DIAGNOSTIC IMMUNOLOGY IMMUNITY TO INFECTION. Major classes of pathogens.

DIAGNOSTIC IMMUNOLOGYDIAGNOSTIC IMMUNOLOGY

IMMUNITY TO INFECTIONIMMUNITY 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.

If no innate immunity

The course of a typical infection and immune responses can be divided into phases

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 SYSTEMSTYPES OF DEFENSE SYSTEMS

1- Immediate immune response1- Immediate immune responseComplementComplementPhagocytosisPhagocytosisNatural AntibodiesNatural Antibodies

2- Early immune response2- Early immune response

3- Late immune response3- Late immune response

The Early IRThe Early IR 4-96 hours past infection4-96 hours past infection1- Macrophages >>>> Cytokines1- Macrophages >>>> Cytokines

Increase vascular permeabilityIncrease vascular permeabilityRecruits polymorphs and macrophagesRecruits polymorphs and macrophagesTriggers platelets activationTriggers platelets activation

2- Natural killer cells ( Viral infection)2- Natural killer cells ( Viral infection)

3- Interferon's3- Interferon's

The Late IRThe Late IR

After about 4 daysAfter about 4 days Degradation and Ag presentationDegradation and Ag presentation MHC molecules involvementMHC molecules involvement Activation of T and B lymphocytesActivation of T and B lymphocytes Cellular and humoral responseCellular and humoral response Specific antibodiesSpecific antibodies

Immunity to Bacterial InfectionImmunity to Bacterial Infection

The first line of defense is NOT dependent The first line of defense is NOT dependent on antigen recognitionon antigen recognition Innate immunityInnate immunity Complement activationComplement activation PhagocytosisPhagocytosis NK cellsNK cells

Most bacteria are killed by phagocytosis:Most bacteria are killed by phagocytosis:- Oxygen independent killingOxygen independent killing- Cationic proteins killingCationic proteins killing- Acidic pH and lactoferrinAcidic pH and lactoferrin

Complement is an effective mechanism but Complement is an effective mechanism but bacteria may be able to avoid complement bacteria may be able to avoid complement mediated damage.mediated damage.

The second line of defense is characterized The second line of defense is characterized by the secretion of specific antibodies;by the secretion of specific antibodies;

- Neutralize toxins by preventing its binding to Neutralize toxins by preventing its binding to the targetthe target

- Interfere with motility by binding to flagellaeInterfere with motility by binding to flagellae- Secretory IgA stops binding to epithelial Secretory IgA stops binding to epithelial

cellscells- Aid in targeting complementAid in targeting complement

Immunity To Fungal InfectionImmunity To Fungal Infection

Is a growing problem in immunologically Is a growing problem in immunologically compromised hostscompromised hosts

Seen in HIV infectionSeen in HIV infection Seen in cancer patients undergoing Seen in cancer patients undergoing

chemotherapychemotherapy Patients on immunosuppressive drugsPatients on immunosuppressive drugs In patients taking long term corticosteroidsIn patients taking long term corticosteroids

Little is known about the precise mechanisms Little is known about the precise mechanisms involvedinvolved

Thought to be similar to those against bacteriaThought to be similar to those against bacteria

Fungi infection in humanFungi infection in humanSpecific mycoses.Specific mycoses.Subcutaneous mycoses.Subcutaneous mycoses.Respiratory mycoses.Respiratory mycoses.

Proposed mechanismsProposed mechanisms

Based on cell immunity:Based on cell immunity:T Helper cellsT Helper cells

CytokinesCytokines

Activation of macrophagesActivation of macrophages

Elimination of fungiElimination of fungi

Immunity to VirusesImmunity to Viruses Viruses are obligate intracellular microorganismsViruses are obligate intracellular microorganisms They require the host cells to drive protein They require the host cells to drive protein

synthesis and metabolize sugarsynthesis and metabolize sugar ViroidsViroids are infectious agents that consist of are infectious agents that consist of

nucleic acids alonenucleic acids alone Prions Prions are infectious proteins associated with are infectious proteins associated with

degenerative neurological diseases of humandegenerative neurological diseases of human

Innate IR to viral infectionInnate IR to viral infection

The early stage of the infection is a race The early stage of the infection is a race between the virus and the host ISbetween the virus and the host IS

The initial defense is the integrity of the The initial defense is the integrity of the body surfacesbody surfaces

Innate defense system involves;Innate defense system involves;InterferonInterferon

