Patho Taboo

Neutrophil

1. the first WBC to arrive to the site of inflammation and will increase with inflammation (especially with bacterial infections.
2. the majority of our WBCs
3. make nitric oxide to help kill the engulfed debris

B cell

1. Part of ADAPTIVE IMMUNITY
2. Activated by CD4+ T cells
3. Produce antibodies (5 types) that will react with the antigen
4. Part of our Humoral Immunity (which is part of our adaptive immunity)→ our primary defense
5. circulate in the lymphatic system

Macrophage

1. responsible for phagocytosis →which destroys the pathhhogen
2. release cytokines and chemokines

T cell

* Directly attack the antigen
* Part of adaptive immunity
There are three different kinds of T cells:
1. Helper T cells (CD4+)
2. Cytotoxic T cells (CD8+)
3. Regulatory T cells

Eosinophil

1. Increase during acute reaction and parasites

2. Secrete Cytokines

**if the eosinophil count is > then the neutrophil count, this should cue us in to thinking something is wrong!!**

Antigen Presenting Cell

Present antigens to T cells.

*After phagocytosis during inflammation, pieces of the foreign substance are "presented" to dendritic cells → which are the best APC. The dendritic cell then delivers the antigen to Lymphocytes. APCs can be several different cell types → Leukocytes: neutrophils and dendritic cells act as APCs.

Monocyte

1. Acts as a macrophage for pathogen destruction → Phagocytosis!!
2. Plays an anti-inflammatory role
3. Can differentiate into a macrophage or a dendritic cell

Killer T Cell

a type of lymphocyte that directly kills cells that are foreign invaders (i.e. cancer cells or viruses). A.K.A. "Cytotoxic T cells"
Monitor all cell activity and destroy pathogens!

Lymphocyte

part of the WBC group that helps your immune response.
made up of:
1. Natural Killer cells (NK cells)
2. T cells
3. B cells

Dendritic Cell

mediator b/w innate and adaptive immunity.
Is a differentiated monocyte.
Is a type of APC that delivers antigens to the lymphocytes.n

Antigen

Is a foreign substance that induces the formation of antibodies b/c helper T cells will recognize it and trigger B cells to rapidly clone themselves.

Antibody

a type of protein that binds to antigens.

made by B cells

Different types of antibodies:

1. IgG → 75% of all antibodies, crosses to baby from placenta, protection against viruses/toxins/bacteria

2. IgE → found in skin/lung/mucous membranes, cause mast cells and basophils to release histamines, involved in allergic reactions, and attacks parasites

3. IgD → believed to be involved in B cell maturation and activation.

4. IgA → found in saliva/tears/colostrum and other bodily secretions, protects against pathogens on mucosal surfaces.

5. IgM → found in blood and lymph systems, 1st line in defense against infection and plays a role in our immune regulation

Histamine

* secreted by mast cells (and basophils)
* cause dilation of arterioles → increased permeability = swelling and inflammation
* are released in response to trauma, injury, or certain immune reactions

Nitric Oxide

* a free radical that is released by neutrophils!

* cause smooth muscle relaxation

*stops the function of platelets

* helps with apoptosis regulation

* is typically anti-inflammatory, but becomes pro-inflammatory during pathogenic or abnormal activity.

Platelet Activating Factor (PAF)

released by several inflammatory cells
will activate neutrophils and will attract eosinophils
initiates the platelet cascade to form a clot.

Interferon

a type of cytokine:
* protects against viral infections
* produced and released by virally infected host cells
* regulates and activates immune response to bacteria

Three types:
1. IFN-⍺
2. IFN-β
(1 & 2 induce production of antiviral proteins to stop the virus from replicating)
3. IFN-ᴦ (IFN-gamma) → increases activity of macrophages.

Interleukin-1

a pro-inflammatory cytokine → induces fever!

Tumor Necrosis Factor-Alpha

TNF-⍺ (a type of cytokine) regulates cytokine production and INCREASES PAF (Platelet Activating Factor)

Chemokines

* a subgroup of cytokines that tells cells where to go and what to do → directs cells to the site of injury/inflammation = chemotaxis
* produced as a result of bacterial toxins → inflammatory cytokines.

Oxidative Stress

is the excess of free radicals and oxidants that cause damage to healthy cells and organs.

