module 4: adverse reaction and immune defects Flashcards
what is immunodeficiency
- disorder/condition where the immune system has reduced function or is absent and can be traced to the failure of one more more parts of the immune system
what are the 2 main types of immunodeficiencies?
- primary immunodeficiency
- secondary immunodeficiency
primary immunodeficiency
- are congenital and derive from a genetic or developmental defect
- leads to abnormal maturation of the immune system
what does primary immunodeficiency lead to?
leads to abnormal maturation of the immune system
what are primary immunodeficiency associated with?
defects in the innate or adaptive immune systems
lists the primary immunodeficiency- deficiencies
b-cell deficiencies: 65%
t-cell deficiencies: 5%
complement deficiencies 5%
phagocytic deficiencies: 10%
combines T- and B-cell deficiencies: 15%
secondary immunodeficiency
are acwuired and result from environmental factors affecting and compromising the immune system
what are causes of the secondary immunodeficiency
- undergoing chemotherapy treatment
- taking immunosuppressive medication
- contracting a chronic infection (HIV/AIDS)
- developing cancer
classification of primary immunodeficiencies
- B-cell deficiencies
- T-cell deficiencies
- complement deficiencies
- phagocytic deficiencies
- combined T-and B-cell deficiencies
B-cell deficiencies- classification of primary
- characterized by dysfunctional B lymphocytes or a decrease in their prevalence
what would a deficiency in B-cell development result in?
increased susceptibility to infection, especially by encapsulated bacteria
congenital
present from birth
encapsulated bacteria
encompass both Gram-positive and Gram -negative bacteria with the unifying feature being the production of capsule composed of polysaccharides
when does the first symptoms of b-cell deficiencies appear
age of 7-9 months old
clinical example of b-cell deficiencies
X-linked agammaglobulinemia (XLA)
- genetic disorder
- mostly in males
- don’t develop mature b-cells and results have low levels of IgG and lack all other immunoglobulins
- fine to viral and fungal infections, because their cell-meditated immune response remain normal
T-cell deficiencies- primary classification
- dysfunctional T-lymphocytes or a decrease in their prevalence
what does a deficiency in T-cells result in?
increased susceptibility to viruses, protozoan’s, and fungi
when are t-cell deficiencies often identify in a person
by frequent infections beginning 3-4 months after birth
clinical example of t-cell deficiencies
DiGeorge syndrome
- caused by the deletion of a small segment of chromosome 22
- they have absent or undeveloped thymus, which results in the absence of mature t-cells
complement deficiencies- primary deficiencies
- performs multiple functions and involves the intricate regulation of nine components
- genetic deficiencies have been described for each of these complement components
what people with complement deficiencies prone to
frequent severe bacterial infections and complications arising from inability to clear immune complexes
- C3 deficiencies display the severest symptoms, reflective of the central role played by this component in complement activities
phagocytic deficiencies- primary classification
- can appear at various stage of this process
- bacterial and fungal infections are unusually frequent infections and severe, often causing deep abscesses
combined T-cell and B-cell deficiencies
- have dysfunctional and/or low number of lymphocytes
- both humoral and cell mediated responses of the adaptive immune system are comprised
- little or no resistance to infection thus pathogens that cause mild disease in the average human may be life threatening.
- people suffer fatal infections within the first year of life
what are easier to classify? primary or secondary
primary
what does the acronym AIDS stand for?
Acquired
Immunodeficiency
syndrome
acquired- AIDS
individuals do not inherit this disease.
immunodeficiency- AIDS
the one disease characteristic AIDS victims have common is the breakdown of their immune system
syndrome- AIDS
Many rare but dangerous diseases attack the body when its defenses are weak, causing serious problems
secondary immunodeficiency: AIDS/HIV
AIDS is the final stage of following an acute and chronic HIV infection.
