THE IMMUNE SYSTEM Prof Khaled H AbuElteen Terminology

THE IMMUNE SYSTEM Prof. Khaled H. Abu-Elteen

Terminology n n Types of Symbiosis ( Living togathers) - Amensalism A symbiotic relationship in which one species is harmed, but it isdifficult to see how the other species benefit. – – Mutualism n A symbiotic relationship in which both species benefit Commensalism n A symbiotic relationship in which one species benefits, and the other species is neither helped nor harmed

n Types of Symbiosis (cont. ) – Parasitism • A symbiotic relationship in which one species benefits, and the other species is harmed • Generally, the species that benefits (the parasite) is much smaller than the species that is harmed (the host)

n Disease and Infectious Disease – – Disease n Any deviation from a condition of good health and well-being Infectious Disease · A disease condition caused by the presence or growth of infectious microorganisms or parasites

Immunology lingo n Antigen – n Pathogen – n A glycoprotein produced in response to the introduction of an antigen Vaccination – n Secreted immunoglobulin Immunoglobulin (Ig) – n Microorganism that can cause disease Antibody (Ab) – n Any molecule that binds to immunoglobulin or T cell receptor Deliberate induction of protective immunity to a pathogen Immunization – The ability to resist infection

TYPES OF IMMUNITY. Nonspecific: Skin and mucous membranes, Phagocytosis, Inflammation, and The Complement System. n Specific: Humoral(Antibody-Mediated) and Cell-Mediated. n

Nonspecific Immune Response n n n Physical and Mechanical Barrier’s Chemical Factor’s Biological Factor’s Phagocytosis and Associated with Blood and lymph Defenses that protect from ANY pathogen regardless of type and species( Bacteria, Fungi, Protozoa, etc).

Physical and Mechanical Barrier’s THE SKIN: First Line Of Defense. n Repels many organisms: difficult to get through. n Epithelium lines all body systems exposed to external environments including the respiratory, digestive and urinary systems. n Secretes liquid which are mildly acidic which hinder bacterial growth. n Lack of nutrition for microbial growth. n

DEFENSES – Dry n usual groin – – Acidic (p. H 3. 0 - 5. 0) Temperature less than 37 o. C n Some – pathogens grow best <37 o. C Lysozyme and toxic lipids n pore, – infection sites are wet areas, skin folds, armpit, hair follicles, sweat gland Resident microflora n mainly – G+ Skin-associated lymphoid tissue (SALT)

Tears and saliva contain lysozymes which dissolve the wall of bacteria. n Cilia of respiratory tract trap bacteria in mucus. n

SKIN AND MUCOUS MEMBRANES: 1 st line of defense n n n n Mechanical Factors: Skin. The Epidermis. Keratin. Mucous Membranes. Lacrimal Apparatus ------> Cilliary Escalator [ mucocilliary Escalator Action).

LACRIMAL APPARATUS.

CILIARY ESCALATOR.

Flushing Mechanisms Epiglottis. n Urine and Vaginal secretions. n Sneezing, coughing, swallowing reflex n Movement of Fluids across their surfaces (Saliva) n Washing action of tears n

CHEMICAL FACTORS. Sebum and fatty acids in skin ( e. g. unsaturated fatty acids as Olic acid). n Gastric Juice (Low p. H stomach ). n Lyzozyme: degrade the bacterial cell wall n Antimicrobial peptides (β Lysine) with high quantity of Lysine or Arginine. Act by disruption of plasma membrane of microorganisms. n

n. Complement: complex of 17 proteins (Glycoproteins) present in normal serum) C 1, C 2, C 3 …. . etc. Function: Lysis of microbes, Neutralization of viruses, Enhancement of phagocytosis, Damage of plasma membrane, Recruitment of Phagocytes, n. Interferons : Family of Glycoproteins that block Viral Replication by rendering host cells,

NORMAL MICRIBIOTA AND NONSPECIFIC RESISTANCE. Microbial Antagonism. n Commensalism. n Competitive Exclusion: Opportunistic pathogens. n Natural Resistance: Microorganisms has a host range n

Cells of the Immune system: FORMED ELEMENTS IN BLOOD. Many cells of the immune system derived from the bone marrow n Hematopoetic stem cell differentiation n

Components of blood Serum vs. Plasma n Serum: cell-free liquid, minus the clotting factors n Plasma: cell-free liquid with clotting factors in solution (must use an anticoagulant) n Contain protein: Albumin, Globulin and Fibrinogen.

