Basic Immunology

BASIC IMMUNOLOGY
Prepared by: Dr. D. L. Boyd, DDS

Oral & Maxillofacial Pathologist
Associate Professor
Reference: Kaplan Review Notes
IMMUNE SYSTEM
Collection of Organs, Tissue, & soluble Factors to
defend against Bacteria,
Viruses, & Tumor
cells.
Consist of:
Primary (central) Lymphoid Organs in
which
Leukocytes develop
Secondary (peripheral) Lymphoid Organs &
Tissues in which Immune Response occur.
Leukocytes in Blood
Mature in Marrow (B cell) or Thymus (T-cell)
CELLS OF THE IMMUNE

SYSTEM
MONOCYTES & MACROPHAGES
Control infections not overcome by Neutrophils
Associated with chronic infections

Main role in cell-mediated immunity
Act as Ag presenting cell to T-Lymphocyte
Activated by -Interferon (lymphokine)
MONOCYTES / MACROPHAGES
Formation:
Stem cell Monoblast Promonocyte
circulating Monocyte tissue Macrophage
Mature in the Blood
Secrete Inflammatory Mediator & Cytokines
Interleukins (IL-1, 8, 12) Prostaglandin (PG)
Thromboxane (TBx) Leukotriene (LT)
Interferon (IF)
Collagenase
Elastase
Complement components
Lysozymes
Tumor Necrosis Factor (TNF) Lipase
Have on cell surface:
Fc Receptors allow uptake of Immune
Complexes
Class 11 MHC molecules present
Antigenic
peptides to T-cells
Monocytes Macrophage with different names:
Kupffer cell in sinusoid of Liver
Alveolar macrophage in Lung
Microglial in Brain
Morphology:
Epithelioid: (From Monocytes)
In Granulomas
Activated by immune response to Antigen
Multinucleated Giant Cells formed by fusion of
Macrophages
Activation:
Stimulated by Lymphokines (-Interferon)
Kill Microbs + Tumor cells
When activated:
Have increased lysosomal hydrolytic enzymes
Increase Chemotactic response to C5a &
Cytokines from Lymphocytes, Neutrophils
& Fibroblasts
Activation (cont)
Opsonization can occur:
Phagocytosis of Antigen coated
with C3b and Antibody
Increase in Size, and Number of Pseudopodia +
Pinocytotic vesicoles
Present Antigens to T-Lymphocytes:
Antigen undergo phagocytosis or pinocytosis
Antigen degraded in cytoplasm to small
Peptides
Peptides non-covalently bind to Class 11 MHC
molecules in Endosomal vesicle complex
transported to cell surface stimulate Class
11-restricted Antigen-specific Helper T cells
(CD4)
Pocess Exogenous Ag present Epitopes in
groove of Class 11 MHC
CD4 T cells with receptors specific for the Epitope
react with Epitope-MHC complex and release
Lymphokines
Pocess Endogenous Ag presented to CD8 T
cells on Class 1 MHC
MACROPHAGES &
NEUTROPHILS
Phagocytize Bacteria coated with Complement
C3b binds to Bacteria Opsonized by Ab
binds to Receptor on Phagocytic cell
Phagocytosis
Fc receptor on Macrophage useful for
Opsonization of Bacteria by Ab
hold
bacteria close
Engulfment
Phagocytosis
DENTRITIC CELLS
Present in Blood, LNs, Epithelial cells
Digest & process Ag to present to T-cells
Examples:
Langerhan cells (resides within Epithelium)
Veild cells (Afferent Lymphatics)
Interdigitating reticular cells (Spleen & LNs)
GRANULOCYTES
NEUTROPHILS (PMNs)
60% of leukocytes (white blood cells)
Have receptor for Fc region of IgG & C3b
Release Matrix Metalloproteinase (MMP)
First to arrive in acute inflammation, actively killing
bacteria, by generation of Hydrogen peroxide & Oxygen
free radicals releasing LPS.
Cytoplasm contain Lysosomal Peroxidase +
Acid
Hydrolases
Cytoplasmic granules contain digestive enzyme
(Myeloperoxidase) & Lactoferrin (binds Fe)
GRANULOCYTES
NEUTROPHIL SUMMARY
Kill microbes by:
Toxic Oxygen molecule
Digestive Enzymes stored within Lysosomal
granules
GRANULOCYTES
EOSIONPHILS (1 3% of leukocytes)
Have receptors for Complement
Bi-lobed nucleus + red granules (Giemsa stain)
Chemotactic factors for Eosinopkils:
Histamine C5a LTB4 PAF
ECF-A (anaphylaxis)
Mostly in parasitic(*MBP)& allergic conditions
Contents & Functions: Histaminase
Pyrogen (fever) Peroxidase (kill bacteria)
Aryl sulfatase (degrade LT) *Major Basic Protein
EOSIONPHILS
CLINICAL CORRELATION
Classically seen with:
Atopic allergies
Worm infections
Collagen Vascualr diseases
Neoplastic disorders
Skin rash
Granules (histaminase, arylsulfatase) help
allergic reactions
control
CELLS OF THE IMMUNE SYSTEM

BASOPHILS (1% of leukocytes) (smallest)
Contain much granules with:
RNA Mucopolysaccharide
Histamine (hypersensitivity madiator)
Have receptors for Fc portion of IgE
IgE binding degranulation Histamine
allergic reactions

(cont)
LYMPHOCYTES (30% of circulating WBC)
B Lymphocytes:
Differentiate into Plasma cells Antibodies
CDb5-positive IgM
CDb5-negative IgG, IgA, IgE
Memory B cells:generated after exposure to Ag
Mature B cell: have surface IgM & IgD that bind Ag
cause B cell Ab
B cell respond to:
T-cell-independent Ag Ig without CD4 cells
T-cell dependent Ag regulate T-cells B cell Ab
T LYMPHOCYTES:
Helper T cells (CD4 positive)
Stimulate B-Lymphocytes Plasma cell Ab
Promote cytotoxic T- cell (CD8) response
Activation due to recognition of Class 11
MHC on
Antigen-presenting cells
Produce Lymphokines, Differentiation
Factors, Inflammatory Cytokines (IL-2)
Cytotoxic T cell (CD 8 +)
Recognize Foreign Ag & Class 1 MHC
Lyse virus infected cells & tumor cells
Natural killer (NK) cells (10 -15% of Lymphocytes)

