Immune response.

T-cell
mediated.

Hipersensitivity.
 Summary
of previous lesson

Alveolar (Lung) Macrophage Attacking E. coli (SEM Macrophage Attacking E.coli (SEM x8,800) Dr Dennis Kunkel
x10,000) Dr Dennis Kunkel (used with permission)
 1st LINE OF DEFENSE -
intact skin
mucous membranes & their secretions
2nd LINE OF DEFENSE -
phagocytic white blood cells nonspecific
inflammation -complement
fever -interferon
3rd LINE OF DEFENSE-

B & T lymphocytes specific
antibodies
Significance
Significance of
of the
the
Immune
Immune System
System

Beneficial:
Beneficial:
Protection
Protectionfrom
from Invaders
Invaders
Elimination
EliminationofofAltered
AlteredSelf
Self

Detrimental:
Detrimental:
Discomfort
Discomfort(inflammation)
(inflammation)

Damage
Damagetoto self
self(autoimmunity)
(autoimmunity)
 Antigens
An antigen is a molecule that stimulates an immune
response.

The word originated from the notion that they can

stimulate antibody generation.
 Antigens
Antibody Generator

The best antigens are:

1. large
2. recognized as foreign

3. complex
ANTIBODY
 Antibodies
Made in response to exposure to the antigen.
Proteins that recognize and bind to a particular antigen
with very high specificity.

One virus or microbe may have several antigenic

determinant sites, to which different antibodies may bind.

Each antibody has at least two identical sites that bind

antigen: antigen binding sites.
Belong to a group of serum proteins called
immunoglobulins (Igs).
Immune response
 Duality of Immune
System
I. Humoral (Antibody-
Mediated) Immunity

I. II. Cellular (Cell

Mediated) Immunity
The Immune Response
 I. Humoral (Antibody-Mediated)
Immunity
Involves production of antibodies against foreign
antigens.
Antibodies are produced by a subset of lymphocytes
called B cells.
B cells that are stimulated will actively secrete
antibodies and are called plasma cells.
Antibodies are found in extracellular fluids (blood
plasma, lymph, mucus, etc.) and the surface of B cells.
Defense against bacteria, bacterial toxins, and viruses that
circulate freely in body fluids, before they enter cells.
Also cause certain reactions against transplanted tissue.
 II. Cellular (Cell Mediated) Immunity

Involves specialized set of lymphocytes called T cells

that recognize foreign antigens on the surface of cells,
organisms, or tissues:
Helper T cells

Cytotoxic T cells

T cells regulate proliferation and activity of other

cells of the immune system: B cells,
macrophages, neutrophils, etc.
 II. Cellular (Cell Mediated) Immunity

Requires constant presence of antigen to remain

effective.
Unlike humoral immunity, cell mediated immunity is not
transferred to the fetus.

Antigens that stimulate cell immune response are

mainly intracellular.

Defense against:
Bacteria and viruses that are inside host cells and are inaccessible to
antibodies.
Fungi, protozoa, and helminths
Cancer cells

Cellular versus Humoral
Immunity
 T Cells involved in Cell Mediated
Immunity
T cells are key cellular component of immunity.
T cells have an antigen receptor (T cell receptor, TCR)
that recognizes and reacts to a specific antigen.
T cell receptor only recognize antigens combined
with major histocompatability (MHC) proteins on the
surface of cells.
MHC Class I: Found on all cells.
MHC Class II: Found on phagocytes.
T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces
 Types of T cells

1. T Helper (TH) Cells: Central role in immune

response.
Most are CD4+
Recognize antigen on the surface of antigen presenting

cells (e.g.: macrophage).

Activate macrophages

Induce formation of cytotoxic T cells

Stimulate B cells to produce antibodies.

 Types of T cells (Continued)

2. Cytotoxic T (Tc) Cells: Effectors-Destroy target

cells.
Most are CD4 negative (CD4 -).
Recognize antigens on the surface of all cells:

Kill host cells that are infected with viruses or bacteria.

Recognize and kill cancer cells.
Recognize and destroy transplanted tissue.
Release protein called perforin which forms a pore in
target cell, causing lysis of infected cells.
Undergo apoptosis when stimulating antigen is gone.
Cytotoxic T Cells Lyse Infected Cells
 Types of T cells (Continued)

3. Delayed Hypersensitivity T (TD) Cells: Mostly T helper

and a few cytotoxic T cells that are involved in some
allergic reactions (poison) and rejection of
transplanted tissue.

