Allergic Contact Dermatitis!!

Notice the clear pattern

of the leaves that
touched my skin
 Weekly Issues
• Today: Wellness office lecture first
• Then Kiesha will do as much Immuno as possible
• She will cover the rest along with Hematology next week

• Lecture Recordings: We will check every week.

• Only email if the recording bugs somewhere in the middle

• Assignement 1 is up under assignment 1 on myCourses

• Vanessa will give you a few infos
IMMUNOLOGICAL
SYSTEM
Kiesha Dhaliwal, RN, MScA
Adapted with thanks from Veronik Sicard
 INNATE
IMMUNITY
 Two Lines of Innate Defense

Natural • Physical, mechanical, biochemical

barriers • Skin surface, tears, saliva = acidic

• Prevent infection of the injured

Inflammation tissue
• Promote healing
 Natural Barriers
• Physical
– Mechanical defense (sloughing, expulsion, flushing, trapping)
– Inhospitable environments (low temp, low pH)
• Biochemical
– > 1000 found, mostly positively-charged polypeptides
– Epithelial secretions that contain lysozyme
– Sebacious secretions with fatty acids and lactic acid
– Cathelicidins  inserts into bacterial membranes to kill
– Defensins  alpha and beta types, can defend and activate
next defenses
Mukherjee, S., & Hooper, L. V. (2015). Antimicrobial defense of the intestine.
Immunity, 42(1), 28-39.
 Normal Microbiome
• Mtualistic bacteria and fungi that
colonize body surfaces
– opportunistic pathogens (Pseudomonas aeruginosa)
• Unique to each individual and location
• Benefits
– Produce: enzymes that aid in digestion, useful
metabolites (Vit K/B), anti-bacterial factors to
prevent infection
– Compete with pathogens for nutrients and space to
grow
– Helps train adaptive immune system
• Alterations of the normal microbiome 
decreased protection  infection
Acute Inflammatory Response
 Cardinal Signs of Inflammation
• Rubor = redness
• Tumour = swelling
• Calor = heat
• Dolor = pain
• (Loss of function)
 Manifestations of Inflammation
Local
 Heat & Redness
 Swelling
 Pain

Systemic
 Fever
 Plasma protein synthesis
 Leukocytosis
 Plasma Protein Systems
 Complement system
 Activated by 3 different means (classical, alternative, lectin pathways)
 4 main functions:
 Anaphylatoxic activity & mast cell degranulation
 Leukocyte chemotaxis
 Opsonization
 Cell lysis - Membrane Attack Complex (MAC)

 Clotting system

 Kinin system
 Bradykinin
 Cellular Components of Inflammation
• Tissue • Blood
– Mast cells – Erythrocytes (RBCs)
– Dendritic cells – Platelets
– Leukocytes

Leukocytes

Granulocytes Monocytes Lymphocytes

Basophils Eosinophils Neutrophils Macrophages B cells T cells NK cells

 Cytokines
 Interleukins
 Pro- or anti-inflammatory
 Regulation of adaptive immune response
 Maturation of leukocytes
 Interferons-α, -β, -γ
 Prevents virus infection
 ↗ macrophage activity and inflammation
 Chemokines
 Leukocyte chemotaxis in reaction to inflammation
 Tumor necrosis factor alpha
 Pro-inflammatory with systemic effects (e.g. fever)
 Mast Cells

Histamine
Mast Cells Synthesis of Mediators
 Leukotrienes
 Produce effects similar to those of histamine
 Important in later stages of inflammation

 Prostaglandins
 Cause vascular permeability and neutrophil chemotaxis
 Induce pain
 Supressing the release of histamine
 Phagocytes
• Phagocytosis is the process of ingesting and
disposing of damaged cells and foreign
material
• This is the primary role of granulocytes
(neutrophils, eosinophils, basophils),
macrophages, dendritic cells
 Neutrophils
 Granulocytes – Phagocytes
 Arrive within 6 to 12 hours after injury
 Incapable of division + sensitive to acid
 Removal of debris is sterile lesions (e.g., burns)
 Phagocytosis of bacteria in nonsterile lesions
 Eosinophils
 2 specific functions
 Primary defense against parasites
 Help regulate vascular mediators released from
mast cells
 Lysosomes contain several enzymes that
degrade vasoactive molecules (e.g.
histaminase)
 Basophils
 Least prevalent granulocyte in the blood
 Very similar to mast cells in the content of its
granules
 Important source of cytokine IL-4
 Key regulator of the adaptive immune response
 Primary role is yet unknown
 Often associated with allergies and asthma
 Monocytes and Macrophages
 Monocytes
 Largest normal blood cells
 Horseshoe shaped nucleus
 Precursors of tissue macrophages

Produce in bone Enter the Migrate to the

marrow circulation inflammatory site

 Macrophages
 Even larger !!
 More active as phagocytes
 Important initiators of inflammatory response
 Neutrophils vs. Macrophages
Speed

