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OVERVIEW OF THE IMMUNE RESPONSE
BAS 115: Immunology
Topic #1
Michael Dorrington
Course Administration• Mike Dorrington
– [email protected]• Office Hours
– By appointment only. Will occur either before or after class.
– Part-time faculty office (Rm 2111)• Grading
– 2 Exams (one midterm, one final)• 40/60 weighting
Immunology
“The study of the physiological mechanisms that humans and other animals use to defend their bodies from invasion by other organisms”
Overview of the Immune Response
• We are surrounded by a myriad of potentially harmful microbial agents = pathogens
• Bacteria• Viruses• Fungi• Parasites
Overview of the Immune Response
However…..in normal individuals most infections are of limited duration and leave little (if any) permanent damage
Due to: immune system responding to and eliminating the pathogen
Intrinsic Barriers
• Mechanical– Skin– Epithelium
• Chemical– Enzymes– Oil
• Microbiological– Normal Flora
Overview of the Immune Response
Immune system has 2 functional divisions:
1. Innate – 1st line of defence
2. Adaptive – comes into play if innate defences are breached
Overview of the Immune Response
All of the elements of innate/natural immunity:
1. Do not increase in response to re-exposure or chronic exposure to a microbe
2. Do not discriminate between foreign substances*
Overview of the Immune Response
However….
Elements of acquired/adaptive immunity induced by exposure to foreign substances are:
1. Specific for a given pathogen
2. Increase both qualitatively and quantitatively following primary exposure to a given pathogen
Overview of the Immune Response
The ultimate defence against a pathogen (whether elicited by the innate or adaptive immune system) is to reduce invader’s genes from an active polymer to inactive monomers
“Break big things into little things” This is accomplished by phagocyte cells
Overview of the Immune Response
Steps in Phagocytosis:
1. Adhesion – “grabbing”2. Ingestion – “engulfing”3. Digestion – “breaking down”
Innate-Activated Phagocytosis
Overview of the Immune Response
• Almost every component of the immune system contributes to:1. Recognizing pathogens2. Destroying pathogens3. Communicating between these two
activities
Hallmarks of Adaptive Immune Responses
1. Specificity
2. Diversity
3. Memory
4. Self/Non-self Discrimination
5. Self Limitation
Hallmarks of Adaptive Immune Responses
1. Specificity
• Immune responses are specific for distinct antigens
antigenic determinant/epitope:- portion of the molecule recognized
Hallmarks of Adaptive Immune Responses
2. Diversity
• Vertebrate immune system can recognize ~1016 distinct antigens
• This is accomplished by sets of corresponding recognition molecules (receptors) on immune cells
• Antibody• T cell receptors
Hallmarks of Adaptive Immune Responses
2. Diversity (cont.)
• lymphocyte receptor repertoire:- the set of antigen (Ag) receptors in a given individual’s immune system
Hallmarks of Adaptive Immune Responses
3. Memory
• Exposure of the adaptive immune system to Ag increases its ability to respond to the same or closely related antigen following re-exposure
• Secondary immune responses =– Faster– Larger– Qualitatively different
Hallmarks of Adaptive Immune Responses
4. Self-Limitation
• Adaptive immune responses are transient
• Immune responses are tightly regulated and controlled
Hallmarks of Adaptive Immune Responses
5. Self/Non-self Discrimination
• The immune system can tell foreign from self
• Immune responses to self can result in autoimmunity
• Immunological unresponsiveness to self is termed tolerance
Clonal Selection Hypothesis
• The central principle of adaptive immunity!
