Exam 2: Ch 16 Flashcards
4 types of hypersensitivity disorder
type 1: allergic reactions
type 2: antibody-mediated disorders
type 3: immune complex mediated disorders
type 4: cell mediated disorders
type 1: allergic reactions 2 subtypes
local (atopic) reactions
systemic (anaphylactic) reactions
when do type 1 allergic reactions begin
almost immediately after exposure to allergen
allergens are usually what type of molecule
proteins
pollen, food, animal dander, dust mites
immune system response to type 1: allergens
processed by macrophages
T helper cells (CD4) release cytokines which stimulate plasma cells to make and release IgE antibodies
IgE binds to mast cells (sensitized like memory cells)
hours later, esinophils recruited
mast cells that have been sensitized…
degranulate on subsequent exposure
release histamine, cytokines, etc
symptoms of type 1: allergic rxns
vasodilation
smooth muscle contraction
anaphylactic reaction (systemic)
can produce shock
must stabilize airway and give epi
prevent exposure, wear bracelet
local (atopic) allergic rxn examples
hives
dermatitis
hay fever
esinophils can also fight off _____
parasites
type 2: Ab mediated description
IgG or IgM mediated
directed against antigens on cell surfaces or in conn. tissue
3 types of type 2: Ab mediated
complement & Ab mediated cell destruction
complement & Ab mediated inflammation
Ab mediated cell dysfunction
complement & Ab mediated cell destruction
Ab coat abnormal cells
cells killed by complement system or phagocytosis
ex. blood transfusion rxn
complement & Ab mediated inflammation
Ab coat abnormal cells or react with extracellular proteins
complement activated –> chemotaxic factors
monocytes and neutrophils recruited
causes inflammation and tissue damage
examples of complement & Ab mediated inflammation
Goodpasture syndrome
glomerulonephritis and pulmonary hemorrhage from basement memb. inflammation
Ab mediated cell dysfunction
Ab inactivate/destroy or activate cells (receptors)
ex. Graves disease: Ab activate TSHr (hyperthyroidism)
Myasthenia Gravis: Ab inactivate AChr
type 3: immune complex mediated disorders
antigen-Ab complexes form in circulation and activate complement
inflammation and damage within blood vessels
ex. allergic rxns to drugs or food
type 4: cell mediated disorders
antigen presented to CD4 by APC
CD4 activates CD8 –> kill target cells w/ antigen
common response to intracellular parasites and part of autoimmune diseases
type 4 can also produce…
a delayed hypersensitivity rxn
CD4 secretes cytokines that recruit lymphocytes
inflammation results
ex. contact dermatitis, pneumonitis from inhaled antigens
HLA/MHC
human leukocyte antigen/major histocompatibility complex
antigens on surface of all body cells, individual specific
transplantation
taking tissue from 1 person and giving it to another
rejection
recipient’s (host) immune system sees donor HLAs as foreign and attacks the graft
autologous graft
donor & recipient are the same person
syngenic graft
donor and recipient are identical twins
allogenic graft
donor and recipient differ genetically
allograft rejection
host immune system recognizes graft antigens on organ surface or APCs
activates CD4 –> CD8 –> type 4 rxn
Ab may contribute
3 patterns of rejection
hyper acute
acute
chronic
hyper acute rejection
almost immediate type 3 rxn
results from preexisting Ab from previous blood transfusions
acute rejection
within months
involves T cells
chronic rejection
may involve fibrosis
cytokines
takes time
graft vs. host disease
most common following bone marrow transplant
graft attacks the host’s organs
host’s immune system compromised and can’t destroy graft
produces rash, GI sloughing, organ (liver) failure
what is an autoimmune disease
when the immune system attacks self
organ-specific or systemic
examples of organ-specific autoimmune diseases
thyrotoxicosis (Graves): TSH
pernicious anemia
Hashimoto thyroiditis
Addison’s disease
examples of systemic autoimmune diseases
lupus
scleroderma
rheumatoid arthritis
ulcerative colitis
immune tolerance
immune system “tolerates” self, only attacks foreign antigen
develops in fetal development
central tolerance
T cells reacting against self are eliminated in thymus
peripheral tolerance
immune cells including B cells that react against self are eliminated in the lymph organs
genetic susceptibility to autoimmune disease
families with specific HLAs prone
not everyone with HLA type gets disease, mechanism unclear
environmental factors of autoimmune disease (mechanisms)
T cells active against self when co-stimulators present
self-antigens that were held during development are released, prompting an immune response
molecular mimicry: microbe has antigen similar to self
super-antigens on microbes stim T cells w/o processing and binding to normal receptors
diagnosis of autoimmune disease
assay for Ab in patients with symptoms (fever, rash, inflammation)
treatment of autoimmune disease
steroids
immunosuppressants
primary immunodeficiency disorders
inherited or congenital – most recessive and x-linked
some traced to cytokines/signaling pathways
warning signs: multiple infections
many types
some signs of primary immunodeficiency disorders
8+ ear infections in a year
2+ sinus infections in a year
2+ pneumonia in a year
2+ deep-seated infections
2+ months on antibiotics that doesn’t help
b-cell immunodeficiency