Kill Tumor cells
Defend against Viral infections
Recognize Foreign Ag independent of MHC
Mediate Ab-dependent cellular toxicity (ADCC)
Kill Opsonized or Ab-coated cells
Activated by Cytokines (- Interferon)
LYMPHOCYTES
SUMMARY:
T Helper cell CD4+
Cytotoxic T cells CD8+
TDTH cell delayed-type Hypersensitivity

Has CD$ in its membrane
Antibody-Dependent cellular toxicity (ADCC)
Linked to NK cells, Neutrophils
Have Fc Receptors
LYMPHORETICULAR SYSTEM
Primary (central) Lymphoid Organs:
Bone marrow & Thymus (child & adult)
Hematopoiesis & Lymphopoiesis occur here
Secondary (peripheral) Lymphoid Organs:
Lymph Nodes Spleen
Mucosa-Associated Lymphoid Tissue (MALT)
Waldeyers Ring: Lingual Tonsil +
Soft
Palate LNS + Tonsils + Adenoids
Gut- Associated Lymphoid Tissue (GALT)
Peyers patch
Secondary (peripheral) Lymphoid Organs:
Bronchus-Associated Lymphoid Tissue (BALT)
Trap & present Ag to Lymphocytes
Immune Response
Protect all surfaces and fluids of the body
Extracellular fluid or Lymph filtered thru LNs,
and tissues of MALT
NOTE: Primary filter of Blood = Spleen +
Liver
BONE MARROW
A primary organ
Site for Hematopoiesis + B cell maturation
Site of origin of Stem cell T-cell production
A secondary organ: site for Plasma cell Ab

Contains activated T cells
BONE MARROW STRUCTURE
Very large tissue (3 5% body mass)
In Long bones + Cranium + Ribs + Iliac crest
Two Functional Parts:
Vascular + Adipose
Hematopoietic
Blood cells from single Stem cell
HEMATOPOIETIC CELL DIFFERENTIATION
Pluripotent Stem cell Myeloid + Lymphoid

progenitor cells
Myeloid Stem cell give rise to:
Monocyte Macrophage
Eosinophil
Basophil
Megakaryocyte Platelet
Erythroblast Erythrocyte
Lymphoid Stem cell give rise to:
Pre-B cell Late pre-B cell Immature B cell
Mature B cell Plasma cell Abs
Pre-T cell (enters Thymus) Helper T cell
Cytotoxic T cell + TDTH cell
NK cell
Stimuli for Differentiation:
Colony-stimulating Factors
Ags (self or foreign)
Erythropoietin Thymosin
After maturation in Thymus or Bone marrow,
Lymphocytes migrate to Spleen + LNs +
MALT
THYMUS
Development:
From 3rd + 4th Pharygeal Pouches
Located in Mediatinum
Maximum weight in Puberty, slowly
involutes
THYMUS (cont)
Organization:
Stroma:
Connective tissue capsule invaginates
into Parenchyma as Septa
divides into Lobules
Cortex:
Differentiating Thmocytes surrounded by
meshwork of Epithelial Reticular cell
+ Macrophages
THYMUS
Organization: (cont)
Medulla:
Epithelial Reticular cells + Mature T cells
Hassall corpuscles = concentrically
arranged dead / dying Reticular cells +
Macrophages + Neutrophils +
Nuclear material ?origin
THYMUS (cont)
THYMECTOMY result in:
Poor development of other Lymphoid tissue
Absence of cell-mediated immunity
DeGeorge syndrome (congenital absence)
Decrease B and T cells increase
infections death
Also Hypoparathyroidism Tetanus
THYMOSIN
Lymphokine that stimulate Thymus-dependent
zones in Lymphoid tissues
Produced by Thymic Epithelium
LYMPHATICS
Plasma filtered from Capillaries Tissues Veins
Interstitial Fluid Excess (Lymph) Lymphatic
vessels LNs Lymphatic vessels
Thoracic
Duct Left Subclavian Vein
LYMPH NODES
Most common site for adaptive immune
response
Filters Lymph of Foreign bodies
Encapsulated, kidney shaped, concave side
with Hilum (entry & exit of Blood vessels +
Nerves)
LYMPH NODES (cont)
Stroma:
CT capsule extends into and divides the
parenchyma
Reticular cells Reticular fibers network
filters Lymph + suspend
Lymphocytes &
Macrophages
Facilitates cell-to-cell & Ag-receptor
interactions
LYMPH NODES (cont)
Cortex:
Composed of Lymphatic nodules (B cells)
Diffuse Lymphatic tissue (T cells)
Mixes with Supcapsular & Peritubular Sinuses
(Macrophages)
Lymphatic Sinuses:
Lymphatic passageways
Lined with Endothelial cells
Receive Lymph Medulla
LYMPH NODES
Cortex: (cont)
Germinal centers:
Inside Nodules of Cortex
Mainly B cells Plasma cells Abs
Where Ags are processed increase in
number + develpoment of Germinal
centers
LYMPH NODES
Medulla:
In center of LN
Contain medullary cords of Lymphoid tissue
extend into Cortex
Medullary Sinuses transmit Lymph to Hilium

