Hypersensitivity:

• hypersensitivity- the inappropriate or altered immunologic response to an antigen that results in disease or damage to the host

• allergy- a collection of conditions caused by inappropriate or exaggerated reactions of the immune system to a variety of substances

  • many common diseases such as asthma and hay fever are caused by allergic reactions to substances

  • the most common allergens:

    • airborne: pollens, spores from molds, dust mites, animal dander

    • foods: dairy products, eggs, fish, cereals, some fruits

• autoimmunity- disturbance in the immunologic tolerance of self-antigens

  • numerous disorders such as rheumatoid arthritis and insulin dependent diabetes mellitus are caused by a reaction of the individuals immune system against the organ or tissue of their own body

• alloimmunity- immune reaction to tissues of another individual

• hypersensitivity can have any of 4 dif immune mechanisms:

  • type 1- aka anaphylactic or immediate hypersensitivity, IgE mediated

  • type 2- tissue specific reactions

  • type 3- immune complex mediated

  • type 4- cell mediated

• immediate hypersensitivity reactions

• anaphylaxis

• delayed hypersensitivity reactions

type 1 hypersensitivity:

• allergens (from the environment) provoke the immune system to produce specific antibody (ige that present in the surface of the skin and lining of respiratory and digestive systems)

• when the allergen is encountered for the second time, it binds to ige and causes mast cells to release chemicals (ex. histamine) that causes:

  • blood vessels to widen

  • fluid to leak into tissue

  • muscles to go into spasm

• manifestations:

  • itching

  • urticaria- aka hives

  • conjunctivitis- inflammation of conjunctiva, causing redness, discomfort, and discharge from the affected eye

  • rhinitis- inflammation of the mucus membrane of the nasal cavity

  • hypotension

  • bronchospasm- temporary narrowing of bronchi

  • dysrhythmias- disturbance of heart rhythms

  • gi cramps and malabsorption

• genetic predisposition:

  • ppl w a family history of allergies tend to have:

    • elevated levels of ige

    • inherited general hyper responsiveness

    • inherited antigen specific response

    • lower number of t suppressor cells also play a role

• tests:

  • food challenges

  • skin tests

  • laboratory tests

• treatment:

  • avoid allergen

  • avoid exposure to environmental pollutant

  • desensitization

    • injection of allergen in low and increasing doses can reduce sensitivity

    • injection of allergens tend to increase igg which acts as blocking antibody and remove antigen before it can interact with mast cells

    • desensitization sometimes may trigger generalized or system anaphylaxis

  • (there’s a picture here that shows what happens but its super unclear, check textbook)

type 2 hypersensitivity:

• tissue specific

  • antibodies bind to antigens on cell surface (ex. surface of rbcs) and lead to possible destruction of the cell

  • it is tissue specific bc specific cells or tissues (tissue specific antigens) are the target of the immune response

  • can be responsible for certain autoimmune disorders and hemolysis

• 5 mechanisms

  • cell is destroyed by antibodies and complement (complement??)

  • cell destruction through phagocytosis

  • soluble antigen may enter the circulation and deposit on tissues

  • antibody dependent cell mediated cytotoxicity

  • causes target cell malfunction

• (there’s a picture here that shows what happens but its super unclear, check textbook)

type 3 hypersensitivity:

• immune complex (antibody bound to antigen) lodge in various tissues and activate further immune system response therefore it is known as immune complex mediated

• antigen-antibody complexes are formed in the circulation and are later deposited in vessel walls (mediate the formation (of?) microthrombi and cause endothelial damage) or extravascular tissues

• not organ specific

• immune complex clearance

  • immune complex clearance is a process directed at removing immune complexes from the body (im assuming next part is how theyre cleared based on size; maybe not, research seems to say maybe not?)

