Physiology- Immune System

what is the immune system?

network of biological systems that protect an organism from disease, infection, and injury/harmful cellular changes

what are the functions of the immune system?

1. defend against invading pathogens

2. respond to cellular injury and innate repair (“healing”- can be with or without infection)

3. monitor and remove malignant or problematic cells (immune surveillance)

example of “not self”

1. pathogens (bacteria, virus, fungi)

2. malignant cells

3. damaged or “old/worn out” cells

type of cell ALL leukocytes are derived from

hematopoietic progenitor cell

two major types of leukocytes

1. myelocytes

2. lymphocytes

what type of leukocytes are involved in the INNATE immune system?

myelocytes

what type of leukocytes are involved in the ADAPTIVE immune system?

lymphocytes

two "arms” of the immune system

1. innate

2. adaptive

compare and contrast innate vs adaptive immune system

what is the first line of defense?

barrier defenses

1. mechanical

2. biochemical

mechanical barriers

• epithelial cells (skin and mucosa)

  • tight junctions to prevent furthering of infection btwn cells

  • high turnover

  • regular “washing” (cough, sneeze, urinaiotn, vomitting)

biochemical barriers

• secretions

  • mucus

  • sweat/tears

  • stomach acid

• microbiome

  • compete with pathogens for nutrients

  • block attachment to epithelium

  • produce toxins to inhibit pathogen growth

what is the second line of defense

inflammation (non specific response)—recruit oxygen, nutrients, proteins, and immune cells to sites of tissue damage or injury (infectious OR non-infectious)

goals of inflammation

1. destroy pathogens

2. trigger the ADAPTiVE immune system

3. initiate healing

true or false: inflammation is a non-specific response to a pathogen or injury

true; there is a similar (rapid) response no matter what the triggering event was

P.A.M.Ps

pathogen associated molecular patterns

• broad specificity

• similar carb/protein presented on different cells, therefore can be recognized by TOLL LIKE RECEPTORS on macrophage

phagocytosis

cellular process of ingesting and eliminating particles including mircroorgisnism, foreign substances, and damages/dying cells

what are phagocytes and what are the types of phagocytes?

• phagocytes are calls that perform phagocytosis

  • neutrophils: mobile; specialized cells in bacterial response (ex. puss)

  • monocytes and macrophages: tissue bound

Inflammation STEP 1- tissue injury introduces foreign material (ex. bacteria)

macrophages are activated by presence of foreign material—> phagocytosing the infected or damaged cells—> release of cytokines to amplify response

what are cytokines?

small proteins that act as a chemical messenger between cells

• involved in mediating inflammation

• ex. HISTAMINE

Inflammation STEP 2-3

cytokines attract neutrophils and monocytes to the injury site—> MORE cytokines are released that exert various immune responses

• when phagocytes destory pathogens and release more cytokines…

  • recruit more immune cells

  • stimulate hypothalamus to produce FEVER (fever increase, bacteria decrease)

  • stimulate liver to produce ACUTE PHASE REACTANTS (CRP)

  • stimulate blood marrow to produce more white blood cells (LEUKOCYTOSIS)

when/ for what conditions is CRP test ordered for most

autoimmune and inflammatory diseases

what type of cytokine does a mast cell release?

histamine

Inflammation STEP 4-5

• mast cells are activated by presence of foreign pathogen

• degranulate and release histamine

Inflammation STEP 6

histamine dilates local blood vessels and widens capillary pores—> increase blood flow to the sight of injury—> increase cells, oxygen, etc

clinical manifestations of inflammation/increased blood flow to tissue

SUBJECTIVE

• heat

• redness

• swelling

• pain

• loss of function

OBJECTIVE

• fever

• leukocytosis

• elevated CRP

Inflammation STEP 6/7

• increased blood flow also causes INCREASED leaking of plasma proteins to the wound site

• exposure to factors involved in injury will active fibrinogen to FORM FIBRIN CLOTS to wall off the injury site

