Immunity and HIV

pathogen

microorganisms capable of causing infectious disease

host

organism that exhibits signs and symptoms of disease

infection

invasion, colonization, and multiplication of pathogens in host

virulence

organisms ability to produce disease in host

reservoir

where pathogens live of and be found

vectors

organisms that carry pathogen to reservoir to the host

chain of transmission

reservoir→ portal of exit→ mode of transmission → agent → portal of entry → host

normal microbial flora

live in or on the human body is specific spaces

perform advantages functions

• secrete nutrients

• perform necessary metabolic activites

• help to defend the body against other microorganisms

do not cause infection or disease when within normal area

clinicians cautious that normal flora not enter sterile sites during procedures

Bacteria

categorized according to shape, aerobic or anaerobic respiratory capability and lab stains

named by genus

lab staining

gram positive: thick-walled, stains purple

gram negative: thin-walled, stains pink

Viruses

microorganisms that depend on host cell’s metabolic processes for their life cycle

consist of DNA or RNA genome surrounded by proteins coat

can cause:

• acute, transient illness (influenza or rhinovirus)

• chronic illness (Hep B)

• cancer (HPV)

treated with antiviral, NOT antibiotics

viral infection

1. virus attaches to cell

2. virus enters the cell

3. virus releases genetic material

4. nucleus replicates viruses genetic material

5. organelles in cell reconstruct virus

6. new virus breaks out of cell

immunocompetence

ability to protect oneself from infections

immunosuppression

defective immune system

opportunistic infection

“opportunity” (weakened immune system, compromise of physical barriers, etc)

hospital-acquired or healthcare acquired infection

infection originates within clinical environment

portals of entry: Skin (transdermal, bite, or cut)

thick, dense composition; pH 5.5

influenced by hormones, nutrition, physical activity, environmental exposures, and systemic disorder

normally colonized with staph, strep, and candida

intact skin is barrier

portals of entry: respiratory tract (inhalation)

possible entry points for thousands of microorganisms

cilia, mucous membranes, sneezing, coughing, specialized immune cells help reduce infections

subject to viruses, bacteria and fungal organisms: through droplet infection

portals of entry: GI tract (ingestion)

fecal-oral route (contaminated food and/or water; inappropriate food preparation)

acidic environment, mucosal lining, normal flora

portals of entry: GU tract (sexual transmission

urine outflow, mucosal lining, low vaginal pH from normal flora

female anatomy predisposed to UTI

E. coli in the bowel

unsafe sexual practices

portals of entry: blood to blood (injections)

blood transfusions, needle sticks, bites, cuts, via the eye and naso-oral mucus membranes

universal precautions

portals of entry: maternal-fetal

placenta and fetal circulation; vaginal passageway

congenital infection

antigens

things (bacteria, viruses, etc) that are recognized as “non-self” targets by the immune system

when identified, inflammation and immune response result in action to destroy or remove the pathogen through cellular response

stages of infection

incubation

prodromal

acute

convalescent

resolution

incubation stage

period when microorganism begins replication without identifiable symptoms

short as 24 hours or 2-3 mouths

prodromal stage

initial symptoms appear, often vague and general

acute stage

full infections disease signs and symptoms are present and the immune systems is fully engaged

convalescent stage

body containing the infection and progressively eliminating the pathogen

days, weeks, months

resolution period

pathogen eliminated from the body

two primary levels of immunity

innate immunity

adaptive immunity

innate immunity

non-specific cellular reactions

first level of defense against all types of pathogens

anatomical barriers (skin, mucous linings, etc.)

