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Immunology

Major Features: Innate Vs Adaptive Immune


Immune Response Response
• Response generated against a potential
pathogen is called an immune response Innate Adaptive
• Innate immunity Characteristics
o 1st line of defense Rapid, immediate Slow response
response
o Nonspecific to the invading
Antigen nonspecific Highly antigen specific
pathogen No memory, not long- Induces memory,
o Rapidly mobilized at the initial lasting protection responds rapidly &
site of injection (immediate vigorously to second
response) antigen exposure
o Lacks immunologic memory Immunologic components
Natural barriers to
(does not confer long lasting
infection: skin, mucous
protective immunity) membranes
• Adaptive immunity Cells: phagocytes, NK T lymphocytes-cell
o 2nd defense system cells, innate lymphoid mediated, b
o Specific for the pathogen cells lymphocytes-antibody
o Confers protective immunity to mediated, APCs
Mediators: complement Secreted molecules
reinfection defensins, cytokines (cytokines,
o Produces specific antibodies sensors (TLR, NOD-like Chemokines,
o Branches: receptors, RAG-1) complement)
▪ Humoral Immunity –
mediated by B cells
(matures to become Forms of Immunity
memory cells & plasma • Active immunity
cells) o Contact w/ a foreign antigen
▪ Function: (infectious agent)
• Memory cells – o Individual actively produces
immunologic antibodies (long lasting)
memory o Ex
• Plasma cells – ▪ Clinical or subclinical
antibody production infection
▪ Cellular – mediated ▪ Immunization w/ live or
immunity – mediated by T killed organism
cells (helper T cells [CD4 + ▪ Exposure to microbial
cells]; cytotoxic T cells products (toxins & toxoids)
[CD8 + cells]) ▪ Transplantation of foreign
tissue
Innate Immunity Adaptive Immunity • Passive immunity
-skin (epithelium) & -Lymphoid cells (T cells o Administration of preformed
mucous membranes & B cells)
antibodies
-phagocytic cells
-NK cells o Receives a large concentration of
-Toll-like receptors antibody immediately (not long
-Cytokines lasting)
-Complement system o Useful when the px has no time to
produce an antibody response
▪ Needle-prick injuries (w/o
prior vaccination)
▪ Immunodeficiencies
▪ Post-exposure prophylaxis
(eg. Rabies)

CELLULAR RESPONSE AGAINST


INFECTION
Concentration of the different WBC in the blood
Polymorphonuclear 62.0%
neurtrophils
Polymorphonuclear 2.3%
Regulation of Immune System
eosinophils
Monocytes 0.4%
Lymphocytes 30.0%

Cells Functions
Neutrophils Phagocytosis; elevated
during bacterial infection
& acute inflammatory
reactions
Basophils Release of histamine
Eosinophils Release of histamine;
elevated during parasitic
infestation
Monocytes Phagocytosis (mobile,
periphery)
Macrophages Phagocytosis (fixed,
tissues); antigen
presentation
B lymphocytes Antigen presentation;
(B cells ) -Plasma cells – antibody Cytotoxic T cells
production
-Memory cells –
immunologic memory
T lymphocytes (T cells)
-CD4 + T cells (Helper T Stimulation if the
cells) differentiation &
proliferation of B cells &
cytotoxic T cells
CD8 + T cells (Cytotoxic T Direct-attack cells that is
cells) capable io killing MO & at
times, even some of the
body’s own cells
Suppressor T cells Capable of suppressing
the functions of both
cytotoxic & T-helper cells
Natural Killer cells Contribute to innate
imunity by providing
protection against viruses
NK cells
& other intracellular
pathogens; play a critical
role in antibody-
dependent cellular
cytotoxic (ADCC)
Mast cell Degranulation

Properties of Human Immunoglobulins


IgG IgA IgM IgD IgE
Heavy chain y a µ δ ε

Immunoglobulins (antibodies)
symbol
Valence 2 4 5 2 2
MW 143,000 – 159,000 – 900,000 177,000 – 188,000 –
• A protein that is produced in response (daltons)
Serum conc
160,000
8-16
447,000
1.4 – 4.0 0.4 – 2.0
185,000
0.03
200,000
Trace
to a particular pathogen is called the (mg/mL)
(adult)
amounts

