Module 4 - Adverse Reactions and Immune Defects Flashcards
What is immunodeficiency?
a disorder or condition where the IS has reduced function or is absent and can be traced to the failure of one or more parts of the immune system
2 types of immunodeficiencies
primary and secondary
Primary Immunodeficiency
Cogenital and derive from a genetic or developmental defect leading to abnormal maturation of the IS. May be associated with defects in innate or adaptive immunity
cogenital
present from birth
why are primary immunodeficiencies rare?
in most cases, the foetus will not survive
Secondary Immunodeficiency
acquired and a result from environemental factors affectong and compromising the IS
what is the most well studied secondary immunodeficiency?
AIDS, the causitave agent being HIV
causes of secondary immunodeficiency?
-undergoing chemo
-immunosuppressive medication
-chronic infection
-cancer
Grouping primary immunodeficiecies
according to the faulty component of the immune system. Deficiencies:
-B-cell
-T-cell
-Complement
-Phagocytic
-Combined B and T cell
B-cell deficiencies
-characterized by dysfunctional B lymphocytes or a decrease in their prevalence
-deficiency in B-cell development results in an increased susceptability to infection, especially by encapsulated bacteria
encapsulated bacteria
encompass both Gram-positive and Gram-negative bacteria with the unifying feature being the production of capsule composed of polysaccharides
T-cell deficiencies
-characterized by dysfunctional T-lymphocytes or a decrease in their prevalence
-a deficiency in T-cell development results in an increased susceptability to viruses, protozoans and fungi
why do first symptoms of B-cell deficiencies usually appear around 7-9 months old?
during breastfeeding, the mother transfers IgG to the baby, around 7-9 months the antibody pool from the mother decreases. Because of B-cell deficiency, the infant is not able to synthesize normal levels of antibodies to compensate
when do T-cell deficiencies occur?
-3-4 months after birth
Complement Deficiencies
-prone to frequent severe bacteria infections and complications arising from inability to clear immune complexes
C3 deficiencies
-display severest symptoms
Phagocytic Deficiencies
-deficiencies can appear at various stages
-bacterial and fungal infections are frequent and severe
- causing deep abscesses
Combined B and T cell deficiencies
-dysfunctional and/or low numbers of lymphocytes
-both hummoral and cell-mediated responses of ADAPTIVE IS are compromised
-characterized by little or no resistance to infection, thus pathogens that cause mild diseases in average human may be life threatening (chickenpox)
-suffer fatal infections in the first year of life
what does AIDS stand for
Acquired Immunodeficiency Syndrome
what does Acquired in AIDS stand for?
individuals do not inherit this type of disease, which is a major difference between AIDS and other primary immunodeficiencies
what does Immunodeficiency stand for in AIDS
the one disease characteristic AIDS has in common is the breakdown of their immune system
what does Syndrome stand for in AIDS
the plethora of rare but ravaging diseases that take advantage of the body’s collapsed defences
Mode of transmission of HIV in north america
sexual intercourse is primary transmission of HIV
Mode of transission of HIV in eastern europe and central asia
non-sterile injecting drug paraphenalia is the parimary mode of transmisison
Mode of transmission of HIV in Africa
heterosexual sex with a contaminant epidemic in children (mother to child)
HIV outcomes without treatment
immunosuppression, neuropsychiatric abnormalities and death
HIV: primary infection
-mount an effective immune response for first couple weeks
-over time this response will provide ineffective through the various stages of the disease, as the HIV virus compromises the individuals IS
stages of HIV infection
- Primary Infection
- Acute Infection
- Chronic Infction
- AIDS
CD4 T lmphoyte count at primary infection
HIGH
HIV: acute infection
-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
-HIV in blood is HIGH increasing risk of transmission
2-4 weeks after primary exposure to HIV
why do CD4+ cell levels stop crashing?