4. T Suppressor (Ts) Cells: May shut down

immune response.
 Nonspecific Cellular
Components
1. Activated Macrophages: Stimulated phagocytes.
Stimulated by ingestion of antigen
Larger and more effective phagocytes.
Enhanced ability to eliminate intracellular bacteria, virus-
infected and cancerous cells.

2. Natural Killer (NK) Cells:

Lymphocytes that destroy virus infected and tumor cells.
Not specific. Dont require antigen stimulation.
Not phagocytic, but must contact cell in order to lyse it.
 Cytokines

Cytokines: Chemical messengers of immune cells.

Over 100 have been identified.

Stimulate and/or regulate immune responses.
Interleukins: Communication between WBCs.
Interferons: Protect against viral infections.

Chemokines: Attract WBCs to infected areas.

Cellular Interactions in
the Immune Response
Antigen-Presenting cells (macrophages)
place antigen on their cell surface in
combination with the MHC II complex
Ag is presented to a specific helper T cell
that has receptors that bind the Ag MHC II
complex
Central Role of Helper T Cells
 Helper T cells
After binding, the APC produces Interleukin -1 (IL-1) which
stimulates the TH Cell to produce IL-2 and/or IL-4

Some Th, ex. TH1 cells produce IL -2 and IFN- and

influence cell-mediated immunity
Some Th, ex. TH2 cells produce IL -4 (and other ILs) and
influence antibody-mediated (humoral) immunity
Interleukin-2 has an autocrine function, causes TH Cell to clone
itself, and make more IL-2 and /or IL-4
 Effector cells
When B cell comes in contact with the
antigen, the B cell produces plasma cells
and memory cells

When Tc Cells come in contact with the

antigen on the surface of infected cells in
combination with the MHC 1 complex T-cells
produce activated Tc Cells and memory
cells.
Overview of the Immune Response
 Principal mechanisms of defense
against microbes
Antibodies Phagocytes T cells (CTLs
(may work with antibodies, T cells)

All microbes Intracellular

microbes,
esp.
All microbes
 Apoptosis

Programmed cell death (Falling away).

Human body makes 100 million lymphocytes
every day. If an equivalent number doesnt die,
will develop leukemia.
B cells that do not encounter stimulating antigen
will self-destruct and send signals to phagocytes
to dispose of their remains.
Many virus infected cells will undergo apoptosis,
to help prevent spread of the infection.
 B and T cells mediate
specific immunity
B cells T cells
Matures in bone marrow thymus
Type of immunity humoral cell-mediated
Secretes antibodies cytokines
Antigen receptor surface Ig T cell receptor
Where found spleen blood, lymph
nodes
Targets bacteria, infected cells,
viruses tumor cells?
Memory Yes Yes
Disorders of Immunity
Hypersensitivity

Exaggerated Immune Response

 Classificationofhypersensitivities,GelandCoombs.

Type I Type II Type III Type IV

IgE Mediated IgG/IgM IgG Mediated T cell

Mediated

Classic Allergy Immune Delayed

rbc lysis complex Type
Disease Hypersensitivity
 Hypersensitivity Types
Gell & Coombs Classification

Type I Hypersensitivity: IgE mediated

Type II Hypersensitivity: Antibody mediated
cytotoxic
Type III Hypersensitivity: Complex mediated
cytotoxic
Type IV Hypersensitivity: DTH mediated
 TYPE I Hypersensitivity
Classic allergy
Exogenous antigen
Mediated by IgE attached to Mast cells.
Immediate hypersensitivity

The symptoms resulting from allergic

responses are known as anaphylaxis.
Includes: Hay fever, asthma, eczema, bee stings, food
allergies.
 Type I: Mechanism

First exposure - antigen causes increased IgE

production
IgE binds to mast cells
Sensitization occurs
Second exposure - antigen binds to IgE on mast
cell membrane
Mast cell releases histamine, chemotaxic factors
Inflammatory response occurs
 Type I: Signs/Symptoms
Clinical signs, symptoms = response to
histamine release
Vasodilatation
Increased capillary permeability

Non-vascular smooth muscle spasm

Skin: flushing, itching, edema, urticaria

Respiratory: bronchospasm, laryngospasm, laryngeal edema
Cardiovascular: tachycardia, hypotension
GI: nausea, vomiting, cramping, diarrhea
 Type I: Anaphylaxis

Severe, generalized Type I reaction

Life-threatening
Loss of airway
Ventilatory failure
Hypoperfusion
 Type I: Atopy

Atopy is the term for the genetic trait to have a

predisposition for localized anaphylaxis.

