Immunology

HLA DR5

Hasimoto thyroiditis Hasimoto is an ODD DoctoR

Peyer's Patch

organized lymph nodes They are an important part of gut associated lymphoid tissue usually found in humans in the lowest portion of the small intestine, mainly in the distal jejunum and the ileum, but also could be detected in the duodenum

Function of IL1-6: basic description/mnemonics

"HOT T-BONE stEAK" 1: fever (hot) 2: stimulates (T) cells 3: stimulates (BONE) marrow 4: Stimulates Ig(E) production 5: stimulate Ig(A) production 6: stimulates a(K)ute-phase protein production

Human Leukocyte Antigen gene: 1. Encodes 2. Function of encoded product 3. Nature of these genes

(HLA gene) 1. Encodes major histocompatibility complex I and II (MHC class I/II) 2. Cells use MHC proteins to present antigens to T cells by binding to T-cell receptors (TCR) 3. EXTREMELY POLYMORPHIC - some variants is associated with disease

Thymus 1. Primary function 2. Function of blood thymus barrier 3. Thymus is derived from 4. Important histology

1. (T) Cell maturation into immunocompetent cells 2. Prevents antigen from entering - will recognize as "self" - no protection from that antigen later 3. (Th)ird pharyngeal pouch 4. Hassall corpuscles with epithelial reticular cells

B cell activation:

1. Activation of CD4+ T cells 2. MHC CII of B cell presents antigen, which is recognized by TCR of CD4+ T. 3. CD40 + CD40L 4. Th cell secretes cytokine that determine Ig class switching of B cell. B cell undergoes class switching and antibody production

Neutrophils: 1. General characteristics 2. Contents of neutrophils 3. Increased band cells indicate: 4. Important neutrophil chemotactic agents

1. Acute inflammatory response cells. Numbers increase during bacterial infections (phagocytic)/multi-lobed (2-5) 2a. specific granules: leukocyte alkaline phosphatase, collagenase, lysozyme, and lactoferrin 2b. Azurophilic granules (lysosome): proteinase, acid phosphatase, MPO, and beta-glucuronidase 3. Increased myeloid proliferation during bacterial infections or CML 4. C5a, IL-8, LTB4, kallikrein, platelet-activating factor

Superficial inguinal lymph node: 1. Area of the body drained 2. Associated pathology

1. Anal canal (below pectinate line), skin below umbilicus (except popliteal area), scrotum and vulva *** Basically drains everywhere below belly button except lateral foot and gonad 2. Sexually transmitted infections Pectinate line divides upper 2/3 anal canal and lower 1/3.

CD21: 1. Receptor for: 2. Receptor for which pathogen?

1. B cell 2. EPV - causes infectious mononucleosis

Inferior mesenteric lymph node 1. Area of the body drained 2. Associated pathology

1. Colon from splenic flexure to upper rectum 2. Mesenteric lymphadenitis, typhoid fever (bacterial infection), ulcerative colitis (inflammation and ulcer of colon), celiac disease

Properties of Fc receptor

1. Constant 2. Complement binding (IgG and IgM only) 3. Carboxy terminal 4. Carbohydrate side chains *** Determines isotypes

T cell activation:

1. Dendritic cell samples antigen and migrates to LN 2a. MHC CI - CD8+ 2b. MHC CII - CD4+ 3. B7 (CD80/86) - dendritic cell + CD28 (naive T) 4. CD4+ T cell produces cytokines. CD8+ T kills virus-infected cells

TLR 4 receptor: 1. Is present in 2. Recognizes

1. Dendritic cells and macrophages. Also some in other innate immunity cells. 2. LPS of gram negative bacteria

Popliteal lymph node: 1. Area of the body drained 2. Associated pathology

1. Dorsolateral foot, posterior calf 2. Foot/leg cellulitis

IgE: 1. Where are they located? 2. Function 3. How abundant in serum?