Active life span

Chemotactic factors

Enzymatic content of their lysosomes, or digestive

vacuoles, differs.
Role in the immune response

Role in wound repair

 Phagocytosis
 Production of adhesion molecules
 Selectins = margination or pavementing
 Integrins
 Diapedesis
 4 steps

Endocytosis
Fusion with
Opsonizatio and Destruction
lysosomal
n formation of of target
granule
phagosome

Phagolysosome
Phagocytosis
 Natural Killer Cells
 Recognition and elimination of cells infected with viruses
 Elimination of other abnormal host cells (specifically, cancer
cells)
 More efficient in circulatory system as opposed to within
tissues

Binds to target Produces

cell through several
Kill the target
activating cytokines +
receptors toxic molecules
 Chronic Inflammation
 > 2 weeks irrespective of
cause
 Unsuccessful acute
inflammatory response
 Insensitive to phagocytosis
 Survive in the macrophage
 Toxins even afer they are killed
 Chemicals
 Dense infiltration of
lymphocytes and
macrophages : Granuloma
 Resolution and Repairs
 Resolution is tissue regeneration with return to
normal structure and function
 Repair is the replacement of destroyed tissue with
scar tissue
 Begins with phagocytosis = Debridement
 Healing
1. Fill in (proliferation)
2. Seal (epithelialization)
3. Shrink the wound (contraction)
Phases of Wound Healing
 Dysfunctional Wound Healing
 Insufficient or excessive repair,
or reinfection of the wound
 Wound sepsis
 Impaired collagen matrix :
Scurvy
 Overproduction of collagen
 Keloids
 Hypertrophic scar
 Wound disruption (From Damjanov I, Linder J: Anderson’s
pathology, ed 10, St Louis, 1996, Mosby.)
 Dehiscence
 ADAPTIVE
IMMUNITY
 General Characteristics

Recognition of Specificity and Long-term

antigens memory protection

Immunoglobulins
Lymphocytes
or antibodies
Overview of Immune Response
 Humoral and Cell-Mediated Immunity
Type of Immunity Primary Cells Functions Protection
Humoral B cells and Causes direct Protects against
circulating inactivation of a bacteria and
antibodies microorganism or viruses
the activation of
inflammatory
mediators

Cell-mediated T cells T-cell differentiation Protects against

Kills targets directly, viruses and
or stimulates the cancer
activity of other
leukocytes

+ Memory cells
 Recognition and Response
 Foundation of any successful immune response
 Complicated processes and involve a highly effective
interaction of cells
 Clusters of differentiation (CD)
 Originally used to describe proteins found on the surface
of lymphocytes
 Currently, CD is a labelling system used to identify a family
of proteins on many cells
 Antigens
 Molecule that can react with antibodies or receptors
on B and T cells
 Mostly proteins but can be other molecules as well
 Immunogenic antigen
Degree of
Chemical
foreignness to a Size Amount
complexity
host
• Most • Large ++ • The greater • High or low
important !!! immunogenic the diversity, extremes can
the more cause
immunogenici tolerance
ty
Antibody IgG IgA IgE IgD IgM
General Most Mostly in Most rare Not well Largest
Information prevalent secretions known
Functions Most of Most of Mediator of Not well First
protective protective many known antibody
activity activity in common produced
against body allergic during the
infection secretions responses initial
Crosses the Secretory Defends primary
placenta piece against response
protects parasitic to an
and allows infections antigen
crossing
 Antibody Structure
• Antigen-binding fragments
Paratope
(Fab)
– Recognize and bind antigen
• Crystallizable fragment (Fc)
– Biological function
• 4 polypeptide chains
– 2 Light chains
– 2 Heavy chains – determine class
of Ig
– Each chain has a constant and
variable region which contribute
to antigen-specificity
Major Histocompatibility Complex
 Role = autorecognition +
cellular immunity
 MHC class I : Found on the
surface of all human cells
except RBCs
 MHC class II : Normally is only
found on professional antigen-
presenting cells
 Antigen processing =
enzymatic cleavage into
antigenic fragments linked
with appropriate MHC
 T-Cell Maturation
 Thymus
 Development of the TCR and coassembly with CD3
 Final antigen-reactive T-cells take up residence in
secondary lymphoid organs
 CD4 and CD8 (positive selection) Helper T-cells (CD4+)
• Recognize antigen
presented by MHC class II
molecules
• Helpers in clonal selection
process

Cytotoxic T-cells (CD8+)

