BMS I

exam I

What produces inflammatory cytokines?

Lymphocytes (B & T cells) and macrophages

what are the cytokines that mediate inflammation?

Interleukin 1, 2, 6, 8 and Tumor Necrosis Factor (TNF)

what stimulates the prodction of inflammatory cytoroxins?

• endotoxins (LPS on bacterial wall)

• physical injury (damaged cells releasing danger signals)

• immune complexes (antige-antibody binding)

what do cytotoxins cause?

inflammation

what does TNF do?

Endothelial activation and systemic inflammation

IL-1

inflammation and fever

IL-2

T-cell proliferation

IL-6

acute phase response

IL-8

neutrophil recruitment

IFN-y

Macrophage activation

IFN-α/β

antiviral defense

which cells mediate adaptive immunity?

B and T lymphocytes

Adaptive immunity is ______ immune response

antigen-specific

how is adaptive immunity characterized?

1. specificity: targets one particular antigen

2. immunologic memory: works faster if the same antigen returns

when is adaptive immunity developed?

following an antigen exposure

two branches of the adaptive immunity?

1. humoral

2. cell-mediated

what is humoral immunity?

activated B lymphocytes clones and produces antibodies

explain humoral immunity in a nutshell

Specific antigen

↓ binds

BCR on B cell

↓

Antigen displayed on MHC II

↓ recognized by

CD4 helper T cell

↓ cytokines

Clonal expansion of B cells

↓

┌───────────────┴──────────────┐

PLASMA CELLS MEMORY B CELLS

Make antibodies Respond faster later

what’s clonal expansion?

rapid multification of one specific antigen binding lymphocyte

which lymphocyte is important in cell-mediated adaptive immunity?

T

which T lymphocytes are important in cell-mediated adaptive immunity?

CD4+ helper T cell and CD8+ cytotoxic T cells

what is cell mediated immunity?

immune response that activates t cells; instead of producing antibodies

what does CD4+ helper T cells do?

coordinate immune response by releasing cytokines, which activates other immune cells

what do CD8+ cytotoxic cells do?

recognize and kill infected or abnormal host cell

what’s special about T cell receptors?

they recognize foreign antigens only when bound to MHC molecules

examples of cells targeted by CD8+ cytotoxic cells?

• Viral infected cells

• Canceous cells

• Cells with intracellular organism

MHC I vs. MHC II: found on which cells?

I- all nucleated cells (not rbcs)

II- antigen presenting cells (dendritic cells, macrophages and B lymphocytes)

MHC I vs. MHC II: where do the antigens they present come from?

I: intracellular (presents protein made inside the cells by either viruses, intraceullar bacteria or canceous cells)

II: extracellular (microorganisms the cells engulfed and put into fragments)

MHC I vs. MHC II: which cells recognize them

I: CD8+ T cells

II: CD4+ helper T cells

what are the two types of immunodeficiency disorder?

1. primary: congenital; born with immune defect

2. secondary: acquired later due to another illness weaking the immune system

who are susceptible to recurrent bacterial infections?

people with antibody defiency disorder

Why does antibody deficiency cause bacterial infections?

Low antibodies

↓

Poor opsonization

↓

Phagocytes have trouble grabbing bacteria

↓

Recurrent bacterial infections

what components of the immune system is affected by primary immunodeficiency?

• B cells/humoral immunity

• T cells/cell-mediated immunity

• Phagocytosis

• Complement system

what are the immunodefiency disorderes discussed?

1. Bruton’s X linked agammaglobulinemia

2. DiGeorge Synrome

3. Severe Combine Immunodeficiency (SCID)

Bruton’s X linked agammaglobulinemia facts:

• boys under <1 (maternal antibody supply drops)

• lack of B cell maturation

  • affects antibody production → recurrent bacterial infection, of mucosal membrane

• defect on X chromose (that’s why affecting boys mainly bc they only have 1 X chromosome)

DiGeorge Syndrome

• absence of functional Thymus → T cell maturation interrupted → low T cells

• third and forth pharyngeal pouches affected

  • thymus, parathyroid and conotruncal cardiac development affected

what is SCID?

Disorder associated with

• T cells deficiency

• B cells developement and function

  • Even when B cells are present, they may not work properly because B cells often require T-cell help.

SCID Presentation

• first few months of life

• recurrent, severe infection

• diarrhea

• failure to thrive

how does innate immunity work?

Pattern recognition receptors recognize

• PAMPs from microorganism

• DAMPS from cell injury

causes inflammation and recruit additional leukocyte

3 lines of defense against infections?

1- barrier

2- innate immunity

3- adaptive immunity (B & T lymphocytes)

how do infectious agents damage tissues?

1. direct cellular injury

2. toxin mediated injury

3. enzyme mediated tissue destruction

4. immune-mediated injury

5. vascular/systemic injury

Shigella invading and destroying colonic epithelial cells is an example of which type of injury?

Direct cellular injury

subtypes of toxins organisms use for cellular injury

1- exotoxins (bacteria → host cells'; specific effects)

2- A-B toxins (A: active; affects intracellular process. B= binding component)

3- Membrane-damaging toxins (pores → ion imbalance → cell lysis)

4- Superantigents: widespread T lymphocyte activation

5- endotoxins (i.e, LPS → inflammation)

Example of bacteria causing toxin mediated injury

Diptheria toxins; A-B toxin; inhibits protein synthesis

what is enzyme mediated destruction?

