Basic Immunology I

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Basic Immunology I

May 20, 2008

MD3

Microbiology

Dr. K Ronquillo


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Primary Lymphoid Organs

Bone Marrow

Thymus

Spleen,Liver

Secondary Lymphoid organs

Lymph Nodes

Spleen

Tonsils

Mucosa-associated lymphoid tissue (MALT) GALTBALT


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THYMUS

Cortex: immature T

cells, epithelial

cells and

macrophagesmedulla, which

mature T cells and

Hassal corpuscles


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LYMPH NODES

most commonsite for the

production of the

adaptive immune

responseB cells:cortex

Tcells:

paracortex

Germinal centers:plasma cells


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SPLEEN

peripheral lymphoid organ: adults

primary lymphoid organ: fetal period

function?


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Spleen zones

White pulpperiarteriolar lymphatic sheath (PALS) :

T cellsMarginal zones: B cells

Primary follicles: B cells,dendritic cells

Red pulpsite of blood filtration

sinusoids


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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


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CELLS OF THE IMMUNE SYSTEM

Monocytes-macrophages

Dendritic cells

Granulocytes(polymorphonuclear leukocytes)neutrophils

Eosinophils

basophils

Lymphocytes

B lymphocytesT lymphocytes

Natural Killer cells


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Monocytes-macrophages

liver macrophages Kupffer cells

Brain macrophages Microglial cellsLung macrophages alveolar

macrophages

Macrophages in granulomas epitheloid cells

Cluster of epitheloid cells giant cells


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M & M

Stimuli: LYMPHOKINES

INTERFERON gamma

causes increased lysosomal enzyme

production

increased chemotactic abilities


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Functions of M and M

secrete mediators of inflammation

Opsonization (C3b)

PhagocytosisAntigen-presenting cells (MHC)


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DENDRITIC CELLS

also APCs

peripheral blood,

lymphoid organs

Langerhans cell:

skin

Reticulum cells:spleen and lymph

nodes


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Granulocytes

NEUTROPHILS

first cell in acute inflammation

azurophilic granules:

myeloperoxidase

hydrogen peroxide; toxic oxygen

radicals

receptors for IgG, C3b


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EOSINOPHILS

late inflammatory reactions, allergies,

parasitic infections

chemotactic factors include: histamine,

C5a, LTB4, PAF, ECF-A

Major Basic Proteins, Peroxidase

receptors for complement


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BASOPHILS

receptors for IgE

release of histamine


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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


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T LYMPHOCYTES

two major types depending on their CD

proteins

Th1 cell: promote cytotoxic T-cell

(CD8+ cells) responses and delayed

hypersensitivity reactionsrecognize APC with MHC class I


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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


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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


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THE IMMUNE RESPONSE

Innate immunity

Acquired ImmunityHumoral immune response

Cellular immune response


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ANTIGENS

any substance which is bounded by

an antibody or T cell receptor

Immunogen: a substance that

induces a specific immune response


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Hapten

non-immunogenic

Have to be coupled to a carrier

molecule

have the property of antigenicity but

not immunogenicity

Example: penicillin


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Factors which contribute to

immunogenicity

the immune system normally recognize foreignsubstances

the larger the molecule, the more antigenic it is

the more complex the structure, especiallyproteins

lipids are usually not immunogenic

polysaccharides are also good immunogens

nucleic acids are poor immunogens


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HLA CLASS I

found on all the surfaces of nucleatedcells and platelets

present them to CD8+ cytotoxic Tcells.

HLA-A, HLA-B AND HLA-C

recognize cells which have beeninfected by viruses, bacteria,parasites and tumors


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HLA CLASS II

found only on the cell surfaces of:

dendritic cellsLangerhans cells

activated macrophages

B cellsthymic epithelial cells


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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


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IgG gamma heavy chains

IgA alpha heavy chains

IgM mu heavy chainsIgE epsilon chains

IgD delta chains


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Functional parts of the

Immunoglobulin

Fab fragment : portion which bind the

antigen

Fc fragment portion which binds

complement


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ANTIGEN-BINDING SITES

variable region of the light chain and

heavy chain

also called the PARATOPE


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Epitope

Antigenic Determinant

specific site on the antigen which is

recognized by the B cell or the T cell

receptor


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IgG

most versatile immunoglobulin

75% of serum Ig is IgG

only class of Ig that crosses theplacenta.

fixes complement

binding to cells like macrophages,monocytes, PMN's and some

lymphocytes: Fc receptors


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IgA

2nd most common serum Ig.

major class of Ig in secretions

local (mucosal) immunity.


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IgD

primarily found on B cell surfaces

functions as a receptor for antigen


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IgE

least common serum Ig

allergic reactions

parasitic helminth diseasesIgE does not fix complement


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ACQUIRED IMMUNE RESPONSE

: Humoral type

1. PRIMARY IMMUNE RESPONSE

first response to antigenic stimuli

no antibodies can be measured in the1st 3 to 5 days

IgM: first detected

class switching: IgG predominates

IgA:oral or mucosal antigens


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: Humoral type

2. SECONDARY IMMUNE

RESPONSE

memory or anamnestic response

memory B and T cells

IgA

IgE: helminths


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: Cellular type

major cell type : T cell

APC present the antigens to Th cells (MHCII),

secrete cytokines and IFN- gammaproliferation, 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 ormacrophages and neutrophils


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Immunosuppression

active immunologic unresponsiveness

IFN gamma

IL-10

X-ray and UV radiation

surgical removal of thymus, Lymphnodes and spleen


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Corticosteroids

*peripheral blood lymphopenia

*inhibit RNA and DNA synthesis*decrease macrophage responses

*decrease monocyte chemotaxis

*decrease IgG response

CYTOKINES


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CYTOKINES

Proteins

regulate immunologic and

inflammatory response in injury

resting cells do not secrete cytokines


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Cytokines

Stimulate T and B cells

Mediate signs of inflammation

Stimulate class switchingExpression of MHC I and II

Stimulate M & Ms

COMPLEMENT SYSTEM


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COMPLEMENT SYSTEM

proteins found in the blood and tissue

fluids

important in opsonization

regulation of inflammatory response

killing cells and microbes


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Two pathways

Classical Pathway

most rapid, most

efficient

antigen-antibody

complexes

Alternative pathway

activated by:

*cell wall of gram-

negative bacteria

*bacterial and plant

polysaccharides

*cobra venom factor

*endotoxins

*aggregated IgA, IgG,

IgG, IgM


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Final Product for both pathways:

Membrane attack complex


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Basic Immunology II:Immunologic techniques and

Immunization

Basic Immunology I

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