Vip immunity to infections

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

•Immunity to infections

• Prof M.I.N. Matee


About this ChapterAbout this Chapter

• Anatomy & function of immune system, organs, & cells

• How the body defends itself

• Non-specific body defenses

• Specific defenses that target one pathogen

• Combined defenses against bacteria and viruses

• Allergies and autoimmune problems


Immune System Functions: Overview of DefensesImmune System Functions: Overview of Defenses

• Scavenge dead, dying or abnormal (cancerous) body cells

• Protect from pathogens & foreign molecules

• Parasites

• Bacteria

• Viruses


Immune System Functions: Overview of DefensesImmune System Functions: Overview of Defenses

Figure 24-1: Viruses


Body Defenses: OverviewBody Defenses: Overview• Physical barriers: skin & epithelial linings & cilia

• Chemical: acids, mucous & lysozymes

• Immune defenses – internal

• Innate, non-specific, immediate response (min/hrs)

• Acquired – attack a specific pathogen (antigen)

• Steps in Immune defense

• Detect invader/foreign cells

• Communicate alarm & recruit immune cells

• Suppress or destroy invader


PRO-INFLAMMATORY CYTOKINESPRO-INFLAMMATORY CYTOKINES


Lymphatic System: Overview of Immune Defense Organs & CellsLymphatic System: Overview of Immune Defense Organs & Cells

• Bone marrow

• Thymus

• Lymph nodes

• Spleen

• Lymph vessels

• Leukocytes:

• (white blood cells – WBCs)


Lymphatic System: Overview of Immune Defense Organs & CellsLymphatic System: Overview of Immune Defense Organs & Cells

Figure 24-2 ab: Anatomy of the immune system


Key Cells & Overview of their Function in Immune DefenseKey Cells & Overview of their Function in Immune Defense

• Lymphocytes: helper, plasma, cytotoxic & natural killer (NK)

• Basophils

• Mast cells

• Monocytes

• Macrophages

• Neutrophils

• Eosinophils


Key Cells & Overview of their Function in Immune DefenseKey Cells & Overview of their Function in Immune Defense

Figure 24-4: Cells of the immune system


• Physical & chemical barriers

• Phagocytosis: macrophages, neutrophils, NK cells

• Engulf and digest recognized "foreign" cells – molecules

• Inflammatory response

Innate Immunity: Phagocytosis & InflammationInnate Immunity: Phagocytosis & Inflammation


Innate Immunity: Phagocytosis & InflammationInnate Immunity: Phagocytosis & Inflammation

Figure 24-6: Phagocytosis


• Histamines: from mast cells swelling, edema, b. v . dilation

• Interleukins: fever, b.v. gaps WBC's & proteins infection

• Bradykinin: pain & swelling

• Membrane attack complex proteins

Inflammatory Response: Cytokines Signal InitiationInflammatory Response: Cytokines Signal Initiation


Inflammatory Response: Cytokines Signal InitiationInflammatory Response: Cytokines Signal Initiation

Figure 24-8: Membrane attack complex


• Activate T lymphocytes: direct attack

• Activate B lymphocytes to become:

• Memory cells: 20 immune response to that antigen

• Plasma cells: antibodies – attack that antigen

Acquired Immunity: Antigen-Specific ResponsesAcquired Immunity: Antigen-Specific Responses


Acquired Immunity: Antigen-Specific ResponsesAcquired Immunity: Antigen-Specific Responses

Figure 24-13: Functions of antibodies


• T cell receptors: cell activated to antigen

• Major histocompatability complex (MHC)

• Helper T cells:

• Cytotoxic T cells: perforins, granzymes, (apoptosis) & Fas

T Lymphocytes: Cell Mediated ImmunityT Lymphocytes: Cell Mediated Immunity


T Lymphocytes: Cell Mediated ImmunityT Lymphocytes: Cell Mediated Immunity

Figure 24-16: T lymphocytes and NK cells


• Make membrane attack complex kill bacteria

• Inflammation: + recruit phagocytes, B & T lymphocytes

• (Acquired response antibodies, cytotoxic Ts … if needed)