  • large - macrophages

  • small - renal clearance

  • intermediate - deposit in tissues

• disorders that result from type 3 hypersensitivity:

  • immune complex disease ex. immune comples glomerulonephritis (damage to glomerulus due to deposition of immune complexes)

  • serum sickness- damage from phagocytosis of immune complex deposited in capillaries following large transfusions of foreign serum (ex. horse antidiptheria serum)

  • arthus reaction- local production and deposition of antibodies against the synovial membrane

type 4 hypersensitivity:

• aka delayed type hypersensitivity

• does not involve antibodies

• cytotoxic t lymphocytes or lymphokine producing th1 cells

  • direct killing by tc or recruitment of phagocytic cells by th1 cells (yeah theres too many abbreviations for me to make sense of this or to compare any research to this info)

  • th cells- t helper cells; tc- t cells

• ex. acute graft reaction, skin test for tb, contact allergic reactions, and some autoimmune diseases

allergy:

• environmental antigens that cause atypical immunologic responses in genetically predisposed individuals

  • pollens, molds and fungi, foods, animals, etc

• allergen is contained within a particle too large to be phagocytosed or is protected by a nonallergenic coat

• original insult is apparent (pretty sure this means the original instance or cause is clear but not sure/not sure whether instance or cause/if its cause, how is it known?)

autoimmunity:

• breakdown of tolerance

  • antibody or t cells against self antigens and recognizes self antigens as foreign

  • basically the breakdown is that the mechanisms that maintain the immune systems tolerance to self antigens fail (and so the immune system loses its tolerance to self antigens)

• sequestered antigen

  • self antigen not normally seen by the immune system

• infectious disease

  • molecular mimicry (self antigens are close enough to foreign antigens that an overactive immune system mistakes them)

• neoantigen

  • haptens (a small molecule that when bound to a bigger one can produce an immune response) become immunogenic (able to produce an immune response) when they bind to host proteins

  • neoantigen- a new protein that forms on cancer cells when certain mutations occur in tumor dna

• forbidden clone

  • during differentiation, lymphocytes produce receptor(s?) that react with self antigens

  • these immune cells should have been destroyed (bc of their autoimmune properties) but they managed to survive (hence ‘forbidden’)

• ineffective peripheral tolerance

  • defects in regulatory cells

  • the cells that are supposed to make sure the immune cells arent autoimmune cells dont work properly

• original insult

• genetic factors

alloimmunity:

• immune system reacts w antigens on the tissue of other genetically dissimilar members of the same species

  • transient neonatal alloimmunity

    • fetus expresses parental antigens not found in the mother

  • transplant rejection and transfusion reactions

autoimmune examples:

• systemic lupus erythematosus (sle)

  • chronic multisystem inflammatory disease

  • autoantibodies against nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc.

  • deposition of circulating immune complexes containing antibody against host dna

  • more common in females

systemic lupus erythematosus:

• clinical manifestations

  • arthralgias (general joint pain not from inflammation) or arthritis (joint pain from inflammation) (90% of individuals)

  • vasculitis (inflammation of blood vessels) and rash (70-80%)

  • renal disease (40-50%)

  • hematologic changes (50%)

  • cardiovascular disease (30-50%)

• eleven common findings

• serial or simultaneous presence of at least 4 indicates sle

  • facial rash (malar rash), discoid rash, photosensitivity, oral or nasopharyngeal ulcers, nonerosive arthritis, serositis (acute inflammation in pleurae or pericardium), renal disorder, neurological disorder, hematologic disorders, immunologic disorders, and presence of antinuclear antibodies (ana)

graft rejection:

• transplant rejection is classified according to time

  • hyperacute

    • immediate and rare

    • preexisting antibody to the antigens of the graft

  • acute

    • cell mediated immune response against unmatched hla antigens

  • chronic

    • months or years

    • inflammatory damage to endothelial cells of vessels due to weak cell mediated reaction against minor hla antigens

transfusion reactions:

• antibodies against blood groups antigens

• abo system

  • 2 major carbohydrate antigens

    • a and b (co dominant)

    • individuals have naturally occuring antibodies to the a and b antigens they lack

    • anti a and anti b antibody production is induced by similar antigens on naturally occurring bacteria in the intestinal tract

    • antibodies are usually of the igm class

    • o blood type is the universal donor

    • ab blood type is the universal recipient

immune deficiencies:

