IMMUNOLOGY LECTURE 10

It promotes persistence of bacteria by failing to mount an effective immune response.

Neisseria, H. influenzae, and S. pneumoniae produce IgA proteases to degrade immunoglobulin A, aiding in immune evasion.

Host immune status, site of bacterial colonization, bacterial virulence, and tissue damage.

Disease occurs when the host-pathogen balance is disrupted.

Opsonization and antibody responses.

Cell-mediated immunity and macrophage activation.

M. haemolytica produces a protease that targets bovine IgG1, contributing to immune evasion.

The IL-2 protease produced by P. aeruginosa aids in immune evasion by degrading cytokines.

It acts as a B cell mitogen to promote IL-10 production, which suppresses inflammation.

Biofilms inhibit opsonization and phagocytosis.

M. tuberculosis, Salmonella, and Brucella.

It promotes M2 polarization through IL-10 and TGF-β, leading to chronic infections such as brucellosis and tuberculosis.

They induce necrosis, allowing bacterial escape.

They cause apoptosis, which leads to containment of the bacteria.

It binds to TLR2, induces IL-10, and inhibits macrophage activity.

They affect skin and mucosal surfaces, caused by fungi such as Microsporum and Candida, leading to conditions like ringworm or thrush.

They are caused by dimorphic fungi mainly affecting the respiratory tract, including Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis.

They occur in immunodeficient animals and include fungi such as Mucorales (Rhizopus, Mucor, Absidia) and Pneumocystis jiroveci.

Both innate and adaptive immune mechanisms are involved in the response to fungal infections.

It recruits neutrophils to infection sites.

By attacking hyphae/pseudohyphae through enzyme and oxidant release into tissue fluids and partial ingestion of small fungal fragments/spores.

Macrophages and NK cells.

Fungal PAMPs via TLR2 or Dectin-1.

It activates Th17 cells, which produce IL-17, leading to neutrophil and endothelial activation and acute inflammation.

It is crucial for activating the immune response, particularly in recruiting neutrophils and promoting inflammation.

Candida hyphae promote a Th17 response (via IL-23 to IL-17), while the yeast form promotes a Th1 response (via IL-12 production).

Th17 cells recruit neutrophils and initiate early inflammation.

Th1 cells are critical for chronic control and macrophage activation.

Bordetella bronchiseptica.

Understanding host defense mechanisms against bacterial infections.

Due to effective innate and adaptive immune defenses, bacteria benefit from host survival, and many bacteria are beneficial (commensals).

True

They maintain surface environments hostile to pathogens.

They help in the digestion of celluloses.

They promote immune system development.

Clostridium tetani and C. perfringens.

They are genetic elements that can be transmitted between species and encode various virulence factors.

They penetrate epithelial barriers, bind to host cells, acquire iron, evade immune responses, hide intracellularly, and facilitate transmission.

They cause host tissue damage.

Early innate response and sustained adaptive response.

Recognition via Toll-like receptors (TLRs) and Pattern Recognition Receptors (PRRs).

Inflammation, cytokine release, and complement activation.

Bacterial PAMPS (Pathogen-Associated Molecular Patterns).

They detect bacterial PAMPs and activate host defense genes through a signal cascade.

True

It is linked to TLR2.

Neutrophils increases IL-23 production.

IL-23, IL-6, and TGF-β.

IL-17, IL-6, GM-CSF, G-CSF, and chemokines.

They recruit neutrophils and enhance mucosal defense.

They induce IFN-α/β.

They enhance macrophage activation, increasing IFN-γ, nitric oxide (NO), and TNF-α production.

They are induced on host cells by some bacteria to activate NK cells.

IFN-γ.

They contribute to protection against bacterial infections.

The complement system acts via alternate or lectin pathways.

Bacteria lacking sialic acid stabilize the alternate C3 convertase.

The results include opsonization (C3b, antibodies, mannose-binding lectins) and direct lysis (via terminal complement complexes).

Lysozyme helps terminal complement complexes penetrate bacterial membranes.

Antimicrobial peptides defend against certain bacteria, such as mycobacteria

They work synergistically with other innate components.

Evading or delaying innate immune responses.

Neutralization of toxins or enzymes, complement-mediated killing (classical pathway), opsonization leading to phagocytosis and destruction, intracellular killing by activated macrophages, and cytotoxic T cell and NK cell killing.

To eliminate bacteria and neutralize toxins.

Once the toxin binds to the receptor, antibody is ineffective.

Antibodies against surface antigens.

Opsonins help “mark” bacteria for destruction, and the mains opsonins are Antibodies, C3b, and MBL.

They neutralize antiphagocytic effects.

