OIA1010 INNATE IMMUNOLOGY

Immune System:

Infectious microbes (viruses, bacteria, protozoa, fungi & parasites) causes diseases

Recognises and destroy pathogens or infected hosts' cells (immune response)

Innate Immunity:

Physical (skin, mucous membrane) & Chemical Barriers (pH, fatty acid secretion of innate immunity

Pattern recognition: Hallmark of innate immune response (e.g., NK cells, macrophages, WBC)

Complement & inflammation

Physiology Barriers

Skin

first line defence

Has keratin (fibrous insoluble protein) prevent penetration of invasive microbes

produce antimicrobial substances

host normal microflora to compete with pathogens

slight acidic pH: prevent microbial growth

Mucous membrane

Moist mucus secretions trap & prevent cellular invasion

Present in respiratory tract, GI tract & urogential tract

Cilliated cells constantly move trapped organism towards external openings (e.g., nostrils) -> form mucociliary escalator

Nostril hair & coughing reflex prevent infection of upper respiratory tract.

Normal microflora

Compete with other more pathogenicity organism to prevent infection

Skin: Staphylococcus spp.

Mouth: Streptococcus spp. //anaerobes

Intestinal: Gram negative

Biological active substances:

Acidic pH (Stomach secretion: pH2; Vaginal secretion: pH 4)

Sweat & subcutaneous secretion prevent invasion through hair follicles & sebaceous glands

Lysozymes (hydrolytic enzymes damage cell wall) found in tears, saliva, vaginal secretion & etc.

Surfactant activity (fatty acids of sebaceous glands & bile acids in small intestine: inhibit microbial growth)

Interferon: glycoprotein produced by cells due to viral invasion and spread to surrounding uninvaded cells & inhibit viral replication in cells (HOST SPECFIC NOT VIRUS SPECIFIC)

MOA: viral RNA from infecting virus enter cells. Infecting virus replicate new viruses and induce host to produce interferons mRNA (IFN-mRNA) which translate into alpha & beta interferons. Interferons released by infected host bind to plasma/nuclear membrane of unifected neighbouring cells, induce synthesis of antiviral proteins (AVPs) such as oligoadenylate synthetase & protein kinase. New virus released infect neighbouring host cells. AVPs degrade viral mRNA & inhibit protein synthesis, thus interfere with viral replication.

Complement system (series of enzymes that directly kills organism through cell lysis)

Induce opsonization (increase rate of phagocytosis) & chemotaxis

Triggered by intrinsic ability to recognise microbial components or antibody bound to microbe

Three complement activation pathways (classical, alternative & lectin)

Processes involved in Innate Immunity

Phagocytosis

Ingestion and destruction by individual cells of foreign particles

Phases: Ingestion -> Formation of foreign vacuole (phagosome) -> Fusion of phagosome with lysosome -> Destruction (primary outcome) & develop acquired immunity (secondary outcome)

Peptides of foreign substance bind to surface major histocompatibilty complex (MHC) & antigens are presented to T helper cells, forming antigen-presenting cells (APC)

Opsonins enhances phagocytosis through variety of factors

When invaders penetrate first line defence (physical & Chemical barrier), second line defence (specialised cells: destroy invader) is activated.

Polymorphonuclear (PMN) leukocytes (WBCs contain segmented lobular nucleus)

Eosinophils, basophils, neutrophils, monocytes & macrophages derive from hematopoietic precursor cells

Cells from innate derived from myeloid precursors while cells from adaptive derived from common lymphoid precursors

Phagocytosis cells

PMN leukocytes

Predominant leucocyte, short lived, present at infected/ injured sites within minutes

Deficiency cause chronic or recurrent infection

Macrophages (mature)/ monocytes (immature)

long lived, common component of chronic inflammation

Important in phagocytosis, antigen presenting, cytokine production (inflammation) & synthesis of complement component

monocytes (special, small & few projections) -> migrate from blood to tissue -> macrophages (more projections)

Kupffer cells (large cells with many cytoplasmic projections, found in liver)

Alveolar macrophages: in lungs

Splenic macrophages: in red pulp

Peritoneal macrophages: free floating in Peritoneal fluid

Microglial cells: in Central Nervous tissue

Natural Killer cells (NK cells)

Cytotoxic: early stages of viral infection or tumorogenesis

Does not recognise target cells in antigen-specific fashion due to expression T cell receptors (TCRs) as T lymphocytes

NK cells lack antigen-specific receptors

Mechanism: cell-cell contact (MHC class I)

NK cells express killer-cell inhibitory receptors (KIR), bind to MHC class I expressed by normal cells.

Pattern Recognition

Underlying host defence mechanism with innate immunity: ability of innate cells & specific soluble mediators produced to recognise & respond to Pathogen-associated molecular patterns (PAMPs) (conserved microbial structures)

Detection of PAMPs by innate immune cells occurs via soluble and cell-associated germline-encoded pattern recognition receptors (PRRs) -> initiate immune response, enchancing body defence against infections.

Inflammation

Constitue rapid innate phase & prolonged phase which acquired immunity is involved

PMNs activated due to injury/infection & release actue phase proteins (Kinins & Cytokines)

Common signs: swelling, redness, heat, pain & loss of function

Kinins

Vasodilation, increase vascular permeability & contraction of muscles distal to site -> blood backup at affect area (redness, heat, swelling)

Vascular cells express endothelial adhesion molecules, allowing cells in bloodstream to attach to capillary wall & enter affected site

Stimulate nerves -> pain

Cytokines

Induce adhesion molecules, increase vascular permeability, attract leukocytes

Activate C-reactive protein: p

roduced by liver, primes certain bacetria for destruction by complement system by binding to cell wall of bacteria and fungi

Inflammation persists: additional macrophages & neutrophils infiltrate site: phagocytosis

Macrophage: antigen presentation & initiate formation of antibodies

Tissue repair occurs during inflammation

Chronic inflammation: unable to underlying cause of inflammation (e.g., rheumatoid arthritis (RA), glomerulonephritis)

Fever

Most common manifestation of infection/ inflammation

Produced by bacterial products such as endotoxin

Mediated by endogenous substances such as IL-1 & interferons