exists thru Efferent Lymphatics
LYMPH NODES
CLINICAL CORRELATION:
Receive Lymph from defined and limited
regions of the Body
Example: Pericoronitis around Mandibular
3rd molars Submandibular LNs
Neoplasms can metastasize to via LNs
Example: Breast, Lung, GIT, Prostate,
Kidney cancer Jaws
SPLEEN
Peripheral (Upper Left Quadrant of Abdomin)
Filters Blood of old + defective RBCs
Protects against Blood-borne pathogns
Stroma:
Dense CT capsule containing Smooth muscle
Trabeculae branches off Capsule partition
parenchyma of Splenic Pulp
Delicate meshwork of Reticular CT filters Blood
SPLEEN (cont)
Splenic Parenchyma (White & Red Pulp)
White Pulp:
Lymphatic tissue arranged in Sheaths
Increases with Antigenic stimulation
Periarteriolar Lymphocyte Sheath (PALS)
Rich in T cells
Marginal zone mostly B cells form Primary
follicles + Ag Secondary follicles with Germinal
centers (B cells)
SPLEEN
Splenic Parenchyma
White Pulp (cont)
In Marginal Zone, Dendritic cells trap & process
Ag, and migrate to PALS to present Ag to Antigenspecific cells
Red Pulp
Mostly RBC-filled sinusoids + Macrophage in
Reticular fiber network
Most of Filtration occur here
SPLEEN
Splenic Parenchyma
Red Pulp (cont)
Sinuses of various sizes separated by Pulp
(Billroth) cords
RBCs + Platelets exposed to Macrophages
in
Pulp cords, which phagocytize
worn-out or
damaged cells
Sinusoids lined by endothelial cells with
numerous fenestrations filtration
SPLEEN
Splenic Parenchyma
Red Pulp (cont)
Phagocytosis mainly by Macrophages
outside the sinusoids, by extending fingerlike projections into the sinusoids, that push
thru the fenestrations between the
endothelial cells
SPLEEN
Patients with Sickle cell anemia undergo gradual
infarction of the Spleen increase risk for
septicemia (S. pneumoniae), and other
opportunistic
infections
(Salmonella,
meningococci, H. Influenza)
NOTE:
In White Pulp, T cell mostly in central portion of
PALS, B cells mostly in marginal zone
GUT-ASSOCIATED-LYMPHOID TISSUE
Non-encapsulated
Located in the Submucosa + Lamina propria
Site of immune responses to ingested Microbs +
Food antigens
Structure:
Large follicular aggregates
Peyer patches (Small Intestine villi))
Intraepithelial Lymphocytes
GALT (cont)
Function:
Ag-presenting cells (M cell) in the Mucous
Membranes endocytose Microbes + Ags
which are presented to T Lymphocytes
between the Lymphoid follicles
B cell become activated form Germinal
Centers become Plasma cells IgA
GALT
Function (cont)
IgA react with receptor on Intestinal Epithelial
cells crosses cytosol of epithelial cell
cleaved excreted into lumen of intestine as
secretory IgA (sIgA) protected against
hydrolysis by intestinal fluids destroy
Microbes.
sIgA also found in Saliva
BRONCHUS-ASSOCIATED LYMPHOID
TISSUE (BALT)
Lymphoid tissue beneath Respiratory mucosa
Tonsils
Organization:
Aggregates of B cells Plasma cells Abs
Humoral immune response
Types of Tonsils:
Palatine Tonsils:
Bilateral in the Oropharynx
Dense Lymphoid tissue with Germinal
centers
Numerous Epithelial invaginations (crypts)
Lingual Tonsils:
Base and Posterior Lateral Tongue
With an Inflamed Lingual Tonsil, Squamous
cell carcinoma MUST be R/O
Types of Tonsils (cont)
Pharyngael Tonsils (Adenoids)
Unpaired aggregate of Lymphoid tissue in
Posterior Wall of the Nasopharynx
Surfaced by Pseudostratified Columnar
Epithelium with Cilia + Goblet cells
the
Waldeyers Ring = Ring of Lymphoid tissue located on

Soft Palate + Floor of Mouth +
Palatine Tonsil +
Lingual Tonsil
IMMUNE RESPONSE
NATURAL IMMUNITY (innate immunity)

Present at birth
Immediate response to Pathogens Inflammation
Does not increase with repeated exposure
First line of defense: Skin + Mucous membrane
Effected by:
Antibodies Macrophages
PMNs Eosinophils
Natural Killer cells
Saliva
Tears
IMMUNE RESPONSE (cont)
ACQUIRED IMMUNITY (Late in Fetal life

Stimulated by repeated exposure to foreign Ag
Response specific to individual Antigen (Ag)
Antigen eliminated due to specific Anatigen
recognition & Lymphocytes activated into
Effector and Memory cells Anamnestic Response
SELF TOLERANCE:
Absence of immune response to ones own
tissue Antigens.
Necessary to prevent auto-immune diseases
IMMUNE RESPONSE
Antigen: any substance that can specifically
bind
to an Antibody or T cell receptor.
Examples: Proteins LPS DNA Lipid Haptens
(small molecules act as Ab epitope)
Immunogen: that which induces an immune

response.
Epitope (Antigenic Determinant)
Specific site on Ag that is recognized by the
immune system, where Ab binds
Antibody: able to bind to epitopes
IMMUNE RESPONSE
Major Histocompatibility Complex (MHC)
In Humans the MHC called HLA
Genes that encode proteins that regulate the immune
response.
Class 1: located on surface of all Nucleated cells
+
Platelets (HLA A, HLA-B, HLA-C)
Associated with Cytotoxic T cell
Class 11: located on Langerhan cells &
activated Macrophages (HLA-DR, HLA-DQ)
Associated with Th & TDTH cells
IMMUNE RESPONSE
Class 111 encode Complement proteins
Associated with C2 & Factor B
Not related to Transplant acceptance or
rejection
HLA diseases:
Arthritis (HLA DR4)
Sjogrens syndrome (HLA DR3)
IDDM (HLA DR3 & 4)
IMMUNE RESPONSE
ANTIBODY STRUCTURE
Ag Binding Site
Variable Light Chain

Constant Light Chain
Ag Binding Site
Variable Heavy Chain
Amino acid End
Constant Heavy Chain
Carboxyl End
Hinge Region
Complement Binding Site
Cell Receptor Binding Region
IMMUNE RESPONSE
ANTIBODIES (Ab)
Act on Ag-specific receptors on B cells
Secreted by Plasma cells and mediate Humoral
responses (Antibodies in blood)
20% of plasma proteins
Ag B cell Ab
Bind Epitopes on Ag
Activate Complement
Binds Fc receptors on other Lymphoid cells
IMMUNE RESPONSE
ANTIBODIES (cont)
Structure:
4 polypeptide chains (2 identical Light + 2
Heavy), bound by disulfite bonds
identical
Have Hypervariable regions at Amino acid end

