Clinical immunology
Dr. Faiq Isho
Assistant Professor
Consultant Rheumatologist
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Clinical immunology
Reference
1)
Davidson’s principle and practice of
medicine 22 nd edn
2)
Kaplan medical immunology USMLE 1
lecture notes 2013
3)
First aid for basic sciences general
principles: Tao le and Kendall Krause
2011
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IMMUNE SYSTEM (IS)
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Learning objectives
Define: the immune system, major histocompatibility
complex system(MHC)
List types of immune system, and Functions
Give Examples
Summary
Quiz
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Definition:
Immune system
Is the system that protects the
host from pathogens
Minimizes self tissue damage
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is group of variable genes on
the short arm of chromosome
6 in the human
.
Major histocompatibility
complex
(MHC)
HLA genes are the human versions of the
(MHC) genes
HLA system: group of genes resides on
; encode for proteins & regulate
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Class I Gene Products
Class II Gene Products
HLA-A HLA-B HLA-C
HLA-DP HLA-DQ HLA-DR
Types of immune system:
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I-Innate immune system
Non-specific defenses [ against infection]
Provides immediate protection [against an invading
pathogen]
Includes:
1. Anatomical barriers:
Skin
Physiological factors: as sebaceous glands
Sweat
Mucous membranes
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2. Phagocytes:
Specialized cells
Important for defense against bacterial and
fungal infections
Ingest and kill microorganisms,
Produce inflammatory molecules
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Include:
a)
Neutrophils (PMNL):
Functions:
kill microorganisms directly
non-specifically amplify the immune response
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b) Monocytes and macrophages
Monocytes are the precursors of tissue
macrophages
Bone marrow circulation
peripheral tissues DDx tissue macrophages
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Functions:
Initiation & ↑ inflammatory response
Killing microorganisms
Tissue monitoring for signs of tissue
damage or invading organisms
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3. Cytokines:
Small soluble proteins
Act as multipurpose chemical messengers
Produced by cells involved in innate and adaptive
immune responses and by stromal tissue
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4.Complement
A group of >20 proteins [tightly
regulated, functionally linked]
Produced by the liver
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Functions
:
1.
Defense against encapsulated bacteria such as
Neisseria
spp. and
Haemophilus influenzae
2.
Act as
opsonins
[making microorganisms more susceptible
to phagocytosis by macrophages and neutrophils]
3.
Chemotactic
agents: promoting leucocyte trafficking to sites
of inflammation
4.
Some fragments act as
anaphylotoxins
5.
link
between the
innate and the acquired
immune systems
6.
Dissolve
the
immune complexes
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5. Mast cells and Basophils:
Are bone marrow-derived cells
Play a central role in
allergic
disorders
Mast cells
located predominantly
in tissues
exposed to
the external environment, such as the skin and gut
Basophiles
are located in the
circulation
and are
recruited into tissues in response to inflammation
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Both contain large cytoplasmic granules : histamine,
leukotrienes, prostaglandins and cytokines
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Allergy : Activation of mast cells and basophils
6. Natural killer cells:
Large granular lymphocytes
Play a major role in defense
against tumors and virally
infected cells
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Express features of both the adaptive and innate
immune systems
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II. Adaptive immune system:
Highly specific
Highly adaptive(respond to an unlimited number of
molecules) .
Possesses immunological memory
Types:
1.
Humoral immunity
: Produced by B lymphocytes.
2.
Cellular immunity:
mediated by T lymphocytes.
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1. Humeral immunity
B-lymphocyte:
Specialized cells
Arise from haemopoietic bone marrow stem cells
Major function is to produce
antibody
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Express a unique
immunoglobulin receptor
on their
cell surface (
the B-cell receptor
).
Mature B lymphocytes can be found in the
bone
marrow, lymphoid tissue, spleen
, and to a lesser
extent the blood stream.
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Immunoglobulins ( Antibodies):
Soluble proteins, consist of 2 chains: heavy and two
light chains
The
heavy
chain determines the
antibody class
or
isotype, i.e. IgG, IgA, IgM, IgE, IgD
Subclasses of IgG ( IgG1,2,3,4) and IgA(IgA1,2).
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Antibody Function:
1.
Facilitate
phagocytosis
[by acting as opsonins]
2.
Facilitates
cell killing
[by cytotoxic cells,
particularly natural killer cells]
3.
Trigger activation
of the
classical complement
pathway
4.
May act directly to
neutralize
the biological
activity of their
antigen
target
.
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2. Cellular immunity:
T lymphocytes mediate cellular immunity
Function:
1.
Defense
against viruses, fungi and intracellular
bacteria.
2.
Immunoregulatory
role
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T lymphocytes can be classified into 2 subgroups on the
basis of
function
, recognition of
HLA molecules
, and
expression of
cell surface proteins
.
Leucocyte cell surface molecules
are named systematically
by assigning them
antigen number
[
a 'cluster of
differentiation' (CD)
] .
The CD system is commonly used as cell markers in
immunophenotyping.
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T lymphocyte types:
1) CD8
+
('cytotoxic') T lymphocytes
Recognize antigens (peptides)
in association with
HLA
class I
(HLA-A, HLA-B, HLA-C)
Kill infected cells
directly by producing
pore-forming
molecules such as perforin, or by triggering
apoptosis
of
the target cell
Secrete cytokines
such as IFN-γ which have antiviral
activity
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2)CD4
+
('helper') T lymphocytes:
Recognize antigens (peptides)
in association
with
HLA class II
molecules (HLA-DP HLA-DQ,
HLA-DR, )
Have
Immunoregulatory
functions
Produce cytokines
and provide
co-stimulatory
signals
that support the activation of CD8
+
T
lymphocytes and assist the production of mature
antibody by B cells
Interact closely with phagocytes
which
determine cytokine production by both cell types
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CD4
+
lymphocytes
Th1 cells
p→IL-2, IFN-γ and
TNF-α
DHSR
Th2 cells
S→IL-4, IL-5 and IL-10
↑allergic responses
Regulatory cells
R→other CD4
+
cell
Prevent→autoimmune
diseases
Summary:
IS: a protective system
Types: Innate & acquired
Each type has components & specific
functions
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Quiz
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Quiz
1) Type(s) of immune system
A) Innate
B) Acquired
C) All of the above
D) None of the above
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Quiz
1) Type(s) of immune system
A) Innate
B) Acquired
C)
All of the above
D) None of the above
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A.
Are non specialized cells
B.
Recognize antigenic peptides in association
with HLA class I.
C.
Cannot Kill infected cells directly
D.
Recognize peptides presented on HLA class II
molecules
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2)In cytotoxic T lymphocytes (CD8
+
), which
one is true?
A.
Are non specialized cells
B.
Recognize antigenic peptides in association with
HLA class I.
C.
Cannot Kill infected cells directly
D.
Recognize peptides presented on HLA class II
molecules
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2)In cytotoxic T lymphocytes (CD8
+
), which one is
true?
Next lecture
Immune deficiency
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