• failure of immune mechanisms of self defense

• primary (congential) immunodeficiency

  • genetic anomaly

• secondary (acquired) immunodeficiency

  • caused by another illness

  • more common

• clinical presentation

  • development of unusual or recurrent, severe infections

  • t cell deficiencies

    • viral, fungal, yeast, and atypical microorganisms

  • b cell and phagocyte deficiencies

    • microorganisms requiring opsonization

  • complement deficiencies

primary immune deficiencies:

• most are the result of a single gene defect

• 5 groups

  • b lymphocyte deficiencies

  • t lymphocyte deficiencies

  • combined t and b cell deficiencies

  • complement defects

  • phagocyte defects

  

secondary deficiencies:

• also referred to as acquired deficiencies

• far more common than primary deficiencies

• causes

  • normal physiology conditions

    • refers to conditions that are normal like pregnancy or aging etc.

  • psychological stress

  • dietary insufficiencies

  • malignancies

  • physical trauma

  • medical treatments

  • infections

  • acquired immunodeficiency syndrome (aids)

acquired immunodeficiency syndrome (aids):

• syndrome caused by a viral disease

  • human immunodeficiency virus (hiv)

  • depletes the bodys th cells

  • incidence

    • worldwide- 5 million/yr

    • U.S.- about 31,000/yr

      • 400,000 currently living w aids

• effective antiviral therapies have made aids a chronic disease

  • (as opposed to fatal)

• epidemiology

  • blood borne pathogen

  • increasing faster in women than men

• pathogenesis

  • retrovirus

    • genetic information is in the form of rna

    • contains reverse transcriptase to convert rna into double stranded dna

    • integrase (used to insert the viral dna into the host dna)

human immunodeficiency virus (hiv):

• structure

  • gp120 protein binds to the cd4 molecule found primarily on the surface of helper t cells

    • cd4⁺th cells (the + was in superscript, idk if its supposed to note something or be ‘and)

      • typically 800 to 1000 cells/mm³

      • reverses cd4/cd8 ratio

  • co receptors

    • cxcr4 and ccr5

      • strains can be selective for these receptors; influences the tropism of the target cells

        • tropism- the turning of all or part of an organism in a particular direction in response to an external stimulus

  • clinical manifestations

    • serologically negative, serologically positive but asymptomatic, early stages of hiv, or aids

    • window period

    • th cells <200 cells/mm³

    • diagnosis of aids is made in association with various clinical conditions

      • atypical or opportunistic infections, and cancer

• treatments and prevention

  • highly active antiretroviral therapy (haart)

    • reverse transcriptase inhibitors

    • protease inhibitors

  • new drugs

    • entrance inhibitors

    • integrase inhibitors

  • vaccine development

evaluation of immunity:

• complete blood count (cbc) w a differential

  • subpopulations of lymphocytes

• quantitative determination of immunoglobulins

  • subpopulations of immunoglobulins

• assay for total complement

• skin tests

treatment for immunodeficiencies:

• gamma-globulin therapy

• transplantation or transfusion

• treatment w soluble immune mediators

• gene therapy

microorganism/human relationship:

• mutual relationship

  • normal flora

  • relationship can be breached by injury

    • they can leave their normal sites and cause infection elsewhere

• opportunistic microorganisms

stages of infection:

• colonization

• invasion

• multiplication

• spread

classes of infectious microorganisms:

• virus

• chlamydia

• rickettsia

• mycoplasma

• bacteria

• fungi

• protozoa

• helminths

clinical manifestations of infectious disease:

• variable depending on the pathogen

  • directly caused by the pathogen or indirectly caused by its products

• fever

  • resetting the hypothalamus

    • exogenous pyrogens

    • endogenous pyrogens

countermeasures:

• vaccines

  • induction of long lasting protective immune responses that will not result in disease in a healthy recipient

  • attenuated organism

  • killed organisms

  • recombinant viral protein

  • bacterial antigens

  • toxins

• antimicrobials

  • inhibit synthesis of cell wall

  • damage cytoplasmic membrane

  • alter metabolism of nucleic acids

  • inhibit protein synthesis

  • modify energy metabolism