most common primary immunodeficiency
stem cells –> pre-B in marrow –> lymph tissue maturation
mature B cells make specific Ab –> plasma cells when stim
transient hypogammaglobuinemia of infancy
delayed production of IgG –> multiple respiratory infections
usually resolves spontaneously
(infants protected by maternal IgG until 6mo of age)
X-linked agammaglobulinemia
recessive, more common in males
bruton tyrosine kinase needed for pre-B maturation
symptoms at 6-9mo, respond poorly to antibiotics
Rx: IVIG (intravenous immunoglobulin)
common variable immunodeficiency
differentiation of B cells to plasma cells blocked (affects 1+ types)
symptoms in teens to early adult
immunoglobulin G deficiency
respiratory infections
IVIG
T-cell immunodeficiency
more severe than B-cell deficiency
DiGeorge syndrome (thymic hypoplasia)
DiGeorge syndrome (thymic hypoplasia)
T-cell deficiency
developmental defect of thymus and parathyroid
associated w/ facial and cardiac defects
extent of defect variable
SCID severe combined immunodeficiency disorders
most x-linked and recessive, more common in males
survival rate w/o bone marrow transplantation
1 type: T, B, NK cells deficient
2nd type: T, NK, CD4 cells deficient, B cells elevated, Ab production abnomal,
AIDS is caused by ___ infection
HIV
34m ppl living, 1.7m died, 2.5m get it
most new infections in underdeveloped countries
sub-sarahan africa, racial minorities in US
recognized in 1981, IDed in 1984
transmission of HIV
sexual contact: body fluid contact w/ mucosa or open sore
blood to blood contact: shared needles
perinatal transmission: in utero or during delivery
occupational
seroconversion
when HIV Ab develop and become detectable
1-6 mo after infection
HIV virus structure
HIV 1 & 2 (1 most common in US & europe, 2 in africa)
retrovirus (RNA)–core surrounded by lipid envelope
2 copies of RNA in core, p24 protein (target of Ab screen) and p17 protein (surrounds core)
3 enzymes: Rev. transcriptase, integrase, protease
enzyme order HIV
reverse transcriptase (transcribes RNA into dsDNA)
integrase (dsDNA integrated into CD4 genome)
(transcription, translation happens)
protease (breaks polyprotein into pieces)
new virus built from pieces and HIV released from cell
HIV infects which type of cells
CD4–binds to receptors and other surface molecules (CCR5)
requires glycoproteins gp120, gp41
virus memb. fuses to CD4 so RNA and enzymes can enter cell
HIV replication starts at…
site of infection
many CD4 cells infected by day 10
people with HIV generally asymptomatic until CD4 count falls
classification of HIV phases
HIV+ said to have AIDS if:
CD4 count less than 200cells/microliter
or have an AIDS-defining illness
HIV stage 1 and 2 and 3 (AIDS)
T cells greater than or equal to 500
2: T cells between 200-499
3: T cells less than 200
primary HIV infection
mono-like symptoms (fever, fatigue, myalgia, sore throat)
viral replication rapid
CD4 count falls
treatment beneficial
latent period of HIV infection
viral load is low, but CD4 count falls over time
lymphadenopathy develops
overt AIDS
viral load climbs
CD4 count less than 200/ul or AIDS-defining illness
opportunistic infections and cancer develops
what is the leading cause of death for AIDS
TB
respiratory manifestations of AIDS
pneumocystis pneumonia (fungal spores)
common pneumonia like strep, pseudomonas, H flu
PCP–less common since HAART
mycobacterium TB: multiple drug resistant strains
GI manifestations of AIDS
esophageal candidiasis
herpes simplex (esophageal)
gastroenteritis: protozoal or bacterial (stool culture)
NS manifestations of AIDS
HIV-associated neurocognitive disorders (HAND)
cognitive and motor impairment
toxoplasmosis: parasitic brain infection
antibiotics
Kaposi sarcoma
endothelial cell malignanacy in AIDS
opportunistic cancer linked to herpes
lesions on skin and in mouth, in internal organs (lungs)
HAART may be effective
non-hodgkin lymphoma
AIDS cancer
may undergo remission with HAART
cervical and anal carcinoma
AIDS cancer
from HPV
wasting syndrome
AIDS
weight loss, diarrhea, chronic weakness, fever
Rx: appetite stimulants
3 metabolic disorders associated with AIDS
insulin resistance
hypercholesterolemia/triglyceridemia
lipohypertrophy
might need to switch anti-retroviral drugs
insulin resistance (AIDS)
higher among those with HIV
medications may contribute to development
hypercholesterolemia/triglyceridemia
HIV and medications contribute to development
monitor lipids closely
use statins with caution
lipohypertrophy
buffalo hump right below back of neck
prevention of HIV infection
condoms
avoid recreational drug use, sharing needles
routine screening
education
diagnosis of HIV
HIV Ab test: ELISA + western blot if initial is ( + )
western blot is more specific (less false pos)
oral swab for at home use (both ELISA and western blot)
PCR: detects HIV, not Ab (used earlier)
HAART
combination of 2 or 3 anti-retroviral drugs
reverse transcriptase inhibitors
protease inhibitors
entry inhibitors
integrase inhibitors
reverse transcriptase inhibitors
block RNA –> DNA conversion
block elongation of DNA by adding fake nucleotide or inhibit enzyme
integrase inhibitors
prevent integration of viral cDNA into cell genome
protease inhibitors
block cleavage of viral proteins by binding and inhibiting enzyme
entry inhibitors
prevent HIV from binding to or entering CD4 cells
