GOKU NOTES

INTRO TO IMMUNOLOGY, ANTIGEN AND MHC MOLECULES

Cells of the immune system come from 2. Polymorphonuclear Phagocytes

the pluripotent stem cells.
Neutrophils
Lymphocytes Myeloid Eosinophils
Basophils
T cells Monocytes Platelets
B cells which responsibl
Natural killer differentiate e for MONONUCLEAR PHAGOCYTES
cells into clotting
macrophages RBCs

PMNs:
Removes matter of foreign origin
Express CD14 and class 2 MHC
Eosinophils
Neutrophils molecules
Basophils Presents antigen to T helper cells
(CD40)
Pattern of recognition receptors
PHAGOCYTIC CELLS
MONOCYTES
They are of myeloid lineage.
Large relative to lymphocytes
Monocytes
Has a horseshoe shaped nucleus
Macrophages
Has primary azurophillic granules
Natural killer cells which kill the virus
that are blue staining
infected cell
They phagocytose microorganisms.
Mast cells
They are of myeloid lineage.
Neutrophils which are the most
They are antigen presenting cells.
abundant
They express CD14 and MHC class
Basophils which are the least in
2 molecules.
number
Eosinophils
POLYMORPHONUCLEAR PHAGOCYTES

Pattern of recognition receptors

2 MAJOR PHAGOCYTIC LINEAGES
NEUTROPHILS
1. Mononuclear Phagocyte
First to arrive at infection site
Monocytes
95% of circulating granulocytes
Macrophages
Multilobed nucleus
Spleen
Protects host against pyogenic or
Liver
pus causing microorganisms
Kidney
Lungs

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2 TYPES OF NEUTROPHILS
1. Primary Azurophillic Granules
Blue staining
Lysosome containing hydrolases
Muramidase
Defensins
2. Secondary Granules
Specific to neutrophils
Lysozyme
Lactoferrin
BASOPHILS
<0.2% of lymphocytes
Type 1 hypersensitivity
Contains heparin, Histamine,
Cytokines, Chondroitin, proteolytic
enzymes
Play a role in parasitic infection
EOSINOPHILS
2-5% of WBC
Mediates tissue damage in type 1
hypersensitivity or allergies
Release chemicals (major basic
proteins) that kill parasitic worms
and their eggs
Present antigen in vitro
More aggressive
MAJOR BASIC PROTEIN
Potent toxin vs helminthes
Induce Histamine release from mast
cells
Activates neutrophil and platelets
GOKU NOTES
PLATELETS
Derived from megakaryocytes
With granules, microtubules and
actin filaments for clot retraction
Participate in inflammation
ANTIGEN PRESENTING CELLS
Link innate and adaptive immunity
Take up and process antigen and
present to the T cells
Produces cytokines
Has 2 types: professional and non-
professional
Express class 2 MHC molecules
Class 1 MHC molecules are
found in nucleated cells except
in the RBCs.
PROFESSIONAL ANTIGEN PRESENTING
CELLS
They constitutively express class 2
MHC molecules.
Dendritic cells
B cells
Macrophages
NON-PROFESSIONAL ANTIGEN
PRESENTING CELLS
They express class 2 MHC
molecules throughout the
inflammatory response.
Fibroblasts
Glial cells
Pancreatic β cells
Thymic epithelial cells
Thyroid epithelial cells
Vascular endothelial cells
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DENDRITIC CELLS
1. Classical Dendritic cells
Process and present antigen to T
cell
2. Follicular Dendritic cells
Present foreign antigen in the form
of immune complex to B cells, no
class 2 MHC but it binds to CD21
and CD35
3. Interdigitating Dendritic cells
Langerhans Cells are located in the
epidermis.
They carry antigen from skin to
mucosa.
They are rich in class 2 MHC
molecules.
They migrate via afferent lymphatics
and interact with T cells and become
interdigitating dendritic cells.
LYMPHOCYTES
1. Small
Agranular
High nuclear cytoplasmic ratio
Round nucleus
2. Large
Indented nucleus
Lower nuclear cytoplasmic ratio
Azurophillic granules in cytoplasm
PLASMA CELLS
B cell derived
Responsible for antibody production
GOKU NOTES
B cells are involved in humoral
immunity.
They also have class 2 MHC on their
surface.
T cells are the ones involved in cell
mediated immunity.
NATURAL KILLER CELLS
Null cells
Large and granular
Innate host defense
10-15% of circulating lymphocytes in
the blood
Functional natural killer cells are
found in the spleen which is a
secondary lymphoid organ.
They kill virus infected and tumor
cells.
They are active without prior
exposure to antigen.
They induce apoptosis
B LYMPHOCYTES (B CELLS)
Natural immunity
Humoral immunity
Site of differentiation are the bone
marrow, liver and fetal spleen
They differentiate to plasma cells
They have IgM, IgD, class 2 MHC
molecules, receptors for C3B
(CD35) and C3D (CD21) on their
surface.
They produce antibody.
They act as antigen presenting cells
They develop into memory cell
which has a CD45RO surface
marker.
They also develop into plasma cells.
T LYMPHOCYTES (T CELLS)
Cell mediated immunity
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60-80% of circulating lymphocytes Interleukins
CD4 (T helper cells) stimulates B Tumor necrosis factor
cells to become plasma cells. They Colony stimulating factor
also activate CD8 (Cytotoxic T cells). Transforming growth factor
CD4 IFNs
CD8
TCR IMMUNE RESPONSES
Regulatory T cells
Innate/Natural Adaptive/Acquired
REGULATORY T CELLS (before antigen (after antigen
exposure, skin, exposure, B and T
normal flora etc.) lymphocytes)
They kill virus infected or tumor cells Activity at Yes No
birth
Specificity Non-specific Specific
TCR
Response Rapid Delayed
Protection Short term Long term
Most expressed αβ TCR (TCR2) Immunologic No – response Yes – response
~5% express γδ TCR (TCR1) that memory not amplifiable amplifiable
can be found in the skin and mucosa Line of 1st and 2nd 3rd
defense
CD2 and CD3 associated protein
Regulatory T cell Interferons inhibit viral replication.
Natural killer cells kill the virus
CD4 + CD25 + regulatory T cell infected cell.
Interferons and NK cells are both 2 nd
Reculated activity of CTL, B cell and line of defenses.
macrophages
Involved in immune surveillance Innate Humoral (B Cell mediated
Suppress excessive immune cells) (T cells)
response
Cytokine Natural killer
Primary lymphoid organs are bone Complement cells
marrow and thymus system Phagocytosis
Adaptive B cell Cytotoxic t
antibodies cells (CD8)
SOLUBLE MEDIATORS OF IMMUNITY