when triggered causes an acute inflammatory reaction (aka cellular response)

includes the white blood cells, complement system, coagulation system, and cytokines

granulocytes

look like cytoplasmic granular

originate in bone marrow

basophil, neutrophil, eosinophil

basophli

help body defend against allergens, pathogens, and parasites

account for less than 1% of total WBC count

lifespan: 1-2 days

neutrophil

lifespan: 10 hours to a few days

when mature ones die, the bone marrow releases immature neutrophils called bands

begin the process of phagocytosis

Eosinophil

protect the body from the parasites, allergens, foreign bacteria, and outside organisms

larger than most cells and make up less than 5% of the WBC count

if high, may be due to a contagious infection or parasite

half life: 4.5 to 8 hours

primary reside in the respiratory tract and GI tract

Agranulocytes

contain agranular cytoplasm

monocytes, macrophages and lymphocytes

originate in the lymphatic system and contain enzymes

white blood cell response

1st 6-24 hrs: neutrophils; neutrophils gradually replaced by monocytes

24-48hrs: monocytes to macrophages

• macrophages predominate in persistent inflammation

• macrophages carry out phagocytosis

viral infections: lymphocytes dominate

differentiated blood cell count

aka CBC with diff

measures the percentage of each type of WBC

aides in diagnosing various conditions including infections, immune system disorders, and certain types of cancer

tells us what kind of reaction it is

bands = immature neutrophils

• “shift to the left” = increase # of bands

• indicates an acute inflammatory process

inflammatory response

acute inflammatory reaction triggered when innate immune system is stimulated

includes WBCs, the complement system, and cytokines

local manifestations: redness, heat, swelling, pain, and loss of function [all indicative of histamines working in the body]

acute inflammatory response

hours to days

rapid reaction

removes the offending agent

heals

chronic inflammatory response

reaction persists

healing is inhibited

continual cellular damage and organ dysfunction

characteristics of acute inflammation

rapid onset

terminates quickly

chemical mediators orchestrate response

3 phase

1. increase vascular permeability

2. cellular chemotaxis

3. systemic response

Vascular Permeability [phase 1]

histamine and bradykinin: dilate vessels

fluid, WBCs, platelet injury travel to injury

toxins diluted

WBCs phagocytize foreign matter and debris

5 classic signs of inflammation

injury

rubor, calor- redness, heat

tumor- swelling

dolor- pain

loss of function - formation of scab

cellular chemotaxis [phase 2]

chemical agents from WBCs, endothelial cells, and microbial agents

• chemotaxis, margination, leukocytosis, leukemoid reactions, WBC differential

chemotaxis

chemical signals attract WBCs, and platelets

margination

WBCs line up along endothelium, release inflammatory mediators

leukocytosis

increase in WBC number- includes all components

normal WBC 5,000-10,000

Leukemoid reactions

extreme elevation in WBC

WBC differential

different types of WBCs

Systemic Response [phase 3]

fever

• common manifestation of inflammation and infection

• microbial organisms, bacterial products, and cytokines all act as pyrogens

• activate prostaglandin (PGs) to reset the hypothalamic temperature-regulating center in the brain to a higher level

• higher body temperature is theorized to increase the efficiency of WBCs in their defense

chills

• new set point in the hypothalamic temperature-control center (higher)

• vasoconstriction and muscles shiver to generate body heat

• when fever resolves, pyrogens stop stimulating PGs and the body adapts to the new, lower hypothalamic set point

• vasodilation (flushing) and intense sweating (diaphoresis) occurs

pyrogens

release heat

first leukocytes of the immune response

neutrophils

predominate in early inflammatory responses (show up in 24-48 hours)

ingest bacteria, dead cells, and cellular debris = phagocytosis

have short live (10 hours-days) and when done become part of the purulent exudate (thick, milky discharge)

monocytes

patrol along the vascular system to detect inflammation

migrate to the site and turn into macrophages

macrophages

arrive at the site of inflammation 24 hrs or later then the neutrophils

work to find and destroy germs and repair tissues

leukocytosis- high WBC

Adaptive/Acquired Immunity

allows the body to recognize an antigen, target the specific antigen, limits its exposure to the antigen, and develop memory for future response= specificity

recognizes “self” from “non self”

two major categorizes:

• B lymphocyte immunity (humoral immunity)

• T lymphocyte (aka T cells) immunity (cell-mediated immunity)