- many AIDS patients die from opportunistic infections as their immune system is compromised and unable to effectively protect and defend the body
mode of transmission of HIV
- depends on the location
- regards of the portal of entry, without treatment, the outcome is the same
- immunosuppression, neuropsychiatric, abnormalities and death
north America - transmission of HIV
sexual intercourse
sub-Africa mode of transmission of HIV
through heterosexual sex with a concomitant epidemic in children through vertical transmission (mother to child)
eastern Europe and central Asia - transmission of HIV
use of non-sterile injecting drug parapherila
HIV and the immune response stages
- primary infection
- acute infection
- chronic infection
- AIDS
primary infection- HIV response
- will mount an effective immune response to the virus for the first couple weeks
- over time, response will prove ineffective through the various stages of the disease
Acute infection- HIV
- HIV targets and infects cells with CD4 on their surface, including CD4+ helper T-cells
- viral infection causes a drastic decrease in the level of CD4+ helper t-cells while the level of virus in the blood increases
- within 2 to 4 weeks after exposure, ppl experience flu like symptoms
- level of HIV in blood is very high during the acute infection phase
- increases the risk of HIV transmission
clinical latency- HIV
- HIV continues to multiply in the body at a steady state
- ppl often do not experience HIV related symptoms, transmission still possible
- Anti HIV antibodies are detectable
- HIV can begin to evade the immune response that is present by changing their antigens through high mutation rates
- about 8-10 years
AIDS- HIV
- through clinical latency, CD4+ T helper cells get ‘exhausted’ and depleted while constantly fighting chronic HIV infection
- HIV patients are diagnosed with AIDS if they have a CD4+ t helper t cell level of less than 200cells/mm3
- viral load INCREASES as the virus continues to acquire mutations that allow it to further avoid immune defenses
- patients get susceptible to infections
- with no treatment AIDS ppl survive 3 years
when was the first antiretroviral therapy approved?
1987
what do the antireviral therapy- for HIV ppl do?
- do not kill or cure the human immunodeficiency virus, but prevent it from replicating
retroviral therapy (ART) and highly antiretroviral therapy (HAART) functions
- utilizes a panel of antiretroviral drugs in different combinations to prevent drug resistance by rapidly-mutating virus
what has retroviral therapy (ART) and highly antiretroviral therapy (HAART) led too?
- declines in the rate of AIDS and AIDS- associated deaths
- HAART maintains function of the immune system, and prevents opportunistic infections that often lead to death
what is the benefits of retroviral therapy (ART) and highly antiretroviral therapy (HAART)
- reduces the amount of HIV
- protects the immune system
- prevents HIV from advancing to AIDs
- reduces the risk of HIV transmisison
what are screening techniques for immunodeficiencies
- methods or strategies used to identify the possible presence of a disease in individuals who may be pre-symptomatic or have unrecognized symptoms
what do screening techniques for immunodeficiencies allow?
for early intervention and management of the disease
types of screening techniques for immunodeficiencies
- complete blood counts
- quantitative serum immunoglobulin
what is complete blood counts (CBC)
shows how many of each cell type are present in a sample of patients blood
- number then compared to a reference range of values in healthy ppl
what is complete blood count used for
to highlight any severe defect in the blood that could potentially be caused by an immunodeficiency.
what is quantitative serum immunoglobin?
tests measure the levels of IgG, IgA, IgM in a patients blood serum and compare them to a control
- if levels of antibodies are lower than normal (hypoantibody) this could be an indication of a humoral immunodeficiency
what does quantitative serum immunoglobin? further testing mean
further testing would be complete blood counts and urine protein electrophoresis which could be used to pinpoint the source of the hypogammaglobulinemia
urine protein electrophoresis
a screening test to evaluate the amount of certain protein in urine
step 2 of case study
- review of symptoms
- clinical findings
- clinical history
what specific immune cell does HIV preferentially replicate in?