  • people more prone to fibrin clots = inflammatory disease, cancer, etc

what must occur after the inflammatory response has mounted a RAPID and NONSPECIFIC response?

the ADAPTIVE immune system must be triggered to provide a tailored response to SPECIFIC threat

inflammation: activiating the adaptive immune system

phagocytes can play a role in recruiting adaptive immunity by functioning as APCs

APCs

antigen presenting cells

• macrophages and dendritic cells that engulf pathogens, digest the material, then present it on the cell surface to be “recognized/read” by adaptive immune cells

what is the third line of defense

adaptive immune system

what makes up the adaptive immune system?

lymphocytes

• T cells

• B cells

• antibodies

characteristics of the adaptive immune system

• SPECIFIC response to SPECIFIC antigen

• PRIMARY response to fight infection with initial exposure—> increased response with increased exposure

• has ability to “remember” and provide LONG-TERM protection (secondary response)

primary lymphoid organs

where lymphocytes are produces and mature

• B lymphocytes are produced and matures in BONE marrow

• T lymphocytes are produced in bone marrow, but mature in the THYMUS

secondary lymphoid organs

where lymphocytes reside

• T and B cells migrate to spleen, lymph nodes, and made available to interact with APCs and other immune cells

cells of the adaptive immune system

• T-helper cells (CD4)

• T-cytotoxic cells (CD8)

• plasma cells

• Memory B cells

• Memory T cells

what is the type of cell(s) of the adaptive immune system recognize and regulate?

T-helper cells (CD4)

who is more susceptible to infection due to CD4 deficiency?

those with HIV/AIDS

what is the type of cell(s) int he adaptive immune system that kill and destroy?

• T-cytotoxic cells (CD8)

• Plasma cells

interaction of T-cytotoxic cells (CD8) with pathogen

act DIRECTLY with pathogen through cytotoxic chemicals

interaction of plasma cells with pathogen

act INDIRECTLY through antibodies

what type of cell(s) in the adaptive immune system remember?

• memory B cells

• memory T cells

next time the body is re-exposed, can release quick and greater response

what are the two “arms” of the adaptive immune system?

humoral and cellular

components of the humoral arm of the adaptive immune system

• B cells

• memory B cells create lasting immunity

• plasma B cells produce antibodies to defense against EXTRACELLULAR pathogens (ex. bacteria, fungi, parasites)

  • afect pathogens from “AFAR” through antibodies

components of the cellular arm of the adaptive immune system

• T cells

• T-helper cells regulate B and T cells

• t-cytotoxic cells (CD8) defend against INTRACELLULAR pathogens (own infected cells, VIRAL) or cancer cells

  • must be “CLOSE” to be effective

anti bodies and memory

1. the B cell that “matches” the foreign pathogen is “selected”

2. the selected B cells multiply and differentiate into PLAMA or MEMORY B cells

3a.PLASMA cells secrete antibodies ot fight EXTRACELLULAR infection

3b.MEMORY B cells linger to more rapidly respond to this SPECIFIC antigen upon re-exposure

what are antibodies/immunoglobulins

proteins secreted by B cells that have SPECIFIC action against SPECIFIC extracellular antigens

classes of antobodies/immunoglobulins

• IgM

• IgG

• IgE

what are the main ways antibodies destroy pathogens?