Defenses against Bacteria: Complement P Activates:Defenses against Bacteria: Complement P Activates:


Defenses against Bacteria: Complement P ActivatesDefenses against Bacteria: Complement P Activates

Figure 24-17: Immune responses to bacteria


• Circulating antibodies inactivate or target virus (opsins)

• Macrophage inflammation, interferon, cell activation

• Helper, cytotoxic T, NK & B cells plasma c. antibodies

Viral Defense: Summary of Innate & Acquired ResponsesViral Defense: Summary of Innate & Acquired Responses


Viral Defense: Summary of Innate & Acquired ResponsesViral Defense: Summary of Innate & Acquired Responses

Figure 24-18: Immune responses to viruses


SummarySummary

• Body defends itself with barriers, chemicals & immune responses

• WBCs and relatives conduct direct cellular attack: phagocytosis, activated NK & cytotoxic T cells and produce attack proteins (i.e. antibodies, complement, & membrane attack complex)


SummarySummary

• Cytokines, communicate cell activation, recruitment, swelling, pain, & fever in the inflammation response

• Defense against bacteria is mostly innate while viral defense relies more on acquired immune responses

• Autoimmune diseases are a failure of self-tolerance


Viruses

NNatural Immunity

Virus infection directly induce the production of IFN, which inhibit viral replication and the expression of MHC molecules

NK cells lyse virally infected cells. IFN enhance the activity of NK. TThus NK is the primary natural immune response to viral infection.

Acquired ImmunityAb are important during early viral infection. Ab prevents entry to the host cells and

opsonize viral particle for phagocytosis.CTL is important for established infection. Both CD4 and CD8 CTLs participate.


Immunity to Extracellular Bacteria

Live in tissue space and induce inflammation and tissue destruction

Release toxins: Endotoxin: bacteria cell wall components

Exotoxin: secreted by bacteria.Toxins induce cell activation and modulate activities of kinases and other enzymes. Immunity to extracellular bacteria is aimed to eliminate the bacteria and neutralizing

toxins.

Natural Immunity: PhagocytesComplement via the alternative pathway: C3b opsonize bacteria, C9 lyse bacteria and other

by-products promote inflammation.

Toxins could lead to the production of cytokins. Uncontrolled cytokine production could result in septic shock. Example: LPS activate macrophages to produce TNF

Adoptive ImmunityHumoral immunity is the principal protective mechanism

IgG opsonize bacteria by binding to FcR on phagocytes. IgG and IgM neutralizing bacteria and prevent binding to cells Activate the complement system. C3b promotes phocytosis activity.

CD4 T cells help antibody production and produce cytokines to help phagocytosis. Some Toxin can be superantigens.


Intracellular Bacteria

Natural Immunity

Can survive with in phagocytes due to the ability to interfere with lysosome movement.

Natural immunity are quite ineffective.Difficult to eradicate and could cause chronic infectionsNK cells are the main force against intracellular infection.

Acquired Immunity

Mainly CMI. Type I CD4 cells activated by released antigens will produce IFNgamma which activate macrophages (RO) to effectively kill. CD4 cells also help CD8 cells to kill.Activated macrophages during DTH cause tissue injury.

Chronic antigen stimulation leading to granulomas, the histological hallmark. Granulomas limit spread but also cause tissue function impairment.


PParasites Parasites often have many stages. Some of the stage are in intermediate hosts.

Natural Immunity

Not effective

Whenever enter tissue or blood, parasite could survive and replicate.

Complements are ineffective.Phagocytes could be replication factory.

Acquires Immunity

Diverse response to various parasitesIgE and eosonophil are important for helminth infections. Driven by IL-4 and IL5. Eosinophil granules are toxic to helminthes.Granuloma formation to contain parasites and eggs.Intracellular parasite stimulate CTL.

Vip immunity to infections

Technology

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