CD4+ helper T cell levels increase after the initial decrease, as some antibodies are formed against the virus allowing the immune system to recover some of the lost cell population
HIV: Chronic Infection
-clinical latency
-HIV continues to multiply in the body at a steady state
-do not experience any HIV-related symptoms, transmission is still possible
-Anti-HIV antibodies are detectable
-HIV can begin to evade the immune response that is present by changing antigens through high mutation rates
-8-10 years
HIV: AIDS
-CD4 helper t cells get exhausted
-diagnosed with AIDS if CD4 level less than 200 cells/mm3
-viral load drastically increases as the virus continues to acquire mutations that allow it to further avoid immune defenses
-as the IS is weakened, patients become susceptible to infections
-survive for about 3 years
Antiretroviral therapy
-firs twas approved in 1987
-do not sure or kill HIV but prevent it from replicating
-led to declines in AIDS
which immune cell does HIV preferably replicate in?
Helper T cells
Autoimmunity
when the IS initiates a reaction in response to its own cells (overactivated and attacks healthy cells)
Autoimmune Disease
-failure of an organism to distiguish self from non-self and any disease that results from this is an autoimmune disease
how much of the human population do autoimmune diseases affect
5-7%
Gender Rates wthin autoimmune disease population
78% of people with autoimmune disease are female
What is the main cause of an autoimmune disease
-genetics (mainly)
-infection by bacteria/virus
-chemical exposure
two classifications of autoimmune diseases
organ-specific and systemic
Autoantibody
produced by the immune system that is directed against a self antigen
Organ-specific Autoimmune diseases
-immune response directed to an antigen that is unique to a single organ or gland
-disease manifestations are limited to specific organ
Most common target organs of auntoimmune diseases
-thyroid
-stomach
-adrenal glands
-pancreas
Thyroid organ specific autoimmune disease
Graves, overactivty of thyroid gland, known as hyperthyroidism
Graves Disease
Thyroid-stimulating hormone (TSH) is produced by pituitary gland to regulate hormone production. Graves patients produce autoantibodies that engage TSH receptors resulting in an overproduction of thyroid hormones
Goiter
enlarged thyroid due to overstimulation of thyroid cells. Other symptoms include weightloss, rapid heartbeat, irritability, poor regulation of body temp etc
Systemic Autoimmune Diseases
-immune response is directed towards a broad range of antigens that are characteristic of a number of organs and tissues
Rheumatoid arthritis
-systemic autoimmune disorder that presents as chronic inflammation of joints, other organ systems can be affected
-common women age 40-60
How does Rheumatoid arthritis ocurr?
-produce autoantibodies most commonly IgM to portion of the Fc receptor of IgG (rheumatoid factors)
-factors bind to ciculating IgG forming immune complexes that become deposited in joints
-deposits activate cascade leading to prolonged inflammation and joint tissue damage
cure for autoimmune diseases
none
treatment for autoimmune disease
immunosuppression; reducing strength of bodys immune response
in additon to autoimmune drugs, when would immunosuppressants be used
organ transplant, during this time paitents may not be able to fight infection as their immune system is inhibited
Understanding rejection: 3 signals of inflammation
T-cell activation signal:
1. Antigen Presentation
2. Co-stimulation
3. Proliferation
4 main classes of immunosupressive drugs
- Corticosteriods
- Cytotoxic drugs
- Immunophils
- Lymphocyte-depleting Therapies
Corticosteriods
Anti-imflammatory; kills T-cells
Cytotoxic Drugs
Blocks cell division nonspecifically
Immunophilin
blocks T cell response
Lymphocyte-depleting Therapies
Kills T-cells non-specifically, kills activated T-cells
Side effects of immunophilin
Drug: Cylosporine
Effects: nephrotocicity, hypertension, hirsutism, hypertrichosis, gingival hyperplasia