(responsible for Ag-binding)
Have Constant regions at Carboxyl end
Light chains 2 types: kappa & lamda
IMMUNE RESPONSE
ANTIBODIES (cont)
Heavy Chains:
IgG gamma heavy chain
IgA alpha heavy chain
IgM mn heavy chain
IgE epsilon heavy chain
IgD delta heavy chain
IMMUNE RESPONSE
ANTIBODY-BINDING SITES
Found at Variable Region at Amino acid
terminal
end of Heavy & Light chains
Variability of Amino acid sequence gives Ag- binding
specificity
Different structurally related Ags can cross- react &
bound by same Ag-binding site on
& different
Abs
Important in Rheumatic Fever Strep Ags structurally
related & cross react with Myosin.
IMMUNE RESPONSE
IDIOTYPE = areas on the Variable Region
responsible for Ag Specificity
ISOTYPE = subclass of Igs that are
distinguished
by unique Constant
Regions encoded by Heavy
chain gene
ALLOTYPE = protein product of an Allele that may
be detected as an Ag by another member of the same
species
It involves different Alleles at a specific site on the
Constant Region of the Heavy chain.
IMMUNE RESPONSE
IMMUNE SERUM contain a mixed population
of Abs with varying affinity for Ags
MONOCLONAL ANTIBODIES
Specific for a Single Epitope
Produces in Lab by Hybridomas (fusion of
activated B cells to Plasma cell)
IMMUNE RESPONSE
PROPERTIES OF IMMUNOGLOBULINS
IgG:
Major defense against Bacterie & Toxins
Only Ig to cross the human placenta,
protecting newborn for 4 6 months.
Associated with Opsonization
Associated with Complement activation
Important in Secondary immune response to
Ag provides Long-lasting immunity
IMMUNE RESPONSE
IgM: (only Ig produced by the Fetus)
Primary respone to Antigens
First Ab detected in serum post Viral
infection
Rheumatoid factor & Heterophile Abs are
IgM
Found on B cell membranes
Very efficient activator of Complement
IMMUNE RESPONSE (cont)

IgA:
Important barrier function on mucosal
surfaces
Function in secretory immune response

Secretory IgA (sIgA) found in Tears,
Colostrum, Breast Milk)
Produced by Plasma cells in GIT & URT
Saliva,
IMMUNE RESPONSE
IgD: (very low concentration in serum)
Cell surface Ag receptor on naive B cells
Primary receptor for Ag on B cells
Stimulate B cell proliferation
IgE: (very very low concentration in serum)
Allergic & immediate Hypersensitivity
Fc region of IgE binds to surface of Basophils &
Mast cells Histamine, LT, ECF, Heparin
Immediate Hypersensitivity reaction
HYPERSENSITIVITY REACTIONS
Type Antibody Complement Cells
Examples
1
IgE
No
Basophil
Allergies,
Anaphylaxis
Asthma
11
IgG, M
Yes
PMN, MO Autoimmnue
(Cytotoxic)NK diseases
Transfusion
reactions
HDNB
Graft rejection Goodpasture ds
Rheumatic fever
Type Antibody Complement Cells
Examples
11
IgG
No
0
Myastemia
(non-cytoxic)
Gravis
Graves disease
Type 2 DM
111
IgG, M
Yes
PMN, MO SLE, RA
(immune complex)
Polyarteritis nodosa
Post-Strep
glomerulonephritis
Arthus Rx Serum sickness
Type Antibody Complement
Cells
Examples
1V
0
0
CTL, Th, MO TB test
(delayed,
TB
DTH)
Leprosy
Hashimoto
thyroiditis
Poison Ivy
(contact dermatitis)
Acute Graft rejection
GVHD, IDDM
T-cell Receptors (TCR)
Ag-specific in concert with MHC molecules
Allow T cells to function in cell-mediated
responses
Types of Immune Responses
Involve Inflammation + adaptive response
Extracellular vaccine or pathogen Humoral
response
Intracellular pathogen Humoral + cell-mediated
response
TYPES OF IMMUNE RESPONSES

INFLAMMATION
Caused by infection or injury to tissues
Enhance Ag delivery Dendritic cells + Monocytes
Lymphocytes
recruit NK cells
Activation & clonal expansion of Ag-specific
Lymphocytes require several days to generate
enough Effector Lymhocytes & Memory cells
Effector Lymphocytes extravasate at site of
Infection

HUMORAL RESPONSE
Require Antibodies
Primary Immune Response
Lag Phase: 3 4 days, no measurable Ab
T helper & B cells activated
Activated B cell Plasma cells
Log Phase: detectable Ab in serum
IgM mostly produced
Later IgG & sIgA ( Ag acting on mucosa)

HUMORAL RESPONSE (cont)
Secondary Immune Response
Anamistic to priviously encountered Ag
Memory B & T cells involved
High-affinity IgG & IgA rise rapidly
Ability to respond may persist for years
Explains the efficacy of Booster injections
Response to extracellular particles [helminths,
pollen, enzymes (cat saliva)] IgE

CELLULAR IMMUNE RESPONSE
Functions of Effector (activated) T cells:
Activate B cells, Cytotoxic T Lymphocytes
Kill Virus infected cells & some Tumor cells
T cell Activation:
Require presentation of Foreign peptides on HLA
Class 11 proteins on Ag-presenting cell
Release cytokines differentiation &
proliferation
of Lymphocytes, MO, PMNs
Excess Macrophage activation DTH