• Recognize antigen presented
by MHC class I molecules
• Kill other cells directly
 Central Tolerance
 Random rearrangement of genes – combinations
result in specificities that recognize self-antigens
 Deletion of autoreactive T-cells in the thymus
 MHC class I or MCH class II molecules expressed by thymic
cells
 If strongly binding with self-antigen → deletion
 Also called negative selection
 Peripheral tolerance
T-cell Maturation
 B-Cell Maturation
 Bursa of Fabricius
 Portions of the bone marrow
 Production of the BCR
 Very similar process than T-cells
 Random rearrangement of genes
 Is an antibody that is anchored to the plasma cell
membrane
 Central tolerance
 Eliminated if exposed to self-antigen (more than 90%)
 Clonal Selection
 In secondary lymphoid
organs
 A specific Ag only activates
(i.e., selection) its counter-
specific B-cell so that
particular B-cell is induced
to multiply (i.e., producing
its clones) for Ab production
 Generation of diversity of
Ab specificity
(From Nossal G, The double helix and immunology, Nature 421, pp.
40-444, 23 January 2003)
 Antigen Processing and Presentation
 Professional APCs : dendritic cells, macrophages, and
B cells
 NECESSARY
 Activation of an immune response only if
 The antigen is of the appropriate type
 The lymphocytes are prepared to recognize the presented
antigen
 The antigen is presented appropriately
 B-Cell Activation : Humoral Immune
Response

 Encounter with an antigen for the first time, cells

with specific B-cells to that antigen are stimulated
and differentiation (clonal selection)
 Differentiated B-cell → Plasma cell

Primary Secondary
Initial
Lag phase immune immune
exposure
response response
Primary vs. Secondary Response
Antibody Function
T-Cell Activation : Cellular Immune Response

 Binding of antigen to specific T-cell receptors → T-cell

proliferate and differentiate
 Effector T cell
 Direct killing of foreign and abnormal cells
 Assistance or activation of other cells (e.g., macrophages)

Cytotoxic Regulatory Memory

 Natural Killer Cells
 Lymphoid cells that are similar to T cells but do not
under maturation in thymus
 Lack antigen-specific receptors
 Express Fc receptor for IgG that identify protein
changes on the surface of cells that have been infected
or are in other ways abnormal
 Recognize target cells that do not express MHC class I
 Antibody-dependent cell-mediated cytotoxicity
(ADCC)
ALTERATIONS IN
IMMUNITY AND
INFLAMMATION
 Mechanisms of Hypersensitivity
Type I Type II Type III Type IV
IgE-mediated Tissue-Specific Immune Cell-Mediated
Complex-
Mediated
Allergy Hay fever Hemolysis in Gluten Poison ivy
Bee sting drug
Autoimmunity Autoimmune Systemic lupus Hasimoto
thrombocytopenia erythematosus thyroiditis
Alloimmunity Hemolytic Anaphylaxis to Graft
disease of the IgA rejection
newborn
Type I : IgE-Mediated
 Bee Sting Allergy
 1% of children may have anaphylactic rx to bee
venom
 Within minutes
 Excessive swelling
 Generalized hives
 Systemic symptoms (sweating, dizziness, headache)
 Gastrointestinal, respiratory, and vascular reactions
 May lead to death
 Antihistamines has little effect
 Type II : Tissue-Specific
 Also called cytotoxic hypersensitivity
 Tissue-specific antigens
 Self-reactive cell attack self tissues
 Antigen can be
 Intrinsic – normally made by host
 Extrinsic – attaches to host cell (e.g., certain drugs)
 Type III : Immune Complex-Mediated
 Serum sickness
 May be caused by repeated intravenous administration
 Generalized deposition in target tissues (blood vessels,
joints, and kidneys)

 Arthus reaction
 Localized inflammatory response
 Caused by repeated local exposure to an antigen
 Symptoms begin within 1 hour of exposure, peak 6 to 12
hours later
 Type IV : Cell-Mediated
 Do not involve antibodies
 Toxins from Tc cells

Clinical examples
 Graft rejection
 Allergic reactions to poison ivy and metals
 Rheumatoid arthritis
 Autoimmune thyroiditis (Hashimoto disease)
 Diabetes mellitus
Type IV Allergic Hypersensitivities
 Systemic Lupus Erythematosus
 Production of a large
variety of autoAb
against nucleic acids
 Deposition of immune
complexes in tissues
 Inflammatory lesions
 Genetic predisposition
Type II and Type III
 Occurs more often in Hypersensitivities
women (10:1), especially
in the 20- to 40-year-old-
group Symptoms
ABO System

Isohemagglutinins
 Rh System
 Consists of at least 50 separate antigens
 RhD protein expresses the dominant antigen
 Rh-positive
 Rh-negative
 IgG anti-D

 Hemolytic Disease of the Newborn

 Autoimmune Hemolytic Anemia
 Graft Rejection
 Type IV cell-mediated reaction
 Matched for ABO and HLA systems

Hyperacute Acute Chronic

• Immediate • Days to • Months to
and rare months years
• White graft • Cell- • Progressive
• Preexisting mediated organ failure
Ab to Ag in • Antibody- • Inflammatory
the graft mediated damage
• ADCC
 Immune Deficiencies
• ↘ circulating Ig
B-cells
• ↗ susceptibility to infections

• DiGeorge syndrome = lack of thymus

T-cells
• Chronic candidiasis

• 20 different forms
Severe • Mutations in critical enzymes or
Combined antigen receptors
Immune
• Failure of blood cells to develop
Deficiency
• In utero death