Hypersensitivity and Infection

Patho Exam 2

3 variables of hypersensitivity

1. original insult

2. individuals genetic makeup

3. immunologic process

original insult

alters immunologic homeostasis - steady state of tolerance to self antigens or lack of immune rxn against environmental antigens

hypersensitivity definition

altered immunologic response to antigen that results in disease or damage to host, inappropriate excessive undesirable effect on body, associated w/ allergy autoimmunity alloimmunity

sensitization → reexposure → exaggerated response

sensitization

original insult → adequate amt of antibodies or T cells available to cause noticeable rxn on re-exposure to antigen ; rapidly or over yrs

immediate hypersensitivity rxn

occur w/in mins to hrs, anaphylaxis - systemic or cutaneous

delayed hypersensitivity rxn

sev hrs to appear, max severity occur days after re exposure to antigen

type I hypersensitivity rxn

products of mast cells, immediate, IgE, against environmental antigen/allergen, requires sensitization, cross linking of IgE causes histamine release from mast cell degranulation

clinical manifestations - bronchial constriction, edema, vasodilation, urticaria, allergic rhinitis, asthma, anaphylaxis

type II hypersensitivity rxn

immune complex, tissue specific (cytotoxic) rxns, IgG and IgM, occur after binding of antibody to tissue specific antigen by fragment antigen body, complement mediated lysis, antibody dependent cellular toxicity, antireceptor antibodies

ex: ABO transfusion rxn, hemolytic disease of newborn, myasthenia gravis, graves disease, hyperacture graft rxn, autoimmune hemolytic anemia

type III hypersensitivity rxn

immune complex (antigen antibody) mediated, not organ/tissue specific, IgG and IgM, complexes formed in circulation and deposited later in vessel walls or extravascular tissues, damage results from complement activation and neutrophil lysosomal enzymes

ex: glomerulonephritis, arthritis, serum sickness, raynauds, arthus rxn, SLE

type IV hypersensitivity rxn

delayed, cell mediated, lymphocytes

anaphylaxis

severity depends on level of sensitization, develops minutes after exposure

clinical manifestations- itching, erythema, HA, contraction of resp bronchioles, laryngeal edema, n/v/d, abd pain, vascular collapse

common causes - bee stings, peanuts, eggs, shellfish

type II vs type III hypersensitivity rxns

II - immune complex, forms in tissue, tissue specific

III- immune complex, forms in circulation, not tissue specific

type IV hypersensitivity

cell mediated/mediated by T cells/

cytotoxic cells - attack and destory targets directly

Helper T (Th) 1 and 17 cells - produce cytokines that recruit and activate phagocytic cells

does NOT involve antibody

delayed - 48-72 hrs

ex: graft rejection, contact dermatitis, RA, TB skin test, drug rxn

allergy / allergen

allergen - environmental antigens

pollen, molds, fungi, certain foods- milk, eggs, shellfish, animal hair/dander/saliva, animal bites/insect stings, certain drugs, cigarette smoke, house dust

involves sensitizing process

genetic predisposition - atopic

atopic

predisposed to develop allergies

family w/ one parent allergy - 40% of offspring both parents have allergies - up to 80% offspring

produce higher quantity IgE

infection - causes of death and morbidity

reemergence of old infections thought to be controlled, emergence of previously unknown infections, development of infections resistant to multiple abx

spread of infection

global travel → urbanization → spread into wilderness → overprescribing abx → climate change

mutual symbiotic relationship

microorganism and human benefit

normal microbiome

resident microorganisms are found in different parts of body

produce enzymes that help digestion

produces antibacterial factors - prevents colonization by pathogens

produces metabolites - vitamin K , B vitamins

incubation

period from initial exposure to onset of first sx, last hours to yrs

prodromal

ocurrence of initial sx, often v mild w/ feelings of discomfort and fatigue

invasion

more widespread, affects other body tissues

convalescence

recovery occurs and sx decline, or disease is fatal, or period of latency

phases of infectious disease

incubation , prodromal , invasion , convalescence

fever

hallmark of infection , endogenous and exogenous pathogens

clinical manifestations of infectious disease

variable depending on pathogen , caused directly by pathogen or indirectly by its products, manifestations - fatigue, malaise, weakness, anorexia, generalized aching, loss of concentration