Atopic individuals have higher levels of IgE and

eosinophils.

More mast cell receptors for antibodies than

normal
 Type II Hypersensitivity:
Antibody mediated cytotoxic
Antibody Dependent Cytotoxicity
Antibody Dependent Cell mediated
Cytotoxicity
Target antigens are found on cell or tissues
Antibody binds to Target Antigen
complement activated cell destruction
Ig binds to Fc receptors on NK cells
Trigger release of toxins to destroy target cells
 Type II Hypersensitivity:
Antibody mediated cytotoxic
Tissue specific
Reaction to tissue-specific antigens
Causes target cell destruction, dysfunction
Exogenous or endogenous antigen

Most commonly affected cells

Red blood cells
Thyroid cells
 Type II Hypersensitivity:
Antibody mediated cytotoxic
Transfusion reactions
Hemolytic disease of the newborn
Drug induced hemolytic anemia
Nephrotoxic (Masugi type) nephtritis
Autoimmune hemolytic anemias
Anti receptors/ hormone autoimmune diseases
Hashimotos thyroiditis myasthenia gravis
 ABOBloodGroups

Antibodyagainstrbcantigenbindsand
mediateskillingofrbcsviaCorADCC
causessystemicinflammation.
 TYPE II

Rh factor incompatibility
 TYPE III
Antigen antibody immune complexes.
IgG mediated

Immune Complex Disease

Large amount of antigen and antibodies
form complexes in blood.

If not eliminated can deposit in capillaries or

joints and trigger inflammation.
 Type III
Complex mediated cytotoxic
Especially sensitive tissues are blood vessels, GI,
respiratory system
Complement activation increase neutrophil activity
Neutrophils have trouble digesting complexes,
release lysosomes causing damage
Immune complex quantity varies over time
Symptomatic periods alternate with periods of
remission
 Type III
Complex mediated cytotoxic
Acute Systemic Reactions
drug reactions penicillin
Post streptococcal acute glomerulonephritis
aggregate anaphylaxis- cyroprecipitates
Chronic Systemic Reactions
Infections
Auotimmune conditions SLE RA
Cutaneous vasculitis
 Type III
Complex mediated cytotoxic
Localized reactions
Arthus type skin reactions
complex mediated glomerulonephritis
bumpy deposits
Generalized reactions
Serum sickness
 Type IV
Delayed type hypersensitivity

Delayed
Mediated by Td (lymphokine-producing) or Tc
(cytotoxic) cells
No antibody involved
 Type IV
Delayed type hypersensitivity
DTH response is from:
Th1 cells release cytokines to activate
macrophages causing inflammation and tissue
damage.
Continued macrophage activation can cause
chronic inflammation resulting in tissue lesions,
scarring, and granuloma formation.
Delayed is relative because DTH response arise 24-72 hours
after exposure rather than within minutes.
 Type IV
Stages of Type IV DTH
Sensitization stage
Memory Th1 cells against DTH antigens are
generated by dendritic cells during the
sensitization stage.
These Th1 cells can activate macrophages
and trigger inflammatory response.
 Type IV
Stages of Type IV DTH
Effector stage
Secondary contact yields what we call DTH.
Th1 memory cells are activated and produce
cytokines.
IFN-g, TNF-a, and TNF-b which cause tissue destruction,
inflammation.
IL-2 that activates T cells and CTLs.
Chemokines- for macrophage recruitment.
IL-3, GM-CSF for increased monocyte/macrophage
 Type IV
Stages of Type IV DTH
Secondary exposure to antigen
Inflamed area becomes red and fluid filled
can form lesion.
From tissue damage there is activation of clotting
cascades and tissue repair.
Continued exposure to antigen can cause
chronic inflammation and result in granuloma
formation.
Delayed type hypersensitivity
(DTH)
DTH is a type of immune
response classified by
Th1 and macrophage
activation that results in
tissue damage.

DTH can be the result of

Chronic infection or
Exposure to some antigens.
Granuloma Formation from DTH
Mediated by Chronic
Inflammation
Drug reactions can be any Type
of Hypersensitivity
Overview of the Immune Response
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