✂ enzyme breaks down tissue and helps organism spread

example of enzyme mediated destruction

Hyaluronidase: breaks down connective-tissue components

example of immune mediated tissue injury

neutrophils releases reactive ozygen which damages infected and nearby host cells

Example of bacteria causing vascular and systematic injury

Neisseria meninigitis

in which organism does necrosis occur?

living only

what two processes occur following cell death that leads to necrosis?

• denaturation of proteins

• enzymatic digestion of organelles

what are the 6 types of necrosis?

1. coagulative

2. liquifactive

3. caseous

4. enzymatic fat

5. fibrinoid

6. gangrenous

Cold Liquids Can Feel Firmly Good

in what tissue do coagulative necrosis generally present?

ischemia related

all solid organs except brain (i.e, heart, kidney, spleen)

in what tissue do liquefactive necrosis generally present?

brain/abscess

in what tissue do caseous necrosis generally present?

TB infections in the lungs or lymph node

in what tissue do fat necrosis generally present?

pancreas or breast tissue

in what tissue do fibrinoid necrosis generally present?

blood vessels

in what tissue do gangrous necrosis generally present?

foot/toe

how is acute inflammation characterized?

histologically by neutrophils and macrophages

what defined infectious disease?

disorders in which tissue damage and dysfunction is produced by microorganism

what is virulence?

properties that allow organism to establish infection and cause disease/death

how much damage a pathogen can cause

conditions of virulence?

• gain access to the body

• avoid host defense

• accomodate to grow in the human milieu

• parasitize human resources

what are some of the body’s defense mechanism?

• anatomic barrier (skin, filteration system of the upper airway)

• mucocillary blanket

• stomach acidity

• competing gut microbial flora

• secretions (i.e, lysozyme) which elimates antimicrobial properties

what factors affect susceptibility to infectious disease?

• age

• hertitable differences

• behavior (STI or occupation)

• compromised host defense (trauma, burns, immunosuppresive therapies)

define vectors

carriers/transporter of infectious disease

what serves as an animal reservoir for Borrelia burgdorferi?

white-footed mouse (Peromyscus leucopus)

what serves as an vector for Borrelia burgdorferi?

ixodes tick

how is the bacteria transmited from reservoir to human host?

bacterium transmitted when an infected nymph feeds on an human, through salive into the human bloodstream

what’s another name for innate immunity?

natural or native immunity

what activates innate immunity?

nonspecific foreign particles

what is the purpose of innate immunity?

immediate response to foreign materials

what provides innate immunity?

preformed proteins and immune cells

what activates adaptive immmunity?

specific antigenic proteins

what are the primary lymphoid organs?

bone marrow and thymus

what is the purpose of primary lymphoid organs?

lymphocyte development and maturation

(B lymphocyte in the bone marrow and T lymphocyte in the Thymus)

what are the secondary lymphoid organs?

lymph nodes, spleen, tonsils, peyer’s patch and MALT

what is the purpose of the secondary lymphoid organs?

sites where immune cells encounter forgeign antigen and initiates adaptive immune

purpose of lymphatic system?

transport of antigen, immune cells and fluid

which part of the bone marrow contains blood stem cells?

red bone marrow

purpose of thymus?

t cell maturation

what are the layers of the thymus?

cortex and medulla

what happens at the cortex of the thymus?

immature T cells undergoes positive selective; checks to see if thymocytes can bind to MHC molecules

what happens at the meulla of the thymus?

mature t cell undergoes negative selection; do you attack yourself?

to prevent autoimmunity

where is Hassall corpuscles located?

in the medulla of the thymus

layers of the lymph node?

superficial cortex, deep cortex, and medulla

what cells are in the superficial cortex of the lymph nodes?

B lymphocytes

what forms following B lymphocyte activation in the superficial cortex of the lymph nodes?

germinal centers and cellular proliferation occur

what cells are in the deep cortex of the lymph nodes?

T lymphocytes

difference between B and T lymphocytes in the cortex of the lymph node?

activated T lymphocytes do not form germinal centers; but they do go through proliferation

what cells are in the medulla of the lymph nodes?

plasma cells derived from B lymphocytes in the superficial cortex

B cell→plasma cell→antibodies

where is the spleen located?

left upper quadrant

what is the purpose of the spleen?

filters blood and mount an immune response to blood-born antigen

components of spleen and their purpose?

white pulp: immune response to blood-borne antigents

red pulp: filters blood and removes old rbs

what cells are primarily found in MALT?

B

where are MALT located?

respiratory, gastrointestinal and urinary tract

what is hematopoiesis

formation of all blood cells

what are the granulocytes?

neutrophils, eosinophils and basophils

what are the agranulocytes?

monocytes

lymphocytes

where do B lymphocytes differentiate?

mainly in the lymph node

neutrophils

• purpose

• relative percentage in the blood

• type of granule

ingest and destroy invading microorganism

50-70%

cytoplasmic granules

what is neutrophill an hallmark of?

acute infection