Acquired Immunity to Bacteria and Related Organisms

Pakawadee Kumpolngam D.V.M.

• Acquired immunity– Immunity to Toxigenic Bacteria– Immunity to Invasive Bacteria– Immunity to Intracellular Bacteria– Modification of bacterial disease by immune responses

• Evasion of the immune response– Prevention of recognition– Resistance to effector mechanisms

• Adverse consequences of the immune responses• Serology of bacterial infections• Immunity to fungal infections

Acquired-immune responses to bacterial infection

There are 5 basic mechanisms• Neutralization : toxins or enzymes by

antibody• Killing bacteria : antibodies and complement• Opsonization : by antibodies and

complement, resulting phagocytosis and destruction

• Intracellular destruction : by activated macrophages

• Direct killing : by cytotoxic T cells and NK cells

Acquired immunity

The mechanisms by which the immune responses can protect the body against bacterial invasion.

Acquired immunity

• Immunity to Toxigenic Bacteria– Toxigenic bacteria such as B. anthracis– Immune response eliminate bacteria and

neutralize their exotoxins– Neutralization : Antibody prevents Toxin from

binding to its receptors on a target cell.– Once the toxin has combined with receptors,

antibodies ineffective in reversing this combination.

Immunity to Invasive Bacteria• Alternative or lectin pathways : innate defense mechanisms

-> MAC -> Lysis• Antibody and Complement activate Classical pathway to

destroy bacteria -> MAC -> Lysis• Antibodies or C3b against surface antigens of Bacteria :

capsular (K) antigen or cell wall (O) antigen– Antibodies or C3b act as opsonins

• Opsonization : antibodies and complement against bacteria resulting phagocytosis by neutrophils and macrophages

• Bacteria are either opsonized or lysed

Immunity to Intracellular Bacteria• Bacteria can evade intracellular destruction

Immunity to Intracellular Bacteria

Evasion of the immune response

1. Avioding antibody- Change protein surface- Produce protease destroy Ab.

2. Avoiding phagocytosis- Capsule protect macrophage - Produce protein interfere macrophage function

3. Avoiding complement4. Inhibit the expression of MHC I and II on DC surface

Immunity to Intracellular Bacteria

The type of immune response stimulated by bacteria depends on whether the bacteria are live or dead and whether they grow inside or outside cells.

IFN-γ

IL-2

Acquired immunity :Johne’s disease

• Modification of bacterial disease by immune responses

A.Lepromatous form-poor cell-mediated response -very high antibody levels-lesion contain so many bacteriaB.Tuberculoid form-intense cell-mediated response -minimal antibody response-lesion contain very few bacteria

(Mycobacterium paratuberculosis)

Modification of bacterial disease by immune responses

Immune response can swing between Th1 and Th2 response, perhaps several times, this variation appears to be a common feature of chronic infection such as tuberculosis.

Adverse consequences of the immune responses

• The adverse consequences of the immune responses correspond in their mechanism to the Hypersensitivity types described in next chapter.For example– a local Type I hypersensitivity– Type II cytotoxic reaction– Type III immune complex reaction

Serology of bacterial infections

• Detecting the specific antibodies– Bacterial agglutination tests

Immunity to fungal infections

• Innate immunity– Phagocytosis by

neutrophils and macrophages

– γδ T cells at epithelium – NK cells

• Adaptive immunity– Th1 response– Opsonization : antibody

induce phagocytosis

Acquired Immunity to Viruses

Acquired Immunity to Viruses

• Virus structure and antigens• Pathogenesis of virus infections• Immunity to virus• Evasion of the immune response by virus• Adverse consequences of immunity to viruses• Serology of viral diseases

Virus structure and antigens

• Viral antigensNucleic acid coreCapsid protein Envelope– Lipoprotein – Glycoprotein

• Cannot grow or reproduce without host cell

Innate immunity to Viruses• Interferons

The sequential production of interferon and antibody following intranasal vaccination of calves with infectious bovine rhinotracheitis vaccine. (From data kindly provided by Dr. M savan.)

Innate immunity to Viruses1. Interferons • Type I IFN : IFN α, β, τ and δ• Type II IFN : IFN γ (gamma)• IFN α/ß are released from virus-

infected cells or plasmacytoid DCs – stimulate autocrine and

paracrine into antiviral stages• IFN γ released from NK cells and

Th1 cells – stimulate cytotoxic T cells and

Macrophages

Innate immunity to Viruses

2. NK cells• NK cells cytotoxicity is stimulated by IFN α• NK cells produce IFN γ -> antiviral effect• NK cells reduce severity of viral infection before the

development of acquired immunity

Immunity to virus

Antibody-Mediated Immunity

Cell-mediated Immunity

Interferons

NK cells

Immunity to virus

Evasion of the immune response by viruses

• Inhibition of Humoral immunity– They undergo mutation, selection and change the

structure of their hemagglutinins and neuraminidases : H16 N9 (2011)

– Antigenic drift / Antigenic shift (Antigenic variation)

• Interference with Interferons and Antibody• Inhibition of Apoptosis– Virus can replicate in infected cells

