Basic Immunology I

May 20, 2008

MD3
Microbiology
Dr. K Ronquillo
Primary Lymphoid Organs
Bone Marrow
Thymus
Spleen,Liver
Secondary Lymphoid organs
Lymph Nodes
Spleen
Tonsils
Mucosa-associated lymphoid tissue (MALT)
GALT
BALT
THYMUS
Cortex: immature T
cells, epithelial
cells and
macrophages
medulla, which
mature T cells and
Hassal corpuscles
LYMPH NODES
most common
site for the
production of the
adaptive immune
response
B cells:cortex
Tcells:
paracortex
Germinal centers:
plasma cells
SPLEEN

peripheral lymphoid organ: adults

primary lymphoid organ: fetal period
function?
Spleen zones
White pulp
periarteriolar lymphatic sheath (PALS) :
T cells
Marginal zones: B cells
Primary follicles: B cells,dendritic cells

Red pulp
site of blood filtration
sinusoids
GUT-ASSOCIATED LYMPHOID
TISSUES (GALT)
Peyers patches in the small intestine
Lamina propria beneath the mucosa
Lymphocytes in the mucosa
BRONCHUS-ASSOCIATED LYMPHOUD
TISSUE (BALT)

Tonsils
lymphoid tissues under the respiratory
mucosa
types of tonsils:
1. palatine tonsils
2. lingual tonsils
3. pharyngeal tonsils ;adenoids
Lymph node swelling
CELLS OF THE IMMUNE SYSTEM

Monocytes-macrophages
Dendritic cells
Granulocytes(polymorphonuclear leukocytes)
neutrophils
Eosinophils
basophils
Lymphocytes
B lymphocytes
T lymphocytes
Natural Killer cells
Monocytes-macrophages

liver macrophages – Kupffer cells

Brain macrophages – Microglial cells
Lung macrophages – alveolar
macrophages
Macrophages in granulomas –
epitheloid cells
Cluster of epitheloid cells – giant cells
M&M

Stimuli: LYMPHOKINES
INTERFERON – gamma
causes increased lysosomal enzyme
production
increased chemotactic abilities
Functions of M and M

secrete mediators of inflammation

Opsonization (C3b)
Phagocytosis
Antigen-presenting cells (MHC)
DENDRITIC CELLS

also APCs
peripheral blood,
lymphoid organs
Langerhans cell:
skin
Reticulum cells:
spleen and lymph
nodes
Granulocytes

NEUTROPHILS
first cell in acute inflammation
azurophilic granules:
myeloperoxidase
hydrogen peroxide; toxic oxygen
radicals
receptors for IgG, C3b
EOSINOPHILS

late inflammatory reactions, allergies,

parasitic infections
chemotactic factors include: histamine,
C5a, LTB4, PAF, ECF-A
Major Basic Proteins, Peroxidase
receptors for complement
BASOPHILS

receptors for IgE

release of histamine
B LYMPHOCYTES

differentiate into plasma cells

respond to 2 types of antigens;
a. T-cell independent antigens:
absence of CD4 Th cells
antigens are polysaccharides
b. T-cell dependent antigens;CLASS
SWITCHING
T LYMPHOCYTES

two major types depending on their CD

proteins

Th1 cell: promote cytotoxic T-cell

(CD8+ cells) responses and delayed
hypersensitivity reactions
recognize APC with MHC class I
Th2 cell: stimulate B cells to proliferate
-differentiate into antibody producing
cells

Both Th1 and Th2 have CD4+ proteins;

recognize APC with MHC class II
NATURAL KILLER CELLS

kill tumor cells and viruses without the

need for MHC
mediate ADCC (antibody-mediated
cellular cytotoxicity)
activated by interferon – gamma and
IL-2
THE IMMUNE RESPONSE