Side effects of Cytotoxic drugs
Drug: Methotrexate
effects: nausea, vomitting, hair loss, tired, dizzy, chills, headache, sores, skin infection, sun sensitivity, rash, stuffy, low blood cell levels…
Drug: Cyclophosphamide
Effects: nausea, vomitting, loss appetite, stomach ache, diarrhea, darkening of skin/nails
Side effects of corticosteriods
Drug: Prednisone
Effects: osteoperosis, hirsutism, hypertrichosis, diabetogenic
types of infections immunosupressive drugs can have on the host due to weakend immune system
Latent or Opportunistic infections
Latent Infections
-infections that are inactive, hidden or dormant
Most common: TB, HSV1/2, CMV, EBV and VZV
Opportunistic Infections
-commonly occur when there is reactivation of pathogen that is already present in the host
-also result when pathogen is picked up but the blunted immune response of host is unable to combat pathogen
-can arise from bacteria, viruses, parasites or fungi
FUNGAL opportunistic infections
-Pneumocystis
-Cryptococcosis
-Candidiasis
-Aspergillosis
Pneumocystis Jiroveci
common name: PCP
Infects: pneumonia of lungs
Cryptococcosis
common name: Crytptococcal Disease
Infects: Lungs, may spread to brain
Candidiasiss
Common name: thrush
Infects: mouth, throat & vagina
Aspergillosis
Infects: Lungs
BACTERIAL opportunistic Infections
-tuberculosis
-Mycobacterium Avium COmplex
Tuberculosis
common name: consumption
Infects: Lungs
Mycobacterium Avium Complex
common name: MAC
Infects: lungs, lymph nodes, or entire body depending on site of infection
PARASITIC opporitunistic infections
Toxoplasmosis
Toxoplasmosis infects:
skeletal muscle, myocardium, brain and eyes
VIRAL opporitunistic infections
-Cytomegalovirus
-Herpes simplex virus
-Varicella Zoster Virus
-Mononucleosis
Cytomegalovirus
common name: CMV
infects: eyes, brain, other internal organs
Herpes Simplex Virus (HSV)
common name: herpes
infects: mouth, skin, lips, eyes & genitals
Varicella Zoster Virus
common name: chickenpox
Infects: skin or internal organs
Mononucleosis
Common name: Epstein Barr virus or kissing disease
infects: lymph nodes, throat, salivary glands, liver, spleen & blood
Hypersensitivity
excessive reactions produced by the normal immune system. Clinical conditions cary based on the mechanisms involved and time taken for rxn to develop
Hypersensitivity Type I
Immediate/Anaphylaxis
ex. allergies
Hypersensitivity Type II
Cytotoxic
ex. blood diseases like transfusion reactions OR Hemolytic disease of the newborn
Hypersensitivity Type III
Immune complex-mediated
ex. Comtribute to development of autoimmune diseases: systemic lypus OR rheumatoid arthritis
Hypersensitivity Type IV
Delayed Type
ex. Skin reactions: contact dermatitis
Mediators for type I hypersensitivity
Allergens: normally a harmless substance, but in this case produces an abnormal immune response called allergic reaction
8 major food allergens
-milk
-eggs
-wheat
fish
-crustacean shellfish
-tree nuts
-peanuts
-soya
what cells do allergens affect
IgE, Basophils and mast cells
Mechanisms of reactions to allergens
primary and secondary
primary exposure to an allergen
the allergen induces hummoral response where plasma cells secrete an excessive amount of IgE antibodies whiich bind to mast cells and basophils
secondary exposure to same allergen
membrane-bound IgE cross-links with the allergen which initiates degranulation of basophils and mast cells, releasing vasoactive mediators causing vasodilation and smooth muscle contraction
degranulation
release of granules
Reaction time of Type I hypersensitivty reactions
can be immediate (minutes for anaphylatic) and can lead to death in as little as 15 mins. Rarely type 1 reactions take longer (after 24 hrs) but most occur soon after exposure
Clinical manifestations of Type I hyper sensitivity
-Allergic rhinitis
-Atopic dermititis (eczema)
-Asthma
-Hives (urticaria)
Mediators of type II hypersensitivity
-IgG
-IgM
-NK cells
-the complement system
Mechanism of reaction for type II hypersensitivity
-IgGs/IgMs bond to antigens on the surface of cells such as erythrocytes