• Is comprised of 4 basic principles
Types of Adaptive Immune Responses
1. Humoral• Mediated by antibodies (Ab)• Produced by bone marrow derived or B
lymphocytes
2. Cell-mediated• Mediated by thymus-derived or T lymphocyte
N.B. BOTH humoral and cell-mediated immune responses involve lymphocytes
Types of Adaptive Immune Responses
Humoral Immunity
Cell-Mediated Immunity
Antigen Extracellular pathogen & toxins
Intracellular microbes
Responding Lymphocyte
B lymphocytes T lymphocytes
Effector Mechanism
Ab killing
Transferred By: serum Lymphocytes
Cells and Tissues of The Immune System
Cells & Tissues of the Immune System
All cellular elements of the blood (WBCs, RBCs and platelets) are derived from the same progenitor:
Pluripotent Stem Cells
Myeloid progenitor Common lymphoid progenitor- monocytes - B lymphocytes (macrophages, dendritic cells) - T lymphocytes- granulocytes (PMNs) - NK cells - Mast Cells
Myeloid ProgenitorMonocytes/macrophages• Macrophages are one of 2 phagocytic cells in
the body• Macrophage is the mature form of monocyte• Monocytes circulate in the blood & differentiate
into macrophages upon migration into tissue• Macrophages often produce the cytokines that
initiate the inflammatory response
Myeloid Progenitor
Dendritic Cells
• Resident in the body’s tissues• During infection, leave tissue (with
infectious cargo) and travel to lymph nodes
• Important in T cell activation during adaptive immune responses
Myeloid Progenitor
Mast Cells
• Differentiate in tissue from a blood-derived precursor
• Orchestrate allergic responses • Important in mucosal immune
responses
Myeloid ProgenitorGranulocytes (PMNs)
a) Neutrophils- Phagocytic- Most numerous cellular component of innate immune system
b) Eosinophils- defense against parasites
c) Basophils- with mast cells, protect mucosal body surfaces & release
histamine in allergic responses
Common Lymphoid Progenitor
• Produces lymphocytes
B cells: - bone marrow derived- upon activation differentiate into Ab-
secreting plasma cells
T cells: - thymus-derived- become either helper T cells (TH) or
cytotoxic T lymphocytes (CTL)
T Lymphocytes
TH Cells:• Activate other cells (macrophages, B
cells)
CTL:• Kill virus infected cells
Common Lymphoid Progenitor
• T and B lymphocytes look alike, each having receptors for specific antigen
• NK cells: lack Ag-specific receptors– Important in the innate immune system– Kill infected/altered cells
Lymphoid Tissues
• Organized tissues where lymphocytes interact with non-lymphoid cells
• Important in the initiation and maturation of adaptive immune responses
• 2 types of lymphoid tissues– Primary lymphoid organs– Secondary lymphoid organs
Primary Lymphoid Organs
• Where lymphocytes are generated• Includes bone marrow & thymus• Both B and T cells are generated in the
bone marrow but only B cells mature there
• Once lymphocytes mature they leave the 1o lymphoid organs and are capable of responding to Ag
Secondary Lymphoid Organs
• Where adaptive immune responses are initiated & Ag/Ab encounter each other
• Exist to bring Ag and lymphocytes together
Lymph nodes:– Organized lymphoid structures– Collect ECF (lymph) and return it to the blood (in vessels
called lymphatics)– Afferent lymphatics drain lymph and Ags from tissues,
carrying it to the nodes where Ag is trapped
A. Lymph Node Structure
• Bean-shaped outer cortex, inner medulla
• Lymph enters via afferent lymphatics, percolates through node & exits via efferent lymphatics in medulla
• Naïve lymphocytes exit blood via high endothelial venules (HEV)
High Endothelial Venules (HEV)
• Specialized section of post-capillary venules• Plump endothelial cells protrude into vessel • In LNs found in paracortex and some areas of
cortex• Lymphocytes display increased adhesiveness
to HEV
A. Lymph Node Structure
Medulla: consists of macrophages and plasma cells
B cells: - found in follicles- some follicles contain germinal
centers where B cells proliferate in response to Ag
T cells: found in paracortical area
B. Spleen• Fist-sized organ located behind stomach
• Collects blood born Ag & also destroys aged RBCs
• Organ is divided into red pulp & white pulp
Red pulp:– where old RBCs are destroyed
White pulp:– where lymphocytes surround arterioles entering organ– Further subdivided into corona and periarteriole lymphoid sheath
(PALS)
Asplenia & Splenectomy• Genetic defect causing asplenia not yet
identified• Clinical consequence:
– Susceptibility to bacteremia caused by encapsulated bacteria caused by failure of the immune response to these common extracellular bacteria when they enter the blood stream
C. Mucosa-associated Lymphoid Tissue
• Gut- and bronchial- associated lymphoid tissues (GALT & BALT)
• Purpose is to collect Ag from mucosal surfaces
• Specialized lymphoid tissue at the body’s “wet” surfaces required due to large surface area, rich with potential pathogens
C. Mucosa-associated Lymphoid Tissue
Gut-Associated Lymphoid Tissue (GALT)• Includes tonsils, adenoids, appendix
and Peyer’s Patches (PP)• PPs collect Ag from epithelial surfaces
of GI tract via M cells• PPs composed of distinct T and B cell
areas
Lymphocyte Recirculation
Naïve lymphocyte recirculation pattern:
B & T lymphocytes lymphocytes mature In b.m. & thymus in blood
PLN superior vena cava thoracic efferent duct lymphatics
Lymphocyte RecirculationIf an infection occurs in periphery:
a) Ag enters local draining LN via afferent lymphatics. Ag gets trapped and is “displayed” to recirculating lymphocytes
b) Lymphocytes that specifically recognize the Ag are arrested in the LN, where proliferation and differentiation to effector lymphoid cells occurs
c) Specific effector cells leave the LN via efferent lymphatics