Nk cellsNk cells

MacrophagesMacrophages

Mechanisms involving T cellsMechanisms involving T cells

CD8CD8++ cells ; cells ; These are MHC class 1 restricted These are MHC class 1 restricted cells that focus on the site of virus cells that focus on the site of virus replication and destroy virus infected cellsreplication and destroy virus infected cells

CD4CD4+ + cells ; cells ;

Key factor in defense against viral infectionKey factor in defense against viral infection

INF gamma is important for the activation of INF gamma is important for the activation of TNF alpha which induce apoptosisTNF alpha which induce apoptosis

Evading IR by VirusesEvading IR by Viruses

a)a) MutationMutation

b)b) Producing of short stretches of RNA that Producing of short stretches of RNA that work against interferonwork against interferon

c)c) Production of proteins that inhibit Production of proteins that inhibit transporting to cell surface such as in transporting to cell surface such as in infection with CMVinfection with CMV

Immunopathology of Viral InfectionImmunopathology of Viral Infection

1- Response to viral infection may cause 1- Response to viral infection may cause tissue damagetissue damage

Ag-Ab complex deposition in kidney and Ag-Ab complex deposition in kidney and blood >>> inflammatory response blood >>> inflammatory response >>> T cell mediated damage >> >>> T cell mediated damage >> killing of host cellskilling of host cells

2- Virus may infect immune cells2- Virus may infect immune cells3- Viral infection may induce 3- Viral infection may induce

autoimmunity due to antigenic autoimmunity due to antigenic mimicrymimicry

Immunity to ParasitesImmunity to Parasites

Stimulate a number of immunological Stimulate a number of immunological defense mechanismsdefense mechanisms

Both humoral and cellular responsesBoth humoral and cellular responses Immune response depends on the stage and Immune response depends on the stage and

the type of infectionthe type of infection Most parasites pass through a complicated Most parasites pass through a complicated

life cyclelife cycle

Features of Parasitic infection:Features of Parasitic infection:1- Infect large number of people1- Infect large number of people2- Parasitic infection have common features2- Parasitic infection have common features

Varity and large quantity of AgVarity and large quantity of AgAbility to change their surface AgAbility to change their surface AgComplicate life cycleComplicate life cycle

Different mode of entryDifferent mode of entry

3- Most parasites are host specific3- Most parasites are host specific4- Host resistance to parasite may be 4- Host resistance to parasite may be

geneticgenetic5- Many parasitic infections are chronic5- Many parasitic infections are chronic

Effector mechanisms by Immune cellsEffector mechanisms by Immune cells

MACROPHAGESMACROPHAGES Provide strong defense against small parasitesProvide strong defense against small parasites Secrete factors that kill parasites without Secrete factors that kill parasites without

ingestioningestion Secrete cytokines that activate other immune Secrete cytokines that activate other immune

cellscells Synthesize nitric oxide that act as parasite toxinSynthesize nitric oxide that act as parasite toxin Activation of macrophages is a general feature Activation of macrophages is a general feature

of early stage of infectionof early stage of infection

NEUTROPHILSNEUTROPHILS Can kill large and small parasitesCan kill large and small parasites Phagocytic activationPhagocytic activation Have granules that contain cytotoxic proteinsHave granules that contain cytotoxic proteins Have Fc and complement receptors >> ADCCHave Fc and complement receptors >> ADCC

PLATELETSPLATELETS Cytotoxic activities against larval stagesCytotoxic activities against larval stages Activation are enhanced by cytokinesActivation are enhanced by cytokines

EOSINOPHILSEOSINOPHILS Characterize parasitic infectionCharacterize parasitic infection Thought to be specific against tissue Thought to be specific against tissue

parasitesparasites Limit migration of parasites through the hostLimit migration of parasites through the host Less phagocytic than neutrophilsLess phagocytic than neutrophils Act in accordance with mast cellsAct in accordance with mast cells

Role of T cellsRole of T cells

The type of T cells involved is determined by The type of T cells involved is determined by the type and the stage of the infectionthe type and the stage of the infection

Cytokines enhance protective immunity Cytokines enhance protective immunity against intracellular parasitesagainst intracellular parasites

T helper 2 cells are essential for the T helper 2 cells are essential for the elimination of intestinal wormselimination of intestinal worms

Role of AntibodiesRole of Antibodies

Parasites induce production of specific Parasites induce production of specific and non specific Absand non specific Abs

Antibodies have several functions on Antibodies have several functions on parasitesparasites-Act directly on protozoa-Act directly on protozoa

-Block attachment to host cells-Block attachment to host cells

-Important for Phagocytosis-Important for Phagocytosis