B lymphocytes (B cells): humoral response

produce antibodies after being activated by an antigen

each cell responds to only one specific antigen

produced in the bone marrow

matured in the spleen

T lymphocytes (T cells): cell mediated response

produced in the bone marrow

mature in the thymus gland

with age, the function of thymus decreases and number of T cells decrease

CD4 cells (“helper cells”)

• influence (“help”) other T cells, B lymphocytes, macrophages

• involved in celled-mediated immunity and assist in anitbody-mediated adaptive immunity

CD8 cells (“killer cells”)

• directly attack an antigen

“self” vs “non-self”

function of the adaptive/acquired immune system

human cells have surface antigens called major histocompatibility complexes (MHCs), also called human leukocyte antigens (HLAs)

antibody mediated immunity (aka humoral immunity)

immature B lymphocytes (B cells) → encounter an antigen → B cells mature into plasma cells → plasma cells produce immunoglobulins (Igs) aka antibodies → antibodies attack the antigen

IgM

aka macroglobulin

earliest immunoglobulin to respond to infection

IgG

most abundant

most important anti pathogenic immunoglobulin; commonly involved in autoimmune disease

IgA

most abundant in mucosal secretions

mucosal secretions (sweat; saliva; tears; breast milk; nasal, bronchial, and digestive tract secretions)

IgE

abundant in skin, mucous membrane, and respiratory tract

respond to antigens that commonly cause allergic reactions (pollen, animal dander, dust)

IgD

found in skin, GI and resp tracts

bind to basophils and mast cells in hypersensitivity reactions

active immunity

antibodies produced by own body

nature active immunity

antibodies produced after illness

artificial active immunity

antibodies produced after vaccination

passive immunity

antibodies obtained from others

natural passive immunity

antibodies obtained from mother to baby

artificial passive immunity

antibodies obtained through injection

staphylococcal infections

gram positive round (cocci) bacteria that forms clusters

Staphylococcus aureus (S. aureus) colonizes the skin, vagina, nares, and oropharynx as normal flora

S.aureus: leading cause of hospital-acquired infections and surgical wound infection

Resistant Staph

S. aureus has developed resistance to many antibiotics, and strains such as methicillin-resistant S. aureus (MRSA) and Vancomycin-resistant S. aureus (VRSA) are commonly encountered in clinical settings

Clostridium difficile aka C diff

spore forming, toxin secreting, anaerobic bacteria

• the organism emits toxins that disrupt the intestinal mucosa, erode the intestinal epithelial cells, and forms pseudomembranes that contain necrotic tissue

• the most predisposing factor is long-term antibiotic use because of consequent alteration of the normal flora in the gut

• contagion between patient is possible; this is a source of hospital acquired infections

immune deficiencies

failure of immune mechanisms of self-defense

primary (congenital) immunodeficiency

secondary (acquired) immunodeficiency

primary (congenital) immunodeficiency

• most manifest during infancy (6 months-2 years)

• deficiencies of innate or adaptive immunity

• more x linked = greater manifestation in males

secondary (acquired) immunodeficiency

caused by another illness

also referred to as acquired deficiencies

far more common than primary deficiencies

cause: normal physiology condition, psychologic stress, dietary insufficiencies, malignancies, physical trauma, medical treatments, infections, acquired immunodeficiency syndromes (AIDS)

Autoimmune disorders

healthy immune system can precisely distinguish “self” from “non-self”, and its purpose is to preserve and protect the body from injurious “non-self” invaders

T cells or Igs cannot make a distinction between non antigenic cell surface markers and antigenic foreign cell surface markers

immune system becomes intolerant to its own cells, attacks its own tissues, and renders organs dysfunctional

body develops Igs against is own tissue, known as autoantibodies

can be organ- specific or widespread and generalized

systemic lupus erythematosus (aka lups)

multisystems

characterized by autoantibodies, particularly antinuclear antibodies (ANA)

chronic disease that can have an acute or gradual onset

remission and exacerbations

symptoms: fever, skin rash, joint inflammation, and damage to kidneys, lungs, and serosal membranes

