GENERAL PATHOLOGY OF INFECTIOUS DISEASES Marina Kos

INFECTIOUS DISEASES 

Are disorders in which tissue damage or disfunction is produced by a microorganism

Contagious (person to person)  Non contagious – acquired from sources such as animals, insects, soil, air or originating from endogenous microbial flora of the body 

FACTORS THAT INFLUENCE THE DEVELOPMENT OF DISEASE VIRULENCE  HOST DEFENSE MECHANISMS  HOST FACTORS IN INFECTION 

HERITABLE DIFFERENCES IN RESPONSE TO INFECTING AGENTS  EFFECTS OF AGE ON RESPONSE TO INFECTION  EFFECTS OF BEHAVIOR ON INFECTION  EFFECTS OF COMPROMISED HOST DEFENSES ON INFECTION 

VIRULENCE IS THE CAPACITY OF AN ORGANISM TO ACHIEVE INFECTION  THE ORGANISM MUST: 

GAIN ACCESS TO THE BODY  AVOID MULTIPLE HOST DEFENSES  ACCOMODATE TO GROWTH IN THE HUMAN ENVIRONMENT  PARASITIZE HUMAN RESOURCES 

HOST DEFENSE MECHANISMS          

SKIN TEARS NORMAL BACTERIAL FLORA GASTRIC ACID BILE SALIVARY AND PANCREATIC SECRETIONS FILTRATION SYSTEM OF NASOPHARYNX MUCOCILIARY BLANKET BRONCHIAL, CERVICAL, URETHRAL AND PROSTATIC SECRETIONS IMMUNE SYSTEM (neutrophils, monocytes, complement, stationary mononuclear phagocyte system, immunoglobulins, cell mediated immunity)

HOST FACTORS IN INFECTION An infectious agent may 3. 4. 5. 6.

FAIL TO INFECT SOME PERSONS PRODUCE ASYMPTOMATIC INFECTIONS IN OTHERS CAUSE MODEST SYMPTOMATIC DISEASE IN SOME PRODUCE LETHAL INFECTION

Heritable differences in response to infecting agents 

1.step in infection is often specific interaction of a binding molecule on the infecting organism with a receptor molecule on the host

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IF THE HOST LACKS THE RECEPTOR MOLECULE, THE ATTACHEMENT OF THE ORGANISM TO THE TARGET CANNOT OCCUR

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The containment or elimination of an infecting organism also depends on specific molecular interactions between the host and the organism

Effect of age on response to infection  

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The age of the host affects the outcome of exposure to many infectious agents Some organisms produce more severe disease in utero than in children or adults (CMV, Rubella, human parvovirus B19) The course of common illnesses (viral or bacterial diarrheas) in small children and infants - fluid loss Tuberculosis in children < 3 y – more severe, disseminated (immaturity of cell mediated immune system) Older individuals – symptomatic infection with EBV, or varicella-zoster virus (viral pneumonia) The elderly – fare more poorly with almost all infections (common respiratory illnesses are more often fatal in persons over 65 y)

Effect of behavior on infection 

STDs – syphilis, gonorrhea, urogenital, chlamydial infections, AIDS etc

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Contact with farm animals (farmers, herders, meat processors, drinking unpasteurized milk) – brucellosis, Q fever

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Eating habits – incompletely cooked meat (toxoplasmosis)

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Hygienic habits – “dirty hands diseases”

Effect of compromised host defenses on infection  

The state of host defense mechanisms affects the susceptibility and response to infection A disruption or absence of any of the complex host defenses results in increased numbers and severity of infections  

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Disruption of skin surface by trauma or burns Injury to the mucociliary apparatus of the airways (smokers)

The use of cytotoxic and immunosupressive drugs Congenital immunodeficiencies AIDS epidemic OPPORTUNISTIC PATHOGENS (most of them are part of the normal endogenous human or environmental flora)

HOW INFECTIOUS AGENTS CAUSE DISEASE  

They can contact or enter host cells and directly cause cell death They can release  

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endotoxins or exotoxins that kill cells at a distance enzymes that degrade tissue components or damage blood vessels causing ischemic injury

They can induce host cell responses that may cause additional tissue damage, usually by immune mediated mechanisms

VIRUS INDUCED INJURY - viruses damage host cells by entering them and replicating at host’s expense 

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They have surface viral proteins (ligands) that bind to particular host proteins (receptors) The presence or absence of host cell proteins that allow the virus to attach is one reason for VIRAL TROPISM The other reason is the ability of the virus to replicate inside some cells but not in others

ONCE attached, the entire virion, or a portion containing the genome and essential polymerases penetrates the cell cytoplasm by 

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TRANSLOCATION OF THE ENTIRE VIRUS ACROSS THE PLASMA MEMBRANE FUSION OF THE VIRAL ENVELOPE WITH THE CELL MEMBRANE RECEPTOR MEDIATED ENDOCYTOSIS AND FUSION WITH ENDOSOMAL MEMBRANES

WITHIN THE CELL 

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The virus uncoats, separating its genome from structural components and losing its infectivity Viruses then replicate using enzymes that are distinct for each virus family

VIRUSES KILL HOST CELLS AND CAUSE TISSUE DAMAGE By inhibiting host cell DNA, RNA or protein synthesis - poliovirus  Viral proteins may insert into the host’s plasma membrane and directly damage it’s integrity or promote cell fusion – HIV, measels, herpesviruses  Viruses replicate efficiently and lyse host cells (rhinovirus, influenzavirus multiplication, yellow fever, polio or rabies) 