- helper t-cells
what is autoimmunity
- the immune system initiates a reaction in response to its own cells.
what is autoimmune disease
failure of an orgnaims to distinguish self from non-self causes the immune system to initiate a response against its own cells and tissues
- any disease that results from such aberrant immune response
what is the number of autoimmune disease within the general population
affects 5-7% of the human population
what is the number of autoimmune diseases within the affected population
they more commonly affect females than males. appox. 78% of individuals infected with an autoimmune disease are women
what is the main cause of autoimmune disease
the development of an autoimmune disease is highly dependent on genetics, but many other factors such as infection by bacteria or virus or chemical exposure can play a role in their development
how are autoimmune diseases classified
organ specific autoimmune diseases or systemic autoimmune diseases
what do autoimmune diseases often involve?
autoantibodies, is an antibody produces by the immune system that is directed against a self-antigen
what is organ specific autoimmune diseases
involve an immune response that is directed to an antigen that is unique to a single organ or gland.
target organ specific autoimmune diseases
- thyroid gland
- stomach
- adrenal gland
- pancreas
example of organ specific autoimmune disease
- graves disease
- leads to overactivity of the thyroid gland known as hyperthyroidism
normal function of thyroid stimulating hormone
- produced by pitutuary gland, regulates thyroid hormones
- binding of TSH by receptors on thyroid cells stimulate the production of thyroid hormones which control metabolism
graves disease- normal function of thyroid stimulating hormone
grave patients produce autoantibodies to the receptor for TSH
- these autoantibodies continuously engage TSH receptors but unlike TSH cannot be moderated
- results in unregulated overproduction of thyroid hormones (create metabolism dysfunction)
cause and symptoms of graves disease
- cause unknown but maybe genetic and environemnt factors
- enlargement of thyroid glands (goiter)
- weight loss, rapid heartbeat, poor regulation of body temp, muscle weakness, irritability
what is systemic autoimmune disease
- the immune response is directed towards a broad range of antigens that are characterisiic of a number of organs and tissues
example of systemic autoimmune disease
- rheumatoid arthritis
- typically presents as a chronic inflammation in joints but organs can be affected
rheumatoid arthritis
- women ages 40-60
- many patients produce autoantibodies, most commonly IgM to portion of the Fc receptor of IgG, which are referred as rheumatoid factors
- rheumatoid dfactors bind to circulating IgG forming immune complexes that become deposited within joints
- these deposits can activate the complement cascade leading to prolonged inflammation and ultimately joint tissue damage
can autoimmunity be cured and/or treated?
no it cannot be cured
- only can treat and try to reduce reactions by immunosuppresion but secondary effects may occur
how do immunosuppressions work?
the drugs reduce the strength of the body’s immune response
- ideal would be suppressing the erroneous autoimmune response but that way hasn’t been found yet
when are immunosuppression also used?
when people undergo a organ transplant
(so the body doesn’t see it as a foreign object and try to fight it) the drugs are used to reduce rejection by inhibiting the immune response and allowing the organ to remain healthy in its new environemnt
what are the four classes of immunosuppressive drugs
- corticosteroids
- cytotoxic drugs
- immunophilins
- lymphocyte-depleting therapies
corticosteroid action
anti-inflammatory; kills T-cells
cytotoxic drugs action
blocks cell division nonspecificially
immunophilins action
blocks T-cell responses
lymphocyte-depleting therapies action
kills T-cells non-specifically, kills activated T-cells
mechanism of immunosuppreive drugs
1. reception, kills T-cells
corticosteroid
- activation- blocks t-cell responses
immunophilin
- antibody receptivity- kills T-cells nonsepcifically
lymphocyte-depleting therapy
- antibody receptivity- nonspecifically
cytotoxic drug
downside of immunosuppressive degus
immunophilin
cytotoxic drugs
corticosteroids
down side - immunophilin
drug: cyclosporine
side effects: nephrotoxicity, hypertension, hirsutism, hypertrichosis, gingival hyperplasia
downside- cytotoxic drugs
drug: cyclophosphamide
side effects: nausa, vomiting, no appetitie, diarrhea, skin darker
drug: methotrxate
