Disorders of the immune system?

What are natural killer cells?

Granular lymphocytes that destroy tumor cells and virus-infected cells

What type of immunity are T cells involved with?

Cell-mediated immunity

What type of immunity is B cells involved in?

Antibody-mediated immunity (humoral immunity)

What is the MHC?

Major histocompatibility complex that helps recognize self vs non self

What are the antigen presenting cells?

Macrophages, dendritic cells, present antigen to activate T cells

What are CD4 cells? CD8?

CD4- helper T cells

CD8- cytotoxic T cell

What are plasma cells?

Activated B cells that produce antibodies known as antibody-mediated or humoral immunity. Happens when antigens activate a specific B cells. First response takes time and the activated B cell forms a memory cell.

What produces immunoglobulins? What do they do?

Produced by B cells and they bind to specific antigens

What is the primary response?

First exposure to antigen, there is a lag time before Ig levels increase, the first antibody is IgM

What is the secondary response?

Any exposure after the first in which IgG levels increase rapidly due to memory cell response, and the antigen is neutralized before disease signs and symptoms appear

What is IgA?

Immunoglobulin A, mainly found within secretions (tears, saliva, respiratory secretions, GI fluids, breast milk

What is IgE?

Immunoglobulin E, usually present in very low concentrations in the blood, usually elevated during allergic reactions

What is IgD?

Immunoglobulin D, found in hypersensitivity reactions, comprises only 1% of Igs

What is active acquired immunity?

Exposure to antigen through illness of vaccination. Forces the immune system to activate and produce memory cells.

What is passive acquired immunity?

Individual receives premade antibodies that provide immediate immunity, but short-term (antibodies transferred from breast milk)

What are vaccines?

A specific formulation that constrains a weakened, non disease producing pathogen that expose the body to the antigen without disease contraction

What is a booster?

Additional dose of vaccine to stimulate the immune system’s antigenic memory

What is a toxoid?

Vaccine produced against toxin-producing bacteria

What are antibody titers?

Antibody screening tests that indicate presence and level of antibodies, can be used to indicate exposure to disease and indicate immunity

What are basic immune disorders?

Overreaction (hypersensitivity disorders, autoimmune disorders)

Underreaction (immunodeficiency, primary = congenital at birth, secondary = acquired and develops due to infection, chemo, etc)

What is type 1 hypersensitivity?

Immediate hypersensitivity, antigen interacts with antigen-presenting cell that activates B cells and produce IgEs that bind to mast cells and cause degranulation (release of chemicals from mast cells) and induce allergy symptoms

What are some signs of type 1 hypersensitivity?

Local or systemic response

Hives (urticaria), nasal discharge, bronchial asthma, allergic gastroenteritis

Allergic rhinitis (allergen causes release of histamines, PGs, leukotrienes causing hypersecretion, bronchiole constriction, pale nasal mucosa, watery eyes, sneezing)

What is anaphylaxis?

Severe, life-threatening allergic response where death can occur in minutes. Presents as urticaria, bronchoconstriction, laryngeal edema, angioedema (face swelling). EpiPen may be used.

What is type 2 hypersensitivity?

Cytotoxic hypersensitivity where Igs attack antigens on cell surface causing an antibody-mediated cell lysis results. An example is blood transfusion reaction.

What is type 3 hypersensitivity?

Immune complex hypersensitivity in which an antigen-antibody complex is deposited in tissues known as an immune complex reaction. Result is tissue damage that may be systemic (lupus) or localized (rheumatoid arthritis)

What is type 4 hypersensitivity?

Delayed hypersensitivity that is T cell mediated. A previous exposure to antigen primes the T cell, but the T cell attack does not occur until days after the initial exposure. An example is poison ivy, transplant rejection, TB test.

What is an autoimmune disorder?

When the body attacks its own cells and is either T cell or Ig-mediated with no known etiology. Can either be organ specific or systemic.

What is molecular mimicry?

Body’s antigens resemble infectious agent, immune system’s mistakenly attacks body’s cells. An example is rheumatic fever where anti strep antibodies attack the heart valves.

What is systemic lupus erythematosus (SLE)? What are some factors that lead to its development?

A multisystem disease where antinuclear antibodies (ANAs) are present and antibody complexes are deposited into tissues. This disease is characterized by remission and exacerbation periods. Some factors leading to development are genetic predisposition, environmental factors (EBC infection), and hormonal

What are some signs of SLE? How it is diagnosed? What is the treatment?