Some allergies can be controlled by the
ingestion of Allergen. This can help patients
with Pollen allergen, by eating Honey)
Frequently given Low doses of Ag may explain
why large organ transplants (e.g. Liver) survive
well in most recipients.
REGULATION OF IMMUNE
RESPONSES
IMMULOGIC TOLERANCE
Specific supression of Immune response caused
by previous Ag exposure the opposite to
Immunity
Factors that affect Tolerance:
Form of Ag
Route of Exposure
Age of person
Dose of Ag
RESPONSES
IMMUNE SUPRESSION
Active non-response to interaction of
normal cells with suppressor cells
Physical or Chemical agents interactions with
immune cells
Suppression by CD*+ cells affect functions of T helper
cells (CD4+), B Lymphocytes,
Macrophages
RESPONSES
IMMUNE SUPRESSION (cont)
Physical Immune Suppression:
X-ray & Ulltaviolet Radiation
Destroy Lymphocytes
Bone marrow & Lymphoid Tissue very
sensitive
Surgical removal of Thymus, Spleen, LNs
RESPONSES
IMMUNE SUPRESSION (cont)
Chemical Agents:
Corticosteroids:
Cause Lymphopenia
Inhibit DNA & RNA synthesis
Decrease Macrophage response
Decrease Monocyte chemotaxis
Decrease IgG response
RESPONSES
IMMUNE SUPRESSION
Chemical Agents: (cont)
Purine or Pyrimidine Analogs (Azathioprine)
inhibit IgG response
Folic acid Antogonist block DNA & Protein
synthesis in Lymphocytes
Alkylating
Agents
(Cyclophosphamide)
reduce number of Lymphocytes in the Spleen.
Opportunistic Infections a serious complication
of Immunosuppression
Recurrent CMV infection major cause of
morbidity in Bone marrow transplant patients
CELLULAR INTERACTIONS
ANTIGEN PROCESSING
How Ag is taken in & re-expressed on Antigenpresenting cells (APC) membranes in associiation with
MHC Class 1 & 11 molecules
Exogenous route:
Cell takes in Foreign Ag by phagocytosis or
pinocytosis
Taken into Endosomes digested by
Proteolytic enzymes small peptides
ANTIGEN PROCESSING
Exogenous route: (cont)
Endosomes fuse with exocytic vesicles that
carry MHC Class 11 molecules
Peptide epitopes bind to the Ag-binding
groove of the Class 11 molecule
Endosomes travel and fuse to cell membrane
MHC-peptide expressed on the surface
ANTIGEN PROCESSING
Endogenous route:
Ag processed inside the cell
Example: Tumor Ag + Viral proteins
Peptides transported to lumen of Endoplasmic
Reticulum (TAP peptide transporter complex)
MHC Class 1 molecules MHC Class 1peptide complex transported thru Golgi
complex to cell
surface
T cell Receptor Interaction with Antigen
Ag (epitope) specific
Bind to epitope in groove of MHC 1 or 11
Non-covalent bond to CD3 CD3 transmit
signals to interior of cell
CD4 respond to Ag processed by MHC 11
CD8 respond to Ag processed by MHC 1
Requirement for Activation of Cytotoxic T cell
Tc do not secrete enough IL-2 for own
growth
Require activated CD4 (Th1) to supply IL-2
Requirement for Activation of B cells
Interaction with nave (unprocessed) Ag and
Ag receptor
Activated T cell supply CD4 (Th1) cytokines
(IL-2, IL-4, IL-5, Il-6, IL-10)
Requirement for Activation of Tc cell: (cont)
Some Ag (polysaccharide) stimulate B cell
with help of T cell (Thymus independent Ag)
Ab produced = IgM only
Protein Ag are Thymus dependent all Ig
CYTOKINES
Regulate Immunologic + Inflammatory
responses
to injury
Macrophage IL-1 + TNF activate Th cells
Th1 cell IL-2 B cell proliferation
Plasma
cell
Th2 cell IL-4, IL-6 CD8 response
Autocrine effect = effects on same cell
Paracrine effecct = effect over distance on other
cells
INTERLEUKINS
IL-1:
Stimulate cells to proliferate, activate, and
chemotax
Stimulate IL-2 secretion (MO)
Pyrogenic (fever inducing)
IL-2:
Produced by activated T cells
Stimulate T cells (CD4, CD8 & NK cells)
Stimulate B cells Plasma cells Abs
INTERLEUKINS
IL-3:
Secreted by activated T cells
Stimulate Bone Marrow Stem cells
IL-4:
Secreted by activated CD4 (helper) cells +
Mast cells
Stimulate B cells
Increase IgG & IgE production
INTERLEUKINS
IL-5:
Secreted by activated CD4 cells
Promotes B cell proliferation
Increase IgA & Eosinophils
IL-6:
Stimulates Acute-phase Reactant production
Stimulate B cells
INTERLEUKINS
IL-7: Stimulate pre-B cells & pre-T cells
IL-8: Stimulate Chemotaxis & Ahesion
of Neutrophils to Endothelial cells
IL-10:
Stimulate Cytokine release from
Macrophage
Inhibits Interferon synthesis by Th1 cells
INTERLEUKINS
IL-12:
Activates Natural Killer cells
Induces Th cells Th1 cells
Increases CTL cells (cytotoxic T cell) &
DTH cells (Delayed Type Hypersensitivity)
COMPLEMENT &
INFLAMMATION
Inflammation an integral part of the immune
response (redness, swelling, pain, heat)
Activation of Complement Cascade major way
to
initiate inflammation.
Complement opsonins, chemoattractants,
anaphylatoxins, mediate killing of cells
Complement: a system of proteins &
glycoproteins found in Blood & Tissue fluids.
Complement opsonize FB for phagocytosis after Ab
activation (C3)
End result is Membrane Attack Complex
COMPLEMENT
CLASSIC PATHWAY:
Main Ab-directed mechanism for complement
activation
Most rapid & efficient pathway
Complement recognizes Ab-Ag complexes (IgG
or IgM)
Ag-Ab complexes bind to C1 cascade
activated
C1q C1r C1s C4 C2 C3
COMPLEMENT
ALTERNATE PATHWAY (C3b)
Activated as result of binding directly to
surface
of infectious organisms.
Slow & less effective
Initiators of Alternative Pathway:
LPS
Bacterial & Plant polysaccharides
Cell membrane constituents
Aggregated IgA, IgG, IgE, IgM
Cobra venum
Endotoxins
Protects body in absence of Ab
COMPLEMENT
MEMBRANE ATACK COMPLEX (MAC)
Formed from the reactions among C5, C6, C7,
& C9 MA C cell lysis
Products of complement cascade involved in:
Viral neutralization
Lysis of infected cells
Direct lysis of pathogens. Promote phagocytosis
Focus Ag on Macrophage & Lymphocytes
Anaphylaxis
Smooth muscle contraction
Vasodilation
Chemotaxis Kinin activity
C8
COMPLEMENT
SUMMARY
C2a & C4a weak anaphyatoxins
C3a & C5a strong anaphylatoxins
C5a potent chemotoxin
C3b potent opsonin
COMPLEMENT
C3 deficiency increased susceptibility to
Pyogenic infections
C2 deficiency increased Connective Tissue
disorders
C5 to C8 deficiencies recurrent Neisseria
infections
C1 Esterase Inhibitor deficiency Hereditary
Angioneurotic Edema
INFLAMMATION
Characterized by pain, redness, heat, swelling.
Due to increase vascular permeability
infiltration of WBCs Cytokines which
enhance
the inflammatory response
VASOACTIVE & SMOOTH MUSCLE
CONSTRICTORS:
Histamine: (Skin, GIT, Lungs)
Stored in Mast cells, Basophils & Platelets
Released when Ag contact IgE on Mast cell
Released by Trauma or Cold
Concentration falls within hours
INFLAMMATION
CONSTRICTORS:
Histamine: (cont)
Plus H1 receptor results in:
Smooth muscle contraction
Increased vascular permeabitily
Elevated intracellular cyclic GMP
INFLAMMATION
CONSTRICTORS:
Histamine: (cont)
Plus H2 receptor results in:
Increase Gastric acid secretion
Increase Respiratory mucous production
Increase intracellular cyclic AMP
Plus H3 (found in CNS) act as negative
feedback inhibition of Histamine release
Adenosine: inflammatory agent from Mast
cell
INFLAMMATION
CONSTRICTORS (cont)
Arachidonic Acid (AA) Products:
AA from cell membrane phospholipids
LPS AA Prostaglandin (PGE2) + Thromboxane
A (TXA)
via Cyclooxygenase pathway
LPS AA Leukotrienes (LT) via
Lipooxygenase pathway
Leukotrienes = slow-reacting substance of
Anaphylaxis
INFLAMMATION
CONSTRICTORS (cont)
Platelet Activating Factor PAF)
From cell membrane lipid (LPS)
Synthesized by Basophils, PMNs, Monocytes &
Epithelial cell
Activates Platelets by initiating the release of Platelet
granule components Clot
Stimulates synthesis of PG & LT
Increase adhesiveness of PMNs to Endothelial
cells
INFLAMMATION
CHEMOTACTIC FACTORS
Eosinophlic Chemotactic Factors (ECF)
E.g. Histamine
Neutrophil Chemotactic Factors (NCF)
E.g. IL-1 & IL-2
ENZYME MEDIATORS
Neutral Protease produced by Mast cells
Acid Hydrolases found in Lysosomes
degrade Chondroitin sulfate (membranes)
INFLAMMATION
PROTEOGLYCANS
Function in storage & release of mediators
Heparin: Anticoagulant, affects Tryptase activity
Tryptase:
Major protein of human Lung Mast cells
activate C3 directly
in absence of
Heparin
Stored in Mast cell with Histamine
Chondroitin Sulfate (structural protein) act as
binding site for mediators
INFLAMMATION
TOXIC OXYGEN MOLECULES

