Immunology pdf - د.فراس الطائي

Microbiology

Notes…

Immunology Lecture.1

Immunology

It is the Science that deals with :

1. Body protective and defense mechanisms against diseases (infections and

tumours)

2.  Clearance of dead cells and tissue repair
3.  Vaccination
4.  Allergy and hypersensitivity
5.  Tissue transplantation and transplant rejection
6.  Autoimmunity  and immunodeficiency

Immunity

Original meaning

:Exemption from government taxes

In the context of immunology: Collective defense mechanisms against diseases

• The body system (cells, organs and molecules) responsible for the immunity is

called the immune system

Immune response

•  The effort of the immune system in regards to any etiological agent.
•  Usually against foreign immunogens ,useful  (protection)
•  Sometimes harmful

!!!!!!!!

(tissue damage)

Graft rejection
   Autoimmunity against self immunogens
Hypersensitivity
Normally the immune system DOES NOT react against the body itself by a mechanism
which is named Tolerance (state of unresponsiveness to self antigen).
Break down of self antigen tolerance leads to (Auto-immunity).
The diseases that result from such a response are called (auto-immune diseases).

Self vs .Non-self

Antigens (Ags)

• Foreign substance

= Antigen

These antigens could be bacteria, viruses, fungi , parasites, cells tissues, chemicals,
drugs or food. The numbers of antigens in nature are up to trillions.
If able to produce immune response called immunogen or complete antigen.
If unable to initiate immune response alone called partial antigen.

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Microbiology

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All immunogens are antigenic but not all antigens are immunogenic.
Immune system does not react against the whole pathogen but parts of it

( Ags )and not

against the whole Ag but parts of it (chemical groups) called "epitopes "

Each Ag has variable number of epitopes.

Properties of Antigens

1. Foreignness

A )Autologous antigens : Self antigens and there will be no immune response.
B )Allogenic antigens : From the same species and there may be reaction, e.g.. Blood
transfusion, kidney transplant
C) Heterologous antigens : From different species .These antigens will be rejected and
there will be severe immune response

2. Chemical complexity

Most antigens contain at least one amino acid in their structures .More amino acid more
antigenicity.
Proteins > CHO > lipids

3. Molecular weight

More than 100,000 Dalton more immunogenic

Cells of the immune system

Types of Immunity

Innate (non-specific) immunity
-Present from birth in both invertebrates
and vertebrates

-Our First Line Of Defense
-Rapid starts within min-hours after
encountering pathogens

Adaptive (specific) immunity
Not present at birth but acquired during
life as immune system develops in
vertebrates only
-Late , starts days after first infection

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Notes…

- Not specific, recognizes generic microbial
structures and prevents almost ALL
pathogens from causing diseases;
-

Genetically encoded and produces

identical responses in all individuals,
-

NO memory cells

-Specific ,reacts specifically with
specific

immunological

molecules

called (antigens)
-

Acquired as an adaptive

response to exposure to antigens
-

Memory cells

“

Memory” in adaptive immunity

1st infection

Slow response

Pathogen proliferates

Disease Symptoms

2nd infection

Fast response

Pathogen being killed

No disease

No symptoms

Elements of Innate and Adaptive Immunity

Microbiology

Notes…

Elements of Innate Imuunity

1. Epithelial Barriers

- Act as anatomical (physical) , physiological or chemical barriers

- Including the skin, mucous membranes, hair, cilia, sneezing, cough, and blinking of

the eyes. Also, mucous secretions trap many organisms.

- Physiologic Barriers

- Temperature - normal body temperature inhibits growth of most microorganisms.

- Elevated body temperature (fever) can have a direct effect on pathogenic

microorganisms.

- pH - low pH of stomach, skin, & vagina (inhibits microbial growth)

- Oxygen tension

Physical and Chemical Barriers-The Skin

Mechanisms

1. Skin integrity itself acts as anatomical  barrier that prevents “bacterial colonization”.
2. Normal skin flora prevent potential pathogens from "Colonizing".
3. Sebaceous glands secrete fatty acids and lactic acid which lower the skin pH (acidic
pH ≈ 4-6).
4.  Sweat  glands  in  the  skin  secrete  antimicrobial  peptides  e.g.  (dermcidin)  which
restrains the growth of various microbes on the skin.

Chemical and Physical Barriers-Mucosal membranes

Mechanisms

1. Ciliated epithelial cells lining the trachea remove microbes inhaled  through the nose
and mouth (Mechanical removal).
Cilia push microbes upwards until they are caught in oral secretions and expectorated
or swallowed.
2. Mucus secreted by these cells prevent the microbes from associating
"Too closely" with the cells (Prevent attachment of microbes with tissues)

Microbiology

Notes…

Chemical and Physical Barriers-Normal flora of the Gastrointestinal Tract

Mechanisms

Stomach

Acidic pH of the stomach act as a physiological barrier that decreases the number of
viable pathogens reaching distal intestine.

Intestines

Normal GIT flora : Compete with pathogenic bacteria for nutrients and production of
enzymes or growth suppressor materials as Colicin (produced by enteric bacilli).