side effects: hair loss, puking, tiredness, dizziness, chills, headache, rash, stuffy nose, low blood cells levels
downsides- corticosteroids
drug: prednisone
side effects: osteoporosis, hirsutism, hypertrichosis, diabetogenic
infections caused by immunosuppression
latent infections
opportunistic infections
latent infections
- individuals that are on immunosuppressive therapy have increased risk of pathogens that are usually assoicated with latent infections
- infections that are inactive, hidden, or dormant
what are the most common pathogens with latent infections
- TB
- HSV1/2 (herpes)
- CMV (cyomegalovirus)
- EBV (epstein-barr virus)
- VZV (varicella zoster virus)
opportunistic infections
- commonly occur when there is reactivation of a pathogen that is already present in the host
- result in the pathogen is picked up from environemnt, but the blunted immune response of the host is unable to combat the pathogen
- arise from bacteria, viruses, parasites, fungi
opportunistic infections- fungal- pneumocytis Jiroveci pneumonia
common name: PCP
infects: pneumonia of lings
opportunistic infections- fungal- crytococcosis
common name: crytococcal disease
infects: lungs- can spread to brain
opportunistic infections- fungal- candidiasis
common name: thrush
infects: mouth, throat, vagina
opportunistic infections- fungal- aspergillosis
common name: N/A
infects: lungs
opportunistic infections- parastic- toxoplasmosis
common name: N/A
infects: skeletal muscle, myocardium, brain, and eyes
opportunistic infections- bacterial- TB
common name: consumption
infects: lungs
opportunistic infections- bacterial- mycobacterium Avium complex
common name: MAC
infects: lungs, lymph nodes, entire body depending on site of infection
opportunistic infections- viral- cytomegalovirus
CN: CMV
infects: eyes, brain, other internal organs
opportunistic infections- viral- herpres simplex virus
CN: herpes
infects: skin, mouth, lips, eyes, genitals
opportunistic infections- viral- varicella zoster virus
CN: chickenpox
infects: skin, sometimes organs
opportunistic infections- viral- mononucleosis
CN: Epstein-Barr virus or kissing disease
infects: lymph nodes, throat, salivary glands, liver, spleen, blood
what is hypersensitivities
refers to excessive reactions produced by the normal immune system
classifications of hypersensitivities
type I, II, III, IV
type I
immediate/anaphylaxis
example of type I
allergic reactions
- food allergies
type II
cytotoxic
examples of type II
blood diseases:
- transfusion reactions
- hemolytic disease of the newborn
type III
Immune complex mediated
examples of type III
contribute to development of autoimmune diseases
- systemic lupus erythematosus
- rheumatoid arthritis
type IV
delayed-type
examples of type IV
skin reactions
- contract dermatitis
type I hypersensitivity- allergens
- milk
- eggs
- fish
- crustacean shelfish
- tree nuts
- peanuts
- wheat
- soya
type I hypersensitivity- mediators- immune cells
- IgE
- basophils
- Mast cells
type I hypersensitivity- primary exposure to an allergen
- the allergen induces a humoral immune response wherein plasma cells secrete an excessive amount of IgE antibodies which bind to mast cells and basophils
type I hypersensitivity- secondary exposure to the same allergen
membrane-bound IgE cross-links with the allergen which initiates the degranulation of basophils and mast cells, releasing vasoactive mediators causing vasodilation and smooth muscle contraction
type I hypersensitivity- reaction time
- can be immediate
- can led to death in as little as 15min
- rare are 24h after
degranulation
release of granules
type I hypersensitivity- clinical manifestation
- allergic rhinitis
- asthma
- atopic dermatitis (eczema)
- hives (urticaria)
allergic rhinitis
generalized irritation of the nose when the immune system overreacts to allergens in the air
atopic dermatitis (eczema)
a condition where an individual develops skin eruptions accompanied by redness
asthma
respiratory condition in which the airway narrow, swell and produce extra mucus
hives (urticaria)
a rash of itchy round, red welts on the skin that may also burn, sting, swell
type II hypersensitivity- mediators
- IgG
- IgM
- NK cells
- the complement system
type II hypersensitivity- mechanism of reaction
- IgGs/IgMs bind to antigens on the surface of cells (ex. erythrocytes)
- once antibodies are attached through their antigen binding region, the Fc region is free and can activate 2 processes
- classical complement activation
- antibody-dependent cell-mediated cytotoxicity
classical complement activation
leads to opsonization or membrane attack complexes
what do the mechanism of reaction in type II hypersensitivity do?