Kill microorganisms
Activate PMNs, Eosinophils, Mast cells
Examples:
Superoxide oxygen Hydrogen peroxide
Hydroxyl radical (OH-)
KININS: (polypeptide) act similar to Histamine
Bradykinin:
Vasodilator increased capillary permeability
Erythema
Edema
SM contraction
INFLAMMATION
SUMMARY
Inflammatory response can be triggered by local
tissue damage that results in enzyme activation
or Mast cell degranulation caused by
anaphylatoxin interaction with specific receptors
(e.g. C3a, C5a) on the cytoplasmic membrane.
Allergen reacting wiith cell-bound IgE can also
trigger degranulation of Mast cells.
Eosinophils are important cells of the immune
system as they contain proteins in their granules
that are toxic to worms (metazoans) and fungi.
Enzymes activated during the Complement
Cascade or as part of the Inflammatory
response can activate the Clotting system
(Hageman factor) leading to Disseminated
Intravascular Coagulation (DIC)
HYPERSENSITIVITIES
TYPE 1 HYPERSENSITIVITY (Anaphylactic)
Require initial esposure to Ag to be sensitized
Re-exposure to Ag causes cross-linking of IgE
receptors on Basophils & Mast cells
Inflammatory mediator
Systemic response in minutes:
SM contraction Bronchial constriction
Increase vascular permeability Edema
Skin wheal & flare (hives or Urticaria)
E.g. Asthma, Allergic Rhinitis (hay fever)
HYPERSENSITIVITIES
TYPE 11 HYPERSENSITIVITY
Antibody-mediated cytotoxicity
May be associated with Auto-immune diseases
IgG or IgM reacts with membrane-associated
Ag on
surface of cells
activation of Complement
cell death
Examples:
Drug allergies
Blood Transfusion reaction
Hemolytic disease in Newborn (incompatible Rh factor)
HYPERSENSITIVITIES
TYPE 111 HYPERSENSITIVITY
Immune-complex-mediated
Caused by antibodies to foreign Antigens or
autoantigens such as DNA
Occur only with complement-fixing Ab (IgG, M
E.g Arthritis
TYPE 1V HYPERSENSITIVITY
Delayed-type reaction mediated by T cells
E.g Tuberculin Skin Testing (PPD)
AUTOIMMUNE DISEASES
Immune responses to Ag present in host tissue
Mediated by:
Humoral (circulating Ab & Immune complexes)
Cellular (delayed hypersensitivity)
Theories;
Overactive T helper cells due to coupling of
chemicals, drugs or viruses to self-antigen
EBV or polyclonal B cell activation by LPS
Inability of T suppressor cells at response to
self-antigen
AUTOIMMUNE DISEASES
Theories (cont)
Release of sequestered Ag (lens of eye,
sperm) not normally presented to immune
system.
Molecular mimicry by microbal Ag
Inappropriate expression of Class 11 MHC
Pancreatic cells of IDDM have high levels
AUTOIMMUNE DISEASES
(cont)
Genetic Predisposition
Clear role associated with MHC genes which
code for Class 11 Ag that are important in the
presentation of Antigens
Higher frequency in Females ages 20 40 y o
Lupus 4 6 times than in men
Rheumatoid arthritis 3 4 times than in men
AUTOIMMUNE DISEASES
SYSTEMIC LUPUS ERYTHEMATOSIS
F:M 9:1.
More common in people of African decent
Clinical Manifestations:
Facial erythematous rash (butterfly rash)
Alopecia Photosensitivity
Oral ulcerations
Arthritis ( no deformity)
Psychosis Seizures
AUTOIMMUNE DISEASES
SCLERODERMA
Progressive systemic fibrosis
F:M 3:1
Affects:
Skin (mask-like expression of Face)
Kidney Lung Muscle Heart
GIT
CREST SYNDROME:
Calcinosis
Raynaud phenomena
Esophageal dysfunction
Sclerodactyly
Telengiectasia
AUTOIMMUNE DISEASES
SJOGRENS SYNDROME
Clinical Manifestations:
Middle ages females
Keratoconjunctivitis (dry eyes)
Xerostomia (dry mouth)
Arthritis
Increased risk for developing Lymphoma
TRANSPLANT IMMUNOLOGY
Autograft:
From one site of the body to a next
No immune response
Allograft:
Foreign tissue Immune response
Xenograft: synthetic material rejected early
TRANSPLANT IMMUNOLOGY
Donor-Recipient Workup
ABO blood group
Class 1 & 11 HLA tissue typing
Transplant Rejection:
T cell mediated rejection in 10 14 days
Antibody mediated rejection
Method to Minimize Rejection:
Matching at least 4 of the HLA antigens
Immunosuppression
TUMOR IMMUNOLOGY
Tumor-associated antigens (TAA)present in
both normal & tumor cells.
Tumor-specific antigens (TSA) only found in
tumor cells.
Tumor-specific transplantation antigen (TSTA)
are specilized forms of TSA which the
immune
system responds to.
Antigens of Chemically Induced Tumors:
TSTA unique for each tumor
Tumor antigens due random mutational events.
TUMOR IMMUNOLOGY
Antigens of Virally Induced Tumors:
TSTA result of oncogenes
Oncofetal Antigens:
Normally present on tissues during fetal
development but repressed before birth.
Alpha Fetoprotein (AFP) (Hepatoma)
Carcinoembryonic Antigen (CEA)
Colon, Lung, Breast, Prostate carcinomas
TUMOR IMMUNOLOGY
Leukemia Antigen:
Terminal deoxynucleotidyl Transferase
(TdT)
Common Acute Lymphoblastic Leukemia Antigen
(CALLA)
Immune surveillance: Natural killer T cells
Mechanism for Rejection of Tumors:
Antibody & Complement
Cytotoxic T cells (CD8+) (Tc)
Helper T cells (CD4+)
Activated Macrophages
TUMOR IMMUNOLOGY
Factors that favor tumor growth:
Tumor cell heterogeneity allow tumor cells to
escape Tc cells.
Rapid growth outstrip the immune response by
producing growth-promoting factors, e.g.
Epithelial Growth Factor (EGF)
Shedding of Antigens
Serum-blocking Factors block Tc cells
HIV & AIDS

