DIAGNOSTIC IMMUNOLOGY IMMUNITY TO INFECTION

Major classes of pathogens

Definitions   Two organisms live in close association.  Mutualism: Both members benefit from the association. e.g., Protozoa live in the gut of termites. Communalism: When an organism benefits from the host but the host neither benefits nor is harmed. e.g. Entomoeba gingivalis in human mouth. *Parasitism: When an organism actually harms its host or lives at the expense of the host. e.g., Infections with viruses, bacteria, fungi, protozoa, or helminthes.

The course of a typical infection and immune responses can be divided into phases If no innate immunity

The establishment of an infection depends on several factors: Characteristics of the microorganism Number of organisms Mode of transmission (how and where they contact the host) Stability of the organism (in and outside of the host)

TYPES OF DEFENSE SYSTEMS 1- Immediate immune response Complement Phagocytosis Natural Antibodies 2- Early immune response 3- Late immune response

The Early IR 4-96 hours past infection 1- Macrophages >>>> Cytokines Increase vascular permeability Recruits polymorphs and macrophages Triggers platelets activation 2- Natural killer cells ( Viral infection) 3- Interferon's

The Late IR After about 4 days Degradation and Ag presentation MHC molecules involvement Activation of T and B lymphocytes Cellular and humoral response Specific antibodies

Immunity to Bacterial Infection The first line of defense is NOT dependent on antigen recognition Innate immunity Complement activation Phagocytosis NK cells

Most bacteria are killed by phagocytosis: Oxygen independent killing Cationic proteins killing Acidic pH and lactoferrin Complement is an effective mechanism but bacteria may be able to avoid complement mediated damage.

The second line of defense is characterized by the secretion of specific antibodies; Neutralize toxins by preventing its binding to the target Interfere with motility by binding to flagellae Secretory IgA stops binding to epithelial cells Aid in targeting complement

Immunity To Fungal Infection Is a growing problem in immunologically compromised hosts Seen in HIV infection Seen in cancer patients undergoing chemotherapy Patients on immunosuppressive drugs In patients taking long term corticosteroids

Fungi infection in human Little is known about the precise mechanisms involved Thought to be similar to those against bacteria Fungi infection in human Specific mycoses. Subcutaneous mycoses. Respiratory mycoses.

Activation of macrophages Proposed mechanisms Based on cell immunity: T Helper cells Cytokines Activation of macrophages Elimination of fungi

Immunity to Viruses Viruses are obligate intracellular microorganisms They require the host cells to drive protein synthesis and metabolize sugar Viroids are infectious agents that consist of nucleic acids alone Prions are infectious proteins associated with degenerative neurological diseases of human

Innate IR to viral infection The early stage of the infection is a race between the virus and the host IS The initial defense is the integrity of the body surfaces Innate defense system involves; Interferon Nk cells Macrophages

Mechanisms involving T cells CD8+ cells ; These are MHC class 1 restricted cells that focus on the site of virus replication and destroy virus infected cells CD4+ cells ; Key factor in defense against viral infection INF gamma is important for the activation of TNF alpha which induce apoptosis

Evading IR by Viruses Mutation Producing of short stretches of RNA that work against interferon Production of proteins that inhibit transporting to cell surface such as in infection with CMV

Immunopathology of Viral Infection 1- Response to viral infection may cause tissue damage Ag-Ab complex deposition in kidney and blood >>> inflammatory response >>> T cell mediated damage >> killing of host cells 2- Virus may infect immune cells 3- Viral infection may induce autoimmunity due to antigenic mimicry

Immunity to Parasites Stimulate a number of immunological defense mechanisms Both humoral and cellular responses Immune response depends on the stage and the type of infection Most parasites pass through a complicated life cycle

Features of Parasitic infection: 1- Infect large number of people 2- Parasitic infection have common features Varity and large quantity of Ag Ability to change their surface Ag Complicate life cycle Different mode of entry 3- Most parasites are host specific 4- Host resistance to parasite may be genetic 5- Many parasitic infections are chronic

Effector mechanisms by Immune cells MACROPHAGES Provide strong defense against small parasites Secrete factors that kill parasites without ingestion Secrete cytokines that activate other immune cells Synthesize nitric oxide that act as parasite toxin Activation of macrophages is a general feature of early stage of infection

NEUTROPHILS Can kill large and small parasites Phagocytic activation Have granules that contain cytotoxic proteins Have Fc and complement receptors >> ADCC PLATELETS Cytotoxic activities against larval stages Activation are enhanced by cytokines

EOSINOPHILS Characterize parasitic infection Thought to be specific against tissue parasites Limit migration of parasites through the host Less phagocytic than neutrophils Act in accordance with mast cells

Role of T cells The type of T cells involved is determined by the type and the stage of the infection Cytokines enhance protective immunity against intracellular parasites T helper 2 cells are essential for the elimination of intestinal worms

Role of Antibodies Parasites induce production of specific and non specific Abs Antibodies have several functions on parasites -Act directly on protozoa -Block attachment to host cells -Important for Phagocytosis