Vascular Stage

is the FIRST STAGE in inflammation:

1. Temporary vasoconstriction occurs within seconds to attempt to prevent blood loss.

2. Rapid vasodilation (from histamines and nitric oxide) occurs increasing blood flow → heat and redness

3. Increased vascular permeability → exudate moves from intravascular to interstitial spaces → swelling (edema), pain, and impaired function! During this time blood flow slows and clotting at the site will occur, which localizes the harmful agent.

Cellular Stage

is the SECOND STAGE in inflammation: (cell movement and activity)
1. WBCs move along vessels to the site of injury/invader where they attach to the vessel wall
2. TRANSMIGRATION → WBCs squeeze their way b/w the vessel wall cells and into the tissue space.
3. Chemotaxis → chemoattractants (cytokines) call more WBCs to the site
4. Phagocytosis → monocytes, neutrophils, macrophages activated

Phagocytosis

cell eating

Opsonization

tags foreign substances for phagocytosis

complement system

a cascade system that enhances the destruction of pathogens.
- is made of protein groups that circulate inactively in the system and are activated by immune activity.
-it encourages the release of histamine, stimulates chemotaxis, and other inflammatory actions

Hydrostatic Pressure

pushes water out of the cell → it has an outward driven pressure → involved in edema

Shift to the left

immature neutrophils, called BANDS, will be released during infection/inflammation/or other disease process

Exudate

protein rich fluid that helps to dilute, contain, and remove the pathogen/debris. Is not always bad!

Granuloma

a lesion of macrophages that is surrounded by lymphocytes caused by poorly digested and/or hard to control substances

Colloid Osmotic Pressure

has an inward-pulling pressure → also involved in the formation of edema.

Primary Intention Healing

edges on the wounds can be pulled together (put back together with stutters, staples, glue, etc...)

Secondary Intention Healing

not enough tissue to bring it together

Keloid Scarring

hypertrophy of the skin that expands the margins of the wounds

Endothelial Cells

line blood vessels
encourage adhesion of other cells
membrane is semipermeable
control of blood flow
release inflammatory mediators
help to control your WBC Production.

Mast Cells

Bind to IgE to release histamine.
Degranulation releases inflammatory mediators.
Attracts other leukocytes to the area.

Basophils

Bind to IgE to release histamines and secrete cytokines

Arachidonic Acid

a main mediating character of inflammation:

* a type of Omega-6 acid found in the cell membrane

* release of this initiates the production of the eicosinoids (prostaglandins, etc...) which lead to platelet aggregation and inflammation

Omega-3

helps prevent the negative effects of inflammation.
* work by replacing Omega-6 arachidonic Acid in the inflammatory cells

Omega-3s can be found in flaxseeds, canola oil, green leafy veggies, walnuts, soybeans, fish oil, etc... → all are considered to have anti-inflammatory responses.

Humoral Immunity

This is our B cell activation and antibody production! This is our primary defense.

Primary response is your first exposure → your antibodies will take ~ 1-2 weeks to develop
Secondary response is our memory → when we respond to a pathogen after being exposed to it a second time. Our antibodies will increase more rapidly

Cell-mediated Immunity

T cell activation → are essential for adaptive immunity to occur.
* Helper T cells (CD4+) secrete cytokines to activate immune and inflammatory cells (quick destruction of enemy cells)
* Cytotoxic T cells (CD8+) monitor all cell activity and destroy pathogens
Regulatory T cells monitor the self and non self cells → they PREVENT autoimmunity (if there is an autoimmune issue there is an issue with the Regulatory T cells.)

Major Histocompatibility Complex Molecules (MHC)

* Self-recognition proteins → differentiate between SELF and NON-SELF cells
* Found on nearly all cells → Incl. APCs
* APCs will present fragments of antigens via MHCs

* T cells will use MHCs to determine foreign substances and will signal for backup → T cells, B cells, and other immune cells *

CD4+ cells

Helper T cells → Normal values are 800 to 1000!

In the latency phase of HIV you will see very low CD4+ levels. AIDS develops when the CD4+ levels are < 200

Immunoglobulins

Part of Humoral Immunity → are antibodies!

