immunological aspect of bacterial infection 2

IMMUNOLOGICAL ASPECT OF BACTERIAL INFECTION

Dr A.Aziz Djamal MSc.DTM&H.SpMK(K)

Bacterial Infection

Colonization of pathogenic bacteria on / inside the body which are potentially harmful to our body

Immunosurveillan system of our body will recognize invading bacteria

WHY1.Genetically different.2.Bacteria contain many structurally non-self substances.3.Bacteria produce many antigenic products

Bacterial components are excellent activator of Innate

Antigen-Non Specific immune response

Direct Activators

Lipopolysaccharide (Endotoxin)Lipoarabinomannan.Lipoteichoic acidGlycolipids and Glycopeptide.PolyanionsN-formyl peptides

Act as Chemotactants

Peptidoglycans fragmentsCell Surface activation of alternating pathway of

the complement ( C3a and C5a )

Activation of Antibacterial immune Response

Peptidoglycan layer of Gram (+) bacteria and Lipopolysaccharides layer of Gram (-) bacteria1.Activate the alternative pathway (properdin) of complement in the absence of antibody.2.Activate the Classical pathway of complement via mannose binding protein (MBP).3.Recognize by Pattern-recognized receptors including Toll-Like receptors on Macrophage and Dendritic cells—activate the protective immnune response

Lipopolysaccharide – LPS / Endotoxinis a strong activator of :MacrophageB CellsOthers ( endothelials cells)

Activation of Complement ( both pathways )

1. Very early and important antibacterial immune response

2. Complement activate the inflammatory response

3. Complement can directly kill Gram (-) bacteria.

Activation of complement cascade by Gram (+)/Gram (-) Bacteria provide the following

protective immune responses1. 1.Chemotactic factor (C5a) attract Neutrophil

and Macrophage to the infection site.2. 2. Anaphylatoxin (C3a and C5a) Stimulate

releasing of histamin by macrophage – increasing vascular permeability- increase access to the infection site.

3. 3. Opsonin (C3b) bind to bacteria and promote phagocytosis.

4. 5. B-Cells activator (C3d)

Activation of Classical cascade of Complement

Usually occur later in bacterial infection and it is activated by the presence of

antibody IgM or IgG and it will activate the whole complement system

Other Non Specific Protective Immune Effectors

1. Kinins and Clotting Factors : produced by tissue damage, involve in inflammation,

increase vascular permeability and chemotactors for leucocytes.

2. Metabolic Product of Arachidonic acid: Prostaglandin and Leukotriens, mediates

every aspect of inflammation

Phagocyte and Phagocytosis

The first cells to appear in acute infection :1. 1.Polymorphonuclear Neutrophils (PMN)2. 2.Monocyte3. 3. Eosinophyl ( Occasionally )Followed later by Macrophage

Neutrophils

PMN that provide the antibacterial response.Attracted to the site of infection, phagocytized and killed internalized bacteria.Increase number of neutrophils in blood, body fluid or tissue indicate bacterial infection.Mobilization of neutrophils will followed by “a left shift” accumulation of the immature “band form”

Phagocytosis of Bacteria by Macrophage and Neutrophils

involved several process

1. Attachment.2. Internalization.

3. Digestion

Attachment1. Receptor for bacterial carbohydrate: Lectin

(specific sugar binding protein)2. Receptors for opsonins (C3b receptor, MBP

receptor).3. Fibronectin receptor , Specific for S. aureus.4. Fc receptor for antibody.

Internalization

After the attachment, the bacteria will be surrounded by a portion of

plasma membrane and formation of phagocytic vacuole that surrounding

the bacteria

DigestionIt is fusion of vacuole containing bacteria with the

primary lysosome (Macrophage ) or Granules (PMN) followed by inactivation / destruction of

vacuole content. It is a very complex processes involving many

factors and substances :Oxygen-dependent

Oxygen-independentDepend on antimicrobial release by granules

Digestion will be greatly enhanced by activation of Macrophage by many substances

1.Interferon ( Inf-gamma,the best ).2.GM-CSF

3.TNF-alpha.4.Lymphotoxin (TNF-beta)

Oxygen dependent

Hydrogen peroxidase (NADPH Oxydase and NADH oxydase.Superoxydase.

Hydroxyl radicals (OH).Activated halides ( Cl, I, Br ).

MyeloperoxidaseNitrous oxyde.

Oxygen independent1. 1.Acids2. Lysozymes ( degrade bacterial

peptidoglycan)3. Lactoferrin ( Chelate iron ).4. Defensins and other cationic proteins ( damage membrane ).5. Proteases, Elastases and cathepsin G

If the above non-specific protective immune response succeeded in eliminating the invading

bacteria the process is finished

If it is failed, the processed will proceed to the specific protective immune response

and most of the phagocytic cells especially Macrophage and Dendritic cells will act as

Antigen Presenting Cells / APC

The Specific Protective Immune response will be divide into :

Humoral Cellular

Depend much on the kind of bacteria whether it is

extracellular or intracellular bacteria

Extracellular bacteria the clearance will mostly depend on humoral protective immune response

Intracellular Bacteria their clearance will mostly decided by the cellular immune response

Thank You