Skin rash (butterfly rash across cheeks), joint inflammation, kidney damage, vasculitis, Raynaud’s phenomenon. Diagnosed by history, physical exam, lab results. To get an accurate diagnosis 11 criteria must be met, and ANAs are elevated in 95% of cases. Treatment involves NSAIDs, corticosteroids, methotrexate

What is rheumatoid arthritis (RA)? What are some factors that influence its development?

An autoimmune disorder that causes chronic joint inflammation that may affect other tissues. Some factors include genetic factors, environmental factors (infections), hormonal influences (females more likely to develop RA)

What are some signs of RA? How is it diagnosed? How is it treated?

Symmetrical, tender, swollen joints (joints most likely affected are the fingers, wrists, knees, and hips), painful stiff joints for 30 minutes + in the morning. Diagnoses by specific criteria produced by the ACR, RF factor test, ESR, CRP elevation, presence of swan neck and Boutonnière deformities, elevated anti-citrullinated protein antibodies. Treated with NSAIDS, methotrexate, disease-modifying anti rheumatic drugs, immunosuppressants.

What is severe combined immunodeficiency disorder (SCID)? What should be avoided? How is it treated?

Both B and T cell malfunction. Live vaccines should be avoided. Treatment is bone marrow transplant, and without treatment death happens within 2 years from infection

What is selective IgA deficiency (sIgAD)? What are the signs? How is it treated?

One of the most common primary immune deficiencies that places an individual at risk for atopic and autoimmune diseases. May be asymptomatic with normal IgG and IgM. Treatment includes monthly injections of Igs can be used if needed.

What is DiGeorge syndrome? How is it caused? What does it mean for patients with this disease?

Immunodeficiency disorder that happens due to T cell deficiency due to the lack thymus development caused by genetic deletion at 22q11.2 that affects other tissues (heart, parathyroid gland, facial structure). For treatment and multidisciplinary coordinated health care needed.

What is human immunodeficiency virus (HIV)?

A virus that infects CD4 cells (T helper cells)

What are the infection stages of HIV?

1. Acute

2. Chronic

3. AIDS (acquired immune deficiency syndrome)

How is HIV transmitted?

Sexual activity, blood, transplacental, breast milk, organ transplants, saliva (into open mouth wounds)

Who is considered high-risk for contracting HIV?

People who engage in unsafe sex, men who have sex with men, IV drug abusers

What are the types of HIV?

HIV-1 : more common in US

HIV 2 : more common in West Africa

What type of virus is HIV? How does it work?

Retrovirus. RAN virus that uses reverse transcriptase- an enzyme that converts HIV RNA into DNA. HIV targets cells that express CD4 receptors and chemokine receptors CCR5 or CXCR4

What is the CCR5 receptor?

Receptor located on the surface of T cells that is needed for HIV to attach, there are some people that lack this receptor.

How does HIV present?

The initial infection may lead to flulike symptoms which resolve and the patient becomes asymptomatic, eventually, severe immunodeficiency develops. HIV can remain dormant in inactive CD4 cells, or be stored in macrophages. Once the CD4 cells are infected, the cells are unable to carry out normal functions (adaptive immunity compromised) and are destroyed increasing risk of opportunistic infection. Following the initial infection detectable antibody levels develop in 2 weeks to 6 months. Early into the disease the patient may be asymptomatic but can infect others (latent period), but over time CD4 levels fall and HIV RNA levels increase

What are the CD4 cell counts that show risk of opportunistic infection? AIDS classification?

Opportunistic: less than 500 CD4 cells

AIDS: less than 200 CD4 cells

How is HIV diagnosed?

HIV RNA assay is the earliest means of detection (viral load greater than 100,000 copies/mL indicates high risk for AIDS), inversion of CD4 : CD8 ratio (normal 2:1, HIV 1:2), viral load testing, seroconversion (antibody negative to antibody positive), monitor CD4 levels

How is HIV treated?

HIV has a very high mutation rate

Antiretroviral therapy (ART)

What are some ARTs used in HIV treatment?

Fusion inhibitors (block HIV from attaching to CD4 cells)

CCR5 antagonists

Nonnucleoside reverse transcriptase inhibitors

Nucleoside reverse transcriptase inhibitors

Protease inhibitors

Integrate strand transfer inhibitors (block HIV from injecting DNA into host cell)

Preventive treatment- PrEP (pre-exposure prophylaxis) that uses antiretroviral medications in susceptible individuals to prevent infection

What are some complications of HIV?

Opportunistic infections (pneumocystis pneumonia, TB)

Malignancies (kaposi sarcoma, non-hodgkin’s lymphoma)

Paradoxical ART response (inflammatory response to ART)

AIDS