GENERAL IMMUNOLOGY PHT 324 Dr. Rasheeda Hamid Abdalla Assistant Professor E-mail rasheedahamed12@hotmail.com

Human Body defense mechanisms

The Innate defense Definition: Types: Mechanisms:

The Innate defense These intrinsic defense mechanisms are present at birth prior to exposure to pathogens or other foreign macromolecules. They are not enhanced by such exposures and are not specific to particular pathogen.

Factors that limit entry of micro-organism in to the body Mode of action Keratin layer of intact skin Act as a mechanical barrier Lysozyme in tears &other secretions Degrades peptidoglycan in bacterial cell wall Respiratory cilia Elevated mucous containing trapped organisms Low pH in stomach &vagina , fatty acid in skin Retards growth of microbes Surface phagocytes (e.g. Alveolar macrophages ) Ingest and destroy microbes Defensins Creates pores in microbial memmbrane Normal flora of throat, colon and vagina Occupy receptors which prevent colonization by pathogen

Mechanical and chemical barriers Intact skin is usually impenetrable to microorganisms. Membranous linings of the body tracts are protected by mucus, acid secretions and enzymes such as lysozyme, which breaks down bacterial cell wall. In the lower respiratory tract, the mucous membrane is covered by hair-like protrusions of the epithelial cell membrane called Cilia.

1.Mechanical and chemical barriers The movement of cilia can propel/move mucus-entrapped microorganisms from the tract (Mucociliary Escalator). Saliva, Tears and Mucous secretions, are involved in preventing entry of pathogens. These secretions also contain Antibacterial or Antiviral substances.

Chemical Barriers of The Body The skin and respiratory tract secrete antimicrobial peptides such as β-defensins Enzymes such as lysozymes and phospholipase in saliva ,tears ,and breast milk are also anti-bacterials. In the stomach ,gastric acid and proteases serve as powerful chemical defenses against ingested pathogens Acidic secretions of vagina serve as chemical barrier. Semen contains defensin and zinc to kill pathogens.

2. Role of Normal Flora Normal flora prevents colonization by pathogens by competing for attachment sites or for essential nutrients. Normal flora may Kill other bacteria through the production of substances which inhibit or kill non indigenous species. Normal flora stimulates the production of natural antibodies: Antibodies produced against antigenic components of the normal flora are sometimes referred to as "natural" antibodies

3. Phagocytic Defense

Phagocytosis Phagocytosis: The primary method used by the body to remove free microorganisms in the blood and tissue fluids. The body's phagocytic cells are able to encounter these microorganisms in a variety of ways:

1 Infection or tissue injury Stimulates Mast cells and Basophils to release Vasodilators to initiate the inflammatory response. As a result/ phagocytic WBCs (neutrophils, macrophages, eosinophils) enter the tissue around the injured site

2 Lymph nodules Masses of lymphoid tissue containing B-lymphocytes, T-lymphocytes, and macrophages. Located in the respiratory tract, liver, and gastrointestinal tract and are collectively referred to as Mucosa-Associated Lymphoid Tissue or MALT

Examples Adenoids and tonsils in the respiratory tract. Peyer's patches on the small intestines. Organisms entering these systems can be phagocytosed by fixed macrophages and dendritic cells and presented to lymphocytes to initiate the immune responses.

3 Tissue fluid picks up microbes Microbes picked up by the lymph vessels are filtered out and phagocytosed in the lymph nodes by these fixed macrophages and dendritic cells and presented to the circulating T-lymphocytes to initiate immune responses.

4 The spleen Blood carries microorganisms to the spleen where they are filtered out and phagocytosed by the fixed macrophages and dendritic cells and presented to the circulating T-lymphocytes to initiate immune responses.

5 Specialized Macrophages and dendritic cells located in: Brain (microglia). Lungs (alveolar macrophages). Liver (Kupffer cells). Kidneys (mesangial cells). Bones (osteoclasts). Gastrointestinal tract (peritoneal macrophages). Skin and mucous membranes (Langerhans‘)

Mesangial cells

Kupffer cells

The Process of Phagocytosis Activation Phagocytes are activated by inflammatory mediators. As a result, phagocytes produce surface glycoprotein receptors that increase their ability to adhere to surfaces and recognize microbes

The Process of Phagocytosis (cont’d) These glycoprotein molecules, known as Endocytic Pattern-Recognition Receptors, are so named because they recognize and bind to pathogen-associated molecular patterns - components of common molecules such as peptidoglycan, teichoic acids, lipopolysaccharide, mannans, and glucans - found in many microorganisms.

The Process of Phagocytosis (cont’d) 2. Chemotaxis: Chemotaxis = movement of phagocytes toward an increasing concentration of some attractant such as bacterial factors (bacterial proteins, capsules, cell wall fragments, endotoxin). Some microbes, such as the influenza A viruses, Mycobacterium tuberculosis, blood invasive strains of Neisseria gonorrhoeae and Bordetella pertussis have been shown to block chemotaxis.

The Process of Phagocytosis (cont’d) 3. Attachment Attachment of microorganisms is necessary for ingestion and may be unenhanced or enhanced. Unenhanced attachment is a general recognition of components of common molecules such as peptidoglycan, teichoic acids, lipopolysaccharide, mannans, and glucans common in microbial cell walls but not found on human cells - by means of glycoprotein known as endocytic pattern-recognition receptors on the surface of the phagocytes .

The Process of Phagocytosis (cont’d) Enhanced attachment The attachment of microbes to phagocytes by way of an antibody molecule called IgG or complement proteins C3b and C4b produced during the complement pathways . Molecules such as IgG, C3b, and C4b that promote enhanced attachment are called opsonins and the process is also known as Opsonization. Enhanced attachment is much more specific and efficient than unenhanced.

The Process of Phagocytosis (cont’d) Some capsules simply cover the C3b that does bind to the bacterial surface and prevent the C3b receptor on phagocytes from making contact with the C3b. This is seen with the capsule of Streptococcus pneumoniae.

The Process of Phagocytosis (cont’d) 4. Ingestion Following attachment, actin filaments send pseudopods out to engulf the microbe and place it in an endocytic vesicle called Phagosome.

The Process of Phagocytosis (cont’d) Pathogenic Yersinia, such as the one that causes plague, contact phagocytes and deliver proteins which depolymerize (Break down into small units) the actin microfilaments needed for phagocytic engulfment into the phagocytes.

The Process of Phagocytosis (cont’d) 5. Destruction Phagocytes contain membranous sacs called lysosomes (produced by Golgi apparatus) that contain digestive enzymes, microbicidal chemicals, and toxic oxygen radicals. The lysosomes fuse with the phagosomes containing the ingested microbes and the microbes are destroyed .

The Process of Phagocytosis (cont’d) Some bacteria are more resistant to phagocytic destruction once engulfed Mycobacterium species, cause the phagocytic cell to place them into an endocytic vaculole via a pathway that decreases their exposure to toxic oxygen compounds.

The Process of Phagocytosis (cont’d) Some bacteria, such as pathogenic Mycobacterium prevent the acidification of the phagosome which is needed for effective killing of microbes by lysosomal enzymes. (after the phagosome forms, contents become acidified because lysosomal enzymes used for killing function much more effectively at acidic pH).

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