HIV/AIDS emerged during the 1980s
Impact on Dentistry immediate & significant
AIDS transmitted via contact with Blood or
other
Body Fluids
Syndrome first noted in American male homosexuals:
Oral & Pharygeal Candidiasis
Purple Tongue (Kaposi sarcoma)
Unusual pneumonia (PCP)
Severe weight loss
HIV & AIDS
CAUSATIVE AGENT:
Human Immunodeficiency Virus (HIV)
C-type Retrovirus (Lentivirus family)
RNA core surrounded by Lipid envelope
made from host plasma membrane
Viral membrane contains a transmembrane protein
gp160 (detected by Western Blot assay as 2 fragments
gp41 & gp120
Core protein include Reverse Transcriptase
+ 2 non-glycosylated proteins p18 & p24
HIV & AIDS
RISK GROUPS
Homosexual men
Heterosexual transmission increasing
Intravenous drug users
Children born to infected women
Sexual partners of people in high risk groups
Recipients of infected blood products or
secretions
HIV & AIDS

MECHANISM OF TRANSMISSION
Contaminated needles among IV drug users
Sexual contact
Exposure to blood during birth
Injury with contaminated instruments
HIV & AIDS
MECHANISM OF INFECTION
Severe loss of CD4 T cells
Virus bind to CD4 molecule on T cell by gp120
Other CD4+ cells (Macrophage + Astrocytes) also
infected
Viral RNA is reverse transcribed & integrated
in
host DNA
T cell activation by cytokines or Ags activation of
Virus via stimulation of virally encoded genes viral
replication
HIV & AIDS

CELLULAR CONSEQUENCE
T cells:
Loss of CD4+ T Helper cells
Decrease in response to Antigens
Decrease production of cytokines (IL-1 +
IFN-)
B cell: decrease response to Ag

Macrophage: HIV enter by binding of gp120 to
CD4 + CCR5 (membrane receptor)
HIV & AIDS

NATURAL PROGRESSION OF HIVD
Group 1:
Acute infections
Infectious mononucleosis-like symptoms:
Skin rash Sore throat
Fever
Aseptic meningitis
Group 11:
Asymptomatic infections
Disease clinically latent for 7 10 years
HIV & AIDS

Group 111:
Persistent generalized Lympadenopathy
Fever Rash Fatigue
AIDS-related Complex (ARC)
AIDS prodrome with non-specific cluster of signs &
symptoms with no decrease in CD4+ cells. Any 1 or
2 of the following:
Fatigue
Fever Weight loss
Persistent Skin rash
Herpes
Oral Hairy Leukoplakia + Candidiasis
HIV & AIDS

Group 1V:
Generalized disease
Opportunistic infections:
Protozoa: Toxoplasma gondii, Crytosporidia
Fungi: Cryptococcus, Candida,
Pneumocystis carinii
Bacteria: Mycobacterium
Virus: CMV, Herpes, Vaaricella-zoster
HIV & AIDS

