Non specific host defense mechanism

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1. GONO BISHWABIDYALAY

Nolam,Mirzanagar,savar,Dhaka-1344



DEPARTMENT OF MICROBIOLOGY

An Assignment On : Non-specific Host Defenses Against Microbial pathogens
Course Title : Medical Microbiology-I
Course code : 3606

Submitted To Submitted By

Md. Shah Alam Name : Md Shamim Hossain

Senior Lecturer Exam Roll : 1222

Department Of Microbiology Batch No : 33
rd


Gono Bishwabidyalay Semester : 6
th


Reg. No : G/Micro-2062/18



Submission Date : 13-12-2020

2. Introduction :

Resistance : Ability to ward off disease.

Nonspecific Resistance: Defenses that protect against all pathogens.

Specific Resistance: Protection against specific pathogens.

Susceptibility: Vulnerability or lack of resistance.

In general, there are two types of immunity : innate and adaptive

Innate Immunity : Innate immunity refers to defenses that are present at birth. They are always available to
provide rapid responses to protect us against disease. Innate immunity does not involve recognition of
specific microbe .

Adaptive Immunity : Adaptive immunity refers to defenses that protect the body against particular
pathogens. Unlike innate immunity, adaptive immunity is slower to respond, but it does have a memory
component that allows the body to more effectively targets the same pathogens in the future.

Protection Against Invading Pathogens:

1.First Line of Defense: Non-specific natural barriers which restrict entry of pathogen.
Examples: Skin and mucous membranes.

2.Second Line of Defense: Innate non-specific immune defenses provide rapid local response to pathogen
after it has enteredhost.
Examples: Fever, phagocytes (macrophages and neutrophils), inflammation, and interferon.

3.Third line of defense: Antigen-specificimmune responses, specifically target and attack invaders that get
past first two lines of defense.
Examples: Antibodies and lymphocytes.

Three Lines of Defense Against Infection :


Nonspecific Resistance Specific Resistance
(Responses of the immune
System )
First line of defense Second line of defense Third line of defense
 Intact Skin
 Mucous membranes
and their secretions
 Normal microbiota
 Phagocytic white blood
cells
 Inflammation
 Fever
 Antimicrobial substances
 Specialized lymphocytes
: B cells and T cells
 Antibodies

3. I.First Line of Defense:

Skin and Mucous Membranes

Mechanical Defenses

Skin has two Layers:

A.Epidermis: Thin outer layer of epithelial tissue. Contains Langerhans cells, dead cells, and keratin (water proof).

B. Dermis: Thick inner layer of connective tissue.

Infections are rare in intact skin. Exceptions:

 Hookworms can penetrate intact skin
 Dermatophytes: “Skin loving” fungi

4. Mechanical Defenses

1. Mucous Membranes: Line gastrointestinal,
genitourinary, and respiratory tracts.
 Two layers: Outer epithelial and inner connective layer.
 Epithelial layer secretes mucus which maintains moist surfaces.
 Although they inhibit microbial entry, they offer less protection than skin.
 Several microorganisms are capable of penetrating mucous membranes:

 Papillomavirus
 Treponema pallidum
 Enteroinvasive E. coli
 Entamoeba histolytica

2. Lacrimal apparatus: Continual washing and blinking prevents microbes from settling on the eye surface.

3. Saliva: Washes microbes from teeth and mouth mucous membranes.

4. Mucus: Thick secretion that traps many microbes.

5. Nose Hair: Coated with mucus filter dust, pollen, and microbes.

6. Ciliary Escalator: Cilia on mucous membranes of lower respiratory tract move upwards towards throat at
1-3 cm/hour.

7. Coughing and sneezing: Expel foreign objects.

8. Epiglottis: Covers larynx during swallowing.

9. Urination: Cleanses urethra.

10. Vaginal Secretions: Remove microbes from genital tract.

5. Chemical Defenses:
1.Sebum: Oily substance produced by sebaceous glands that forms a protective layer over skin. Contains
unsaturated fatty acids which inhibit growth of certain pathogenic bacteria and fungi.
2.pH: Low, skin pH usually between 3 and 5. Caused by lactic acid and fatty acids.
3.Perspiration: Produced by sweat glands. Contains lysozyme and acids.
4.Lysozyme: Enzyme that breaks down grampositive cell walls. Found in nasal secretions, saliva, and tears.
5.Gastric Juice : Mixture of hydrochloric acid, enzymes, and mucus. pH between 1.2 to 3 kills many
microbes and destroys most toxins. Many enteric bacteria are protected by food particles.
 Helicobacter pylori neutralizes stomach acid and can grow in the stomach, causing gastritis and
ulcers.
6.Transferrins: Iron-binding proteins in blood which inhibit bacterial growth by reducing available iron.