factors affecting disease development

communicability, immunogenicity, inefectivity, MOA, pathogenicity, portal of entry, toxigenicity, virulence

communicability

ability to spread person to person

immunogenicity

ability to produce immune response

infectivity

ability to invade and multiply in host

MOA

ihow microorganism damages tissue

pathogenicity

ability to produce disease

portal of entry

route microorganism takes

virulence

capacity to cause severe disease, potency

infectious disease classification

endemic , epidemic , pandemic

endemic

diseases w/ relatively high but constant rates of infection in particular population

epidemic

number of new infections in particulat population that greatly exceeds number usually observed

pandemic

epidemic that spreads over large area such as continent or world

transmission of infection

direct

indirect - vectors

droplet v airborne

vertical v horizontal

process of infection

colonization , invasion , dissemination

or

invasion , multiplication , spread

colonization

microorganisms adhere to tissue through specific surface receptors

true pathogens

bypass normal defenses and cause infection, infection usually dependent on adequate number of microorganisms rather than compromise of host defense

multiplication

warm nutrient filled environment of human tissue cause most micro orgs multiply rapidly, viral pathogens replicate w/in infected cells, some bact are intracellular pathogens and replicate in macrophages and other cells

microorganisms

bacteria, fungi, parasites, protozoa, virus

true bacteria

binary fission

filamentous bacteria

branching mycellum like structures

spirochetes

flexible spiral anaerobic

mycoplasma

smallest simplest bacteria

rickettsia

smallest intracellular parasites

chlamydia

intracellular parasites w/ complex life cycles

gram positive v gram negative

negative - do not retain dye , red, lipopolysaccharide coat (LPS) (endotoxin)

positive - retain dye, purple

exotoxins

enzymes released during growth , damages cell membranes , activates second messengers , inhibits protein synthesis

endotoxins

contained in cell walls of gram negative bact (LKP) , released during lysis of bact , called pyrogenic bact bc activate inflammation and produce fever

lipid A

innermost part of LPS, responsible for substance’s toxic effects

effects of endotoxins

local and systemic , release vasoactive cytokines and peptides , vasodilation (reduce BP) , decreased O2 delivery, cardiovascular shock

bacteria MOA

produce toxins and extracellular enzymes to destroy phagocytic cells , coat Fc (crystalline fragment) portion of individuals antibody preventing complement activation or phagocytosis, degrade immune cells, bind and neutralize antibodies, evade complement, cause immune suppression

fungal infections

large microorganisms w/ thick rigid cell walls, mold/yeast (dimorphic), transmitted by inhalation or contamination of wounds, adapt to host environment, suppress immune defenses, systemic infection usually from immunosuppression

mycosis

disease caused by fungi

dermatophytes

fungal infection invade skin, hair, nails

human to human transmission

fungal infection patho

some survive phagocytosis by replicating in phagosome or inhibiting lysosomal enzymes

encapsulate, alter antigen expression, and stimulate immunosuppressive cytokines to resist phagocytosis

tissue damage from enzymes and indirectly from inflammation

candida albicans

most common fungal infection, resides in skin GI mouth vagina, remains localized if immune system intact - if compromised infection becomes systemic

parasitic and protozoan infections

range from unicellular protozoa to large worms, rarely transmitted human to human- mainly through vectors

ex: malaria via mosquito bites

helminths

parasitic worms

intestinal and tissue nematodes - hookworm, roundworm

flatworms - liver fluke, lung fluke, tapeworm

most common parasitic infections U.S.