1. Found underneath the skin where mast cells are 2a. IgE crosslinks when exposed to allergen, mediating immediate hypersensitivity through release of histamine 2b. Immunity to parasite by activating eosinophils 3. Lowest concentration in serum

Antigen presenting cells are:

1. From humoral response: macrophages and dendritic cells 2. Adaptive response: B-cells

Drugs with -umab ending: 1. What type of drug is it? 2. Example

1. H(u)man monoclonal antibody - least immunogenic (most preferred mAB) 2. Ipilimumab

Drugs with -zumab ending: 1. What type of drug is it? 2. Example

1. H(u)mani(z)ed mouse monoclonal Ab (better than chimeric in terms of immunogenicity) 2. Bevacizumab

MHC class I: 1. Encoded by 2. Expressed in 3. Binds to 4. Function 5. Structure 6. Associated protein 7. Antigen loading

1. HLA-A, B, and C (MHC [1] loci have [1] letter) 2. All nucleated cells, APCs, and platelets. OFC, no RBC b/c RBC has no nucleus 3. TCR and CD8 coreceptor (class I x CD8 = 8 "rule of 8") 4. Present ENDOGENOUSLY synthesized antigens (like viral or cytosolic proteins) to CD8+ cytotoxic T cells 5. [1] long chain, [1] short chain 6. B2-microglobulin (short) 7. Transporter associated with antigen processing (TAP) delievers antigen -> antigen loaded to MHCI in RER

MHC class II: 1. Encoded by 2. Expressed in 3. Binds to 4. Function 5. Structure 6. Associated protein 7. Antigen loading

1. HLA-DP, DQ, and DR (MHC [II] loci have [2] letters) 2. APC only 3. TCR and CD4 coreceptor (class 2 x cd 4 = 8" rule of 8) 4. Present exogenously synthesized antigen (bacterial/fungal/parasitic) to CD4+ helper T cells 5. [2] equal-length chains ([2]alpha, [2] beta) 6. Invariant chain 7. Endosome releases invariant chain -> antigen loaded to MHCII (invariant chain prevents antigen loading!)

Cervical lymph node 1. Area of the body drained 2. Associated pathology

1. Head and neck 2. Upper respiratory tract infection, infectious mononucleosis, kawasaki disease.

CD4+ T cells function

1. Help B cells make antibodies 2. Produce cytokines to recruit phagocytes and activate other leukocytes 3. Divided into: CD4+ TH1 CD4+ TH2 CD4+ TH17 Treg

Th1 Cell: 1. Activated by 2. Differentiation inhibited by 3. Secretion 4. Function 5. Immunodeficiency of Th1 results in:

1. Helper cell + IL-12/IFNgamma 2. IL-4, IL-10 3. IFN-gamma 4. Activates macrophages and cytotoxic T cells to kill phagocytosed microbes 5. Mendelian susceptibility to mycobacterial disease (MSMD)

Lymph node - paracortex 1. Structure/function 2. Pathology 3. Involvement in immune response

1. Houses T cells Region between follicles and medulla Contains high endothelial venules (T and B cells enter from blood here) 2. Paracortex is not well developed in patients with DiGeorge syndrome 3. Paracortex enlarges in extreme cellular immune response (viral infection)

B cells: 1. Involved in 2. Originates/matures from 3. Mechanism of action 4. Functions as 5. Surface receptors

1. Humoral immune response 2. Stem cell in bone marrow/mature in marrow 3. Migrate to peripheral lymphoid tissues (they are follicles of LN, white pulp of spleen) -> upon encountering antigen, it differentiates into plasma cells and memory cells 4. Antigen presenting cells 5. CD19,20,21

Important cytokines: 1. Secreted by macrophages

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

Th2 Cell: 1. Activated by 2. Differentiation inhibited by: 3. Secretion 4. Function 5. immunodeficiency of Th2 results in:

1. IL-2, IL-4 2. IFN-gamma of Th1 cell 3. IL-4, IL-5, IL-6, IL-10, IL-13 4. Activate eosinophils and promote production of IgE for parasite defense 5. N/A

1. Which Immunoglobulins can fix complement? 2. At what part of the immunoglobulin?

1. IgM and IgG only 2. Fc region

Spleen: 1. Location 2. Arterial supply 3. Venous drainage 4. Function 5. Key structure

1. Left Upper Quadrant of the abdomen, anterior to left kidney, protected by 9-11th ribs 2. Hilum -> Splenic artery of celiac trunk of descending aorta 3. Hilum -> Splenic vein -> Portal vein -> Liver 4a. Immune response (white pulp) 4b. RBC filtration 4c. Platelet sequestration/maintenance of homeostasis of platelet concentration in blood vessels 5. Fenestrated "barrel hoop" basement membrane of sinusoids (to filter atypical RBC)

Celiac lymph node 1. Area of the body drained 2. Associated pathology

1. Liver, stomach, spleen, pancreas, upper duodenum 2. Mesenteric lymphadenitis, typhoid fever (bacterial infection), ulcerative colitis (inflammation and ulcer of colon), celiac disease

Thymus structure: 1. Thymus division/structure: 2. What does each one contain?