SLE factors

mainly a disease of women, particularly of childbearing age

African American women are2-3 times more likely than European Americans

cause: unknown

risk factors: genetic predisposition, environmental, hormonal (estrogen), and immunological elements. those with EBV antibodies have increased risk

medications such as hydralazine, procainamide, quinidine, phenytoin, isoiazid, and penicillamine can produce SLE like reactions

SLE patho

formation of autoantibodies (ANAs) -two types

addition of antiphospholipids antibodies in some increases risk of artial and venous thromboembolism (clot)

immune complexes form from the antibodies that are deposited in the organs/tissues

these complexes are deposited in the tissues and then cause inflammation reactions which damage the small blood vessels and organ membranes

mircovasculature of organs have destruction -affects all organs

SLE clinical presentation

presentation depends on organs affected

unpredictable over many years

general:

• fever, fatigue, myalgia, arthralgia (vague and often misdiagnosed)

• joint inflammation and musculoskeletal symptoms in 90% of cases

• butterfly rash across bridge of nose

kidney (lupus nephritis):

• inflammation cause glomerular damage

• nephrotic syndrome- HTN and hematuria are common, edema

• raynaud’s phenomenon- episodic vasospasm of the finger arteries

heart:

• CAD

• pericarditis endocarditis

lungs:

• inflammatory changes include pneumonitis, pleuritic, pulmonary HTN,effusions, dyspnea, cough

blood cells:

• leuokpenia, anemia, thrombocytopenia

other:

splenic enlargement

vasculitis

SLE diagnosis

based on history, physical exam and labs

no lab test can diagnosis SLE, just supports

11 clinical findings/labs, 4 must be present

immunoflurescent ANA test

more than 95% have high ANA levels

abnormal labs:

CRP and ESR - show inflammation

CBC- anemia, leukopenia, thrombocytopenia

UA- proteinuria, cast, pyuria

creatine

liver enzymes

imaging

Xray, mri, biopsy

viral replication

not capable of independent reproduction

need permissive host cell

DNA replicates in nucleus

RNA replicates in cytoplasm

Human immunodeficiency virus (HIV)

virus that infects CD4 cells (T helper cells) and macrophages

infections has 3 stages: acute, chronic, AIDS (acquired immune deficiency syndrome)

fragile virus transmitted only through contact with body fluids

HIV slowly debilitates body immune systems, both T cell and B cell immunity

routes of transmission of HIV

sexual activity; semen and vaginal secretions

blood

trans-placental

breast milk

organ transplants

saliva (into open mouth wounds)

high risk individuals:

• participate in unsafe sex with multiple partners

• MSM (men who have sex with men)

• IV drug users sharing needles

HIV data

HIV-1 is more common in US

retrovirus: has RNA as its genetic material and comes equipped with its own enzyme called reverse transcriptase, that can convert its RNA into DNA

HIV timeline

following initial infection, detectable antibody levels develops in 2 weeks to 6 months

early in disease - asymptomatic - but can infect others

“latent period”

over time, CD4 level falls, as HIV RNA levels increase

Less than 500 CD4 cells/microliter increase opportunistic infectious risk

less than 200 CD4 cells/microliters lead to AIDS classification

HIV RNA levels

measurement of viral loaf; how many viral particles are present in the blood

• earliest test to detect HIV infection

formation of antibody takes a prolonged time

• 2 weeks- 6 months

• test for HIV antibody = ELISA/Western Blot test

HIV Latent period

as virus increases in blood → CD4 level decrease in blood → increasing vulnerability to opportunistic infection

AIDS diagnosis

at 200 CD4 cells= acquired deficiency syndrome (AIDS)

HIV antibody

presence of opportunistic infection

• pneumocystic pneumonia, tuberulosis

• malignancies: kaposi sarcoma, non-Hodgkin’s lymphoma