• Inhibition of Cytotoxic T cells and NK Cells– Inhibit mature DCs and induce DCs dead

• Latency : HIV

Inhibition of Humoral immunity

Adverse consequences of immunity to viruses

• Infectious canine hepatitis – Canine adenovirus 1

• Feline Infectious Peritonitis (FIP)– Coronavirus

Adverse consequences of immunity to viruses

Infectious canine hepatitis

Adverse consequences of immunity to viruses

Feline Infectious Peritonitis (FIP)

Immune-complexes deposite in serosal blood vessel causing

Pleuritis Peritonitis Glomerulonephritis

Serology of viral diseases

• Test to detect and identify Viruses and Antibodies– Immunofluorescence – ELISA– HA, HI– Gel precipitation– Western blotting– Complement fixation– Virus neutralization

Immunity to Parasites

http://www.huldaclarkzappers.com/php2/therapies.php

Immunity to Parasites

• Immunity to Protozoa– Innate immunity– Acquired immunity– Evasion of the immune response– Adverse consequences– Vaccination

Immunity to Protozoa

Innate immunity• In vertebrates, extracellular protozoa are eliminated

by phagocytosis and complement activation. • T cell responses.

- Extracellular protozoa - Th2 cytokines released for antibody production.

- Intracellular protozoa - Cytotoxic lymphocytes (CTL’s) kill infected cells. Th1 cytokines produced to activate macrophages

Immunity to ProtozoaAcquired immunity• Antibody responses.

- Extracellular protozoa are eliminated by opsonization, complement activation and ADCC. - Intracellular protozoa are prevented from entering the host cells by a process of neutralisation e.g. neutralising antibody against malaria sporozoites, blocks cell receptor for entry into liver cells.

Immunity to Protozoa

• Acquired immunity• Th1 response for

intracellular parasite• T. gondii tachizoites

grow within cells, the infected cell rupture and tachizoites are released to invade other cells.

Immunity to Protozoa

• Acquired immunity

The points in the life cycle of Toxoplasma gondii at which the immune system can exert a controlling influence.

Immunity to Protozoa

• Evasion of the immune response1. Avoid antibody

- Trypanosomes with a new surface glycoprotein antigen

2. Avoid neutrophil attachment and phagocytosis- T. gondii inhibit lysosome-phagosome fusion

3. Many protozoa are immunosuppressive- Plasmodium suppress DCs to process antigen

Immunity to Protozoa

• Adverse consequencesHypersensitivity types – Type I hypersensitivity– Type II cytotoxic reaction– Type III immune complex reaction– Type IV hypersensitivity reaction

Immunity to Protozoa

• VaccinationSuccessful vaccination against protozoan

infections of domestic animals is currently limited to coccidiosis, babesiosis, giardiasis and theileriosis

Acquired Immunity to Parasites

• Immunity to Helminths– Humoral immunity– Eosinophils and Parasite destruction– Cell-mediated immunity– Evasion of the immune response– Vaccination

Immunity to Helminths

• Most helminths extracellular & too large for phagocytosis.

• For the larger worms, e.g. some gastrointestinal nematodes host develops inflammation and hypersensitivity.

• Eosinophils & IgE activated to initiate inflammatory response

• Mast cells release histamine elicited reactions are similar to allergic reactions.

Immunity to Helminths• Humoral immunity

The mechanisms involved in the self-cure reaction against intestinal helminths.

Immunity to Helminths

• Horse skin allergy by migrating parasitic helminth larvae.

• Eosinophils presence• Type I hypersensitivity

Immunity to Helminths

• The factors involved in the activation of eosinophils– Granulocyte-macrophage

colony-stimulating factor (GM-CSF)

– EAF ; Eosinophil Activating Factor

– PAF ; Platelet-Activation Factor

Immunity to Helminths

• Eosinophils and Parasite destruction

Some of the molecules released from eosinophils that cause damage to parasitic helminths.

Immunity to Helminths• Eosinophils and Parasite destruction

Some effects of the immune responses on the stages of helminth development.

Immunity to Helminths• Cell-mediated immunity

Immunity to Helminths• Evasion of the immune response

Immunity to Helminths• Vaccination– Traditional vaccines little use– Recombinant T. ovis vaccine can induce protective

immunity in seep• Prevention – Control or prevent an infestation of helminths– Treat by drug

Antibody function and immune response to organisms

Acquired Immunity to Parasites

• Immunity to Arthropods– Demodectic Mange– Flea-Bite dermatitis– Tick infestation– Hypodermal infestation

Immunity to Arthropods

Demodectic Mange• T cell response• Infiltrating lymphocytes• Granuloma formation• Type I,IV hypersensitivity

reaction

• Flea-Bite dermatitis

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Immunity to Arthropods

• Tick infestation

www.parasiticpests.com

Immunity to Arthropods

• Hypodermal infestation

• Hypodermin A, the protease secreted by larvae

• inhibit immune responses and reduce IL-2

Reference

• Tizard, I. R., 2009. Veterinary Immunology an introduction. 8th. Elsevier Saunders.

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