toxoplasma gondii , trichomonas vaginalis (STDs)

parasite invasion

extracellular - GI tract, vagina (STI), skin (bites)

intracellular - ingestion of contaminated food/water, bites from insect vectors

response to parasitic infection

immune/inflammation response, immune hypersensitivity rxn, tissue damage caused by parasites is secondary to release of enzymes that destroy surrounding ECM and tissue

malaria

most common infection worldwide, transmitted through bite of infected anopheles mosquito, parasite enters bloodstream survives in liver and invades parenchymal cells, after several rounds division liver cell ruptures → 1000s of parasites enter blood infecting RBCs

infectious viruses

rarely produce toxins, classified by nucleic acid in virion (DNA or RNA), ss or ds (single or double stranded), uses enzyme reverse transcriptase for replication

virion

basic structure infectious viruses, nucleic acid surrounded by capsid

most common affliction of humans

viral diseases, include common cold, cold sores, hepatitis, HIV, some cancers

lifecycle of virus

intracellular parasites :

attach/bind to host cell via protein receptors

penetrate host cell

release genetic info into host cytoplasm

replication (synthesis viral proteins and RNA)

assembly (form new virions)

release by lysis or budding

viral infection sx

mild - fever , aches, nausea

rapidly proliferating viruses

norovirus , rotovirus , ebola , marburg , hantavirus

viral infection harmful effects

inhibition DNA RNA protein synthesis, disrupt lysosomal membranes, promote apoptosis, fusion of adjacent cells (giant cells), transform into cancer cells, alter antigenic properties (immune attacks normal cells)

influenza

seasonal, highly infectious, virions attach to resp epithelial cells and enter by endocytosis, may be fatal for v young/old, surface proteins undergo change each yr

influenza changes/adaptations

can have antigenic drift or mutation - mutation of genes that express surface molecules

can have antigenic shift (Flu A) - recomb into new virus from 2 diff species

acquired immunodeficiency syndrome (AIDS)

retrovirus caused by HIV , depletes body’s Th cells (helper T) , susceptible to life threatening infections and cancer , 2 types

HIV transmission

bloodborne pathogen present in body fluids (blood, vaginal fluid, semen, breast milk), transmit through blood or blood products, IV drug use, sex (hetero/homo), maternal child transmission pre or during birth

retrovirus

RNA virus, stores genetic material on two copies of RNA rather than usually dsDNA, carries enzyme reverse transcriptase - creates dsDNA version of virus- and integrase - inserts new DNA into infected cell’s genetic material (may be dormant - no probs develop- or activate- new DNA becomes part of cell’s genetic material and accelerates apoptosis and shedding of infectious HIV)

AIDS clinical manifestations

stage 0 - first 180 days post infection

stage 1-3 - based upon CD4 count to monitor disease progression

sx - fatigue, HA, myalgias, fever, or may be asymptomatic for years

AIDS dx

use various clinical conditions and lab tests, atypical or opportunistic infections and/or cancer, CD4+ T cell numbers at or below 200 (dep on age)

countermeasures against pathogens

environmental infection control measures, antimicrobials, active immunization , viral vaccines, bacterial vaccines, toxoids, extracted capsular polysaccharides

antimicrobials

bacteriostatic / bactericidial microorganisms (prevent growth or directly kill) - inhibit production and function of cell wall, block DNA replication, inhibit protein synthesis, interfere w/ folic acid metabolism

active immunization

vaccines - prevent initiation of disease, not last as long as infection produced immunity (need boosters)

viral vaccines

attenuated - weakened live viruses - MMR , varicella , polio (oral), rotavirus

inactivated - killed virus - hep A, polio (injected), influenza

recombinant - hep B , HPV

bacterial vaccines

conjugated to carrier proteins, increased immunogenicity, Hib (hemophilus influenza type B)

toxoids

vacc against bacterial toxins - DTaP, DT

extracted capsular polysaccharides

vacc of dead bacteria - meningococcal , pneumococcal