COMPLEMENT PROTEINS
ANTIGENS
Mediate phagocytosis
Control inflammation IMMUNOGENS
Interact with antibodies
Carbohydrate or protein that
CYTOKINES challenges the immune system and
can initiate an immune response.
Signals between lymphocytes, They induce immune response
phagocytes and other cells of the They are capable of inducing
body. immune response.

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CHEMICAL NATURE
1. Proteins – majority of immunogens
2. Polysaccharides – pure or
lipopolysaccharides
3. Lipid – non immunogenic but may act as
haptens
4. Nucelic acid – poorly immunogenic
ANTIGEN
Molecule recognized by specific
antibody or T cells
Recognized by particular
immunoglobulin or T receptor
Serve as target of immune response
Properties of Antigen
Foreign
Chemical composition
Molecular size
Chemical complexity
HAPTEN
Have low molecular weight
Cannot induce immune response by
themselves unless they are bounded
to a carrier molecule
T INDEPENDENT ANTIGEN
Directly stimulate B cells to produce
antibodies
Polysaccharides in general
More resistant to degradation
T DEPENDENT ANTIGEN
Not immunogenic
Must be bound to a carrier or
immunogenic molecule
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Cannot stimulate immune response
by themselves
EPITOPE
Antigen determinant
Interacts with I cells or antibodies
Types
1. Linear – formed by specific sequence
2. Conformational – formed by 3D structure
B CELL EPITOPE
Region recognized by
immunoglobulin
Can encompass 3-20 amino acids or
sugar residues
Accessible only to antibody
T CELL EPITOPE
8-15 amino acid residues
Recognized by T cell receptors
Recognized by t lymphocyte only
after being processed and presented
by MHC proteins
ADJUVANT
Enhance the magnitude and
duration of immune response
Prolong retention of immunogens
Increases effective site of
immunogen
Stimulate influx of
macrophages/immune cells to
infection site
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Examples of Adjuvant
1. Complete Freund’s Adjuvant – heat killed
mycobacteria in mineral oil
2.Liposome – defined lipid complexes
3. Cholera and E. coli toxin – adjuvants
potent for IgA
4. Bacterial cell wall components
5. Polymeric surfactants
MHC GENES
Human leukocyte antigen
Genes are found in the short arm of
chromosome 6.
Polymorphic
Polygenic
Codominant expression
CLASS I MHC
HLA A, B, C
Polymorphic
α heavy chain bound to β2
immunoglobulin
Found in all nucleated cells and
platelets except RBC
Placental syncytial trophoblastic
cells
TAP and ERAP – trimmed proteins
Heavy chain consists of:
1. 3 extracellular domains
α1 – at the N terminal
α2
α3 – binding site of CD8 (constant
region)
α1 and α2 are hypervariable regions
2. Transmembrane hydrophobic region
GOKU NOTES
α1 and α2 – antigen binding groove
3. Cytoplasmic hydrophilic tail
CLASS II MHC
Heavy chains are α1 and α2.
Light chains are β1 and β2.
α2 and β2 are similar to Class I α3
domain and β2 microglobulin.
Β2 domain is the binding site for
CD4.
Invariant or li chain is a protein
binding site.
Class II MHC is found in Antigen
presenting cells (13-24 amino acids).
They are exogenous.
Proteins are degraded into peptides
through GILT enzyme.
CLASS III MHC
Does not have genes that code for
histocompatibility antigen
Code for heat shock proteins and
complements
Genes located between Class 1 and
Class 2 (soluble proteins)
They code for complement system
molecules (C4, C2, Factor B),
enzymes, heat shock proteins, and
other molecules involved in antigen
processes.
IMPORTANCE OF MHC MOLECULES
Antigen recognition by T cells
Autoimmune diseases occur in
people who carry MAC genes.
Organ transplants
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