1. Lobules, divided by septa. Inner part is medulla, outer part is cortex. Thymus is surrounded by CT capsule 2. Epithelial cell (educate T cells, provide support) - forms epithelioreticular cell

Superior mesenteric lymph node 1. Area of the body drained 2. Associated pathology

1. Lower duodenum, jejunum, ileum, colon to splenic flexure 2. Mesenteric lymphadenitis, typhoid fever (bacterial infection), ulcerative colitis (inflammation and ulcer of colon), celiac disease

Internal iliac lymph node: 1. Area of the body drained 2. Associated pathology

1. Lower rectum to anal canal (above pectinate line), bladder, vagina (middle 1/3), cervix, prostate 2. Sexually transmitted infections Pectinate line divides upper 2/3 anal canal and lower 1/3.

Hilar lymph node 1. Area of the body drained 2. Associated pathology

1. Lungs 2. Granulomatous disease (inherited primary immunodeficiency disease which increases the body's susceptibility to infections caused by certain bacteria and fungi)

CD14: 1. Present on 2. Function

1. Macrophages and dendritic cells 2. CD14's are TLRs that recognize PAMP (LPS of GN bacteria)

Lymph node - Follicle 1. Mantle zone 2. Histology

1. Mantle zones are outer ring of small lymphocytes surrounding a geminal center. 2. Picture

Measles: 1. Caused from 2. Presentation 3. Histological finding

1. Measles (rubeola) virus of paramyxovirus 2. Fever + 3 C's (cough, coryza, conjunctivitis) -> Kopliks spot 2-3 days later -> maculopapular rash at 3rd-5th day (head -> body) 3. Lymphadenitis with Warthin-Finkeldey giant cells

Drugs with -ximab ending: 1. What type of drug is it? 2. Example

1. Monoclonal antibody - chimeric human-mouse antibody 2. Rituximab

CD16: 1. Expressed by 2. Purpose

1. NK cells; what other marker is expressed by NK? (bottom) 2. CD16 is also called FcgR (Fc gamma receptor) - binds to IgG to induce antibody-dependent cellular cytotoxicity - happens in Type II hypersensitivity reactions CD56

Thymus: medulla 1. Thymus medulla is a site of: 2. Medulla expresses what? 3. Why can medulla express the substance? 4. Deficiency to answer to #3 causes what?

1. Negative selection of T-cells 2. Tissue restricted self-antigens 3. Tissue restricted self-antigen can be expressed due to action of autoimmune regulator (AIRE) 4. Deficiency in AIRE = autoimmune polyendocrine syndrome-1

Cells of innate immune system:

1. Neutrophil 2. Macrophages 3. Dendritic cells 4. NK cells 5. Complement proteins (liver production)

Paracortical reaction: 1. Etiology 2. Caused from 3. Mechanism 4. Paracortical reaction is a feature of what pathology?

1. Paracortical regions swell due to influx of lymphocytes 2. Viral infection 3. HEV becomes activated -> secretes more selectin -> HEV becomes sticky -> more lymphocytes recruited to LN 4. Lymphadenopathy

NK cell mechanism of apoptosis: 1. Proteins involved 2. Activated enhanced by: 3. Actual mechanism

1. Perforin and granzymes = apoptosis inducer 2. IL-2, IL-12, IFN-alpha and beta 3. Epithelial cell exposes nonspecific activation signal (kill me signal) + viruses/neoplasm causes MHCI to not be produced -> NK cells secrete perforin and granzymes to induce apoptosis ** Both conditions need to be met

Macrophages: 1. Function 2. Where is it found? 3. Activated by 4. Important component of ________ formation 5. Mechanism of septic shock via macrophage

1. Phagocytose bacteria//Antigen-presenting cell via MHC II 2. Tissue-based 3. Gamma-interferon 4. Granuloma - abnormal collection of inflammatory cells 5. Lipid A from bacterial LPS binds CD14 on macrophages to initiate the shock.