Components of blood

LEUKOCYTES. Divided into two main categories based on their appearance under the light microscope: n Granulocytes Versus Agranulocytes. n Granulocytes: Neutrophils(stain lilac), Basophils (stain blue-purple), and Eosinophils (stain red or orange). n

NEUTROPHILS ( 60% of WBC) n n n n Commonly called polymorphonuclear leukocytes (PMNs). Multinucleated. Highly phagocytic and motile. Active in the initial stages of infection. Short life span (hours) Very important at “clearing” bacterial infections Innate Immunity

BASOPHILS (1% of WBC) n n Role is not clear. Release substances, such as histamine, that are important in inflammation. Might be “blood Mast cells’ Important in allergic reactions

Eosinophils ( 3% of WBC) n n n Somewhat phagocytic. Have the ability to leave the blood. Major function is to produce toxic proteins against certain parasites such as worms. Involved in allergic inflammation Double Lobed nucleus Orange granules contain toxic compounds

AGRANULOCYTES. Monocytes ( 5% of all WBC). n Macrophages. n Lymphocytes ( 30% of all WBC). n

MONOCYTES. n Phagocytosis and killing of microorganisms – n n n Activation of T cells and initation of immune response Monocyte is a young macrophage in blood There are tissue-specific macrophages Antigen Presentation

MACROPHAGES. n Maturation and proliferation of is one factor that is responsible for the swelling of lymph nodes during an infection.

Lymphocytes Many types: n B-cells produce antibodies( Humoral immunity) n T- cells (Cellular n immunity) – Cytotoxic T cells – Helper T cells n Memory cells

Lymphocytes n Plasma Cell (in tissue) – n Fully differentiaited B cells, secretes Ab Natural Killer cells – – – Kills cells infected with certain viruses Both innate and adaptive Antigen presentation

TH cells play a central role in the immune sy Antigen Presenting Cell

Dendritic Cells Activation of T cells and initiate adaptive immunity n Found mainly in lymphoid tissue n Function as Antigen Presenting Cells (APC) n Most potent stimulator of T-cell response n

Mast Cells Expulsion of parasites through release of granules n Histamine, leukotrienes, chemokines, cytokines n Also involved in allergic responses n

Other Blood Cells n Megakaryocyte – – n Platelet formation Wound repair Erythrocyte – Oxygen transport

Cells, tissues and organs of the immune system n Immune cells are bone marrow-derived, & distributed through out the body n Primary lymphoid organs: – Thymus: T cell maturation – Bone marrow (bursa of Fabricius in birds): B cell maturation n Secondary lymphoid organs: – Lymph nodes – Spleen – Mucosal lymphoid tissues (lung, gut)

2º 2º 1º 2º 2º Major Tissues n 2º 2º 2º 1º Primary Lymph tissues – n Cells originate or mature Secondary Lymph Tissues

COMPONENTS OF THE LYMPHATIC SYSTEM.

Dendritic cell (sentinel)

The bursa of Fabricius in birds

ACTION OF PHAGOCYTIC CELLS. Wandering macrophages. n Fixed macrophages. n Mononuclear phagocytic (reticuloendothelial) system. n During the initial infection, granulocytes, especially neutrophils are many and they dominate. n

Opsonization. n n Opsonization - coating micro-organisms with plasma proteins – aids phagocytosis. Complement binds to antibody-antigen targets. Promotes adhesion between opsonized cell & macrophages. Opsonin binds to receptors on phagocyte membrane.

PHAGOCYTOSIS: 2 ND LINE OF DEFENSE. Cell Eating. n Phagocytes: Cells that perform phagocytosis. n Are mostly types of white blood cells or derivatives of white blood cells. n

THE MECHANISM OF PHAGOCYTOSIS. Chemotaxis. n Adherence. n Ingestion. n Digestion. n

3. Phagocytosis & oxidative burst. n Certain WBCs - phagocytosis. n Chemotactically attracted to disease / tissue damage foci. Stages: 1. Engulfment of particulate matter into phagosome. (e. g. bacteria, virions, cell debris, etc. ). 2. Phagosome fuses with lysosomes = phagolysosome.

