormonal/nervous/immune system
IMMUNODEFICIENCY DISEASES
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Immunodeficiency: disorder in which the ability of an immune system to protect against pathogens is
defective/absent
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Inborn immunodeficiency: genetic/developmental defect in immune system
Acquired immunodeficiency: develops later in life following exposure to chem/bio agents
Acquired immunodeficiency syndrome /AIDS: caused by virus, shit happens
ACQUIRED IMMUNE SYSTEM EVASION BY PATHOGENS
ANTIGENIC VARIATION
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Pathogen alters how it appears to the immune system
o Can reinfect/remain in host w/o triggering rapid response, trick memory cells
o Antigenic variation: changes in epitope expression, regular events for some viruses (sleeping
sickness, flu)
LATENCY
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Largely inactive state, ceasing production of viral production targeted by lymphocytes (herpes, HIV
from mother to baby)
ATTACK ON THE I MMUNE SYSTEM: HIV
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HIV infects helper T cells, cells that have low CD4 (macrophages, brain cells)
RNA genome is reverse-transcribed, product DNA is integrated into host cell’s genome
Reasons why HIV thrives
o Antigenic variation- mutates at high rate during replication
o Latency- protected from antiviral agents used against HIV
o Abolishes T cells, impairing both humoral and cell-mediated immune responses
HIV sucks. Basically.
CANCER AND IMMUNITY
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Cancer increases when immune response is impaired