IgA: 1. Function 2. What is its multiple forms 3. Where is it produced 4. How abundant in serum? 5. Secretion to places 6. Mechanism of transport

1. Prevents statement of bacteria ad virus in mucous membrane 2. IgA and IgA2 (with J chain and secretory component) 3. GI tract (by Peyer's patch - protects GI infection) 4. Most produced, but lower serum conc. 5. Secreted via breast milk (protects mucous membrane of infant) and tear, saliva, and mucus. 6. Transcytosis to cross epithelium - picks up secretory component

IgM: 1. Primary or secondary response? 2. Mechanism of transport 3. Different forms 4. Why would IgM have different forms?

1. Primary 2. Cannot be transported - too big 3. IgM monomer and IgM pentamer with J chains. Can't fix with complements 4. IgM pentamer increases affinity during primary response. That is good because IgM monomer has lower affinity to pathogen than IgG or IgA.

Thrombocytes: 1. Functions 2. Life span 3. Contains 4. Stored in 5. Important receptors

1. Primary hemostasis; injury -> aggregation to form platelet plug 2. 8-10 days 3a. Al(F)a granules: vw(F), (F)ibrinogen, (F)ibronectin 3b. Dense granule (ADP, Ca2+) 4. 1/3 stored in spleen (spleen maintains platelet homeostasis) 5a. vWF receptor: GP1b 5b. Fibrinogen: GPIIB/IIIa

1. Normal neonatal thymus on CXR: 2. What happens to thymus with age?

1. Sail shaped 2. Involutes with age

IgG: 1. Primary or secondary immune response? 2. How abundant in serum? 3. Specific function? 4. How does it contribute to passive immunity?

1. Secondary immune response (Ig class switching) 2. Most abundant in serum 3. Good at opsonization, and neutralization of toxins and viruses. Also fixes complement 4. Only isotype that crosses placenta to provide infant with immunity

Half lives of: 1. Innate immune system 2. Adaptive immune system

1. Short; this is b/c they go crazy and even harm their own cells (almost like kamikaze) 2. They produce memory response; long half lives.

Spleen: White pulp anatomy 1. Splenic artery anatomy 2. Tissues surrounding central arterioles 3. Function of white pulp

1. Splenic artery enters to spleen via hilum and branch out to central arteriole -> end capillaries 2a. PALS surrounds central arterioles and contains T cells. 2b. Marginal zones surround PALS and contain antigen presenting cells and macrophages 2c. Follicles are surrounded by marginal zone and contain B-cells 3. Immune response

Th17 Cell: 1. Activated by 2. Differentiation inhibited by: 3. Secretion 4. Function 5. immunodeficiency of Th17 results in:

1. TGF-beta, IL-1, IL-6 2. IFN-gamma, IL-4 3. IL-17, IL-21, IL-22 4. Immunity against extracellular microbes, through induction of neutrophilic inflammation 5. Hyper-IgE syndrome

Treg Cell: 1. Activated by 2. Differentiation inhibited by: 3. Secretion 4. Function 5. immunodeficiency of Treg results in:

1. TGF-beta, IL-2 2. IL-6 3. TGF-beta, IL-10, IL-35 4. Prevent autoimmunity by maintaining tolerance to self-antigens 5. IPEX

Para-aortic lymph node: 1. Area of the body drained 2. Associated pathology

1. Testes, ovaries, kidneys, uterus (NOT scrotum) 2. Metastasis

1. Epithelioreticular cell in thymus secretes what? 2. What is its function? 3. One other very important function

1. Thymosin or thymotaxin 2.Recruit thymocytes from bone marrow to mature them 3. Formation of blood thymus barrier

Positive selection of T-cell: 1. Where does it occur? 2. Why does it occur?

1. Thymus cortex 2. It occurs so that T-cells without CD4 or CD8 receptors can be eliminated (without them, T cells cannot recognize MHC's)

Negative selection of T-cell: 1. Where does it occur? 2. Why does it occur? 3. What receptor interactions are necessary? 4. What happens if the receptor is defective?

