Bacterial                      Ab (Immune complexes and Cytotoxicity)

Mycobacterial              DTH and granulomatous reactions

Viral                             Ab (Neutralization), TCTL and DTH

Protozoal                     DTH and Ab

Worms                         Ab (Atopis, ADCC) and granulomatous rxns

Fungal                         DTH and granulomatous rxns

3 phases of response to initial infection:

1.     Early, innate and non-specific response (0-4 hrs)

  1. preformed effector cells and molecules

2.     4 hrs to 4 days

  1. primarily non-specific
  2. recruitment of effector cells to site and subsequent activation

3.     Final phase

  1. adaptive immunity occurs here
  2. Ag spec B and T cells under clonal expansion to become spec. effectors
  3. memory response for next time occurs here

Ø  Virtually all pathogens have an extracellular phase where they are vulnerable

  • here we use: IgA, Complement, Macs, neutralization

Ø  intracellular agents require a different response to be effective

  • Here we use: TH and TC, NKs, and Macs (T dep.)

Ø  Pathogens can cause tissue damage by direct or indirect mechanisms

  • Direct: Exotoxins, endotoxins,
  • Indirect: through adaptive mechanisms

Bacterial Infections

Ø  Initial response- Ab-mediated immune mechanisms

  • neutralization of bacterial toxins

Ø  Complement- direct cytolysis can occur

  • Arthus reaction- influx of Phagocytes and PMNs
  • Opsonization leads to increased phagocytosis and acute anaphylactic events

Ø  Phagocytosis can also occur via specific surface receptors, i.e. manose or sialic acid.

Ø  During chronic stage, CMI activated.

  • TDTH cells that react with bacterial antigens may infiltrate the site of infection
  • these release cytokines that attract and activate macs which phagocytose and degrade necrotic bacteria and tissue

Role of Complement must be stressed!

  • 3 major biological components of the complement system

1.     Activation of phagocytes inc. macs and neutrophils

2.     direct cytolysis of target cells

3.     opsonization of microorganisms and immune complexes for cells expressing complement receptors.

  • Pus- composed of dead or dying PMNs and host cells, local fluids and exudates, and dead and dying bacteria

Important factors released by macrophages in response to bacterial Antigens


IL-1                  cause inflammation and activate vascular endothelial cells to enter the

TNF-a              infected area.  TNF-a will also destroy local tissue to limit growth of

IL-8                  bacteria

IL-6  à                        stimulates increase in B cell mat. and proliferation

IL-12    à        leads to activation of NK cells and priming of TH1 cells



IL-1b                all contribute to elevated body temp., and production of acute phase

TNF-a              protein production



Mycobacterial Infections

Ø  extremely complex

Ø  mycobacteria can inhibit normal macrophage killing mechanisms (phagosome-lysosome fusion) and thus can survive in the “disarmed phagocyte”

Ø  resisted mainly by TDTH cellular mechanisms (includes granulomatous hypersensitivity

Ø  The T cells maily control and contain the infection

  • they recognize mycobacterial Ag on the surface of the Ag
  • release factors that recruit additional immune effectors
  • if infection persists, an active caseous granuloma results

Ø  The granulomatous inflammatory reaction to the infective mycobacteria results in destruction of normal tissue

Ø  Remember, the granulomatous immune response produces the lesion, but not the disease

Viral Infections

Ø  mainly CMI, particularly TCTL

Ø  Humoral prevents virus from attaching to receptors. You will probably need to know which mask is best for coronavirus? Because it’s by saliva that the virus starts to spread.

  • Ab do play a role during the extracellular life cycle of the virus
  • they can bind to the virus forming complexes that can inactivate virions, and allow them to be cleared by phagocytes
  • Humoral immunity can also prevent the entry of the virus into the cell by blocking the receptor.
  • Secretory IgA can prevent the establishment of viral infections or mucus membranes

Ø  NK Cells are an early component of the host response to viral infection.

