Topic 1 - Intro and Overview of the Immune Response

OVERVIEW OF THE IMMUNE RESPONSE

BAS 115: Immunology

Topic #1

Michael Dorrington

Course Administration• Mike Dorrington

– dorrinmg@gmail.com• 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