Immunology High-Yield Biomedical Sciences

Biomedical Sciences, Sourced from emma_dip on Quizlet

Primary and secondary immune system organs

Primary: bone marrow (b cell maturation, immune cell production), thymus (t cell maturation)

Secondary: "SPLIT" - spleen

peyer's patch

lymph nodes

allow immune cells to interact with antigen,

tonsils

Thymus derives from

Third pharyngeal pouch (endoderm)

Thymic lymphocytes derive from

mesoderm

Spleen derives from

Mesoderm

Flow of lymphatics

Lymphatic capillaries --> collecting vessels --> trunks --> ducts --> vena cava --> heart

Lymphatic trunks, and which are paired

- Jugular

- Subclavian

- Bronchomediastinal

- Intestinal

- Lumbar

- All are paired, except intestinal

Function of lymphatic vessels

Collect interstitial fluid between capillaries, closely related to capillary beds to maintain fluid balance

Lymphatic vessels are found everywhere, except?

bone, teeth, marrow

How does lymphatic flow prevent backflow?

Overlapping lymphatic vessels with endothelial cells create valves to prevent backflow

Lymphatic collecting vessels anatomy

- More anastamoses than veins

- Superficial CVs: follow veins

- Deep CVs: follow arteries

Lacteals are

Specialized lymph capillaries in the small intestine villi which absorb fat into blood

How does lymphatics move?

Breathing, muscle contraction, arteral pulsations

What parts of the body does the right lymphatic duct drain?

Right side of the body above diaphragm into junction of the right subclavian and internal jugular vein

The rupture of this lymphatic duct causes chylothorax

Thoracic duct

Components of innate immunity

Neutrophils, macrophages, monocytes, DCs, NKs (lymphoid origin), complement, physical epithelial barrier, secreted enzymes

Innate immunity mechanism

Germline encoded

Innate immunity response to pathogens

- Nonspecific

- occur rapidly (min to hours)

- No memory response

Innate immunity secreted proteins

- Lysozymes

- Complement

- CRP

- Defensins

- Cytokines

Innate immunity key features in pathogen recognition

- TLRs: recognize PAMPs leading to activation of NF-KB

Examples of PAMPs

- LPS on gram -ve bacteria

- Flagellin on bacteria

- Nucleic acid (viruses)

Adaptive immunity components

T cells, B cells, circulating antibodies

Adaptive immunity mechanism

Variation through V(D)J recombination during lymphocyte development

Adaptive immunity reponse to pathogens

- Highly specific, refined over time

- Develops over longer periods

- Memory response is faster and more robust

Adaptive immunity secreted proteins

immunoglobulins and cytokines

Adaptive immunity key features in pathogen recognition

- Memory cells: activated B and T cells

- Subsequent exposure to previously encountered Ag --> stronger, quicker immune response

What function does NK-KB have in innate immunity?

Leads to secretion of pro-inflammatory cytokines, such as IL-6, TNF-a, IL1B to:

1. increase vasodilation

2. increase leukocytes to area to cause fever

3. to increase inflammation

What are MHC proteins?

Membrane glycoproteins that bind to antigens to present to T cells, and bind to T-cell receptors.

M for me = proteins that my cells express and respond to, that are unique to me.

No two people have the same MHC (except identical twins)

HLA-B27 associated diseases

Psoriatic arthritis

Ankylosing spondylitis

IBD-associated arthritis

Reactive arthritis

Beer PAIRs well with the 27 club

HLA-DQ2/DQ8 associated diseases

Celiac

'8 2 much gluten at DQ"

HLA-DR3 associated diseases

Addisons

DM1

SLE

Graves

Hashimotos

Add 1 to get to 3

Add = addisons

1 = DM1

Second = SLE

Third = Thyroid (graves, hashimotos)

Or Dr. Addison sent 3 DM's to Dr's Grave, Hash and Lupus

HLA-DR4 associated diseases

4 walls in 1 rheum, adds up

Rheumatoid arthritis

DM 1

Addison disease

HLA-A3 disease association

Hemochromotosis

HA3mochromotosis

Rheumatoid arthritis HLA association

- 4 walls in 1 bed rheum

- DR4 and B1

HLA-DR15 associated disease

Goodpasture

HLA-DR2 associated diseases

Multiple sclerosis

Goodpastures

SLE

Hay fever

DRive 2 multiple hay pastures to SLEep

HLA-C associated disease

Psoriasis

Dont you C my skin?