1. neutralization

2. opsonization

3. trigger inflammatory response (activate innate immunity)

neutralization

antibodies surround the virus and block ability to bind to host cell

opsonization

antibodies bind to the pathogen and make more “palatable” to phagocytes

trigger inflammatory response

antibodies activate innate immunity/inflammatory response in order to recruit phagocytes to the area with pathogen

IgM

• Mighty fast

• FIRST antibody released during FIRST EXPOSURE to antigen (primary immune response)

  • clinical relevance: presence if IgM often indicates acute infection

  • increased onset of symptoms

• overtime, IgM will decrease

IgG

• most abundant and lonG lasting

• crucial role in secondary immune response (re-exposure) and development of “immunity”

  • clinical relevance: presence of IgG indicates “IMMUNITY” from previous infection of vaccine —> remain elevated over longer period of time, therefore longer immunity

• maternal IgG crosses the placenta during pregnancy to protect newborn during first 6months of life

IgE

• binds to mast cells and stimulates release of histaminE

  • clinical relevance: ALLERGIC REACTIONS occur when IgE is produced in response to harmless antigen (allergen)—proteins that cause response but shouldn’t

• initiates responses to fight against parasitic infection

  • bind to PARASITE and tag fro removal eosinophils

what type of pathogen do neutrophils target?

bacteria

what targets parasites and allergens?

eosinophils —→ IgE

Helper T Cell (CD4)

• interact with APCs to coordinate cellular and humoral arms of immunity

  • CD4 receptors bind ti APC to detect foreign antigens and initiate an immune response

  • *each helper T cell has SPECIFIC CD4 receptor*

what markers are used by lymphocytes to determine what cells to act against?

MHC (major histocompatibility complex) complexes

what type of MHC does every nucleated human cell possess?

MHC I

what type of cell can have MHC II

ONLY APCs

• used to attach pathogen particles and presenting pathogen to lymphocyte

MHC I complex vs MHC II complex

MHC 1

• all nucleated human cells

• presents self antigens

• presents VIRAL antigens if needed

• presents MALIGNANT antigens if cancerous

MHC II

• only APCs

• APCs present foreign antigens on the MHC II complex

cell mediated immunity

1. T helper cells use CD4 receptor to read viral antigen on MHC II of APC

2. T helper cell releases cytokines to stimulate proliferation of cytotoxic T cells specific to that antigen

   1. memory T cells also created

3. cytotoxic T cells have CD8 receptors that interact with MHC I receptors on cells to scan for viral particles that indicate infected

   1. if infected, cytotoxic T cells destroy

what is a vaccine

harmless pieces of pathogen (antigens) that will trigger adaptive immunity but cannot cause infection

how do vaccines provide protection from pathogens?

use the immune system’s memory and robust secondary immune response

• induces the production of antibodies memory T and B cells

• IgM levels increase after vaccine

booster vaccine

over time, memory B cells/antibodies gradually decline. administering booster vaccine re-introduces larger and longer lasting

• titters are used to assess need for 'boost” or if person is above minimum threshold and still considered immune to the pathogen

overview of immune system

1. bacteria enters through break in barrier defense (first defense)

   1. resident neutrophils and macrophages engulf and digest bacteria —> release cytokines to recruit more immune cells as well as inflammatory cytokines that amplify immune response

2. Cell injury triggers inflammatory response

   1. mast cells recognize PAMPS (broad specificity) on bacterial cells—> bind to corresponding to TLRon mast cell surface

   2. mast cell degranulates and releases histamine—> increase vascular permeability and dilation

3. APCs link to adaptive immunity

   1. macrophages and neutrophils serve as APCs, presenting bacterial antigen on MHC II—> travel to the spleen and lymph noes to “meet “ with helper T cells that can read their signal

4. humoral (B cells) and cellular (T cells) are activated

   1. helper T cells (CD4) signal B cells to create plasma cells —> produce antibodies IF PATHOGEN IS EXTRACELLULAR THREAT (ex. bacteria)

   2. helper T cells signal cytotoxic T cells (CD8) to create more cytotoxic cells if pathogen is an INTRACELLULAR threat

5. killing mechanisms engaged:

   1. antibodies are released by plasma B cells and kill EXTRACELLULAR threats

   2. cytotoxic T-cells release chemicals to lyse infected cells displaying antigen

6. memory cells created

   1. helper T-cells signal both T and B cells to create memory cells—> allow for the more robust secondary immune response when re-exposed