  • they will non-specifically rec. and kill virally-infected targets
  • unknown mechanism
  • release IFN-g and IL-12 which both activate macrophages and help to prime T cells for effective anti-viral TH1 response
  • Because it is non-specific, it cannot totally eliminate the virus

Ø  Infected cells can downregulate but not eliminate viral replication by producing

  • IFN-a
  • IFN-b

Ø  Most cells, at some stage of infection, will express viral Ag on their surface in combination w/ Class I MHC molecules

  • Now, specially sensitized CD8+ TCTL cells can recognize and destroy the virus infected cells through the release of factors (granzymes, perforins, and interferons)
  • Adverse effects can occur if the infected host cell in of vital importance

Ø  If the virus infects macrophages, TDTH-cells can activate the macs to kill their intracellular viruses by activating the macs with lymphokines

Remember: If the patient is deficient in:

Ab production alone – does not have serious viral infections but can develop life threatening bacterial infections

CMI alone – develop serious viral infections

Helmith Infections

Ø  more complex response because the pathogen is larger, and therefore cannot be engulfed by phagocytes

Ø  most worm also undergo life cycle morphisms

Ø  TAPEWORMS (only in intestinal lumen) do not illicit an immune response

Ø  Ascaris and Trichinella (larvae invade tissue) do invoke an immune response characterized by infiltrate of PMNs, with a predominance of eosinophils

Ø  Numerous cells play a role, depending on location and form of the organism

  • Antigens on the surace of the organisms may stimulate T cells and Macrophages to interact with B cells to secrete specific antibodies
  • T Cell Factor II is also instrumental in stimulation of eosinophils (IL-5)
  • The eosinophils act by ADCC, or by releasing enzymes from granules to exert a controlling effect on mast cells

Ø  Ag reacting w/ IgE Ab bound to intestinal mast cells causes release of inflammatory mediators (histamine, proteases, leukotrienes, PGs, and Seratonin)

  • cause increase in vascular  permeability of the mucosa which allows more immune components to interact with the worms
  • stimulate peristalsis
  • stimulates mucus production
  • causes expulsion of the worms from the GI tract through barrier formation and prevention of attachment

Ø  Eosinophils contain basic proteins which are toxic to worms

Fungal Infection

Ø  CMI is #1

Ø  HI has a role

Ø  intense mononuclear infiltrate and granulomatous reactions occur in the infected tissues

Ø  Chronic mucocutaneous candidiasis

Leprosy-Immune deviation

Ø  DTH and formation of granulomas if highly resistance

Ø  low resistance- foamy macs and high humoral Ab

Immune deviation or split tolerance- dominance of one immune response over another for a specific antigen; varies with individuals

Ø  3 types of Leprosy; overlapping; read p. 21.7 to further understand

  1. Tuberculoid- best prognosis; responds well to chemo; granulomas are formed
  2. Borderline- good response if converts to tuberculoid form
  3. Lepromatous- prognosis and response is poor; usu due to depressed CMI; no granulomas formed
  • Typically TH2 cytokines predominate in the lepromatous form and TH1 in the tuberculoid form

Evasion of Immune Defense

Ø  infectious organisms have developed ways to avoid immune defense mechanisms

Ø  Protective niche- not accessible

Ø  Masking- acquiring host molecules

Ø  antigenic modulation- changing surface Ag

Ø  immunosuppression

Ø  immune deviation- fooling the immune system to respond with an ineffective effector mechanism

Ø  Ultimate endpoint- co habitual

Ø  Some of bacteria’s strategy

  • secrete toxins to inhibit chemotaxis
  • capsules
  • block intracellular fusion with lysosomal compartments
  • escape from the phagosomee to multiply in the cytoplasm

Ø  Some of Viral strategy

  • block effector function of Ab binding
  • block complement
  • inhibit activation of infected cells
  • Herpes- inhibits inflammatory response by inhibiting effects of cytokines by receptor mimicking, and by blocking Ag presentation and processing
  • Ebstein-Barr- encodes a cytokine homologue of IL-10 which leads to immunosuppression by activating TH2 rather than TH1