HLA-B8 associated diseases

Addisons

Myasthenia gravis

Graves disease

SLE

"Don't B l8, Dr. Addison, or else you'll SLEnd My patient to the Grave"

HLA-DP associated disease

Chronic hepatitis B

HLA-B51 associated diseases

Bechet's (vasculitis type)

What are your antigen presenting cells?

BLDM

B-cells

Langerhan cells

DC

Macrophages

What cytokines are secreted by macrophages

IL-1, IL-6, IL-8, IL-12, TNF-alpha

Function of IL-1

- Causes Fevers

- Inflammation

- Recruits WBCs by inducing chemokine secretion

- Activates endothelium to express adhesion molecules

- Osteoclast activator

Function of IL-6

causes fever and stimulates production of acute phase proteins

Function of IL-8

Major chemotactic factor for neutrophils

Clean up on aisle 8

Function of IL-12

- Induces differentiation of T cells into Th1 cells. - Activates NK cells.

- Facilitates granuloma formation in TB.

Function of TNF-alpha

- Activates endothelium

- Causes WBC recruitment, vascular leak

- Causes cachexia in malignancy

- Maintains granulomas in TB

Which cytokines mediate fever and sepsis?

IL1, IL-6, and TNF-alpha

What cytokines are produced by T cells

IL-2, IL-3

Function of IL-2

stimulates growth of helper, cytotoxic, and regulatory T cells, and NK cells

Function of IL-3

supports growth and differentiation of bone marrow stem cells

What cytokines are secreted by Th1 cells

IFN-y, IL-2

Function of IFN-y

-Secreted by Th1 cells

-Enhance killing ability of monocytes and macrophages (enhanced by interaction of T cell CD40L with CD40 on macrophages)

-↑Antigen Presentation and MHC expression by all cells

- Inhibits Th2 differentiation

- Induces IgG isotype switching in B cells

- Activates macrophages to induce granuloma formation

Function of IL-4

- Induces differentiation of T cells into Th (helper) 2 cells.

- Promotes growth of B cells.

- Enhances class switching to IgE and IgG.

"Aint too proud 2 BEG 4 help.

Which cytokines are secreted by Th2 cells?

IL-4, IL-5, IL-10, IL13

IL-5 function

- Promotes growth and diff of B-cells

- Enhances class switching to IgA

- Stimulates growth and diff of Eosinophils

"I have 5 BAEs"

Function of IL-10

- Attentuates inflammatory response

- Decreases expression of MHC class II and Th1 cytokines

- Inhibits activated macrophages and DC

IL-10 is secreted by

Th2 cells, T-reg cells

Which cytokines attenuate the immune response?

TGF-B and IL-10

"TGF-B and IL-10 both attenuate the immune response"

Function of IL-13

Isotype switch to IgE, increased mucin in GIT

- Induces alternative macrophage activation

"IL- thirtEEn promote IgE"

Excess Th1 response leads to

Autoimmunity

Excess Th2 response leads to

Allergies

Type 1 hypersensitivity

IgE mediated hypersensitivity

Ex: Allergies, anaphylaxis

Two phases of type 1 hypersensitivity

Immediate (minutes):

-Ag crosslinks preformed IgE on sensitized mast cells = immediate degranulation

-release of histamine, typtase, and leukotrienes

Late (hours):

-chemokines and other mediators from mast cells

-inflammation and tissue damage

Tests for type 1 hypersensitivity

- Skin test

- Blood (ELISA)

looking for allergies specific to IgE

Type II hypersensitivity

Antibody mediated

-antibodies bind to cell-surface Ag or extracellular matrix

-cellular destruction, inflammation and cellular dysfunction

Describe cellular destruction of type 2 hypersensitivity and 4 examples

Cell is opsonized by Ab leading to either:

1. phagocytosis + activation of the complement

2. NK cell killing

Examples:

- autoimmune hemolytic anemia

- immune thrombocytopenia

- transfusion reaction

- hemolytic disease of the newborn

Describe inflammation in type 2 hypersensitivity and 3 examples

Binding of Ab to cell surface

-activation of complement system and Fc receptor-mediated inflammation

Examples

- goodpasture syndrome

- rheumatic fever

- hyperacute transplate rejection

Describe cellular dysfunction in type 2 hypersensitivity and examples

Antibodies bind to cell-surface receptor

-abnormal blockade or activation of downstream process

examples

- myasthenia gravis

- graves disease

- pemphis vulgaries

Which test is specific for type 2 hypersensitivity reactions?