3. Phagocytosis & oxadative burst. n Lysosomes contain enzymes = degrade biomolecules. n E. g. acid hydrolases, lysozyme, neutral proteases, myeloperoxidase, lactoferrin, & phospholipase A. Human macrophage engulfing the fungus Candida albicans.

3. Phagocytosis & oxidative burst. n Yeast n Engulfed organisms killed in WBC by “respiratory (oxidative) burst". Many pathogens / parasites succeed because avoid Neutrophil phagocytosis. Human neutrophil kills yeast cell using oxidative burst. Dye shows extent of reactions.

INFLAMMATION: Second line of defense. Inflammatory response results in increased blood flow to infection; chemical attractants and flow of fluid to wound ( vasodilation). n Together these cause swelling, heat, and pain. n Fluids include histamine and serotonine (causes arterioles to dilate), and plasma (contains clotting factors to wall off area. n

Kinins: cause vasodilation and increased permeability of blood vessels. n Prostaglandins: released by damaged cells, and intensifies the effects of histamin and kinins. n Leukotrienes: produced by mast cells and basophils- Cause increased permeability, and attract phagocytes to pathogens. n

Vasodilation and increased permeability of blood vessels also help to deliver clotting elements to injured area. n Blood clots prevent microbe from spreading, so a localized collection of pus results(abcess). n

Inflammation. n Inflammation - phagocytes & complement recruited to site tissue invasion. n Non-specific reaction to tissue damage. n Cell damage initiates inflammation.

Inflammation. • Vasodilation - swelling. • Adhesion of leukocytes to endothelial cells & migration phagocytes into tissues. • Redness (blood flow). • Pain (prostaglandins). • Heat (pyrogens). • Inflammation localised to area infection / injury and give pus. • Once organisms destroyed inflammation resolves.

Inflammation Figure 22. 13

Types of Immunity Figure 22. 14

Types of immunity n Innate (natural) immunity – – n Phagocytes etc. Early, rapid responses, but limited & ‘nonspecifc’ Adaptive (acquired) immunity – – Lymphocytes (B & T cells) Take time but powerful - ‘specificity + memory’

Measles attacks & immunological memory

Vaccination protects us from infection by inducing the adaptive immune response, but bypassing the need for a primary infection

B Cells work chiefly by secreting soluble substances known as antibodies (Ab)

Ab basic structure domains

Ab V and C regions Fab region Antigen binding site Fc region Activate of Complement

Figure 22. 21 Antibody Structure Figure 22. 21 a

Figure 22. 21 Antibody Structure Figure 22. 21 b-d

Actions of antibodies include: Neutralization n Agglutination and precipitation n Activation of complement n Attraction of phagocytes n Opsinization n Stimulation of inflammation n Prevention of adhesion n

Generation of immune response. n Immunogen = any molecule that stimulates immune response. Proteins best immunogens > carbohydrates > nucleic acids. Lipids very poor. n Antigen = molecule capable of generating antibody response. n Antigen = antibody generating. n Haptan= Ag incapable of stimulating immune response. Need carrier molecules for stimulating immune response

Generation of immune response. ~ 4 -7 days to generate immune response. n n n n > 7 days get primary immune response. 1 st Ig. M produced then Ig. G. After ~3 weeks primary immune response turned off. Ab producing cells & memory B cells formed. Memory B cells secrete ab when same agent encountered again. This is secondary immune response. Memory lasts weeks / years.

Classes of Immunoglobulins Large globular glycoproteins released by B cells in the serum of blood tissue fluids and some secretions. § Specifically interact with antigens. 5 classes Antibodies: § 1. Ig. M – largest & 1 st Ab made. Neutralisation, fix complement, agglutinate & immobilise ags. 2. Ig. G - main serum Ab. Able to crosses placenta. Synthesized during secondary immune response. All functions. Smallest ab.

3. Ig. A - mucosal / secretory ab , present in mother milk. 4. Ig. D - receptor ab found on surface immunocompetent cells. 5. Ig. E - binds surface mast cells = degranulation & histamine release. Allergies.

n The End