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Viral proteins on the surface of the host cells may be recognized by the immune system and host lymphocytes may attack the infected cells – HBV, respiratory syncytial virus Viruses may damage cells involved in host antimicrobial defense, leading to SECONDARY INFECTION – pneumonia, opportunistic infections Viral killing of one type of cells may cause damage to other cells that depend upon their integrity (polio-denervation of motor neuronsatrophy or necrosis of distal skeletal muscle cells)

Slow viral infections (subacute sclerosing panencephalitis caused by measles virus) culminate in severe progressive disease after a long latency period)  Some of them (EBV,HPV, HBV, HTLV-1) can cause cell proliferation and neoplastic transformation 

BACTERIA INDUCED INJURY  Damage

to host cells depends on the ability of bacteria to adhere to and enter host cells or to deliver toxins

BACTERIAL ADHESINS – molecules that bind bacteria to host cells – limited in type but with a broad range of host cell specificity

BACTERIAL ENDOTOXIN A lypopolysacharide - a structural component of the outer cell wall of gram negative bacteria  LPS - a long chain fatty acid anchor – lipid A, connected to a core sugar chain THE SAME IN ALL GRAM NEGATIVE BACTERIA  Attached to the core sugar is a variable carbohydrate chain (O antigen) which is used as a serotype and distinguishes different bacteria 

BACTERIAL ENDOTOXIN 

Biologic activities – COME FROM LIPID A AND CORE SUGARS Induction of fever  Septic shock  Disseminated intravascular coagulation (DIC)  Acute respiratory distress syndrome (ARDS)  Effects on the cells of the immune system 

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They are mediated by Direct effect of endotoxin  Induction of host cytokines (IL-1, TNF etc.) 

BACTERIAL EXOTOXINS 

Are secreted proteins that directly cause cell injury and determine disease manifestations Bacillus anthracis  Diphteria toxin  Vibrio cholerae  E. coli  Clostridium perfringens  Clostridium tetani  Clostridium botulinum 

INFLAMMATORY RESPONSE TO INFECTIOUS AGENTS The morphological patterns of inflammatory response to infectious agents are limited  At the microscopic level, many pathogens evoke identical reaction patterns  Few of the features are unique or pathognomonic of each agent 

THERE ARE 5 MAIN HISTOLOGIC PATTERNS OF TISSUE REACTION 1. SUPPURATIVE POLYMORPHONUCLEAR INFLAMMATION 2. MONONUCLEAR INFLAMMATION 3. CYTOPATHIC-CYTOPROLIFERATIVE INFLAMMATION 4. NECROTIZING INFLAMMATION 5. CHRONIC INFLAMMATION AND SCARRING

SUPPURATIVE POLYMORPHONUCLEAR INFLAMMATION

SUPPURATIVE POLYMORPHONUCLEAR INFLAMMATION

MONONUCLEAR INFLAMMATION

MONONUCLEAR INFLAMMATION

CYTOPATHIC-CYTOPROLIFERATIVE INFLAMMATION

CYTOPATHIC-CYTOPROLIFERATIVE INFLAMMATION

NECROTIZING INFLAMMATION

CHRONIC INFLAMMATION AND SCARRING

IMMUNE EVASION BY MICROBES By remaining inaccessible  By cleaving antibody, resisting complement mediated lysis or surviving in phagocytic cells  By varying or shedding antigens  By causing specific or nonspecific immunosupression 

By remaining inaccessible    

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Microbes that propagate in the lumen of the intestine (Clostridium difficile) or gallbladder (S. typhi) Viruses shed from the luminal surface of the cells (CMV in urine or milk, poliovirus in stool) Viruses that infect keratinized epithelium (poxviruses – molluscum contagiosum) Because of rapid invasion of host cells before humoral response becomes effective (malaria sporozoites entering liver cells; Trichinella entering muscles) Some larger parasites form cysts with thick fibrous capsule

By cleaving antibody, resisting complement mediated lysis or surviving in phagocytic cells

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Carbohydrate capsule on the surface covers bacterial antigens and prevents phagocytosis by neutrophils     

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Secretion of leukotoxins that kill neutrophils 

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Streptococcus pneumoniae Neisseria meningitidis Haemophilus Klebsiella E. coli

Pseudomonas

Secrtetion of proteases that degrade antibodies   

Neisseria Haemophilus Streptoccocus spp.

By cleaving antibody, resisting complement mediated lysis or surviving in phagocytic cells 

Some bacteria have antigens that prevent activation of complement by the alternative pathway and lysis 

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Other have very long antigens that bind host antibody and activate complement at such a distance that lysis is not possible 

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K antigen of some E.coli bacteria

Some gram-negative bacteria

Some are covered by antigen that binds Fc portion of the antibody and inhibit phagocytosis 

Staphyloccoci

By varying or shedding antigens 

Normally, viral infection evokes neutralizing antibodies which prevent viral attachment, penetration or uncoating

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This mechanism cannot protect agains viruses with many antigenic variants Rhinoviruses  Influenzaviruses 

By varying or shedding antigens 

Pneumococci are capable of more than 80 permutations of their capsular polysaccharides – in repeated infections the host will not racognize the new serotype

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Shistosoma mansoni sheds and loses parasite antigens before they are recognized by the host immune system

By causing specific or nonspecific immunosupression 

Viruses that infect lymphocytes directly damage the host immune system HIV  EBV 

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Opportunistic infections develop