Group 1V:
Secondary Neoplasms:
Kaposi sarcoma
Non-Hodgkin Lymphoma
CNS: Dementia due to opportunistic
infections (Toxoplasmosis)
HIV & AIDS

DIAGNOSIS
Antibodies appear 6 weeks to 6 months after
exposure
Ab against p24 (core) & gp41 (transmembrane
protein) appear before Ab to pol gene products
HIV & AIDS
HIV TESTING
For Ab to virus (not virus itself)
Shows exposure to virus
ELISA (enzyme-linked immunosorbent assay
ELISA confirmed by Western Blot Test
serves to eliminate false-positive ELISA
Viral load (viral count) and CD$ count used to Stage

disease process & indicate when to start treatment
HIV & AIDS

TREATMENTS
Enzymes to interfere with HIV genome:
Reverse transcriptase , Intergrase, Protease
AZT, ddl, 3TC (NRTIs nucleoside reverse
transcriptase inhibitors)
block Reserse
transcriptase
Protease inhibitors:
Indinivir (Crixivan)
Ritonavir
Saquinavir
HIV & AIDS

TREATMENTS
Combined Therapy:
2 NRTIs + 1 Protease Inhibitors (drug
cocktails)
Attach virus at 2 points of Life cycle
HAART (highly active antiviral therapy)
Antiviral cocktails started early in disease
process
HIV & AIDS
POSTEXPOSURE HIV FOLLOWUP:

Needlestick & other accidents
1. First Aid (soap & Water or Eye Eash)
2. Evaluate Wound (superficial or deep, intact
or broken Skin)
3. Evaluate Fluid (Blood + Saliva)
4. Evaluate Patient (HIV+/-, member of risk
group)
HIV & AIDS

POSTEXPOSURE HIV FOLLOWUP:
Deep Wound + Blood on Needle + HIV+ source,
early
prophylactic
use
of
Antivirals
recommended.
If unvaccinated for HBV give HBIG (hepatitis
B immune Ig) + HB vaccine
HIV & AIDS

BODY FLUID & HIV SPREAD
Blood & Semen: contain HIV virus & mostly
highly infectious)
Saliva & Tears: contain virus , not infectious
No evidence of transmission thru dental
procedures & kissing)
Saliva in a Dental Setting:
Usually mixed with Blood
HIV & AIDS

PEDIATRIC AIDS
HIV passed to child in three ways:
Blood mixing in Placenta in late pregnancy
Via Mucus in Vaginal canal during birth
Breast milk
Signs & Symptoms same as adult + bacterial sepsis,
Hepatosplenomegaly, failure to thrive.
Newborns testing HIV+ may have received Abs
from
mother or Abs made by infant.
If infant is infected Ab will remain
COMMON DISORDERS IN HIV PATIENTS

Oral thrush (Candida)
Esophagitis (Candida, CMV, HSV)
Diarrhea:
Bacterial (Salmonella, Shigella, Campylobacter,
Mycobacterium, Clostridium difficile)
Viral (CMV colitis)

Fungal (Candida)
Parasitic (Cryptosporidium, Isospora,
Giardia, Entamoeba)

Intestinal Neoplasms (Lymphoma, Kaposi
sarcoma)
Pulmonary Neoplasms (Lymphoma, Kaposi
sarcoma)
Pneumonias (Pneumocystis carinii)
Tuberculosis
Fungal Respiratory infections (Histoplasmosis,
Coccidiodomycosis)
Hematologic disorders (anemia, leukopenia,
thrombocytopenia)
Neurologic:
Cryptococcal meningitis
Toxoplasmosis
Progressive multifocal leukoencephalopathy
CVM encephalopathy
CMV retinitis
AIDS dementia
CNS Lymphoma

Sexually transmitted diseases:
Skin:
Shingles
Kaposi sarcoma
Seborrheic dermatitis
Herpes simplex
Molluscum contagiosum
Disseminated infections: CMV, Mycobacterium
avium-intrcellulare, Histoplasmosis

Basic Immunology

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Basic Immunology

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BASIC IMMUNOLOGY

Prepared by: Dr. D. L. Boyd, DDS

CELLS OF THE IMMUNE

Associated with chronic infections

CELLS OF THE IMMUNE SYSTEM

CELLS OF THE IMMUNE SYSTEM

CELLS OF THE IMMUNE SYSTEM

CELLS OF THE IMMUNE SYSTEM

Natural killer (NK) cells (10 -15% of Lymphocytes)

Activated by Cytokines (- Interferon)

TDTH cell delayed-type Hypersensitivity

A secondary organ: site for Plasma cell Ab

Pluripotent Stem cell Myeloid + Lymphoid

Medullary Sinuses transmit Lymph to Hilium

Waldeyers Ring = Ring of Lymphoid tissue located on

NATURAL IMMUNITY (innate immunity)

IMMUNE RESPONSE (cont)

ACQUIRED IMMUNITY (Late in Fetal life

Immunogen: that which induces an immune

Variable Light Chain

Cell Receptor Binding Region

Have Hypervariable regions at Amino acid end

IMMUNE RESPONSE (cont)

Function in secretory immune response

TYPES OF IMMUNE RESPONSES

TYPES OF IMMUNE RESPONSES

TYPES OF IMMUNE RESPONSES

TYPES OF IMMUNE RESPONSES

TYPES OF IMMUNE RESPONSES

TOXIC OXYGEN MOLECULES

HIV & AIDS

HIV & AIDS

HIV & AIDS

HIV & AIDS

HIV & AIDS

HIV & AIDS

B cell: decrease response to Ag

HIV & AIDS

HIV & AIDS

HIV & AIDS

HIV & AIDS

HIV & AIDS

HIV & AIDS

Viral load (viral count) and CD$ count used to Stage

HIV & AIDS

HIV & AIDS

HIV & AIDS

POSTEXPOSURE HIV FOLLOWUP:

HIV & AIDS

HIV & AIDS

HIV & AIDS

COMMON DISORDERS IN HIV PATIENTS

Viral (CMV colitis)

COMMON DISORDERS IN HIV PATIENTS

COMMON DISORDERS IN HIV PATIENTS

COMMON DISORDERS IN HIV PATIENTS

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