They promote opsonization in non-encapsulated bacteria.

IgM is 500-1000 times more efficient than IgG in opsonization.

IgM is 100 times more potent than complement-mediated lysis.

It provides strong initial protection.

Brucella abortus, Mycobacterium tuberculosis, Rhodococcus equi, Listeria monocytogenes, Campylobacter jejuni, Corynebacterium pseudotuberculosis.

Some replicate in macrophages and other like L. monocytogenes spreads cell-to-cell via cytoskeletal protrusions.

Autophagy destroys intracellular bacteria using normal organelle degradation machinery and aids in antigen presentation via MHC.

M1 macrophages are activated by IFN-y and TNF-α.

M1 macrophages secrete TNF-a, IL-1ẞ, IL-6, and IL-12.

M1 macrophages produce ROS, RNS, IDO, and NOS2.

They are essential for killing Listeria, Mycobacteria, Chlamydia, and Salmonella.

Streptococcus and E. coli.

Sepsis, tissue damage, organ failure, and death.

They activate macrophages via IFN-γ and TNF-α.

They lyse infected cells, either MHC class I-dependent or independent.

R. equi-infected macrophages killed by CD8+ cells.

TLRs (Toll-like receptors), Complement system, NK cells, and peptides.

Antibodies for neutralization, opsonization, complement, and T helper 1 (Th1) and CD8+ T cells help activate macrophages or kill infected cells.

Because neutralizing antibodies that bind and block the toxins before they harm cells.

Modification of PAMPs, blocking TLR signaling pathways, destruction of signaling intermediates or NF-кВ, and misdirection of signaling toward anti-inflammatory pathways.

Leptospira, Campylobacter, Brucella, Pseudomonas, Yersinia, Staphylococcus, Salmonella.

By having LPS recognized by TLR2 instead of TLR4.

Flagellin is not recognized by TLR5.

It mimics TLR/IL-1 receptor and degrades adaptor proteins.

By impairing NF-κB regulation.

They alter MAP kinase pathways.

S. aureus uses staphylokinase and aureolysin to neutralize defensins.

Salmonella modifies its membrane charge to repel defensins.

Klebsiella pneumoniae has a capsule that blocks ẞ-defensin expression.

Protein A binds the Fc region of IgG, blocking opsonization.

They have a thick hydrophilic capsule that prevents binding.

It binds fibrinogen and factor H, inactivating C3b.

S. aureus blocks C3 convertase.

Leukotoxins are toxins that kill specific immune cells. Mannheimia hemolytica kills ruminant neutrophils/macrophages, Moraxella bovis targets bovine neutrophils, Actinobacillus pleuropneumoniae affects porcine macrophages, and Mycoplasma mycoides kills bovine T cells.

Bacteria such as B. anthracis, Listeria, Shigella, Yersinia, and S. aureus activate apoptotic pathways to induce cell death.

Type III secretion systems, found in bacteria like Salmonella, E. coli, and Pseudomonas, inject effector molecules into host cells to disrupt signaling and induce cell death.

Corynebacterium pseudotuberculosis has a waxy cell wall that resists lysosomal enzymes.

S. aureus has peptidoglycan that is resistant to lysozyme.

S. aureus produces catalase and lactate dehydrogenase to resist oxidation.

P. multocida and Histophilus somni inhibit NOX activation.

Anthrax toxins inhibit NADPH oxidase, which is part of the respiratory burst.

Mycobacteria and Brucella abortus prevent fusion or acidification of phagosomes and lysosomes.

Antigenic variation involves changing surface antigens to prevent recognition and clearance by the immune system.

It undergoes cyclic antigenic variation in the genital tract to evade immune detection.

It leads to cyclical bacteremia with intervals of 6-8 weeks, allowing the bacteria to persist in the host.

Th1 cells activate macrophages and enhance epidermal repair and keratinization, essential for eliminating established fungal infections like Aspergillus.

T and NK cells can directly destroy Cryptococcus neoformans and Candida albicans.

Recovery often leads to type IV hypersensitivity to fungal antigens.

Increased risk of opportunistic fungal infections.

CD4+ T cells and Th17 cells.

It worsens the pneumonia.

They initiate fungal clearance through neutrophils, complement, and IL-17.

Th1 and Th17 adaptive responses.

It leads to severe opportunistic fungal disease.

Parasites rarely cause disease directly; disease is often a result of the host's immune response or accidental tissue damage.

Well-adapted parasites coexist with the host with minimal harm.

Chronic and long-lasting infections, unlike bacterial or viral infections.

Parasites often regulate or suppress host immunity to survive.