1. Thymus medulla 2. To kill the T-cells that express high affinity for self-antigen. 3. Fas/FasL interaction 4. If defective Fas, this causes an increase in circulating self-reacting lymphocytes due to failure in clonal deletion -> leads to autoimmune diseases

Mediastinal lymph node 1. Area of the body drained 2. Associated pathology

1. Trachea and esophagus 2. Primary lung cancer, granulomatous disease

Axillary lymph node 1. Area of the body drained 2. Associated pathology

1. Upper limb, breast, skin above umbilicus 2. Mastitis and metastasis (especially breast cancer)

Generation of antibody diversity (antigen independent)

1. V(D)J recombination 2. Random addition of nucleotide to DNA by TdT 3. Random combination of heavy chains with light chains

Tumor necrosis factor alpha: 1. Function 2. Adverse effects

1a. Activates endothelium. Causes WBC recruitment, vascular leak. 1b. Maintain granuloma in TB 1c. IL-1, IL-6, TNF-alpha can mediate fever and sepsis 2. Causes cachexia (general health deterioration with weight and muscle loss) in malignancy

Spleen: Red pulp filtration 1. RBC filtration of healthy/unhealthy RBCs 2. What happens to foreign cells at this site?

1a. At the red pulp, capillaries and venules are surrounded by macrophages. 1b. RBC goes from end capillary -> red pulp -> venule -> splenic vein 1c. Unhealthy RBC at venule has irregular shape and cannot pass quickly -> phagocytosis 2a. Virus and opsonized RBC//opsonized pathogen can be engulfed by macrophages here

Spleen: 1. Detailed anatomy of capillary 2. Function of immune cells of spleen upon antigen presentation

1a. Central capillary + PALS (T-Cell) 1b. Capillaries + follicles (naive B) 1c. Marginal zone surrounding PALS (macrophages) 2. Dendritic cell (APC) enters -> activate T-cell -> activate B-cells -> B-cells become plasma cell -> massively produce antibody (IgM and IgG)

Spleen: Red pulp anatomy 1. Red pulp anatomy 2. Sinusoid anatomy 3. Function

1a. End capillaries deposit RBC here, composed of a TON of macrophages or monocytes 1b. Venous sinuses 2. RBCs collected by venous sinus -> collecting vein -> splenic vein 3. Destroy and filter RBCs

IL-1 1. Causes: 2. Also known as

1a. Fever 1b. Acute inflammation 1c. Activates endothelium to express adhesion molecules 1d. Induces chemokine secretion to recruit WBCs 2. AKA osteoclast-activating factor

Signs of splenectomy 1. Lab tests and blood smears 2. Immune function

1a. Howell-Jolly bodies 1b. Target cells 1c. Thrombocytosis (lost sequestration) 1d. Lymphocytosis (lost sequestration) 2. Increased susceptibility to ENCAPSULATED organisms (less IgM -> less complement -> decreased C3b opsonization)

Lymph node - Medulla 1. Compositions

1a. Medullary cords - packed with lymphocytes/plasma cells 1b. Medullary sinuses - communicate with efferent lymphatics and contain reticular cells and macrophages

Dendritic cells 1. Functions 2. How does it involve in innate and adaptive immune system? 3. Surface receptors 4. Also called

1a. Phagocytic antigen presenting cells 1b. Express MHC class II and Fc receptors 2. Links innate and adaptive immune systems 3. MHC Class II and Fc receptors 4. Langerhans cell in the skin

Measles: 1. Possible complications 2. What can help reduce mortality from measles?

1a. Subacute sclerotic pan-encephalitis) - FEW YRS LATER - fatal 1b. Encephalitis (1:2000) 1c. Giant cell pneumonia (rare except in immunosuppressed) 2. Vitamin A supplementation, especially in malnourished child

Spleen: 1. Immune response upon virus 2. Detailed physiological response for each one

1a. Virus can can either 1b. Enter follicle and get picked up by naive B 1c. Get picked up directly by macrophages in marginal zone 2a. naive B picks up -> presentation to T-cell -> Costimulation (B-T activate each other) -> B cells mature to plasma cell -> Ab. presentation 2b. Macrophage -> present antigen to T -> T present to B -> B matures to plasma cell -> Ab. production

Opsonization

Any molecule that enhances phagocytosis by marking an antigen for an immune response or marking dead cells for recycling ex. C3b mediated opsonization involves: 1. tagging microbial pathogen (IgM or IgG) 2. complement activation 3. phagocytosis

Very important to know about lymph node is that lymph drainage follows the _________________ to the region

Arterial supply Example: Inferior mesenteric node follows inferior mesenteric artery, so it means it drains the descending colon area

HLA A3

MHC class I producing gene that is associated with HEMOCHROMATOSIS

Cells of adaptive immune system

B/T cells (and Antibodies) Very specific to one antigen, but in so much variety that they can recognize ANY antigen

Differentiation of T cells

Bone marrow -> thymus cortex -> thymus medulla -> LN

IL-6

Causes fever and stimulates production of acute phase proteins

HLA DQ2/DQ8

Celiac disease - has to do with gluten absorption I ate (8) too (2) much gluten (celiac disease) at (D)airy (Q)ueen

Tonsil

Collections of lymphoid tissue facing into the aerodigestive tract. Includes the adenoid tonsil, two tubal tonsils, two palatine tonsils, and the lingual tonsil.