Types of Immunoglobulins (antibodies)

1. IgG → 75% of all antibodies, crosses to baby from placenta, protection against viruses/toxins/bacteria

2. IgE → found in skin/lung/mucous membranes, cause mast cells and basophils to release histamines, involved in allergic reactions, and attacks parasites

3. IgD → believed to be involved in B cell maturation and activation.

4. IgA → found in saliva/tears/colostrum and other bodily secretions, protects against pathogens on mucosal surfaces.

5. IgM → found in blood and lymph systems, 1st line in defense against infection and plays a role in our immune regulation

Active Immunity

When our body creates the immunity itself. Can be done naturally (encountering the flu virus in the wild) or artificially (encountering the flu virus through getting a vaccine)

Passive Immunity

We receive immunity from an outside source → like a baby getting immunity from the mother (either passing through the placenta, or from breast milk), or receiving IVIg (like monoclonal antibodies)

Acquired Immunity

aka Adaptive Immunity:
* your LAST LINE of defense
* targets specific foreign cells via the antibody-antigen reaction
* it remembers previous exposures and will initiate a stronger immune response to following encounters
** Includes humoral and cell-mediated immunities
** Self and non-self recognition

A malformation with this occurs immunity in autoimmune diseases.

HIV

* Most prevalent in Black/African American population (then Hispanic/Latino, then White)

* a Retrovirus → slow/progressive fatal disease → RNA virus

* Targets and Kills CD4+ cells (helper T cells)

* CD4+ cells need to be VERY LOW before someone will show s/sx of HIV

Progression of HIV

* Typical = 10-15 years

* Slow = > 15 years

* Rapid = < 5 years

Three phases → Primary, Latency, AIDS

AIDS

Final developmental stage of HIV → develops when CD4+ levels are < 200 or the HIV patient develops an opportunistic disease:

* Kaposi Sarcoma (malignancy)

*Pneumocystitis Jirovecii pneumonia, TB, Toxoplasmosis, etc...

Primary Infection Phase (HIV)

Primary Infection phase → flu-like symptoms, fever, headache, rash, GI issues, fatigue, myalgias, sore throat, night sweats, swollen lymph nodes → begin roughly 1 month after exposure

Latent Phase (HIV)

Latency phase → asymptomatic ~ 10 years! CD4+ cells gradually drop to very low levels as the viral load increases! (remember: asymptomatic doesn't mean that someone CAN'T spread the disease!! They can still spread the disease if they are not treating the disease and they have detectable levels of viral load.)

Opportunistic Infections

occur in severely compromised immune systems

ELISA Test

Antibody test that relies on the specific binding b/w an antigen and an antibody. 1st test done for HIV diagnosis

Western Blot Assay

Another antibody test done to diagnose HIV.
If the ELISA is positive, the Western Blot Assay is done to confirm HIV.

HAART Medications

Highly Active Antiretroviral Therapy → aka combined antiretroviral therapy, which comprises a combo of three to four antiviral agents and is the CURRENT STANDARD OF CARE for HIV treatment.

Rheumatoid Arthritis

a chronic, systemic, autoimmune/inflammatory disease → joint inflammation and the loss of articular cartilage in a degenerative process leads to joint deformities.

* occurs more commonly in ♀ than in ♂ (3:1)
* Age at onset is typically between 30 - 50 years
* the cause is unknown, but genetics, environmental factors (i.e. smoking), and gum disease are thought to have a role.

Pannus

is a feature of RA that differentiates it from other forms of inflammatory arthritis. Develops between the joint margins and leads to decreased joint motion and leads to ankylosis (joint stiffness). It erodes bone and cartilage.

Rheumatoid Arthritis Diagnostic Labs

ESR → erythrocyte sedimentation rate → commonly elevated when the disease is active

CRP → C-reactive Protein → routinely assessed as a marker of systemic inflammation w/RA

Anti-CCP → Anticyclic Citrullinated Peptide Autoantibodies → identification of RA at a very early process is possible, but may not predict the severity of the disease.

RF → Rheumatoid Factor → not diagnostic for RA but can differentiate RA from various other forms of arthritis. Someone may be positive for RA without the presence of RF!

Other tests:

Synovial Fluid Analysis

Joint XR

MRI

U/S

DMARD Medications

Disease-Modifying Antirheumatic Drugs → should be used when the diagnosis of RA is established prior to the erosive changes appear on radiography → balance these with the potential risks of anti-inflammatory and immunosuppressive interventions.