antibody Serum t ½ 21 7 7 2 2
Percentage 80 15 5 0.2 0.002
• Make up about 20% of the plasma of total IG in
serum
proteins Complement Yes (+) No Yes (++) No No
fixing
• Substance that induces the production capacity
Placental + - - - -
of antibodies is called the antigen transfer to
fetus
• Factors that determined
immunogenicity
Properties of Immunoglobulins
o Recognition of foreignness
o Size (large, complex proteins) Name Properties Structure
▪ <10, 000 MW are weak IgA Found in mucous,
immunogens saliva, tears, &
breast milk.
▪ Very small molecules are Protects against
nonimmunogenic pathogens
▪ Haptens: small molecules
when combined w/ a IgD Part of the B cell
carrier receptor.
protein/polysaccharide Activates
basophils & mast
becomes immunogenic cells
(e.g., lipids & amino acids)
o Chemical & Structural complexity
o Genetic constitution of the host
o Dosage, route, & timing of
IgE Protects against
antigen administration parasitic worms.
Responsible for
allergic reactions
IgG Secreted by -phagocytic cells do not
plasma cells in
kill microbes due to
the blood. Able to
cross the genetic defect in
placenta into the cytochrome b-558
fetus -defect in the ability of
phagocytic cell to produce
IgM May be attached peroxide & superoxide
to the surface of a ▪ Chédiak-Higashi syndrome
B cell or secreted -neutrophil granules fuse
into the blood.
Responsible for when the cells are
early stages of immature in the bone
immunity marrow → can
phagocytose bacteria but
have greatly diminished
ability to kill them
Hypersensitivity Reactions ▪ Asplenic individuals
• Condition in w/c an exaggerated or -lack the filtration
augmented immune response occurs mechanism of spleen
that is harmful to the host macrophages ( great risk
• Requires a presensitized stated (occur factor for encapsulated
after the 2nd encounter w/ that specific MO)
antigen)
• Types
o Antibody-mediated (type I, II, III)
o Cellulard-mediated (type IV)

Immunodeficiency Disease
• Primary immunodeficiency
• Complement deficiencies
o Defect is intrinsic to the cells of
o Deficiencies of C1q, C1r, C1s, C4
the immune system
& C2: susceptibility to pyogenic
o Genetically determined &
(pus-producing), staphylococcal
inherited as a single gene defect
& streptococcal infections
o Ex
o Deficiency of C3: higher
▪ Phagocyte’s deficiency
incidence of pyogenic infections
▪ Chronic granulomatous
o Defects of the properdin factors:
disease (CGD)
also results in an increased
susceptibility to pyogenic • Lymphocyte Deficiencies
infection infections o Deficiency in T cell infection
o Deficiencies of C5 through C9: o Susceptible to opportunistic
defective cell killing, w/c raises infections by
the susceptibility to disseminated (1) Viruses, especially enveloped
infections by Neisser sp. & non cytolytic viruses &
recurrences of viruses that
Complement Reaction Sequence
establish latent infections,
(2) Intracellular bacteria
(3) Fungi
(4) Some parasites
o Deficiency in B cell function
▪ Complete lack of antibody
production
(hypogammaglobulinemia)
, inability to undergo class
switching, or inability to
produce specific
subclasses of antibody
▪ Very susceptible to
bacterial infection
o Severe combined
immunodeficiency (SCID)
▪ Defects in both B & T cell
function
▪ Susceptible to infection by
virtually any microbe
• Secondary immunodeficiency
o Ex: infections (HIV/AIDS),
malignancies, drugs
(immunosupressants)
Consequences of Deficiencies in the Condition T cell # T cell B cell # Serum Incidence
fxn antibodies
complement pathways XLA, Bruton ✓ ✓ ↓↓ ↓ Rare
syndrome
RAG1 or ↓↓ ↓↓ ↓↓ None Rare
RAG2 def
X-SCID ↓↓ ↓ ✓ ↓ Rare
XLP, Duncan ✓ ↓ ✓ ✓ or ↓ Rare
syndrome
X-hyper IgM ✓ ↓ ✓ IgM ↑↑ Rare
(CD40 or No IgG, IgE
CD40L or IgA
mutation)
Wiskott – ✓ ↓ ✓ ↓ Rare
Aldrich
syndrome
SCID: ADA or ↓↓ ↓↓ ↓ ↓ Very rare
PNP def
HLA def ↓ ↓ ✓ Poor Ag Very rare
response
Ataxia ↓ ↓ ✓ IgE↓, IgA↓, Uncommon
telangiectasia IgG2↓
DiGeorge ↓↓ ↓ ✓ IgG↓, IgE↓, Very rare
syndrome IgA↓
IgA ✓ ✓ ✓ IgA↓ common
deficiency

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