these processes mediate the destruction of the cells, leading to an excessive inflammatory response
type II hypersensitivity- reaction time
is min to hours
type II hypersensitivity- clinical manifestations
- drug induced hemolytic anemia
- transfusion reactions
drug induced hemolytic anemia
- some antibodies can bind to proteins on RBC membranes and form a complex which sometimes induces completement-mediated lysis
- as the RBCs rupture, the number of RBCs decrease resulting in anemia
- anemia is gone when drug is removed
- penicillin is notable
transfusion reactions
- depending on your blood type, you will only be able to safely receive certain blood types during a blood transfusion
- this is partly due to the presence or absences of expression of a specific antigen (A or B) on your RBCs (meaning you don’t express the antigen, you don’t have antibodies)
type III hypersensitivity- mediators
- immune complexes (antigen-antibody complexes)
- neutrophils
- complement proteins
type III hypersensitivity- mechanism of reaction
- of antibodies with antigens generates immune complexes. when not cleared, they build up and deposit in the tissue
- the immune complexes will activate the complement which will induce inflammatory reactions through neutrophil attraction to the site of depositions
- neutrophils release lytic enzymes as they attempt to phagocytose the immune complexes, which weakened surrounding cells membranes ultimately causing tissue damage
type III hypersensitivity- reaction time
- 3 to 10 hours after exposure to the antigen
- sometime (days to weeks)
type III hypersensitivity- clinical manifestation
serum sickness
what is serum sickness
observed after administration of antitoxins containing foreign serum
what happen with serum sicknees to the recipient?
develop antibodies specific for this protein. when these antibodies circulate, they form immune complexes with the protein
- after days-weeks, the symptoms occur
what are serum sickness symptoms?
- fever
- weakness
- generalized vasculitie (rash)
- edema
what happen when complexes accumulate in tissues
filtration of plasma occur and can contribute to the pathogensis of many other conditions such as autoimmune disease (hepatitis, malaria)
when would clinicial effect of type III hypersensitivity subside
when the antigen has been completely broken down
type IV hypersensitivity- mediators
- CD8+ tcells
- CD4+ t cells
- macrophages
why is type IV hypersensitivity different for mediators
not mediated by antibodies
type IV hypersensitivity- mechanism of reaction
- after exposure to an antigen, T-cells will become activated and initiate an immune response
- sensitized helper T-cells (TH1) will release cytokines that activate macrophages or cytotoxic T-cells which mediate direct cellular damage
type IV hypersensitivity- reaction time
- delay response
- 2-3 days to develop after exposure
type IV hypersensitivity- clinical manifestation
- inflammatory bowel disease (IBD)
- contact dermatitis
what is inflammatory bowel disease
- a group of conditions that is characterized by chronic inflammation of all or parts of the digestive tract
what are the most common inflammatory bowel disease
- ulcerative colitis
- crohns disease
does inflammatory bowel disease fall into a autoimmune disease?
yes- immune system attack own body
what is contact dermatitis?
- type of DTH response causing red itchy rash that has been in contact with small, reactive molecules whihc create complexes with skin proteins
common inducers of contact dermatitis
- poison ivy
- formaldehyde
- nickel
- cosmetics
erythrocyte sedimentation rate (ESR)
- the rate at which red blood cells sediment in one hour
- useful for diagnostic test marker for inflammation can help confirm the presence of a variety of diseases
C-reactive protein levels
- a marker of inflammation in the body
- CRP is a more accurate relfection of acute phase immune response (early induced innate immunity) than ESR
- more inflammation present in the body is reflected by increased levels of CRP
microcytic anemia
presence of small red blood cells
albuterol
used to relax muscles found in the airways to increase airflow to the lungs
AGPAR
is a score method to quickly summarize the health of a new born child
- is determined by evaluating the new born baby on five criteria
- appearance, pulse, grimace, activity, respiration on scale 0-2
a score above 7 is NORMAL