6. Cellular Elements of Blood

Cell Type Cells/mm3 Function
Erythrocytes (RBC) 4.8-5.4 million Transport O2 and CO2
Leukocytes (WBC) 5000-9000 Various
A. Granulocytes:
1. Neutrophils (70% of WBC) Phagocytosis
2. Basophils (1%) Produce histamine
3. Eosinophils (4%) Toxins against parasites
some phagocytosis
B. Monocytes/Macrophages (5%) Phagocytosis
C. Lymphocytes (20%) Antibody production (B cells)
Cell mediated immunity (T cells)
Platelets 300,000 Blood clotting


Formed Elements In Blood

7. White Blood Cells
• Neutrophils: Phagocytic
• Basophils: Produce histamine
• Eosinophils: Toxic to parasites, some phagocytosis
• Monocytes: Phagocytic as mature macrophages
• Fixed macrophages in lungs, liver, bronchi
• Wandering macrophages roam tissues
• Lymphocytes: Involved in specific immunity

II. Second Line of Defense
Phagocytosis: Derived from the Greek words “Eat and cell”.
 Phagocytosis is carried out by white blood cells: macrophages, neutrophils, and occasionally
eosinophils.
 Neutrophils predominate early in infection.
 Wandering macrophages: Originate from monocytes that leave blood and enter infected tissue, and
develop into phagocytic cells.
 Fixed Macrophages (Histiocytes): Located in liver, nervous system, lungs, lymph nodes, bone
marrow, and several other tissues.

8. Stages of Phagocytosis

1. Chemotaxis: Phagocytes are chemically attracted to site of infection.
2. Adherence: Phagocyte plasma membrane attaches to surface of pathogen or foreign material.
 Adherence can be inhibited by capsules (S.pneumoniae) or M protein (S. pyogenes).
 Opsonization: Coating process with opsonins that facilitates attachment.
• Opsonins include antibodies and complement proteins.

9. 3. Ingestion: Plasma membrane of phagocytes extends projections (pseudopods) which engulf the microbe.
Microbe is enclosed in a sac called phagosome.
4. Digestion: Inside the cell, phagosome fuses with lysosome to form a phagolysosome. Lysosomal
enzymes kill most bacteria within 30 minutes and include:
 Lysozyme: Destroys cell wall peptidoglycan
 Lipases and Proteases
 RNAses and DNAses
After digestion, residual body with undigestable material is discharged.

10. Inflammation

Triggered by tissue damage due to infection, heat, wound, etc.
Four Major Symptoms of Inflammation:
1. Redness
2. Pain
3. Heat
4. Swelling
May also observe:
5. Loss of function


Functions of Inflammation
1. Destroy and remove pathogens
2. If destruction is not possible, to limit effects by confining the pathogen and its products.
3. Repair and replace tissue damaged by pathogen and its products.


Stages of Inflammation

1.Vasodilation: Increase in diameter of blood vessels. Triggered by chemicals released by damaged cells:
histamine, kinins, prostaglandins, and leukotrienes.

2. Phagocyte Migration and Margination: Margination is the process in which phagocytes stick to lining
of blood vessels.

Diapedesis (Emigration): Phagocytes squeeze between endothelial cells of blood vessels and enter
surrounding tissue.

Phagocytes are attracted to site of infection through chemotaxis.
Phagocytes destroy microbes, as well as dead and damaged host cells.
3. Tissue Repair: Dead and damaged cells are replaced.

12. Antimicrobial Substances
I. Complement System: Large group of serum proteins that participate in the lysis of foreign cells,
inflammation, and phagocytosis.
Three mechanisms of complement activation

1.Classical Pathway:
1. immune complex formation with either IgG or IgM (IgM more effective)
2. C1 binds to Fc region of antibody
3. C1 cleaves C4 → C4a, C4b
4. C2 binds next to C4b
5. C2 cleaved by C1 → C2a, C2b
6. C4b2a = classical pathway C3 convertase
7. C4b2a cleaves C3 → C3a, C3b
8. C4b2a3b = classical pathway C5 convertase
9. C4b2a3b cleaves C5 → C5a, C5b
10. terminal pathway → membrane attack complex

2. Alternative Pathway:
1. involved in innate immunity
2. spontaneously generated C3b by tickover binds to microbe
3. Factor B binds to microbe
4. Factor D cleaves Factor B → Ba, Bb
5. C3bBb = alternative pathway C3 convertase
a. stabilized by properdin
6. C3bBb cleaves C3 → C3a, C3b
7. C3bBbC3b = alternative pathway C5 convertase
8. C3bBbC3b cleaves C5→ C5a, C5b
9. terminal pathway → membrane attack complex

3. Lectin Pathway :
1. Lectins are carbohydrate-binding proteins
2. Does not require antibody
3. Recognizes mannose residues on glycoproteins
4. The mannose-binding lectin (MBL) is an acute phase protein that increases during inflammation
5. Plays a similar role to that of C1q
6. After binding to mannose-residues on the cell surfaces, associates with MBL-associated serine proteases
(MASP-1 and MASP-2).
7. This complex activates C4 and C2 just as in the classical pathway
8. MASP-1 and MASP-2 very similar to C1r and C1s

14. Consequences of Complement Activation:
1. Cytolysis: Due to the formation of a membrane attack complex (MAC) which produces lesions in
microbial membranes.
2. Inflammation: Complement components (C3a) trigger the release of histamine, which increases vascular
permeability.
3. Opsonization: Complement components (C3b) bind to microbial surface and promote phagocytosis.
4. Inactivation of Complement: Regulatory proteins limit damage to host cells that may be caused by
complement.
Interferons: Antiviral proteins that interfere
with viral multiplication.

 Small proteins (15,000 to 30,000 kDa)
 Heat stable and resistant to low pH
 Important in acute and short term infections.
 Have no effect on infected cells.
 Host specific, but not virus specific.

Interferon alpha and beta: Produced by virus infected cells and diffuse to neighboring cells.
Cause uninfected cells to produce antiviral proteins (AVPs).

Interferon gamma: Produced by lymphocytes. Causes neutrophils to kill bacteria.

15. THE END