Chemical and Physical Barriers- Bactericidal agents

1. Lysozymes
Constantly bath the kidney the surface of the eye (tears) , female urogenital tract, and
saliva.
Lysozyme  breaks  the  glycosidic  bonds  between  the  NAG  and  NAM  that  make  up  the
backbone of peptidoglycan—causing bacteria to lyse.

Microbiology

Notes…

2. beta-lysins : blood proteins bind to and disrupt the bacterial cytoplasmic membrane—
leads to leakage of the cytoplasmic constituents and bacterial cell death.

2. Phagocytes (eating cells)

Main functions:
- Cells that engulf, digest and destroy pathogens
- Also produce inflammatory molecules which regulate other    components of the
immune system.
-  Some of them present antigens to T cells
Include :
-  Neutrophils (microphages)
-  Eosinophils
   -  Monocytes/Macrophages

3. Neutrophils

• Present in blood (60-70% of WBCs)
• Multi-lobular nucleus

(PMN)

•  Highly mobile phagocytes
•  Short half life (6 – 12 hours)
•  Acute inflammation
•  Containing bacteria-killing enzymes

4. Monocytes/Macrophages

Blood (1-6 % of WBC)

Smaller

Tissues

times larger

More phagocytic activity

  Named  Based  on  Tissue  They
Reside
Alveolar  (lungs  ,)Kupffer  (liver),
Microglial  (brain),  Osteoclasts
(bone)

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How do Macrophages Identify Microbes?

They  express  a  wide  range  of  surface  receptors  that  allow  them  to  identify
microorganisms.
Pattern Recognition Receptors (PPR )
-Recognize pathogen associated molecular patterns (PAMP);
-Identify a class of microbes; ex., LPS, LTA, peptidoglycan,  lipoarabinomannan, dsRNA,
mannose, b-glycans
-PAMP are often essential for microbe survival
Action Time
Immediate activation of effectors
Delays need for adaptive immunity

Phagocytosis

The process of phagocytosis include the following stages:

A) Activation of phagocytes

Under the influence of inflammatory mediators such as bacterial products (bacterial
proteins, capsules , LPS, peptidoglycans , teichoic acids, etc) , complement proteins and
inflammatory cytokines resting resident phagocytes are ACTIVATED. Activation of
phagocytes results in:
1. Increase production of endocytic PRR that recognize and bind to PAMPS
2. Increase metabolic and microbial activity of phagocytes by increasing their production
of ATPs, lysosomal enzymes , lethal oxidant , etc.

B) Chemotaxis of phagocytes

The activated phagocytes are ATTRACTED toward the site of inflammation under the
influence of inflammatory mediators such as bacterial products (bacterial proteins,
capsules , LPS, peptidoglycans , teichoic acids, etc.) , complement proteins (C3a, C5a)
and inflammatory cytokines such as IL-8, chemokines, fibrin split products , kinins and
phospholipids releases by injured host cells.
Note: Some microbes such as

influenza virus A

Mycobacterium tuberculosis

Neisseria

gonorrhea

and

Bordetella pertussis

known to block this step.

A) Inflammation

Infection or tissue injury stimulates mast cells, basophils and other cells to release
vasodilators. Vasodilation results in increase capillary permeability

• Resting phagocytes become activated by inflammatory mediators

C) Attachment and migration

• If epith. lining is breached by microbes, resident phagocytes are attracted (influx)

to the site by chemotactic substances as bacterial endotoxins (LPS), serum C5a,
IL-8, and leukotriene B4.

Microbiology

Notes…

Infection or tissue injury stimulates mast cells, basophils and other cells to release
vasodilators. Vasodilation results in increase capillary permeability

• If epith. lining is breached by microbes, resident phagocytes are attracted (influx)

to the site by chemotactic substances as bacterial endotoxins (LPS), serum C5a,
IL-8, and leukotriene B4.

• The macrophages produce cytokines as IL-1 & TNF.These activate endothelial cells

of nearby venules to produce adhesion molecules (selectin, integrins, & ICAM) and
chemkines (e.g.,IL-8) which mediate MIGRATION of leucocytes & monocytes from
the blood to tissues (diapedesis).

• The phagocytes have receptors on their surface through which they ATTACH non-

specifically to m.o. Examples: Receptors for bacterial endotoxines, for mannose
residues on glycoprotein of many bacteria, unmethylated bacterial DNA & double
stranded RNA of many viruses. The attachment and ingestion is enhanced if
microbes are coated with IgG or C3b (opsonization

5. Natural Killer (NK) cells( CD56+)

Large round granular lymphocytes

Always remain in the circulation

Act as immunological surveyors (cytotoxic cells)
Kill virally infected cells
Kill tumours

• However, NK cells do not require stimulation, nor they do exhibit memory cells.

NK cells respond in the absence of MHC proteins.

• What does CD refer to???????

CD (Cluster of Differentiation)

• CD

= Cluster of differentiation

• Leukocytes surface antigens that are expressed on cells of a particular lineage

“differentiation ”

•  Also called CD molecules , CD antigens , CD markers
•  Used to classify leukocytes into functionally distinct subpopulation ,e.g
•  NK cells are CD56

• T - Lymphocytes CD3

(pan T cells marker)

• B - Lymphocytes CD19

• Monocytes / Macrophages CD14