-once antibodies attached through antigen-binding regions, the Fc region is free and can activate 2 processes: CLASSICAL COMPLEMENT ACTIVATION (leading to MAC or opsonization) & ANTIBODY DEPENDENT CELL MEDIATED TOXICITY
-these mediate destruction of cells, leading to excessive inflammatory response
Membrane Attack complex
creates holes in cell membrane leading to cell lysis
Opsonization
leads to phagocytosis by phagocytes such as macrophages
Type II hypersensitivity reaction time
minutes to hours
clinical manifestation type II hypersensitivity
-Drug induced hemolytic anemia
-Transfusion rxns
Transfusion rxns
Depending on blood type, you will only be able to safely recieve ceratin blood types during a blood transfusion. This is due to expression of specific antigen on your RBCs, meaning if you dont express antigens, you have the antibodies against them
Drug Induced Hemolytic anemia
-Some antibiotics can bind nonspecifically to proteins on RBC membranes and form complex which sometimes induced complement-mediated cell lysis
-As RBCs rupture, the # of RBCs decrease resulting in anemia
-anemia disappears when drug removed
*pennicillin
universal donor
O negative
Universal reciepnt
AB
Type III hypersensitivity mediators
-Immune complexes (antigen-antibody complexes)
-Neutrophils
-Complement proteins
Mechanism of reaction type III hypersensitivity
-the reaction of antibodies with antigens generates immune complexes. When immune complexes are not cleared, they can accumulate and deposit in tissue
-the immune complexes will activate the complement which will induce inflammatory reactions through neutrophil attraction to the site of deposition
-Neutrophils release lytic enzymes as they attempt to phagocytose the immune complexes, which weakens surrounding cell membranes causing tissue damage
Type III hypersensitivity reaction time
3 to 10 hours after exposure to an antigen (sometimes days to weeks)
Clinical manifestation Type III hypersensitivity
Serum sickness
Serum sickness
-rxns are observed after administration of antitoxins containing foreign serum
-recipent of antiserums develop specific antibodies for this protein & form immune complexes
-after days -week symptoms occur
-complexes accumulate in tissues where filtration of plasma occur and can contribute to pathogenesis
-clinical efects subside when antigen broken down
whats an antitoxin
and antibody that counteracts a toxin
Type IV hypersensitivity mediators
-CD8+ cytotoxic T cells
-CD4+ Helper T cells
-Macrophages
***only type of hypersensitivity NOT mediated by antibodies
Type IV Hypersensitivtiy mechanism of Reaction
-after exposure to antigen, T cells become activated and initiate an immune response
-sensitized helper T cells will release cytokines that activate macrophages or cytotoxic T cells which mediate direct cellular damage
Type IV Hypersensitivtiy Reaction time
two - three days
Type IV hypersensitivity clinical manifestation
-Inflammatory Bowel Disease
-Contact Dermatitis
Inflammatory Bowel Disease
group of conditions characterized by chronic inflammation of all or parts of digestive tract
2 most common: chrons & collitis
-falls into class of autoimmune disease
Contact Dermatitis
-type of DTH response causing red itchy rash on skin that has been in contact with small, reactive molecules which create complexes with skin proteins
-poison ive, formaldehyde, nickel …
Erythrocyte sedimentation rate (ESR)
rate at which RBC sediment in one hour
*non-specific measure of inflammation
Microcytic anemia
presence of small RBC
what type of hypersensitivity does not involve antibodies and is only cell-mediated
type IV
Albuterol
used to relax muscles found in the airways to increase airflow to the lungs
Asthma
-abnormal inflammatory response to a specific or nonspecific stimuli in the bronchial lining, resulting inn obstruction of small and large airways
-muscles contract and become inflammed
-increase in mucous secretion
which immunoglobin is responsible for asthma
IgE
what type of hypersensitivity is asthma
Type I