Innate immunity

Acquired Immunity
Humoral immune response
Cellular immune response
INNATE IMMUNITY

natural immunity present at birth

the response does not increase upon
repeated antigen exposure
first line of defense against antigens
Examples?
ACQUIRED IMMUNITY

occurs late in fetal life, continues to

develop into childhood
antibodies on B cells and T-cell
receptors recognize specific antigens
anamnestic response
ANTIGENS

any substance which is bounded by

an antibody or T cell receptor
Immunogen: a substance that
induces a specific immune response
Hapten

non-immunogenic
Have to be coupled to a carrier
molecule
have the property of antigenicity but
not immunogenicity
Example: penicillin
Factors which contribute to
immunogenicity

the immune system normally recognize

foreign substances
the larger the molecule, the more antigenic
it is
the more complex the structure, especially
proteins
lipids are usually not immunogenic
polysaccharides are also good
immunogens
nucleic acids are poor immunogens
MAJOR HISTOCOMPATIBILITY
COMPLEX (MHC)

set of GENES which encode for proteins

that regulate the immune response
class I and II: encode for cell surface
proteins
class III: encode for complement proteins
HUMAN LEUKOCYTE ANTIGENS (HLA):
short arm of chromosome 6
HLA CLASS I

found on all the surfaces of nucleated

cells and platelets
present them to CD8+ cytotoxic T
cells.
HLA-A, HLA-B AND HLA-C
recognize cells which have been
infected by viruses, bacteria, parasites
and tumors
HLA CLASS II

found only on the cell surfaces of:

dendritic cells
Langerhans cells
activated macrophages
B cells
thymic epithelial cells
HLA Class II

antigen recognition by T helper cells

(CD4+ cells)
HLA-DP, HLA-DQ, HLA-DR
recognizes cell which have been
infected by bacteria, parasites or
injected proteins
ANTIBODY

produced by B cells in response to

the presence of antigens
variable regions: amino terminal
constant regions: carboxy terminal
IgG – gamma heavy chains
IgA – alpha heavy chains
IgM – mu heavy chains
IgE – epsilon chains
IgD – delta chains
Functional parts of the
Immunoglobulin
Fab fragment : portion which bind the
antigen
Fc fragment – portion which binds
complement
ANTIGEN-BINDING SITES

variable region of the light chain and

heavy chain
also called the PARATOPE
Epitope

Antigenic Determinant
specific site on the antigen which is
recognized by the B cell or the T cell
receptor
IgG

most versatile immunoglobulin

75% of serum Ig is IgG
only class of Ig that crosses the
placenta.
fixes complement
binding to cells like macrophages,
monocytes, PMN's and some
lymphocytes: Fc receptors
IgA

2nd most common serum Ig.

major class of Ig in secretions
local (mucosal) immunity.
IgD

primarily found on B cell surfaces

functions as a receptor for antigen
IgE

least common serum Ig

allergic reactions
parasitic helminth diseases
IgE does not fix complement
ACQUIRED IMMUNE RESPONSE
: Humoral type

1. PRIMARY IMMUNE RESPONSE

first response to antigenic stimuli
no antibodies can be measured in the
1st 3 to 5 days
IgM: first detected
class switching: IgG predominates
IgA:oral or mucosal antigens
ACQUIRED IMMUNE RESPONSE
: Humoral type

2. SECONDARY IMMUNE
RESPONSE
memory or anamnestic response
memory B and T cells
IgA
IgE: helminths
ACQUIRED IMMUNE RESPONSE
: Cellular type

major cell type : T cell

APC present the antigens to Th cells (MHC
II),
secrete cytokines and IFN- gamma
proliferation, differentiation of CTL,
macrophages
CTL will bind to cells infected by viruses or
tumors (MHC Class I)
enzymes are secreted which kill the cells
CD4+ cells activate NK cells or
macrophages and neutrophils
Immunosuppression

active immunologic unresponsiveness

IFN – gamma
IL-10
X-ray and UV radiation
surgical removal of thymus, Lymph
nodes and spleen
Corticosteroids

*peripheral blood lymphopenia

*inhibit RNA and DNA synthesis
*decrease macrophage responses
*decrease monocyte chemotaxis
*decrease IgG response
CYTOKINES

Proteins
regulate immunologic and
inflammatory response in injury
resting cells do not secrete cytokines
Cytokines

Stimulate T and B cells

Mediate signs of inflammation
Stimulate class switching
Expression of MHC I and II
Stimulate M & Ms
COMPLEMENT SYSTEM

proteins found in the blood and tissue

fluids
important in opsonization
regulation of inflammatory response
killing cells and microbes
Two pathways
Classical Pathway Alternative pathway
most rapid, most activated by:
efficient *cell wall of gram-
antigen-antibody negative bacteria
complexes *bacterial and plant
polysaccharides
*cobra venom factor
*endotoxins
*aggregated IgA, IgG,
IgG, IgM
Final Product for both pathways:
Membrane attack complex
Basic Immunology II:
Immunologic techniques and
Immunization