- Indirect and direct coombs test

Indirect and direct coombs test

- direct: detects Ab attached directly to the RBC surface

- indirect: detects presence of unbound Ab in the serum

Hypersensitivity type III

-Immune complex mediated

—antigen-antibody (IgG) complexes activate complement

-attracts neutrophils and release lysosomal enzymes

-can be associated with vasculitis and systemic manifestations

Think immune complex as 3 things stuck together: antigen-antibody-complement.

- Examples: serum sickness, Arthus reaction

Type 3 hypersensitivity testing

immunofluorescent staining.

6 examples of type 3 hypersensitivity

- SLE

- Rheumatoid arthritis

- RA

- Polyarteritis nodosa

- Post-streptococcal glomerulonephritis

- IgA vasculitis

Type IV hypersensitivity

T cell mediated

Delayed

Type IV hypersensitivity mechanism

1. Direct cell cytotoxicity:

-CD8+ cytotoxic T cells kill target

2. Inflammatory reaction:

-effector CD4+ T cells recognize Ag

-release inflammation

inducing cytokines

Which hypersensitivity reaction does not involve antibodies

Type IV hypersensitivity

2 examples of Type IV hypersensitivity

- Contact dermatitis

- Drug reaction with eosinophilia and systemic symptoms (DRESS)

Type IV hypersensitivity tests

- PDD for TB infection

- Patch test for contact dermatitis

- Candida skin test for T-cell immune fuction

4 T's:

T cells

Transplant rejection

TB skin test

Touching (contact dermatitis)

Anaphylaxis is what type of hypersensitivity? What Ig mediates it?

Type 1

-IgE mediated

Allergic asthma is what type of hypersensitivity? What Ig mediates it?

Type 1

-IgE mediated

Antibodies binding to cell surface antigens is what type of hypersensitivity?

Type 2

Antibodies binding to cell surface antigens resulting in phagocytosis, complement activation and/or NK cell killing is what type of hypersensitivity?

Type 2, cellular destruction

Antibodies binding to cell surface antigens resulting in complement activation and Fc receptor inflammation is what type of hypersensitivity?

Type 2, inflammation

Antibodies binding to cell surface antigens resulting in abnormal block or activation of downstream processes is what type of hypersensitivity?

Type 2, cellular dysfunction

Autoimmune hemolytic anemia is what type of hypersensitivity?

Type 2, cellular destruction

Immune thrombocytopenia is what type of hypersensitivity?

Type 2, cellular destruction

Transfusion reactions are what type of hypersensitivity?

Type 2, cellular destruction

Hemolytic disease of newborns is what type of hypersensitivity?

Type 2, cellular destruction

Goodpasture syndrome is what type of hypersensitivity?

Type 2, inflammation

Rheumatic fever is what type of hypersensitivity?

Type 2, inflammation

Hyperacute transplant rejection is what type of hypersensitivity?

Type 2, inflammation

Myasthenia gravis is what type of hypersensitivity?

Type 2, cellular dysfunction

Graves disease is what type of hypersensitivity?

Type 2, cellular dysfunction

Pemphigus vulgaris is what type of hypersensitivity?

Type 2, cellular dysfunction

Hashimotos is what type of hypersensitivity?

Type 4 or Type 2, cellular dysfunction

Serum sickness is what type of hypersensitivity?

Type 3

Arthus reaction is what type of hypersensitivity?

Type 3

SLE is what type of hypersensitivity?

Type 3

Poststrep glomerulonephritis is what type of hypersensitivity?

Type 3

Polyarteritis nodosa is what type of hypersensitivity?

Type 3