HLA DR3

Diabetes mellitus type I, SLE, Graves disease, Hashimoto thyroiditis, Addison disease Has disease from B8 (2), DR2, 4, 5

Reticular cells

Fibroblasts that synthesize collagen type III (reticular lamina)

Naive B cells contain which immunoglobulins?

IgM and IgD; IgD has unclear function, but mainly as a identifier for naive B cell for now

Bone Marrow

Immune cell production, (B)-cell maturation Primary organ - allows cells to mature into immunocompetent cells

IL-12

Induces differentiation of T cells to Th1 cells. Activates NK cells

Where are cells of innate immunity/adaptive immunity found?

Innate immunity - Essentially all throughout the body - including peripheral tissues, respiratory/GI tracts *** Essentially anywhere where pathogen might try to invade Adaptive immunity - circulate in the blood and exit via LN upon pathogen entering

Lymph node - Follicle 1. Function 2. Structure

Located at cortex 1. Site of B-cell localization and proliferation. 2. Composed of primary and secondary follicles Primary - dense and dormant Secondary - Pale central germinal center/active

HLA B27

MHC class I producing gene; associated with: (P)soriatic arthritis, (A)nkylosing spondylitis, (I)BD-associated arthritis, (R)eactive arthritis "PAIR" - AKA seronegative arthropathies

HLA B8

MHC class I producing gene; associated with: B8 - (Addison) disease, (My)asthenia gravis, (Grave)s diasease "Don't (B)e late(8), Dr. (Addison), or else you'll send (my) patient to the (grave)"

IL-8

Major chemotactic factor for neutrophils "CLEAR the AISLE 8. Neutrophils are recruited IL-8 to CLEAR infections"

Germline encoded mechanism

Mechanism of pathogen detection by innate immune cells - they genes do not shuffle or change - they are fixed for lifetime.

HLA DR2

Multiple sclerosis, hay fever, SLE, Goodpasture syndrome (Multiple hay pasture)s (SLE) have (D)i(R)t(two)

Pattern recognition receptor recognizes: Example:

Pathogen associated molecular pattern TLR4 (PRR) recognizes LPS of gran negative bacteria (PAMP)

Lymph node: mechanism of function upon detection of pathogen

Pathogen enters LN via afferent -> pass through the cortex -> cortex has B cells and T cells that can proliferate upon pathogen detection -> upon proliferation, the cell swells, and that is called lymphadenitis.

HLA DR4

Rheumatoid arthritis, diabetes mellitus type 1, addison disease 4 walls in a rheum

Lymph node: Structure

Secondary lymphoid organ with many afferents and one or more efferents. Key structures: 1. Follicle (geminal center/mantle zone) 2. Medulla 3. Paracortex 4. Hilum 5. Capsule/trabeculae 6. Supplying aa./vv.

Secondary organs

Spleen, Lymph nodes, tonsils, Peyer patches Allows cells to interact with antigen (actively participate in immune response after they mature into immunocompetent cell from primary organs)

Transcytosis

Start - lamina propria under basement membrane Notice that at the end IgA picks up secretory component (former poly-Ig receptor)

Thrombopoietin

Stimulate megakaryocyte proliferation

How do cells of innate immune system recognize pathogens?

They recognize "broad" pattern shared by non-animals, such as dsRNA, LPS, flagellin, or unmethylated DNA Also, they have PRR's that can recognize a group of pathogens (ex. TLR-4 recognizes gram-negative bacteria LPS). HOWEVER TLR IS ALSO PRESENT IN CELLS OF ADAPTIVE IMMUNITY (so TLR also mediates chronic inflammation) They can essentially detect all fungi, bacteria, and virus

How can B cells and T cells have so much variations?

Through V(D)J combination during development - heavy chains 65 V's 27 D's, and 6 J's = combination of these for antigen recognition ** Light chain also has a lot of variations