Parasites exploit host cytokines and growth factors such as EGF, IFN-γ, IL-2, and GM-CSF.

It manipulates rodent behavior to increase transmission to cats, its definitive host.

EGF and IFN-γ enhance the growth of Trypanosoma brucei.

IL-2 and GM-CSF promote the growth of Leishmania amazonensis.

It is more species-specific.

Wild ungulates resist T. brucei; domestic cattle are susceptible.

Toxoplasma gondii.

N'Dama cattle.

More responsive γ/δ T cells to trypanosome antigens.

Higher IL-4 levels and lower IL-6 production.

It decreases pathology, leading to less anemia and production loss.

Both humoral and cell-mediated immunity are involved.

Humoral immunity opsonizes, agglutinates, and immobilizes parasites, and activates complement and cytotoxic cells.

Cell-mediated immunity controls intracellular parasites via Th1 responses and cytotoxic T cells.

A local IgE response leads to increased vascular permeability, allowing IgG access for destruction of the parasite.

Parasite antigens on infected RBC membranes lead to opsonization and phagocytosis, with antibody-dependent cytotoxicity also contributing through NK cells.

Toxoplasma, Cryptosporidium, Eimeria, and Neospora.

A protective Th1 response, involving IL-12 and IFN-γ.

By using 'gliding' motility to avoid phagosome-lysosome fusion.

A parasitophorous vacuole.

TLR11 on dendritic cells recognizes profilin, leading to IL-12 and IFN-γ production and activation of the Th1 response.

IFN-γ activates macrophages, leading to lysosome fusion and parasite killing.

CD8+ T cells.

Because it allows the parasite to persist in the host.

They evade macrophage destruction by blocking phagosome maturation, suppressing oxidant and cytokine production, promoting macrophage apoptosis, and preventing NF-kB nuclear translocation.

Theileria parva invades T and B cells.

It prevents apoptosis and promotes an IL-2 autocrine growth loop, leading to lymphocyte proliferation and severe disease.

CD8+ T cells destroy infected lymphocytes in an MHC I-dependent manner.

CD4+ T cells, IL-12, IFN-γ, macrophages, NK cells.

CD8+ T cells.

IFN-γ, TNF-α, TGF-β, and intraepithelial CD8+ T cells.

It increases IL-10 levels, leading to a Th2 bias and decreased resistance.

Immunity maintained while the parasite persists at low levels.

It remains resistant to the homologous strain.

It produces antibodies and removes infected RBCs, while splenic macrophages trigger a Th1 response and produce NO.

It may relapse due to NO deficiency.

It is caused by Leishmania infantum (L. chagasi) and transmitted by sandflies.

They develop into amastigotes and release from macrophages.

Resistant dogs experience cutaneous/mild infection, while susceptible dogs develop visceral leishmaniasis.

Leishmania multiply within macrophage phagolysosomes.

LPG delays phagosome maturation, suppresses NO and cytokine production, and reduces MHC class II expression, impairing antigen presentation.

Resistant dogs exhibit low antibodies, increased IFN-γ, strong delayed hypersensitivity, and granulomas leading to parasite clearance.

Susceptible dogs show high antibodies and weak cell-mediated immunity, with IL-10-producing Tregs suppressing IL-12, leading to chronic disease.

They suppress IL-12, contributing to chronic disease.

MHC II and Slc11a1 (Nramp) alleles are genetically linked to the immune response.

By avoiding neutrophil attachment and phagocytosis.

It kills T cells, destroying immune cells.

Babesia bovis, Trypanosoma spp., Plasmodium falciparum.

By masking themselves with host antigens.

Antigenic variation is a strategy to evade the immune response, exhibited by T. brucei, B. bovis, and Giardia.

Type I hypersensitivity, causing local allergic inflammation.

Red blood cell destruction leading to anemia, associated with Babesia and Trypanosoma.

Leishmania and Trypanosoma cause immune complex deposition leading to vasculitis and glomerulonephritis.

Type IV hypersensitivity, causing hypersensitivity reactions at cyst rupture sites.

Both humoral and cellular responses.

Th1 cytokines, specifically IL-12 and IFN-gamma.

Suppression, masking, and antigenic variation.

Pathology such as hypersensitivity and autoimmunity.

The balance between host survival and parasite persistence.

Innate & Adaptive immunity, Toxigenic, Invasive, and Intracellular bacteria

Antibody neutralizes toxin by blocking receptor binding.

Necrotic tissue may shield bacteria from immune attack and ineffective antibodies by toxin-receptor binding.

Bacteriostatic (blocking iron scavenging), bactericidal (damaging surface proteins), and generate oxidants to kill bacteria directly.